{"text": "MicroRNAs are ~17\u201324 nt. noncoding RNAs found in all eukaryotes that degrade messenger RNAs via RNA interference (if they bind in a perfect or near-perfect complementarity to the target mRNA), or arrest translation (if the binding is imperfect). Several microRNA targets have been identified in lower organisms, but only one mammalian microRNA target has yet been validated experimentally.We carried out a population-wide statistical analysis of how human microRNAs interact complementarily with human mRNAs, looking for characteristics that differ significantly as compared with scrambled control sequences. These characteristics were used to identify a set of 71 outlier mRNAs unlikely to have been hit by chance.C. elegans and Drosophila, many human microRNAs exhibited long exact matches (10 or more bases in a row), up to and including perfect target complementarity. Human microRNAs hit outlier mRNAs within the protein coding region about 2/3 of the time. And, the stretches of perfect complementarity within microRNA hits onto outlier mRNAs were not biased near the 5'-end of the microRNA. In several cases, an individual microRNA hit multiple mRNAs that belonged to the same functional class.Unlike the case in Drosophila and C. elegans.The analysis supports the notion that sequence complementarity is the basis by which microRNAs recognize their biological targets, but raises the possibility that human microRNA-mRNA target interactions follow different rules than have been previously characterized in  C. elegans and Drosophila [MicroRNAs (miRNAs) are small, ~18\u201324 nt. noncoding RNAs that are found in all eukaryotes and are cleaved from larger ~70 nt. precursors via the action of Dicer enzyme [reviews: ref. [osophila ,4.Drosophila [C. elegans [Drosophila [Drosophila microRNAs recognize 5\u20136 nt. common motifs within the target, these motifs are not a general feature of mammalian microRNAs [C. elegans and Drosophila.Five different papers have recently appeared that used computational approaches to predict microRNA targets in osophila -7, and mosophila ,9. Theseosophila ,11. In c elegans  and Drososophila , known microRNAs . Thus, iC. elegans and Drosophila, and identify a short-list of promising candidate microRNA-mRNA target pairs that are unlikely to have arisen by chance.In the present paper, we have performed an unbiased statistical analysis of the manner in which human microRNAs interact complementarily with human mRNAs present in the NCBI human RefSeq database, looking for characteristics that differ significantly as compared with scrambled versions of the same microRNA sequences. The results demonstrate several novel features of human microRNA-mRNA interactions that differ from Population-wide statistical analyses were first carried out by examining the types of complementary interactions that occur between the set of microRNAs listed in Lagos-Quintana et al , and theTo define the types of interactions that can occur by chance, ten independent sets (\"replications\") of scrambled microRNA counterpart sequences were generated and examined for complementarity with the mRNA population. Our underlying assumption is that scrambled sequences will hit mRNA at random and define the \"noise\" level in any given situation, whereas microRNA sequences will hit the same number of \"noise\" interactions plus any true targets. Unless otherwise noted, the scrambled sequences were random permutations of the microRNA sequences, keeping constant the overall nucleotide composition. Because microRNAs have a distinctive nonrandom di-nucleotide composition, we also confirmed that key findings were obtained when using scrambled sequences that had similar di-nucleotide composition to the microRNAs.First, we characterized the length distribution of exact complementarity between the population of mRNAs vs. the set of nonredundant microRNAs (i.e. those that overlapped by 10 or more bases were collected into groups and the longest member of the group was chosen as nonredundant). MicroRNAs produced significantly longer exact \"hits\" on mRNAs than their scrambled counterparts when G:U matches were excluded (fig. -9) and suggests that about 1/4 of the total hits in this \"10+ set\" occur upon \"true\" biological mRNA targets. Our approach is to identify further the mRNAs that represent statistical outliers (i.e. that are unlikely to be hit by chance) within this larger \"10+ set\" by comparing properties of hits made by the set of microRNA sequences vs. the set of scrambled sequences. At any given parametric value, the number of hits observed in the microRNA set, minus the number of hits in the scrambled set, provides an estimate of the number of true microRNA targets that satisfy that parametric value. We examined three different hit properties \u2013 a) exact hit length, b) gapped BLAST score and c) presence of multiple hits \u2013 both alone and combined with each other. Starting from the \"10+ set\" estimated to contain only 26% true targets (see above), we added additional criteria to compile a list of candidates estimated to contain over 80% true targets.As shown in figure The most important single parameter for discriminating hits produced by microRNAs vs. scrambled sequences appears to be exact hit length. At a cut-off of 17 exact hit length, there were 14 mRNAs hit by the microRNA set that satisfied this criterion, vs. an average of 1.9 mRNAs hit by each of the scrambled sequence sets  gave better discrimination power than using any single feature, supporting the idea that they are relevant to identifying biologically relevant mRNA targets. We examined three different combinations of parameter cut-off values: 1) One combination consisted of targets with multiple hits from distinct microRNAs less than 25 bases apart, with at least one exact hit \u226513 bases and with at least one gapped BLAST score \u2265185 (not counting G:U). For the next two lists, we scored only exact hits \u226510 bases long and that occurred \u226450 times within the entire mRNA population; this minimized \"noise\" arising from common or low-complexity target sequences, albeit at the cost of removing some target sequences that are shared within protein families. 2) Criteria required two or more hits from distinct microRNAs \u2264100 bases apart, at least one exact hit \u226514 bases and one gapped-BLAST score of \u2265190 (not counting G:U). 3) This required hits \u2264500 bases apart, at least one exact hit \u226514 bases, and at least one gapped-BLAST score > 89% of the best-possible score including G:U matches (this takes into account the fact that longer microRNAs have greater possible absolute scores than shorter microRNAs). for additional data files including a fully annotated outlier mRNA set, a list of all microRNA hits upon this set (extended with and without including G:U matches), and a list of the nonredundant microRNAs together with their putative mRNA targets.All three approaches produced lists of outlier mRNAs that had overlapping members, shared similar characteristics and exhibited similar discrimination ratios. For simplicity and robustness, these have been combined  into a single list consisting of 71 outlier mRNAs . As well, individual microRNAs hit multiple (up to 17) distinct members of the outlier set, which again happened significantly more often than by chance fig. . These fC. elegans and Drosophila. For example, there was no preference for microRNA hits to be located within 3'-untranslated regions: 5% of hits were located in the 5'-UTR, 1% at the 5'-UTR/coding junction, 67% in the protein coding region, 1% at the coding/3'-UTR junction, and only 26% in the 3'-UTR. This distribution was not significantly different from hits produced by the scrambled sequences. As well, the best microRNA hits upon candidate mRNA targets did not have relatively better target complementarity near their 5'-end: Only 13% of hits had \u2265 7 exact hit length starting at position 1 or 2 relative to the 5'end of the microRNA (vs. 17.5% of hits produced by scrambled sequences).The outlier mRNA set contained very similar types of targets as predicted by previous computational studies -8, inclu), further suggesting that this is likely to be a true biological target for microRNA regulation.MicroRNA 145 is particularly interesting because it hits 17 distinct targets on the candidate list, of which a disproportionate number (6) are in the signal transduction category and three of these are related to GTPase activation (Rho GTPase-activating protein (RICS), G protein gamma 7, and hypothetical protein FLJ32810 \u2013 containing RhoGAP and SH3 domains; Table By comparing how the population of microRNAs vs. their scrambled counterparts interact with the population of human RefSeq mRNA sequences, we estimate that the probability of detecting a true microRNA target increases a) as the length of exact complementarity of a \"hit\" between microRNA and target increases, b) as the overall complementarity of a \"hit\" increases , and c) as two or more distinct microRNAs hit the same mRNA in closer proximity. Targets in the outlier mRNA set also received more hits per unit length and more multiple hits from distinct microRNAs than expected by chance. Finally, we found cases in which an individual microRNA hit multiple mRNAs that belonged to the same functional class. The analysis suggests that target complementarity is a major factor in identifying biologically relevant mRNA targets: As values of each parameter increase, the difference between the number of hits in the microRNA set vs. the scrambled set increases steadily, and combining all three parameters gives better discrimination power than using any single feature.Drosophila [Drosophila targets: 1) Human microRNAs hit mRNAs with exact hit lengths extending much longer than observed in Drosophila, up to and including perfect complementarity. 2) Human microRNAs hit candidate mRNA targets within the protein coding region about 2/3 of the time.  3) Drosophila and C. elegans was simply obscured by the fact that we searched the large sequence space represented by all human mRNA sequences \u2013 the larger the sequence space, the greater the chance that any given target criterion will be satisfied by scrambled sequences, hence the more difficult it can be to detect true targets above the noise level. We agree that this can be a problem using very large sequence databases, such as the human EST database or the entire human genome. As well, using cut-off levels of parameter distributions to define the candidate list probably excludes many true human mRNA targets. However, human RefSeq was demonstrably not too large for our analysis, since very strong trends were observed in a variety of other parameters  Sequences in RefSeq > 20,000 bases long were removed from consideration because they were hit by many, if not all microRNAs, and a few sequences > 15,000 bases long were removed from the final candidate list because they had a relatively high false-positive probability. B) When counting the number of hits over the population of mRNAs, two hits were counted as redundant if the entire region around the hit (plus or minus 25 nucleotides on each side) was identical. C) When counting distinct hits by microRNAs on the same target, two hits were counted as redundant if they shared the same exact hit. This minimized possible artifacts due to overlapping microRNAs, as well as removed cases in which microRNAs hit exactly-repeating sequences within the target. D) In tabulating hits onto mRNA targets, we did not count hits that contained low-complexity sequences as detected by the DUST algorithm encoded by a Perl script provided by Lincoln Stein . E) WhenTo decide whether the number of observed microRNA hits were significantly different from chance, 10 replications of scrambled sequences were used to estimate prediction intervals. The prediction interval allows one to say with 95% confidence that any single new replication of the scrambled set will be below the value of the microRNA set. Prediction intervals were chosen as more conservative and more appropriate than confidence intervals.NS contributed biological expertise, whereas VT contributed statistical and computational expertise. The analyses were carried out together, and both authors read and approved the final manuscript."}
{"text": "MicroRNAs (miRNAs) are a new class of 18\u201323 nucleotide long non-coding RNAs that play critical roles in a wide spectrum of biological processes. Recent reports also throw light into the role of microRNAs as critical effectors in the intricate host-pathogen interaction networks. Evidence suggests that both virus and hosts encode microRNAs. The exclusive dependence of viruses on the host cellular machinery for their propagation and survival also make them highly susceptible to the vagaries of the cellular environment like small RNA mediated interference. It also gives the virus an opportunity to fight and/or modulate the host to suite its needs. Thus the range of interactions possible through miRNA-mRNA cross-talk at the host-pathogen interface is large. These interactions can be further fine-tuned in the host by changes in gene expression, mutations and polymorphisms. In the pathogen, the high rate of mutations adds to the complexity of the interaction network. Though evidence regarding microRNA mediated cross-talk in viral infections is just emerging, it offers an immense opportunity not only to understand the intricacies of host-pathogen interactions, and possible explanations to viral tropism, latency and oncogenesis, but also to develop novel biomarkers and therapeutics. MicroRNAs (miRNAs) are small RNA molecules which have recently gained widespread attention as critical regulators in complex gene regulatory networks in eukaryotes. These small RNA, processed from non-coding regions of the genome into 18\u201323 nucleotide long single stranded RNA, have been shown to regulate translation of messenger RNA (mRNA) by binding to it and effecting target cleavage or translational block depending on the extent of sequence complementarity with the target [MicroRNA mediated regulation has been lately shown to encompass a wide spectrum of host biological processes ranging from growth and development to oncogenesis -5. RecenMicroRNAs have recently been implicated in the intricate cross-talk between the host and the pathogen  in viralCaenorhabditis elegans [MicroRNAs were initially discovered in 1993, in a genetic screen for mutants that disrupt the timing of post-embryonic development in the nematode  elegans , and wasMicroRNAs have been classically thought to be transcribed from intergenic regions, but recent large-scale genome-wide cloning experiments  have shoMicroRNAs are transcribed by RNA Polymerase II as primary microRNAs (pri-miRNAs) which range from hundreds to thousands of nucleotides in length and resemble protein-coding transcripts in that they are poly-adenylated and capped . These pThe mechanism of action of microRNAs is considered to be by two modes \u2013 translational repression and target degradation. The former is common in mammalian systems while the latter is found predominantly in plants. The basic difference in the two mechanisms is thought to be primarily governed by the levels of complementarity between microRNAs and their target transcripts. Perfect or near perfect complementarity as is common in plant microRNAs and in a small class of eukaryotic microRNAs causes target cleavage and degradation , analogoIn fact, one microRNA can have binding sites in multiple targets  and one target can be repressed by multiple microRNAs (multiplicity and co-operativity) . Moreovevide infra). A recent report by Bhattacharyya et al suggests that microRNA mediated mechanism of post-transcriptional repression of gene expression is indeed reversible [Recent evidence suggests that microRNAs can also regulate protein expression through non-classical ways. Genome-wide expression analysis of microRNA targets have shown to decrease the transcript levels . But wheversible , suggestde novo prediction of microRNA still remains a challenging task. This is especially important in the case of viruses as viral microRNAs do not share close homology even in the same class. We hope the prediction algorithms will improve with a better understanding of the sequence and structural components of precursor hairpins involved in microRNA biogenesis [de novo method (unpublished results) for microRNA prediction in viruses based on Support Vector Machines, rationalizing that virus encoded microRNA precursor hairpins would share the sequence and structure features with that of host as they share the same microRNA processing machinery. The algorithms for microRNA target prediction also have been significantly improved from first-generation algorithms which rely on sequence complementarity rules, thermodynamic stability and conservation [Computational predictions have been the mainstay for discovery of microRNAs and their targets. The algorithms for microRNA prediction range from custom-made programs to search for hairpin loops and energetic stability to advanced algorithms employing machine learning approaches -25. Evenogenesis . We haveervation ,27,28 byervation .Viruses are obligate intracellular parasites and use the cellular machinery for their survival and replication. The success of the virus essentially depends on its ability to effectively and efficiently use the host machinery to propagate itself. This dependence on the host also makes it susceptible to the host gene-regulatory mechanisms. Though the gene regulatory mechanisms involving both host and viral proteins have been extensively studied, data on small RNA mediated gene regulation in viral infections is just emerging. Interestingly, it seems that the cellular microRNAs, in addition to their normal regulatory roles in cellular gene expression also double up as fortuitous agents that target foreign nucleic acids, as in the case of viruses. The inventory of microRNAs encoded differs between cell types, and thus may contribute to the tissue tropism of viruses. Some of these are elaborated in the subsequent sections.et al [Lecellier et al , for thenef. The targets were found to be highly conserved in all of the viral clade sequences with the exception of clade O. The fact that defective nef is well known to be associated with a long term non-progressor state led us to speculate that the levels of the cellular microRNAs would be a decisive factor in determining the progression of the disease. The targets have been experimentally validated (unpublished results) by cloning the target site in the 3'UTR of Green Fluorescent Protein (GFP) reporter gene. Analysis of previously reported microarray data [We have earlier shown , using rray data  of theseray data  . Two human encoded microRNAs mir-507 and mir-136 had potential binding sites in Polymerase B2 (PB2) and Hemagglutinin (HA) genes respectively. The target regions in the respective genes were not only found to be conserved across different viral strains, but were also found to fall in highly accessible regions of the predicted target RNA structure. Moreover, analysis of previously reported  microarrBoth the genes PB2 and HA are known to be critical for the pathogenicity of the virus. While HA is the surface glycoprotein involved in direct binding of the virus to the cell surface, HA in the H5N1 subtype carries a polybasic site, cleavage at which, by cellular proteases is an essential step in establishing infection. PB2 is one of the three components of the Ribonucleoprotein which is responsible for RNA replication and transcription. Recent evidence, from recombinant viruses generated by combinations of murine and avian viruses identified PB2 as one of the two genes associated with virulence. The polymerase activity was directly correlated with the high virulence of the murine strain in their cognate host . Anotheret al [Jopling et al  reportedInterestingly viruses have also evolved to evade RNAi by a variety of strategies. The suppressors of antiviral RNAi is better understood in plant viruses. To counteract the small RNA mediated interference, viruses express suppressors that interfere with microRNA as well as siRNA pathways . The virThe interest in discovering novel microRNA candidates using both computational tools and experimental validation of the predicted candidates have shown that viruses also encode microRNAs  latency associated transcript (LAT) encodes for a microRNA which target critical genes of the apoptosis pathway [Of late, Cui V genome . Subsequ pathway  includinSuch a mechanism could operate in other related herpes viruses like Epstein-Barr virus, which not only causes latent infection, but also associated with a wide spectrum of neoplasms in humans including Burkitts lymphoma and nasopharyngeal carcinoma. It is all the more probable that oncogenic herpes viruses like EBV and KSHV encoded microRNAs can target critical genes involved in oncogenesis. This is especially so in the case of EBV encoded microRNAs as they have been shown to be differentially expressed in different phases of the viral life . Our anaet al, using a combinatorial approach incorporating both computational prediction and experimental validation demonstrated the possibility that a virus-encoded microRNA could auto-regulate itself. A nef derived microRNA could down regulate nef expression in vitro suggesting that it could be a mechanism of maintaining low viremia in Long term non-progressor (LTNP) states [nef derived microRNA also suppress transcription [Omoto ) states . This ficription  by reducIn yet another instance, a virus encoded microRNA, is effectively used by the virus to tune down a set of genes and thereby evade cytotoxic T cell response . Simian Recently microRNA expression profiles have been analyzed for viral infections like HIV . MicroRNMicroRNAs and anti-microRNA oligonucleotides (AMOs) have been proposed as novel therapeutics ,56. ReceMicroRNAs are promising candidates for developing novel bio-therapeutics against viruses, as it requires only partial complementarity unlike siRNAs and thus can tackle the high rate of mutations in viruses better than siRNAs. Initial experiments creating microRNAs based on siRNA design rules have shown promising results . Our groWith evidence demonstrating that both host encoded and virus encoded microRNAs interact with host and virus transcripts respectively, in addition to their roles in regulating their own transcripts warrants a comprehensive analysis of host and virus microRNAs and their targets to elucidate a holistic picture of microRNA mediated host-virus interaction model Figure . The cha"}
{"text": "The name of first author Marina de Moraes Mour\u00e3o was written incorrectly in the citation. The correct name is: Mour\u00e3o MM. The correct citation is: Mour\u00e3o MM, Dinguirard N, Franco GR, Yoshino TP (2009) Phenotypic Screen of Early-Developing Larvae of the Blood Fluke, Schistosoma mansoni, using RNA Interference. PLoS Negl Trop Dis 3(8): e502. doi:10.1371/journal.pntd.0000502."}
{"text": "Tonsillar lipomas are rare benign tumors, with only a limited number of cases reported in the literature. Excision of the lipoma along with tonsillectomy has been proposed as the usual treatment option. We report a case of tonsillar lipoma which was managed by excision of the lesion without the need for a tonsillectomy. No recurrence was reported at a 2-year followup. A worldwide literature review was done to better define the clinical and histopathological features of these lesions. The authors propose that routine tonsillectomy is not required for these benign lesions and that simple excision of the stalk of the lipoma is sufficient. Benign tumors of the palatine tonsil are rare, usually presenting as polypoidal masses, and include papillomas, lymphangiomas, fibromas, and lipomas . AlthougA 28-year-old male presented with a one-year history of progressively increasing respiratory difficulty which was exacerbated in the left lateral decubitus position. The patient gave a history of multiple apneic spells at night. Upon initial examination of the oral cavity, no abnormality was observed. However, the patient, on making an effort, regurgitated a smooth surfaced polypoidal mass from the oropharynx. A large multilobulated polypoidal mass was seen arising from the inferior pole of the right tonsillar fossa and extending into the oropharynx . LaryngeWe present a case of tonsillar lipoma in a young adult which was managed with excision of the lesion without the need for a tonsillectomy and showed no recurrence at 2-year followup. The case highlights the fact that tonsillar lipomas can present with airway obstruction and that simple excision of the lesion without the need for tonsillectomy is sufficient for the management of these lesions.Benign tumors of the palatine tonsil are rare and usually take the form of a polyp. The polypoidal lesions of the tonsil are named on the basis of the predominant tissue component found on histological examination as squamous papillomas, lymphangiectatic fibrous polyp, fibrovascular polyp, haemangioma, and lipoma. Of all these benign polypoidal lesions of the tonsil, squamous cell papillomas are the most common, followed by lymphangiomas .Lipomas of the palatine tonsil are extremely rare lesions and only 23 cases have been reported so far . A revieTonsillectomy with the excision of the lesion has been described as the most common treatment option for tonsillar lipomas, while surgical excision of the lipoma and stalk, without tonsillectomy, has rarely been described in the literature , 12. TheWe present a case of tonsil lipoma presenting as sleep apnea and airway obstruction. Based on the twenty-three cases reported worldwide, it appears as though age and gender do not play a significant role in their development. While tonsillectomy remains the most frequently reported approach to removal of lipomas of the palatine tonsil, excision of the mass, without tonsillectomy, may represent a means of reducing risks of postoperative complications while maintaining low rates of recurrence."}
{"text": "The sulfonyl and aniline rings are rotated relative to each other by 53.0\u2005(1)\u00b0. In the crystal, pairs of N\u2014H\u22efO(S) hydrogen bonds link the mol\u00adecules into centrosymmetric dimers.The mol\u00adecule of the title compound, C N-(ar\u00adyl)-amides, see: Arjunan et al. -methane\u00adsulfonamides, see: Gowda et al. (2007N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Gelbrich et al.  \u00c5                           b = 11.959 (1) \u00c5                           c = 11.428 (1) \u00c5                           \u03b2 = 112.87 (2)\u00b0V = 1433.6 (2) \u00c53                                                   Z = 4                           K\u03b1 radiationMo \u22121                        \u03bc = 0.59 mmT = 293 K                           0.44 \u00d7 0.38 \u00d7 0.28 mm                                 Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.780, T                           max = 0.851Absorption correction: multi-scan (5752 measured reflections2924 independent reflectionsI > 2\u03c3(I)2361 reflections with R                           int = 0.013                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.036                           wR(F                           2) = 0.103                           S = 1.04                           2924 reflections177 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.28 e \u00c5\u22123                        \u0394\u03c1min = \u22120.38 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811030819/bt5590Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811030819/bt5590Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "The C\u2014SO2\u2014NH\u2014C torsion angle is \u221293.9\u2005(2)\u00b0. The benzene rings are tilted relative to each other by 61.9\u2005(1)\u00b0. The crystal structure features inversion-related dimers linked by pairs of N\u2014H\u22efO hydrogen bonds.In the title compound, C N-(ar\u00adyl)-substituted amides, see: Gowda et al. -aryl\u00adsulfonamides, see: Gowda et al.  \u00c5                           b = 9.479 (1) \u00c5                           c = 10.103 (2) \u00c5                           \u03b1 = 84.90 (2)\u00b0\u03b2 = 78.49 (1)\u00b0\u03b3 = 79.28 (1)\u00b0V = 743.46 (19) \u00c53                                                   Z = 2                           K\u03b1 radiationMo \u22121                        \u03bc = 0.93 mmT = 293 K                           0.48 \u00d7 0.44 \u00d7 0.32 mm                                 Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.663, T                           max = 0.754Absorption correction: multi-scan (4974 measured reflections3027 independent reflectionsI > 2\u03c3(I)2423 reflections with R                           int = 0.014                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.038                           wR(F                           2) = 0.104                           S = 1.03                           3027 reflections184 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.36 e \u00c5\u22123                        \u0394\u03c1min = \u22120.29 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  I, global. DOI: 10.1107/S160053681104219X/rz2649Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681104219X/rz2649Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "The C\u2014S\u2014N\u2014C torsion angles are \u221267.4\u2005(2) and 63.8\u2005(2)\u00b0 in the two independent mol\u00adecules. In one of the mol\u00adecules, a methyl group is disordered over two sets of sites with a site-occupation factor of 0.661\u2005(16) for the major occupany component. In the crystal, mol\u00adecules are packed into chains running along [101] through N\u2014H\u22efO(S) hydrogen bonds.The asymmetric unit of the title compound, C N-(ar\u00adyl)-amides, see: Bhat & Gowda -sulfonamides, see: Gowda et al. (2005N-(aryl\u00adsulfon\u00adyl)-amides, see: Shakuntala et al.  \u00c5                           b = 16.351 (1) \u00c5                           c = 13.351 (1) \u00c5                           \u03b2 = 96.485 (8)\u00b0V = 2565.8 (3) \u00c53                                                   Z = 8                           K\u03b1 radiationMo \u22121                        \u03bc = 0.25 mmT = 293 K                           0.46 \u00d7 0.44 \u00d7 0.40 mm                                 Oxford Diffraction Xcalibur diffractometer with Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.896, T                           max = 0.908Absorption correction: multi-scan (9793 measured reflections5225 independent reflectionsI > 2\u03c3(I)3538 reflections with R                           int = 0.015                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.045                           wR(F                           2) = 0.127                           S = 1.06                           5225 reflections306 parameters5 restraintsH atoms treated by a mixture of independent and constrained refinementmax = 0.25 e \u00c5\u22123                        \u0394\u03c1min = \u22120.32 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811027838/bt5569Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811027838/bt5569Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "Further, the N\u2014H bond in the C\u2014SO2\u2014NH\u2014C segment is syn with respect to the meta-methyl group in the aniline benzene ring and the ortho-methyl group in the sulfonyl benzene ring. The C\u2014SO2\u2014NH\u2014C torsion angle is \u221249.72\u2005(18)\u00b0. The sulfonyl and aniline benzene rings are tilted relative to each other by 71.6\u2005(1)\u00b0. The crystal structure features inversion-related dimers linked by pairs of N\u2014H\u22efO hydrogen bonds.In the title compound, C N-(ar\u00adyl)-amides, see: Gowda et al. (2007a            N-(ar\u00adyl)-methane\u00adsulfonamides, see: Gowda et al. (2007b            N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Gelbrich et al. -aryl\u00adsulfonamides, see: Gowda et al.  \u00c5                           b = 8.1604 (9) \u00c5                           c = 12.456 (1) \u00c5                           \u03b1 = 80.991 (9)\u00b0\u03b2 = 72.903 (8)\u00b0\u03b3 = 78.979 (8)\u00b0V = 771.04 (14) \u00c53                                                   Z = 2                           K\u03b1 radiationMo \u22121                        \u03bc = 0.38 mmT = 293 K                           0.50 \u00d7 0.44 \u00d7 0.40 mm                                 Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.832, T                           max = 0.862Absorption correction: multi-scan (5220 measured reflections3126 independent reflectionsI > 2\u03c3(I)2631 reflections with R                           int = 0.008                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.037                           wR(F                           2) = 0.109                           S = 1.05                           3126 reflections187 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.25 e \u00c5\u22123                        \u0394\u03c1min = \u22120.28 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811041341/nc2250Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811041341/nc2250Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "The mol\u00adecule is twisted about the N\u2014S bond with a C\u2014SO2\u2014NH\u2014C torsion angle of 44.55\u2005(17)\u00b0. The two aromatic rings are inclined relative to each other by 66.2\u2005(1)\u00b0. In the crystal, N\u2014H\u22efO hydrogen bonds link the mol\u00adecules into infinite chains parallel to the b axis.In the mol\u00adecule of the title compound, C N-(ar\u00adyl)-amides, see: Arjunan et al. methane\u00adsulfonamides, see: Gowda et al. (2007N-(ar\u00adyl)aryl\u00adsulfonamides, see: Gelbrich et al.  \u00c5                           b = 9.7830 (7) \u00c5                           c = 15.897 (1) \u00c5                           \u03b2 = 97.284 (7)\u00b0V = 1394.33 (17) \u00c53                                                   Z = 4                           K\u03b1 radiationMo \u22121                        \u03bc = 0.42 mmT = 293 K                           0.44 \u00d7 0.40 \u00d7 0.32 mm                                 Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.837, T                           max = 0.877Absorption correction: multi-scan (5245 measured reflections2841 independent reflectionsI > 2\u03c3(I)2438 reflections with R                           int = 0.009                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.036                           wR(F                           2) = 0.103                           S = 1.06                           2841 reflections177 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.28 e \u00c5\u22123                        \u0394\u03c1min = \u22120.36 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811029400/bt5582Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811029400/bt5582Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "The dihedral angle between the phenyl\u00adsulfonyl and aniline rings is 41.7\u2005(1)\u00b0. In the crystal, mol\u00adecules are packed into centrosymmetric dimers through pairs of N\u2014H\u22efO(S) hydrogen bonds.Mol\u00adecules of the title compound, C N-(ar\u00adyl)-amides, see: Arjunan et al. -methane\u00adsulfonamides, see: Gowda et al. (2007N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Gelbrich et al.  \u00c5                           b = 8.312 (1) \u00c5                           c = 16.043 (2) \u00c5                           \u03b2 = 97.27 (1)\u00b0V = 1470.8 (4) \u00c53                                                   Z = 4                           K\u03b1 radiationMo \u22121                        \u03bc = 0.22 mmT = 293 K                           0.48 \u00d7 0.36 \u00d7 0.20 mm                                 Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.901, T                           max = 0.957Absorption correction: multi-scan (5256 measured reflections2685 independent reflectionsI > 2\u03c3(I)2107 reflections with R                           int = 0.021                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.043                           wR(F                           2) = 0.125                           S = 1.04                           2685 reflections188 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.28 e \u00c5\u22123                        \u0394\u03c1min = \u22120.28 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811031102/bt5591Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811031102/bt5591Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "The amide and carboxyl C=O groups are syn to each other. Furthermore, the C=O and O\u2014H bonds of the carboxyl group are in syn positions with respect to each other. The dihedral angle between the benzene ring and the amide group is 47.8\u2005(2)\u00b0. In the crystal, mol\u00adecules are connected by pairs of O\u2014H\u22efO hydrogen bonds, forming inversion dimers. The dimers are further linked by N\u2014H\u22efO hydrogen bonds into double chains along the b-axis direction.In the title compound, C N-(ar\u00adyl)-amides, see: Gowda et al. -methane\u00adsulfonamides, see: Jayalakshmi & Gowda (2004N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Gowda et al.  \u00c5                           b = 4.7784 (7) \u00c5                           c = 23.892 (5) \u00c5                           \u03b2 = 121.20 (1)\u00b0V = 2322.2 (8) \u00c53                                                   Z = 8                           K\u03b1 radiationMo \u22121                        \u03bc = 0.32 mmT = 293 K                           0.42 \u00d7 0.10 \u00d7 0.08 mm                                 Oxford Diffraction Xcalibur with Sapphire CCD detector diffractometerCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.877, T                           max = 0.975Absorption correction: multi-scan (4399 measured reflections2322 independent reflectionsI > 2\u03c3(I)1680 reflections with R                           int = 0.020                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.062                           wR(F                           2) = 0.128                           S = 1.19                           2322 reflections152 parameters2 restraintsH atoms treated by a mixture of independent and constrained refinementmax = 0.28 e \u00c5\u22123                        \u0394\u03c1min = \u22120.25 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  I, global. DOI: 10.1107/S1600536811054638/yk2035Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811054638/yk2035Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "Further, the C=O bond and the meta-Cl atom in the benzoyl ring are also anti to each other. The dihedral angle between the sulfonyl and the benzoyl benzene rings is 72.4\u2005(1)\u00b0. In the crystal, mol\u00adecules are linked by pairs of N\u2014H\u22efO hydrogen bonds, forming inversion dimers.In the title compound, C N-(ar\u00adyl)-amides, see: Bowes et al. -methane\u00adsulfonamides, see: Jayalakshmi & Gowda (2004N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Gowda et al. (2003N-(substitutedbenzo\u00adyl)-aryl\u00adsulfonamides, see: Suchetan et al.  \u00c5                           b = 12.046 (1) \u00c5                           c = 15.596 (2) \u00c5                           \u03b2 = 118.77 (2)\u00b0V = 2971.3 (6) \u00c53                                                   Z = 8                           K\u03b1 radiationMo \u22121                        \u03bc = 0.40 mmT = 293 K                           0.40 \u00d7 0.36 \u00d7 0.32 mm                                 Oxford Diffraction Xcalibur diffractometer with Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.856, T                           max = 0.882Absorption correction: multi-scan (5996 measured reflections3024 independent reflectionsI > 2\u03c3(I)2463 reflections with R                           int = 0.012                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.042                           wR(F                           2) = 0.113                           S = 1.03                           3024 reflections185 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.45 e \u00c5\u22123                        \u0394\u03c1min = \u22120.64 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD ; data reduction: CrysAlis RED  I, global. DOI: 10.1107/S1600536811050574/bt5728Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811050574/bt5728Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "In the crystal, every water mol\u00adecule forms four hydrogen bonds with three different mol\u00adecules of 4-chloro-N-(3-methyl\u00adbenzo\u00adyl)benzene\u00adsulfonamide. One of the water H atoms forms a bifurcated hydrogen bond with both the sulfonyl and the carbonyl O atoms of the same mol\u00adecule. Mol\u00adecules are linked into layers in the ab plane through N\u2014H\u22efO and O\u2014H\u22efO hydrogen bonds.In the title compound, C N-(ar\u00adyl)-amides, see: Gowda et al. (2004N-(ar\u00adyl)-methane\u00adsulfonamides, see: Jayalakshmi & Gowda (2004N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Gowda et al. (2003N-(substitutedbenzo\u00adyl)-aryl\u00adsulfonamides, see: Suchetan et al.  \u00c5                           b = 12.864 (2) \u00c5                           c = 46.314 (5) \u00c5                           V = 2987.7 (7) \u00c53                                                   Z = 8                           K\u03b1 radiationMo \u22121                        \u03bc = 0.41 mmT = 293 K                           0.46 \u00d7 0.14 \u00d7 0.06 mm                                 Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.834, T                           max = 0.976Absorption correction: multi-scan (5972 measured reflections2684 independent reflectionsI > 2\u03c3(I)1959 reflections with R                           int = 0.037                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.105                           wR(F                           2) = 0.185                           S = 1.35                           2684 reflections200 parameters3 restraintsH atoms treated by a mixture of independent and constrained refinementmax = 0.33 e \u00c5\u22123                        \u0394\u03c1min = \u22120.34 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811051932/bt5739Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811051932/bt5739Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "The conformation of the N\u2014H bonds are anti to the ortho-methyl groups of the sulfonyl benzene rings in all the mol\u00adecules. The sulfonyl and the aniline benzene rings are tilted relative to each other by 43.0\u2005(2), 37.0\u2005(2) and by 46.0\u2005(1)\u00b0 in the three mol\u00adecules. In the crystal, inter\u00admolecular N\u2014H\u22efO hydrogen bonds link each of the mol\u00adecules into centrosymmetric dimers.The asymmetric unit of the title compound, C N-(ar\u00adyl)-amides, see: Gowda et al. (2000N-(ar\u00adyl)-methane\u00adsulfonamides, see: Gowda et al. (2007N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Gelbrich et al. -aryl\u00adsulfonamides, see: Gowda & Shetty  \u00c5                           b = 12.585 (1) \u00c5                           c = 18.523 (2) \u00c5                           \u03b1 = 96.404 (9)\u00b0\u03b2 = 95.279 (9)\u00b0\u03b3 = 103.39 (1)\u00b0V = 2257.4 (4) \u00c53                                                   Z = 6                           K\u03b1 radiationMo \u22121                        \u03bc = 0.39 mmT = 293 K                           0.46 \u00d7 0.28 \u00d7 0.20 mm                                 Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.840, T                           max = 0.926Absorption correction: multi-scan (15326 measured reflections8214 independent reflectionsI > 2\u03c3(I)3972 reflections with R                           int = 0.033                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.070                           wR(F                           2) = 0.152                           S = 1.02                           8214 reflections559 parameters3 restraintsH atoms treated by a mixture of independent and constrained refinementmax = 0.30 e \u00c5\u22123                        \u0394\u03c1min = \u22120.27 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811040876/bt5662Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811040876/bt5662Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "In the crystal, mol\u00adecules are linked via N\u2014H\u22efO(S) hydrogen bonds into helical chains running along the b axis.In the title compound, C N-(ar\u00adyl)-amides, see: Bowes et al. -methane\u00adsulfonamides, see: Jayalakshmi & Gowda (2004N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Gowda et al. (2003N-(substitutedbenzo\u00adyl)-aryl\u00adsulfonamides, see: Suchetan et al.  \u00c5                           b = 5.0577 (6) \u00c5                           c = 23.488 (3) \u00c5                           \u03b2 = 90.43 (1)\u00b0V = 1412.6 (3) \u00c53                                                   Z = 4                           K\u03b1 radiationMo \u22121                        \u03bc = 0.44 mmT = 293 K                           0.46 \u00d7 0.20 \u00d7 0.10 mm                                 Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.822, T                           max = 0.957Absorption correction: multi-scan (4873 measured reflections2840 independent reflectionsI > 2\u03c3(I)2204 reflections with R                           int = 0.017                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.058                           wR(F                           2) = 0.105                           S = 1.20                           2840 reflections202 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.35 e \u00c5\u22123                        \u0394\u03c1min = \u22120.35 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  I, global. DOI: 10.1107/S1600536811054857/bt5758Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811054857/bt5758Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "The main mol\u00adecule is planar by symmetry and its conformation is stabilized by an intra\u00admolecular O\u2014H\u22efO hydrogen bond. In the crystal, N\u2014H\u22efO and O\u2014H\u22efO hydrogen bonds link the mol\u00adecules into a three-dimensional network.The title compound, C N-(ar\u00adyl)-amides, see: Gowda et al. -methane\u00adsulfonamides, see: Jayalakshmi & Gowda (2004N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Shetty & Gowda  \u00c5                           b = 20.3357 (5) \u00c5                           c = 17.1671 (4) \u00c5                           V = 2356.42 (11) \u00c53                                                   Z = 8                           K\u03b1 radiationMo \u22121                        \u03bc = 0.35 mmT = 293 K                           0.81 \u00d7 0.25 \u00d7 0.12 mm                                 Oxford Diffraction Xcalibur diffractometer with a Ruby (Gemini Cu) detectorCrysAlis PRO 1131 reflections with R                           int = 0.027                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.044                           wR(F                           2) = 0.128                           S = 1.07                           1310 reflections118 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.25 e \u00c5\u22123                        \u0394\u03c1min = \u22120.44 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis PRO  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811052573/bt5742Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811052573/bt5742Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "In the crystal, inter\u00admolecular N\u2014H\u22efO hydrogen bonds link the mol\u00adecules into C(4) chains propagating in [001].In the title compound, C N-(ar\u00adyl)-amides, see: Bhat & Gowda -methane\u00adsulfonamides, see: Jayalakshmi & Gowda (2004N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Gowda et al.  \u00c5                           c = 19.8709 (9) \u00c5                           V = 5390.6 (4) \u00c53                                                   Z = 16                           K\u03b1 radiationMo \u22121                        \u03bc = 0.47 mmT = 293 K                           0.48 \u00d7 0.34 \u00d7 0.14 mm                                 Oxford Diffraction Xcalibur diffractometer with Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.807, T                           max = 0.937Absorption correction: multi-scan (5852 measured reflections2752 independent reflectionsI > 2\u03c3(I)1701 reflections with R                           int = 0.021                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.042                           wR(F                           2) = 0.120                           S = 1.01                           2752 reflections166 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.23 e \u00c5\u22123                        \u0394\u03c1min = \u22120.21 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811028935/bt6816Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811028935/bt6816Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "The conformations of all the N\u2014H, C= O and C\u2014H bonds in the central amide and aliphatic segments are anti to their adjacent bonds. The mol\u00adecule is bent at the S atom with an C\u2014SO2\u2014NH\u2014C(O) torsion angle of \u221276.4\u2005(3)\u00b0. The dihedral angle between the benzene ring and the SO2\u2014NH\u2014C(O) segment in the two halves of the mol\u00adecule is 67.2\u2005(1)\u00b0. In the crystal, N\u2014H\u22efO(C) inter\u00admolecular hydrogen bonds link the mol\u00adecules into chains along the b axis.In the crystal structure of the title compound, C N-(ar\u00adyl)-amides, see: Arjunan et al. -methane\u00adsulfonamides, see: Gowda et al. (2007N-(aryl\u00adsulfon\u00adyl)-amides, see: Rodrigues et al.  \u00c5                           b = 15.835 (2) \u00c5                           c = 10.106 (1) \u00c5                           \u03b2 = 112.31 (1)\u00b0V = 1188.1 (2) \u00c53                                                   Z = 2                           K\u03b1 radiationMo \u22121                        \u03bc = 0.26 mmT = 293 K                           0.22 \u00d7 0.20 \u00d7 0.06 mm                                 Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD detectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.944, T                           max = 0.984Absorption correction: multi-scan (4285 measured reflections2174 independent reflectionsI > 2\u03c3(I)1326 reflections with R                           int = 0.027                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.058                           wR(F                           2) = 0.139                           S = 1.04                           2174 reflections149 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.24 e \u00c5\u22123                        \u0394\u03c1min = \u22120.18 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811029783/nc2239Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811029783/nc2239Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "Further, the conformation of the N\u2014C bond in the C\u2014SO2\u2014NH\u2014C segment is gauche with respect to the S=O bonds. The C\u2014SO2\u2014NH\u2014C torsion angle is 54.9\u2005(2)\u00b0. The sulfonyl and aniline benzene rings are tilted relative to each other by 82.8\u2005(1)\u00b0. The crystal structure features inversion-related dimers linked by pairs of N\u2014H\u22efO hydrogen bonds. There are also weak C\u2014H\u22efO hydrogen bonds between these dimers.In the crystal of the title compound, C N-(ar\u00adyl)-amides, see: Gowda et al. (2003N-(ar\u00adyl)-methane\u00adsulfonamides, see: Gowda et al. (2007N-(ar\u00adyl)-aryl\u00adsulfonamides, see: Gelbrich et al.  \u00c5                           b = 8.0794 (5) \u00c5                           c = 16.470 (1) \u00c5                           \u03b2 = 101.575 (7)\u00b0V = 3007.0 (4) \u00c53                                                   Z = 8                           K\u03b1 radiationMo \u22121                        \u03bc = 0.57 mmT = 293 K                           0.50 \u00d7 0.46 \u00d7 0.42 mm                                 Oxford Diffraction Xcalibur diffractometer with a Sapphire CCD DetectorCrysAlis RED; Oxford Diffraction, 2009T                           min = 0.764, T                           max = 0.796Absorption correction: multi-scan (10045 measured reflections3067 independent reflectionsI > 2\u03c3(I)2555 reflections with R                           int = 0.018                                                            R[F                           2 > 2\u03c3(F                           2)] = 0.046                           wR(F                           2) = 0.124                           S = 1.09                           3067 reflections186 parameters1 restraintH atoms treated by a mixture of independent and constrained refinementmax = 0.42 e \u00c5\u22123                        \u0394\u03c1min = \u22120.73 e \u00c5\u22123                        \u0394\u03c1                                 CrysAlis CCD  used to solve structure: SHELXS97  I, global. DOI: 10.1107/S1600536811040189/bq2307Isup2.hkl            Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811040189/bq2307Isup3.cml            Supplementary material file. DOI:  crystallographic information; 3D view; checkCIF report            Additional supplementary materials:"}
{"text": "Recognizing the factors affecting the number of blood donation and blood deferral has a major impact on blood transfusion. There is a positive correlation between the variables \u201cnumber of blood donation\u201d and \u201cnumber of blood deferral\u201d: as the number of return for donation increases, so does the number of blood deferral. On the other hand, due to the fact that many donors never return to donate, there is an extra zero frequency for both of the above-mentioned variables. In this study, in order to apply the correlation and to explain the frequency of the excessive zero, the bivariate zero-inflated Poisson regression model was used for joint modeling of the number of blood donation and number of blood deferral. The data was analyzed using the Bayesian approach applying noninformative priors at the presence and absence of covariates. Estimating the parameters of the model, that is, correlation, zero-inflation parameter, and regression coefficients, was done through MCMC simulation. Eventually double-Poisson model, bivariate Poisson model, and bivariate zero-inflated Poisson model were fitted on the data and were compared using the deviance information criteria (DIC). The results showed that the bivariate zero-inflated Poisson regression model fitted the data better than the other models. Blood transfusion is so important in health system that it plays a big part in saving many people's lives in normal and emergency situations. Furthermore, it has a noticeable impact on improving the quality of life and consequently the life expectancy of chronic patients. Nevertheless, many patients either die due to lack of access to safe blood transfusion or at least suffer from it. According to the World Health Organization report, about one percent of the population of every country is in need of blood donation . Today, Poisson regression model belongs to the family of generalized linear models in which the response variable is a count one and has followed Poisson distribution. The equality of the variance and the mean of the dependent variable is one of the important hypotheses of Poisson regression analysis. In most practical applications, response observations are overdispersed ; thus fitting the Poisson regression model on the data will not yield the desired results. In a univariate case, the best solution to the problem of overdispersion is to use a negative binomial regression model , 13. In Due to calculation problems while fitting these models, researchers were not able to use zero-inflated bivariate count model for a long time . Recent This study seeks to determine the factors which affect the number of return for donation and also deferral from donation. The data is of the type of count data and, to explain it, it is necessary to use a count regression model. On the other hand, the data has a large number of zeros, and also there is a positive correlation between the number of return for donation and the number of deferral. In order to model these two variables obtained from blood transfusion data, the bivariate zero-inflated Poisson regression model was used. The remainder of the paper is organized as follows: in The data used in this research was obtained from a longitudinal study in which a random sample of donors who had a first-time successful donation were followed up for a maximum of five years and their number of return for blood donation and number of blood deferral were measured as response. A full description of the data can be seen in .  FigureY1 and Y2 are bivariate Poisson distribution and are shown as  ~ BP if their joint probability mass is given by \u03bbi > 0 and y1, y2 = 0, 1, 2, 3,\u2026. Marginal distribution of Y1 and Y2 is Poisson distribution with parameters of \u03bb1 + \u03bb3 and \u03bb2 + \u03bb3, respectively. Mean and variance of Y1 and Y2 are \u03bb1 + \u03bb3 and \u03bb2 + \u03bb3, respectively. The covariance between Y1 and Y2 is \u03bb3, which shows a measure of dependency between Y1 and Y2. Bivariate Poisson distribution can be defined using latent variables. Assuming Z1, Z2, and Z3 are mutually independent Poisson random variables with parameters \u03bb1, \u03bb2, and \u03bb3, respectively, then the covariance between Y1 and Y2 will beY1 and Y2 is given as\u03bb3 = 0; we have a special case which yields that Y1 and Y2 are independent. This way, the bivariate Poisson distribution becomes multiplication of two univariate Poisson distributions and is known as double-Poisson model [The discrete random variables of on model , 21.P0 < 1 and \u03bb = \u03bb1 + \u03bb2 + \u03bb3.Here, we use a bivariate zero-inflated Poisson (BZIP) model, which is a mixture of bivariate Poisson and a point mass at . The joint probability mass function of BZIP model is defined as , 23(4)fBThe marginal distributions of BZIP model are zero-inflated univariate Poisson distribution, whose probability mass function isgiven as (6)EYk=1\u2212yi1, yi2), i = 1,\u2026, n, is an observation from the bivariate zero-inflated Poisson and \u03bbk, k = 1,2, 3 [P0) via logit link function. We assume \u03b2 and \u03b3 are vectors of regression parameters for \u03bb1 and \u03bb2, respectively, and let \u03bb3 = exp\u2061(\u03b1).Assuming l\u03b8 =  is a vector of all regression parameters. We choose noninformative prior distributions for regression parameters as normal with zero mean and large variance of 1000. \u03b2i ~ N, \u03b3i ~ N,\u2009\u2009i = 1, \u2026, p, and \u03b1 ~ N.Suppose P0. We assume that the prior distributions of all parameters of model are independent of each other. Suppose there are n individuals under study whose responses are represented by yi = \u2032; i = 1, \u2026, n and Dobs =  is a vector of all observations. If L is likelihood function and \u03c0(\u03b8) and \u03c0(P0) are prior distributions of \u03b8 and P0, then the joint distribution of the data and the parameters is \u03b8, P0) will beIi is an indicator that  are both zero at which Ii = 1 and 0 otherwise. The posterior density of parameters is very complicated; thus, we use simulation approach of Markov chain Monte Carlo (MCMC) to estimate the parameters.Also, we choose uniform distribution in the  interval for The codes of the programs related to the models were written using the WinBUGS software version 1.4.3. To make sure of the convergence of parameter's chains, both graphical and analytical convergence diagnostics were used. In the graphical method, the behavior of the trace plots and the autocorrelation function were checked. Also, in order to study the convergence analytically, two parallel chains with a burn-in of 5000 samples and 30000 observations after that were run. The samples obtained from posterior distributions of the parameters were fed into R software and the modified Gelman-Rubin  scale reP0) are 0.43 and , respectively. In other words, in BZIP regression model, the posterior estimate of the parameter P0 = P is equal to 0.43. Since the number of the observed  in the response variables was 411, the observed proportion of zeros was 411 to 864, that is, 0.48. This value is close to the posterior estimate of the inflation parameter obtained from the BZIP regression model. In the univariate model, the posterior estimate of extra zero parameters in the zero-inflated Poisson regression model is obtained at 0.448 for the number of return for donation and 0.67 for the numbers of blood deferral. So, if the dependency between the two response variables is not considered, and the responses of the number of return for donation and deferral are assumed independent, then the probability of P will be equal to P(Y1 = 0) \u00b7 P(Y2 = 0), which will be estimated as 0.448\u22170.67, and result is 0.30, which is an underestimation compared to the BZIP model and the true proportion of zeros. The estimated value of the correlation coefficient of the BZIP model in absence of covariate using estimated moments is equal to 0.282, which is very close to the Spearman correlation coefficient of the original data (r = 0.276) that, in turn, shows the qualified fitting of the model.The posterior mean and 95% credible interval for the zero-inflation parameter (proportion of extra zeros) in model  were important factors to the number of blood donation. Results, also, showed that weight is an important factor to the number of blood deferral. To compare the models, deviance information criteria (DIC) were used ; the resThe findings showed that, among the independent variables, the only ones which influenced the number of donation were weight and job . Also, students returned to donate, most of all jobs, and housekeepers did so the least of all. Weight had a positive effect on the number of blood deferral as well; it looks like people with higher weights return for donation more than other people, which in turn causes a higher rate of blood deferral too.All the prior distributions for parameters of this model were noninformative, so the values of hyperparameters of prior distributions were selected in a way that their variance would be bigger. As another study, it is proposed to use bivariate zero-inflated negative binomial model with our data and results could be compared with BZIP model.This article mainly aims at discovering the factors influencing number of return for blood donation and number of blood deferral. To do so, the bivariate zero-inflated Poisson regression model was applied using a Bayesian approach via MCMC simulation. Since the proposed response is naturally bivariate, using ordinary univariate zero-inflated regression models will not yield the desired results. A positive correlation between dependent variables and zero frequency more than Poisson distribution in each of the dependent variables are the main characteristics of the data in this study. The idea of using the bivariate zero-inflated Poisson (BZIP) model was strengthened by these two features because this model not only explains the positive correlation between the two responses (as BP model does) but also explains overdispersion and underdispersion conditions (which BP does not). The bivariate zero-inflated Poisson model is an ideal model as it has overcome the problems of bivariate Poisson model .According to the estimate of the DIC in"}
{"text": "We argue that people will often eschew explicit victim blame  because it is counternormative and socially undesirable, yet they might still engage in subtle victim blame by attributing victims\u2019 suffering to behaviors the victims can control . We found support for this argument in three online studies with US residents. In Studies 1 and 2, participants viewed a victim posing either a high threat to the need to believe in a just world, which should heighten the motivation to engage in victim blame, or a low threat. They then rated explicit blame items and attributions for the victim\u2019s suffering. Explicit blame was low overall and not influenced by victim threat. However, participants attributed the high threat victim\u2019s suffering, more than the low threat victim\u2019s suffering, to high control causes, thus showing a subtle blame effect. In Study 2, explicit blame and subtle blame were less strongly associated (in the high threat condition) for individuals high in socially desirable responding. These results are consistent with our argument that explicit and subtle blame diverge in part due to social desirability concerns. In Study 3, most participants believed others viewed the explicit blame items, but not the attribution items, as assessing blame. Thus, attributions to high control causes can be seen as \u201csubtle\u201d in the sense that people believe others will view such statements as reflecting constructs other than blame. Our studies suggest a way of responding to innocent victims that could be particularly relevant in a modern context, given increasing social undesirability of various negative responses to disadvantaged and victimized individuals. The phenomenon of blaming innocent victims for their fate  has received intensive study in several scholarly literatures see \u20133). Rese. Rese3])In most victim blame studies, researchers assess explicit blame, with items such as \u201cTo what extent do you think that [victim\u2019s name]\u2019s behavior is to blame for [victim\u2019s condition]?\u201d e.g., ,9). One . One 9])Only a few researchers have investigated subtle, negative appraisals of innocent victims. For example, although not assessing victim blame per se, Aguiar, Vala, Correia, and Pereira  and DawtIn the current research, we add to the nascent literature on subtle, negative appraisals of innocent victims by investigating subtle blame of innocent victims. Specifically, we examine whether, in the absence of obvious cues about cause, people attribute victims\u2019 suffering to a cause that is under the victims\u2019 control; that is, a \u201chigh control cause.\u201d For instance, a person sustains injuries from driving into a lamppost. An example of a high control cause is reckless driving, whereas an example of a less controllable cause is swerving when an animal darts into traffic. For a victim suffering concussion, playing a high-risk sport without protective headgear is a high control cause, whereas slipping on the ice outside one\u2019s home is a less controllable cause.Research on Weiner\u2019s theory of responsibility and stigma e.g., ,22) show show22])The closest research to the present studies was conducted by Bal and van den Bos . Though In the present studies, we investigated subtle victim blame from a justice motive theory perspective, as did Bal and van den Bos . Our resIn Studies 1 and 2, we manipulated the threat that a victim posed to the need to believe in a just world. We then measured attributions to high control causes  and low control causes (a control variable), as well as explicit blame. The high threat condition should heighten the motivation to defensively blame the victim. Thus, one might expect participants to blame the victim more in the high threat than in the low threat condition. We predicted such evidence of victim blame, but only on our measure of subtle blame. Specifically, we predicted that participants in the high threat condition would attribute high control causes to the victim to a greater degree than participants in the low threat condition, thus showing a subtle blame effect; and we predicted that this effect should occur controlling for attributions to low control causes (Hypothesis 1). Note that, if the subtle blame effect reflects merely an underlying desire to find any cause for the high threat victim , then it should not occur when controlling for attributions to low control causes. Given that explicit blame is often counternormative, at least in a modern context, we predicted that participants would report low levels of explicit blame in both the high and low threat condition (Hypothesis 2).In Study 2, we also assessed individual differences in socially desirable responding. If explicit blame is counternormative and socially undesirable, whereas attribution to high control causes  is not, then the relation between these two variables should be moderated by individual differences in socially desirable responding. Our reasoning for this claim is based on the finding that social desirability concerns moderate the correlation between explicit and subtle  forms of various constructs . For exaIn Study 3, we tested whether attributions to high control causes can be seen as \u201csubtle\u201d blame in the sense that people do not think others will view such statements in terms of victim blame. Participants were asked open-ended questions about the meaning of the attribution and explicit blame items from Studies 1 and 2. We predicted that participants would view the explicit blame, but not the attribution items, as meant to assess victim blame (Hypothesis 4).In summary, our aim was to examine one way in which people might engage in subtle victim blame; specifically, by attributing a victim\u2019s suffering to causes perceived to be under the victim\u2019s control. We conducted three studies to achieve this aim. In Study 1, we tested whether people would subtly blame the victim when their motivation to engage in victim blame is heightened, and whether this would occur in the absence of a similar effect for explicit blame. In Study 2, we attempted to replicate the findings of Study 1 and test our reasoning that explicit and subtle blame diverge due to the social undesirability of the former. In Study 3, we attempted to clarify that the form of subtle blame investigated in these studies is subtle in the sense that people do not believe others will see such attributions in terms of blame. In each study we found support for our hypotheses.10.17605/OSF.IO/GZ3WH.We report all measures, manipulations, and exclusions in these studies. In addition, sample sizes were determined before any data collection, and were based on a priori power analyses, except for Study 3, for which we recruited enough participants to yield at least 30 individuals per condition. Data and materials for all studies are publicly available and can be found at DOI For each study in this paper, participants gave informed consent by reading an online informed consent letter, and then clicking on \u201cYes.\u201d All studies were reviewed and approved by Brock University\u2019s Social Science Research Ethics Board.completely unavoidable/no control to 7 = completely avoidable/complete control). Avoidability and control ratings were highly correlated (mean r = .71), thus we averaged them to create a composite measure of control. Participants also rated how likely they thought it was that each behavior could cause sepsis, the illness contracted by the victim in our studies . Sepsis was defined as a bacterial infection of the blood . Finally, participants were debriefed and paid $0.50.Fifty US residents were recruited over Amazon\u2019s Mechanical Turk (MTurk). After providing informed consent, participants rated the extent to which each of 12 behaviors are avoidable and under a person\u2019s control  was greater than the scale midpoint, t(49) = 25.43, d = 3.60, p < .001, indicating relatively high control. For the low control behaviors, average control  was less than the midpoint, t(49) = -2.39, d = -0.34, p = .02, indicating relatively low control. Average control for the high control behaviors was greater than for the low control behaviors, t(49) = 14.77, d = 2.09, p < .001. However, the high control  versus low control behaviors  were seen as equally likely to cause sepsis, t(49) = -1.28, d = -0.18, p = .21. Finally, a principal components analysis with varimax rotation yielded two components. The low control behaviors had high loadings on Component 1 (> .86) and low loadings on Component 2 (< +/-.14), whereas the high control behaviors had high loadings on Component 2 (> .75) and low loadings on Component 1 (< +/-.05).We selected two high control behaviors  and two low control behaviors . For the high control behaviors, the average for the composite control measure .We recruited 254 US residents through MTurk . The woman was said to be 21 years old and about to enter nursing school. She was still in hospital and was extremely distressed. After this video, participants were told they would soon view a second video offering further information about the victim\u2019s situation. We manipulated threat to the need to believe in a just world through these instructions by varying participants\u2019 expectations about the severity of the victim\u2019s suffering . I). I27]).Before watching the second video, participants completed the following measures: a manipulation check; attribution items (including those assessing subtle blame), which were presented in random order; explicit victim blame items; and filler questions disguising the focus of the study . Attribution items preceded the explicit blame items.All participants viewed the video described in the low threat condition. At the end of the study, participants provided demographics, and were debriefed and paid $1.00.very poorly to 7 = very well).As a manipulation check, participants rated how well the victim was doing (1 = r = .41) was the reason the victim had contracted sepsis . Participants similarly rated the two low control behaviors (r = .51). We averaged the ratings for the two high control and the two low control behaviors to yield two composite scores. The high and low control behaviors were presented along with two of the unselected behaviors from the pretest that were seen as unlikely to cause sepsis. These extra behaviors masked our focus on only a few causes.Subtle blame was assessed by having participants rate the likelihood that each of the two high control behaviors . Responses were averaged to create a composite, explicit blame score (Cronbach\u2019s \u03b1 = .80).Explicit blame was assessed with four items  than the mild suffering condition , t(252) = -1.72, p = .09. Finally, responses to an open-ended question asking how the victim likely contracted sepsis were not analyzed because we failed to establish a reliable coding scheme for high versus low control causes.Aside from the explicit blame items, there were two items assessing character derogation and four items assessing psychological distancing from the victim and her situation. Neither of these variables was significantly affected by the suffering manipulation (or the purpose manipulation), though victim character derogation was marginally greater in the severe suffering condition  thought the victim was doing better than did participants in the severe suffering condition , t(252) = 8.76, d = 1.10, p < .001. Thus, our manipulation of victim suffering  was effective. Correlations among the variables used to test hypotheses are in Participants in the mild suffering condition  than did participants in the mild suffering condition , F = 9.55, p = .002, \u03b7p2 = .04, 95% CImean diff . An ancillary ANCOVA showed that ratings for the low control behaviors (controlling for high control behaviors) did not differ by condition , F = 0.83, p = .37, \u03b7p2 = .003, 95% CImean diff . An ancillary Victim Suffering (mild vs. severe) X Controllability of Causes (low vs. high control behaviors) mixed ANOVA yielded a significant interaction, F = 5.07, p = .03, \u03b7p2 = .02, showing that victim suffering affected the ratings for high control behaviors, p = .003, d = 0.38, 95% CImean diff , independent of the (null) effect on ratings for low control behaviors, p = .61, d = 0.07, 95% CImean diff . Details for the mixed ANOVA are in the Supporting Information (We conducted an ANCOVA with Victim Suffering (mild vs. severe) as the independent variable and the perceived likelihood that the high control behaviors caused the victim\u2019s sepsis as the dependent variable. We controlled for the perceived likelihood that the low control behaviors caused the victim\u2019s sepsis. A sensitivity analysis showed that the ANCOVA had 80% power to detect an effect size of \u03b7ormation . Taken tt test to test Hypothesis 2. A sensitivity analysis showed that the t test had 80% power to detect an effect size of d = 0.35, with \u03b1 = .05. Victim suffering did not affect explicit blame, t(252) = .44, d = 0.06, p = .66, 95% CI , and explicit blame was low overall . Thus, as hypothesized, participants did not appear to resolve the threat posed by the severely suffering victim by explicitly blaming her, presumably because of the counternormative nature of victim blame.We used a In summary, we found evidence that, under conditions that should heighten the desire to engage in victim blame, people will subtly blame a victim by attributing the victim\u2019s suffering to a behavior that the victim could have avoided. Furthermore, our findings suggest that this subtle blame can occur in the absence of similarly motivated, explicit blame.For Study 2, we attempted to replicate the effect of victim suffering on the perceived likelihood that high control behaviors caused the victim\u2019s illness. We also tested Hypothesis 3: Subtle blame  will be less strongly associated with explicit blame for participants high versus low in socially desirable responding, especially in the severe suffering  condition.Mage = 36.54, SDage = 12.87; 78% White; 48% Christian, 44% atheist/agnostic).We recruited 300 US residents through MTurk. Four participants\u2019 data were removed\u2014two in the severe and one in the mild suffering condition\u2014because they did not watch the complete videos, leaving 296 cases  and self-deceptive enhancement (\u03b1 = .82) subscales .M = 5.35, SD = 1.29) thought the victim was doing better compared to participants in the severe suffering condition , t(294) = 12.02, d = 1.39, p < .001. Thus, the manipulation of victim suffering  was effective. Correlations among the variables used to test hypotheses are in Participants in the mild suffering condition  than did participants in the mild suffering condition , F = 5.65, p = .02, \u03b7p2 = .02, 95% CImean diff . An ancillary ANCOVA showed that ratings for the low control behaviors (controlling for high control behaviors) did not differ by condition, , F = 2.55, p = .11, \u03b7p2 = .01, 95% CImean diff . An ancillary mixed ANOVA yielded a significant Victim Suffering X Controllability of Causes interaction, F = 6.73, p = .01, \u03b7p2 = .02, showing that ratings for high control behaviors were affected by victim suffering, p = .03, d = 0.24, 95% CI , independent of the (null) effect on low control behaviors, p = .21, d = -0.15, 95% CI . Details are in the Supporting Information (An ANCOVA with Victim Suffering (mild vs. severe) as the independent variable was conducted on the perceived likelihood that the high control behaviors caused the victim to contract sepsis. We controlled for the perceived likelihood that the low control behaviors caused the victim\u2019s sepsis. The analysis had 80% power to detect an effect size of \u03b7ormation .t test used to test Hypothesis 2 had 80% power to detect an effect size of d = 0.33, with \u03b1 = .05. As predicted, victim suffering did not affect explicit blame , t(294) = 1.53, d = 0.18, p = .13, 95% CI .A f2 = .03, with \u03b1 = .05, and 8 predictors.To test Hypothesis 3, we ran one hierarchical regression for each BIDR subscale. The victim suffering manipulation, individual differences in socially desirable responding (centered), subtle blame , and the perceived likelihood ratings of low control behaviors were entered on the first step; the two-way interactions were entered on the second step; and the three-way interaction was entered on the third step. Explicit blame was the criterion. The analyses had 80% power to detect an effect size of b = -0.34, t(287) = -1.77, p = .08, sr2 = .01, 95% CI . Though only marginal, the pattern is consistent with Hypothesis 3, in that subtle blame predicted explicit blame to a lesser extent for individuals high (M + 1 SD), b = 0.25, t(287) = 3.55, p < .001, sr2 = .03, 95% CI  versus low (M\u20141 SD), b = 0.39, t(287) = 4.72, p < .001, sr2 = .06, 95% CI , in self-deceptive enhancement. Moreover, this interaction was superseded by a significant three-way interaction, b = -0.77, t(286) = -2.00, p = .046, sr2 = .01, 95% CI  that was also consistent with Hypothesis 3  = -2.68, p = .008, 95% CI , but not the mild suffering, b = 0.02, t(286) = .09, p = .93, 95% CI , condition. Within the severe condition, again subtle blame predicted explicit blame to a lesser extent for individuals high, b = 0.20, t(286) = 2.71, p = .007, sr2 = .02, 95% CI , versus low, b = 0.50, t(286) = 5.50, p < .001, sr2 = .08, 95% CI , in self-deceptive enhancement. The analysis involving the impression management subscale yielded no interactions, all ps > .23. Detailed statistics for the regressions are in the Supporting Information  and explicit constructs (see ). SpecifStudies 1 and 2 show evidence of subtle victim blame via the attribution of high control causes. We argued that these attributions constitute subtle blame in the sense that participants do not think the attribution items are meant to assess blame, and thus are not viewed as victim blame in the eyes of others. In Study 3, we asked participants open-ended questions about the meaning of either the explicit blame or the attribution items. If our claim is correct, consistent with Hypothesis 4, participants given the explicit items should be more likely to say the items assess blame, whereas participants given the attribution items should be more likely to say the items assess other constructs.Mage = 37.22, SDage = 11.47; 77% White; 49% Christian, 41% atheist/agnostic).We recruited 64 US residents through MTurk  video. They then answered filler items followed by either the explicit blame or the high and low control attribution items from Studies 1 and 2. Following the blame/attribution items, participants answered two open-ended questions: \u201cWhy do you think we are asking this question?,\u201d and \u201cWhat do you think this question is measuring?\u201d Participants then viewed the video in which the victim was doing well, provided demographics, and were debriefed and paid $1.00.Two individuals who were blind to participants\u2019 condition independently coded the open-ended responses into those reflecting \u201cblame and related constructs,\u201d and \u201cother.\u201d Interrater reliabilities were \u039a = .96 for the first open-ended question, and \u039a = .87 for the second question. Disagreements were resolved through discussion. The most common \u201cother\u201d responses indicated that the study or measures assessed health knowledge  or indicated uncertainty .w = .35, with \u03b1 = .05, df = 1. For \u201cWhy do you think we are asking this question?,\u201d \u03c72 = 18.67, p < .001, phi = -.54, and \u201cWhat do you think this question is measuring?,\u201d \u03c72 = 17.07, p < .001, phi = -.52, the proportion of participants endorsing each response category varied by the type of measure  X 2  contingency table analysis for each open-ended question. The analysis had 80% power to detect an effect size of sure see . As hypoVictim blame has a long history of study in the social sciences, with the vast majority of studies focussed on explicit blame. We investigated one way in which people more subtly engage in victim blame\u2014by attributing victims\u2019 fate to a cause that is under their control. In two experiments (Studies 1 & 2), we found evidence of this phenomenon. Supporting Hypothesis 1, participants exposed to a victim who presumably threatened a need to see the world as just, compared to participants exposed to a less threatening victim, reported a greater likelihood that the victim had contracted her illness through behaviors over which she had a high degree of control. Supporting Hypothesis 2, this effect occurred despite no similar effects for explicit blame , and despite no obvious cues regarding the cause of the victim\u2019s illness. Our interpretation of these findings is that explicitly blaming innocent victims for their fate is often counternormative e.g., \u201312), inh, inh12])These studies add to previous work by Bal and van den Bos . Bal andAlso unlike Bal and van den Bos , we measWe argue that the blame expressed in attributions to high control causes is subtle because perceivers\u2019 causal statements about an individual\u2019s suffering can be construed as reflecting a construct other than blame; in the present case, perceivers\u2019 objective knowledge of the victim\u2019s affliction. Indeed, supporting Hypothesis 4, results from Study 3 suggested that participants believed others view the attributions as indicative of constructs other than their tendency to blame the victim; most notably, their health knowledge. Although attributions can partly reflect knowledge, perceivers can also hide a desire to blame victims behind the mantle of expressing their knowledge of the causes of various conditions (see ).Our findings extend justice motive theory by suggesting a strategy for defending a belief in a just world other than those commonly investigated (see ). As sucThe implications of our research reach beyond justice motive theory. We examined victim blame in the context of a threat to the need to believe in a just world. However, we expect that subtle blame, in the absence of explicit blame, could also occur under other forces that compel individuals to engage in victim blame, as long as explicit blame is viewed as counternormative. Other forces include a heightened desire to engage in system justification , certainOur findings also add to the general literature on subtle versus explicit judgments. For example, in the attitude literature, there is evidence of greater correspondence between implicit evaluations (a form of subtle judgment) and explicit evaluations when concerns about self-presentation are weak . In theFrom a practical perspective, our results suggest that, in the absence of explicit blame, innocent victims might yet be subject to subtle blame. Interestingly, subtle blame could be as damaging to victims as explicit blame, given that attributions to high control causes can negatively affect the desire to help victims . Thus, rThe extremity of our victim stimulus (a woman who suffered amputations) likely maximized the chance of certain results. The more extreme the victimization, perhaps the more counternormative is victim blame, and thus the more people will express subtle blame in the absence of explicit blame. Aguiar et al.  found noIt is unclear whether our findings generalize to other victim situations. However, we believe that our findings would generalize beyond our specific scenario given that Bal and van den Bos  found siOur findings do not address whether endorsing high control causes as a form of subtle blame is a conscious or unconscious act of victim blaming. In Study 2, participants prone to self-deception  showed greater divergence of explicit and subtle blame. Thus, perhaps people engaging in subtle blame via attributions to high control causes believe others will not see their attributions as blaming the victim (as suggested by our Study 3), and do not consciously view their appraisals as victim blame. Furthermore, the fact that we found moderation by self-deceptive enhancement but not impression management presents the intriguing possibility that people avoid explicit blame primarily due to a tendency to see themselves in an overly positive light rather than a desire to make a good impression on others. These issues warrant further investigation.In conclusion, victim blame can come in many forms. We found evidence that people will eschew explicitly blaming a victim yet, when compelled by motivational forces, will still subtly blame that individual for his or her fate. Interestingly, if explicit victim blame is becoming more counternormative, the prevalence of subtle blame in the absence of explicit blame could increase.S1 Table(DOCX)Click here for additional data file.S2 Table(DOCX)Click here for additional data file.S1 Text(DOCX)Click here for additional data file.S2 Text(DOCX)Click here for additional data file. 31 Oct 2019PONE-D-19-24829Experimental evidence of subtle victim blame in the absence of explicit blamePLOS ONEDear Dr. Hafer,Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE\u2019s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.I have received reviews from two experts related to justice reasoning and responses to victims. As you can see from their comments below, both reviewers had very positive things to say about your manuscript. I also read the paper prior to reading their reviews to form my own independent impression and my response mirrored that of the reviewers. Most of the suggestions the reviewers made were fairly minor, so I will not restate them here. Reviewer 1, for example, thought more discussion of why the \u201cself-deception\u201d subscale, specifically, of the BIDR moderated the effects would be beneficial. Similarly, Reviewer 2 wondered if some examples of high versus low control causes might be helpful in the introduction.https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.We would appreciate receiving your revised manuscript by Dec 15 2019 11:59PM. 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This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.We look forward to receiving your revised manuscript.Kind regards,Daniel WisneskiAcademic EditorPLOS ONEJournal Requirements:http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf1. When submitting your revision, we need you to address these additional requirements. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at [Note: HTML markup is below. Please do not edit.]Reviewers' comments:Reviewer's Responses to QuestionsComments to the Author1. Is the manuscript technically sound, and do the data support the conclusions?The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: YesReviewer #2: Yes**********2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: YesReviewer #2: Yes**********3. Have the authors made all data underlying the findings in their manuscript fully available?PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data\u2014e.g. participant privacy or use of data from a third party\u2014those must be specified.The Reviewer #1: YesReviewer #2: Yes**********4. Is the manuscript presented in an intelligible fashion and written in standard English?PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.Reviewer #1: YesReviewer #2: Yes**********5. Review Comments to the AuthorPlease use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. Reviewer #1: Thank you for the opportunity to review this paper. Across three studies, the authors investigated whether people engage in subtle victim blaming by attributing victims\u2019 suffering to high control behaviors despite eschewing overt blame, and whether this is explained by social desirability concerns (because overtly blaming victims is counter-normative).The findings complement and extend recent research on overt and covert responses to victims and other stigmatized groups. This is an interesting topic, and the findings have important methodological (in terms of how responses to victims are measured/what we can expect given different means of measuring them) and theoretical implications.Overall, the paper is well written and a pleasure to read. The studies are well and designed, complementary to each other, and the findings clearly support for the authors\u2019 arguments and hypotheses. I have only a few, relatively minor suggestions.- Effect of suffering on attributions to low and high control causes in Studies 1 and 2. I appreciate the appropriateness of ANCOVA given hypothesis 1. It would be informative to show also whether the effect of suffering on low and high control causes differs in the way that the ANCOVA\u2019s (on high control) and t-test\u2019s (low control) might imply, but do not confirm \u2013 i.e., whether there is an interaction such that suffering increases attributions to high (compared to low) control causes more strongly. The results clearly suggest that greater suffering motivated ppts. to find fault with the victim\u2019s behavior in particular, rather than more strongly endorse any old cause. If suffering does increase high control attributions significantly over and above low control attributions, I think a stronger conclusion can be drawn. These additional analyses could be reported briefly in a footnote or supplementary materials.- Self-deception vs. impression management. In Study 2, the relation between implicit and explicit blame was moderated (under high suffering) by the self-deception, but not the impression management subscale, of the BIDR. The pattern of results supports the idea that people resort to subtle over overt blame due to social desirability concerns in general. Yet, might this pattern also suggest something about the specific locus of these concerns? My understanding is that the self-deception subscale measures the tendency to maintain a positive self-image (I don\u2019t want to see myself as counter-normative/a person who blames victims), whereas the impression management subscale pertains to managing others\u2019 impressions of the self (I don\u2019t want to be seen by others as behaving counter-normatively). Space permitting, I think it would be good to briefly address this.Minor Comments- It would be helpful to provide intercorrelations between measures in Study 1- There is a (presumed) typo on line 177 - A reference is needed on line 384 (research on relation between explicit/implicit constructs)Reviewer #2: Review of PONE-19-24829The authors report three studies testing subtle victim blame effects. In Study 1, they found that under conditions of just world threat, participants subtlety blamed the victim by attributing the victim\u2019s suffering to a behaviour that the victim could have avoided (high control cause). Study 2 found that the Study 1 effect was modulated by self-deception. Study 3 shed light on the idea that people don\u2019t perceive subtle blame as blame (vs. explicit blame judgments).Taken together, the studies are providing important new insights into how people respond to the suffering of innocent victims. Although some recent work has begun to explore similar ideas in the context of subtle victim derogation , none have examined how subtle victim blame can manifest as one response to the suffering of an innocent victims. The authors show that one way such subtle blame can manifest is through people endorsing causes for someone\u2019s suffering that don\u2019t, prima facie, seem like blame judgments.I only have a few suggestions that might help improve the work:1) I think some concrete examples of high vs. low control causes might help provide the reader with a bit more context for the work. Somewhere around line 83.2) Lerner\u2019s theorizing about the two forms of the justice motive\u2014basically, implicit vs. explicit--doesn\u2019t seem to be given much coverage here. It might not be exactly relevant to the current work, but mention of this theorizing might provide a bit more theoretical grounding for the research.3) I wondered whether it would have been more appropriate to control for high control variables when testing the effect of suffering status on low control behaviors (as was done for low control behaviors)4) Most of the theorizing in the introduction about the role of SDR was in general terms but the authors analysed impression management and self-deception separately. I think this is fine given the known two subcomponents of the BIDR, but it would be good to see more discussion of why the effects were observed for SDE and not impression management. What are the differences between these forms of SDR that might shed light on why effects were observed for one and not the other?Signed reviewMitch Callan**********what does this mean?). If published, this will include your full peer review and any attached files.6. PLOS authors have the option to publish the peer review history of their article  digital diagnostic tool,  6 Dec 2019Reviewer #11) - Effect of suffering on attributions to low and high control causes in Studies 1 and 2. I appreciate the appropriateness of ANCOVA given hypothesis 1. It would be informative to show also whether the effect of suffering on low and high control causes differs in the way that the ANCOVA\u2019s (on high control) and t-test\u2019s (low control) might imply, but do not confirm \u2013 i.e., whether there is an interaction such that suffering increases attributions to high (compared to low) control causes more strongly. The results clearly suggest that greater suffering motivated ppts. to find fault with the victim\u2019s behavior in particular, rather than more strongly endorse any old cause. If suffering does increase high control attributions significantly over and above low control attributions, I think a stronger conclusion can be drawn. These additional analyses could be reported briefly in a footnote or supplementary materials.Our response: The analysis suggested by Reviewer #1 is a Victim Suffering (mild vs. severe) X Controllability of Causes (low control vs. high control behaviors) mixed ANOVA with repeated measures on the second factor. The dependent variable is the perceived likelihood that the behaviors caused the victim\u2019s sepsis. We conducted this mixed ANOVA for Studies 1 and 2. In both cases, there is a significant interaction between victim suffering and controllability of causes: Participants in the severe suffering condition rated the high control behaviors as more likely to have caused the victim\u2019s sepsis than did participants in the mild suffering condition, whereas ratings for the low control behaviors did not differ by condition. Thus, as Reviewer #1 suggests should be the case, greater suffering increases high control attributions significantly, independent of any such effect on low control attributions. In the revised manuscript, we briefly state the findings of these mixed ANOVAs in the first paragraph of the \u201cVictim blame\u201d section of the Results for Studies 1 and 2. We refer to new supplemental information files  for details.2) - Self-deception vs. impression management. In Study 2, the relation between implicit and explicit blame was moderated (under high suffering) by the self-deception, but not the impression management subscale, of the BIDR. The pattern of results supports the idea that people resort to subtle over overt blame due to social desirability concerns in general. Yet, might this pattern also suggest something about the specific locus of these concerns? My understanding is that the self-deception subscale measures the tendency to maintain a positive self-image (I don\u2019t want to see myself as counter-normative/a person who blames victims), whereas the impression management subscale pertains to managing others\u2019 impressions of the self (I don\u2019t want to be seen by others as behaving counter-normatively). Space permitting, I think it would be good to briefly address this.Our response: Reviewer 1\u2019s point is related to our comment at the end of the \u201cLimitations and future directions\u201d section regarding the conscious versus unconscious nature of subtle blame. Thus, we added a sentence to this paragraph stating one implication of our finding that only self-deceptive enhancement moderated the relation between subtle and explicit blame.3) - It would be helpful to provide intercorrelations between measures in Study 1Our response: We revised Table 1 so that it now contains intercorrelations for Study 1 and Study 2. We also moved Table 1 to immediately after its first mention (the end of the 1st paragraph for the Results and Discussion of Study 1). 4) - There is a (presumed) typo on line 177 Our response: The Reviewer is correct. We have changed \u201cdata analysis\u201d to \u201cdata collection\u201d (see the 1st paragraph of Study 1).5) - A reference is needed on line 384 (research on relation between explicit/implicit constructs)Our response: We have added a citation (see 2nd paragraph of the Discussion for Study 2).Reviewer #21) I think some concrete examples of high vs. low control causes might help provide the reader with a bit more context for the work. Somewhere around line 83.Our response: We have included two examples of high and low control causes (see the end of the 4th paragraph of the Introduction).2) Lerner\u2019s theorizing about the two forms of the justice motive\u2014basically, implicit vs. explicit--doesn\u2019t seem to be given much coverage here. It might not be exactly relevant to the current work, but mention of this theorizing might provide a bit more theoretical grounding for the research.Our response: We have added Lerner\u2019s notion of deliberative/rational versus intuitive/defensive processes with respect to the justice motive (see the 3rd paragraph of the Introduction).3) I wondered whether it would have been more appropriate to control for high control variables when testing the effect of suffering status on low control behaviors (as was done for low control behaviors)Our response: We have replaced the t tests using low control behaviors as the dependent variable with ANCOVAs, as Reviewer #2 suggests (see the 1st paragraph of the \u201cVictim blame\u201d section of the Results for Studies 1 and 2).4) Most of the theorizing in the introduction about the role of SDR was in general terms but the authors analysed impression management and self-deception separately. I think this is fine given the known two subcomponents of the BIDR, but it would be good to see more discussion of why the effects were observed for SDE and not impression management. What are the differences between these forms of SDR that might shed light on why effects were observed for one and not the other?Our response: See our response to Reviewer #1\u2019s Point 2.AttachmentResponse to Reviewers.docxSubmitted filename: Click here for additional data file. 16 Dec 2019Experimental evidence of subtle victim blame in the absence of explicit blamePONE-D-19-24829R1Dear Dr. Hafer,We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements.Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication.https://www.editorialmanager.com/pone/, click the \"Update My Information\" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact With kind regards,Daniel WisneskiAcademic EditorPLOS ONEAdditional Editor Comments :Reviewers' comments: 18 Dec 2019PONE-D-19-24829R1 Experimental evidence of subtle victim blame in the absence of explicit blame Dear Dr. Hafer:I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. onepress@plos.org.If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact plosone@plos.org. For any other questions or concerns, please email Thank you for submitting your work to PLOS ONE.With kind regards,PLOS ONE Editorial Office Staffon behalf ofDr. Daniel Wisneski Academic EditorPLOS ONE"}
{"text": "Background: Despite extensive research in the field of psychotherapies, few studies have compared the primary psychotherapies of naturalistic design, which represents real-life situations.Objective: The objectives of this study were to evaluate three modalities of evidence-based psychotherapy for clinical, psychosocial, and biological outcomes and to identify the mediators and confounders of this process. Our primary hypothesis is that all psychotherapies will improve clinical and psychosocial outcomes and will increase BDNF levels.Methods:Design: longitudinal, naturalistic. Participants: One hundred twenty-six patients who underwent one of three evidence-based modalities of individual psychotherapy  were included. Measure: Primary outcomes are divided into three domains of variables: clinical , biological (serum BDNF levels), and psychosocial . Confounding/mediator variables included clinical , psychosocial , and other (religiosity) factors. Procedure: The follow-up period will be baseline and 6 months and 1 year after entering the study. The study will include 42 controls for biological variables only. Sample size calculation considered a significance level of 5% and a power of 80% to detect a difference of 0.22 with a standard deviation of 0.43, assuming losses of 20\u201330% of patients. The comparison between the modalities of psychotherapy will be by generalized estimating equations (GEE) model, the analysis of mediators by the Hayes method, and confounders by multivariate logistic regression.Discussion: The findings of this study are intended to demonstrate the outcomes of evidence-based psychotherapies for clinical, psychosocial, and biological parameters and to understand the mediators and confounders of this process in a real-life setting for patients with severe mental illness, thus contributing to the establishment of evidence-based public health policies in the field of psychological interventions. Psychotherapies are effective interventions for most mental disorders \u20134. A sysComparisons between different types of psychotherapy have long been a source of controversy , even wiAlthough there have been many randomized clinical trials (RCTs) evaluating the outcomes of psychotherapies, this is the first protocol of a study to evaluate main available evidence-based psychotherapies using a naturalistic longitudinal design and including patients referred from primary and secondary centers with complex and severe disorders. This design has the advantage of evaluating clinical outcomes in a real-world situation. Clinical trials, on the other hand, have the standardization of interventions, but can suffer from a lack of rigorous control related to the criteria for inclusion of patients; also, longitudinal studies have a level of evidence lower than that of randomized clinical trials and meta-analyses . To our Reviewing the longitudinal studies in psychoanalytical psychotherapy published on PubMed, PsychInfo, and Embase databases within the last 5 years, we found seven studies \u201316, all The question of how to evaluate outcomes in psychotherapy is quite complicated and has been the subject of numerous studies . The mosPsychotherapies can function by environmental epigenetic mechanisms, altering gene expression through methylation of the DNA of the serotonin transporter gene (5HTT) and altering imaging exams. However, this subject has been rarely studied . The seaChanges in BDNF have already been investigated in different psychotherapies  in cliniPatients with borderline personality disorder who underwent behavioral dialectical psychotherapy had a change of methylation of the BDNF gene at the end of the treatment that was associated with change scores in depression, hopelessness, and impulsivity . PatientDespite the extensive literature of comparative studies of psychotherapies, there are still issues related to the effects of moderators and mediators in the psychotherapeutic process, especially considering a view of protective factors, biological factors, and outcomes that encompass factors of positive psychiatry such as quality of life and resilience. In addition, further studies are needed in naturalistic and severe patient contexts that assess psychotherapy in practice, seeking external validity.Our primary aim is to evaluate the outcomes associated with different forms of individual psychotherapy  in a public outpatient clinic for mental disorders. Our primary outcomes are divided into three domains of variables: clinical , biological (serum BDNF levels), and psychosocial .Our secondary aim is to evaluate potential confounders/mediators/moderators for the main outcomes: personality traits, type of psychotherapy, number of sessions, the therapist\u2019s duration of training, concomitant use of pharmacological treatment, history of previous psychotherapeutic treatment, medical and psychiatric comorbidities, psychiatric diagnosis, therapeutic alliance, and defense mechanisms.Our main hypothesis is that all three modalities of therapy will produce reduction of symptoms in the clinical domain and improvement in the psychosocial domain. All psychotherapies will increase BDNF at 6 months of follow-up. As secondary hypotheses, the mechanisms of improvement will be mediated by the therapeutic alliance, motivational status, and defense mechanisms (for PDT). The confounders of this therapeutic improvement will be number of sessions, comorbidities, and medication use. The moderating factors will be gender, age, personality traits, religiosity, and defense mechanisms (for CBT).The Longitudinal Investigation of Psychotherapy Outcome (LIPO) study will compare three modalities of psychotherapy  in a longitudinal course, in a naturalistic setting. The choice of the three modalities of psychotherapy is evidence-based and listed in guidelines for indication of first-line treatment for depression , 31.The evaluations will take place in three moments: in the baseline (until the fourth session of psychotherapy) and 6 and 12 months after entering the study. The invited participants will be the patients who are undergoing any psychotherapy in the outpatient clinic of the Hospital de Cl\u00ednicas of Porto Alegre (HCPA).All patients included at the HCPA psychotherapy clinic will be evaluated by a fourth-year psychiatry resident with training in psychotherapy. Patients will be referred from the outpatient clinic of clinical psychiatry, pain medicine, or preoperative bariatric surgery. Each patient who agrees will undergo up to five evaluation interviews and engage in discussions with a supervisor. They will be next referred, based on clinical judgment, to the most suitable modality of psychotherapy. The clinic offers three methods of individual psychotherapy: PDP, IPT, and CBT.The psychotherapy modality will be indicated by general criteria , considePsychotherapeutic care will be provided by psychiatry residents in their second, third, and fourth years of residency in psychiatry under weekly supervision of dialogued interviews. The residents have weekly theoretical seminars related to each of the psychotherapeutic techniques offered throughout the period of residence. They also engage in weekly clinical seminars in which patients are interviewed by teachers to prompt discussions about the clinical aspects related to cases. When there is doubt about patient management, the patient is interviewed by the supervisor.For the purposes of this study, outcomes were divided into clinical, psychosocial, and biological domains to make the study as comprehensive as possible in understanding the complex processes of change that may occur in psychotherapies (Table 1). The clinical domain refers to the more traditional measures of symptoms used to mediate the effectiveness of psychotherapy , 14. TheThe Symptom Checklist-90-Revised (SCL-90-R) is a self-administered scale consisting of 90 items distributed over nine dimensions: somatization, depression, interpersonal, obsessive\u2013compulsive sensitivity, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism. The scales of answers range from 0  to 4 (an extreme degree of injury). Over the 6 months after discharge from the clinical follow-up, only paranoid ideation and the psychosis domains are considered. This situation results in a total of 16 items. The next follow-ups are conducted face to face, which allows for the application of the entire checklist .These self-report rating inventories, developed by Beck, aim to measure symptoms of depression and suicidal ideation [Beck Depression Inventory (BDI)] and anxiety [Beck Anxiety Inventory (BAI)] .Blood Collection\u2003Serum samples will be obtained by venipuncture, and the blood will be immediately centrifuged at 3,000 \u00d7 g for 5 min. The samples will be stored at \u221280\u00b0C until biochemical analysis.\u00ae, Houston, TX, USA), according to the manufacturer\u2019s instructions, with techniques standardized by our group. The total quantity of proteins was measured according to the Lowry method.The levels of neurotrophins (BDNF) will be measured using a sandwich ELISA kit .The World Health Organization Quality of Life\u2014BREF (WHOQOL-BREF) is an abbreviated quality of life instrument developed by the World Health Organization. It consists of 26 items that are answered in response scales ranging from 1 to 5, and it is based on a four-domain structure  , 36.The Connor\u2013Davidson Resilience Scale (CD-RISC) is a widely used self-report consisting of a 25-item questionnaire for evaluating individual resilience. It is divided into four domains: tenacity, adaptability\u2013tolerance, reliance on support from the outside, and intuition , 38.The Medical Outcomes Study (MOS) Social Support Survey consists of 20 self-reported items .The SF-6D was adapted to Brazilian Portuguese\u2013Brazil (version 2002). This self-administered instrument produces a unique score, which ranges from 0 to 1. The score represents the strength of an individual\u2019s preference for a given health condition; 0 corresponds to the worst health status and 1 corresponds to the best health status .The mediating factors will be therapeutic alliance, motivation, and defense mechanisms (for PDT only). The moderating factors will be gender, age, religiosity, stressors, social support, personality traits, and defense mechanisms (for CBT and IPT). The confounding factors considered will be diagnosis, medication use, number of sessions, and comorbidities.The psychodynamic diagnosis was based on Operationalized Psychodynamic Diagnosis (OPD II), a multiaxial diagnostic system for psychodynamicaly oriented therapists and psychiatrists , 42.The Personality Inventory for DSM-5  (PID-5)\u2014Adult . A set oThe Life Events Questionnaire (LEQ) evaluates the occurrence of 14 stressful life events over the last 12 months and the impact of these events on the subject\u2019s life. The LEQ also focuses on the stressors\u2019 association with the onset of current psychiatric problems .The California Psychotherapy Alliance Scale (CALPAS) is a 24-item self-applicable questionnaire .The Defense Style Questionnaire (DSQ-40) is a 40-item self-applicable questionnaire that aims to identify derivatives of defense mechanisms .The University of Rhode Island Change Assessment (URICA) assesses motivation for change by providing scores on four stages of change: precontemplation, contemplation, action, and maintenance .meaning of life) located in the psychological domain of the WHOQOL-BREF (The Duke University Religion Index (DUREL) is a five-item measure of religious involvement. It was developed for use in large cross-sectional and longitudinal observational studies , 49. TheQOL-BREF , 50.Our sample size calculation relied on the study of Schaf  using BDThe study will include a subsample of healthy controls for control of blood samples that were recruited from the HCPA blood bank. The exclusion criteria for the control group included conditions (current or past) that precluded participation in the study , immune disorders, use of immunosuppressants, anti-inflammatory drugs used for fewer than 3 weeks, smoking, abuse and/or drug addiction, and infectious diseases for fewer than 3 weeks.t tests will be performed. To determine differences between categorical variables, the chi-squared test will be used. For nonparametric distributions, we will use the Wilcoxon test and Mann\u2013Whitney U test to compare nonrelated and related means, respectively. A generalized estimating equations (GEE) model will be used to investigate multivariate repeated measurements. The Hayes method will be used to analyze the mediators . The statistical analyses will be performed using the SPSS version 20.0 software package .The data will be expressed as mean \u00b1 standard deviation (SD), and a The study will be disseminated through the presentation of its protocol in meetings with the outpatient services of the HCPA that refer patients to the psychiatry service, such as the internal medicine, pain, and bariatric surgery outpatient clinic.The researchers will not participate in the indication of treatment of patients or in their assistance. Patients will be sought weekly in the HCPA outpatient medical records and through contact with resident physicians screening new patients. Those who fall into the eligibility criteria will be contacted by phone by the research assistant and invited to participate. It will be explained that refusal to participate will not entail any loss to the treatment. If they agree to participate, they will be asked to attend the HCPA Clinical Research Center (CPC-HCPA), where they will receive the informed consent form, sociodemographic interview, OPD interview, BDNF blood collection, and protocol with self-administered questionnaires. The consent form and OPD will be applied by the researchers. Patients will be contacted by telephone for the follow-up of 6 and 12 months .This study will be conducted in the city of Porto Alegre in the state of Rio Grande do Sul in far-southern Brazil. This region has Portuguese, Italian, German, and African influence. It has a population of 1.4 million, and it is the 10th most populous city in Brazil. Its ethnic distribution is as follows: White (79.2%), Black (10.2%), and Pardo  people (10.6%). Its religious distribution is as follows: Catholic (83%), Protestant (9%), and others and atheists (8%). Brazil is a country with a high level of religiosity, and it is common for people to associate improvements in their health as being due to their faith . The rolThe only naturalistic longitudinal study that we found concluded that there was no significant difference in outcomes between therapies, as well as among therapists. However, these results need to be viewed with caution given some limitations related to loss, incomplete data, and the lack of long-term follow-up. Our study used direct contact with patients, which increased the number of variables and collection of BDNF as a possible biomarker in response to psychotherapy intervention.Historically, studies in psychotherapy have been difficult to perform because they involve multiple factors and variables that are interrelated. Many variables may act as only associated factors, and others  may have varying effect sizes. We had difficulty defining some variables as mediators or confounders because the mechanism by which psychotherapies work is a matter of debate . We are Regarding the biological factors, studies of biomarkers such as BDNF may provide insights into the possible mechanisms of illness and recovery from serious disorders such as depression, bipolar disorder, and schizophrenia . A few sConsidering the severity profile of patients referred to a tertiary medical center and the level of experience of resident physicians, the magnitude of improvement is lower than in other more favorable clinical settings. This improvement should be more pronounced in the 12-month follow-up considering the long-term effects of psychotherapies. The level of therapeutic alliance may possibly mediate this improvement. We believe that it will also reflect patients\u2019 psychosocial factors and increase BDNF.Limitations of this study include the heterogeneity of the training and experience of the resident psychiatrists and the absence of evaluation from their point of view in the psychotherapeutic process. As a study is naturalistic, there is no way to control the impact of the researchers\u2019 interviews. We will collect a series of demographic data, use of medications, and number of sessions to control possible confounders, but we know that because it is an open study, there is no way to control all differences between groups. Also, psychotherapy studies often have large amounts of losses . To contStudies such as this one seek to contribute to the foundations of public health policies and investments for the treatment of patients with severe mental illnesses who are at risk of hospitalization and suicide. These types of investigations also seek to promote mental health, rehabilitation, and social reintegration. Understanding the mediating and biological mechanisms of the psychotherapeutic process can help to optimize these interventions and facilitate their indication according to the psychopathological profile and the severity of the patients.This project was approved by the Ethics Committee of Hospital de Cl\u00ednicas de Porto Alegre (GPPG\u2013HCPA no 97-2015), and it is recognized by the CONEP Conselho Nacional de \u00c9tica em Pesquisa\u2014National Council of Ethics in Research.LG and NR codeveloped the project. NR coordinated the project in HCPA. LG, GB, and CR were responsible for implementing, conducting, and collecting project data.This study was financed in part by the Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior\u2013Brasil (CAPES)\u2014Finance Code 001 and by Hospital de Cl\u00ednicas de Porto Alegre Research Incentive Fund (FIPE).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
{"text": "Demand side barriers to vaccination among rural and hard-to-reach populations in Chad are not yet well understood. Although innovative approaches such as linking human and animal vaccination increase vaccination uptake among mobile pastoralist communities, vaccination coverage in these communities is still lower than for rural settled populations. We hypothesize that mobile pastoralists\u2019 communities in Chad face specific demand side barriers to access vaccination services. Understanding the factors that caregivers in these communities consider, explicitly or implicitly, in order to decide whether or not to vaccinate a child, in addition to understanding the provider\u2019s perspectives, are essential elements to tailor vaccination programmes towards increasing vaccination acceptance and uptake.We conducted a qualitative study in a rural health district in southern Chad in April 2016 with 12 key informant in-depth interviews and four focus group discussions (FGDs) including 35 male and female participants. Participants in the study included caregivers, traditional chiefs, local and religious leaders from mobile pastoralist communities, and health officials and staff. We conducted a content analysis using a pre-defined set of categories for vaccine hesitancy covering issues on harmful effects of vaccination, mistrust with vaccination programmes/services, issues with the health system and other issues.n\u2009=\u200994), followed by health system issues , and concerns related to potential harm of vaccines . Concerns identified by caregivers, health professionals and community leaders followed a similar pattern with issues on programme mistrust being most frequently reported and issues with harm least frequently reported. None of the health professionals reported concerns about vaccinations being potentially harmful.The groups of demand side barriers reported most frequently in focus group discussions were mistrust on the expanded programme on immunization (EPI) and polio vaccination outreach services (53%, Mobile pastoralist communities face specific demand side barriers to vaccination. Understanding these barriers is essential to reduce vaccine hesitancy and increase vaccination uptake. Local health systems must plan for the periodic presence of pastoralist communities in their zones of responsibility and create more mutual trust. Vaccination is one of the most successful and cost-effective interventions in public health . In 2015Although increasing access to vaccination has been the main strategy employed to improve vaccination coverage during the last three decades, policy makers and international institutions have more recently focused on \u201cvaccine hesitancy\u201d (demand side barriers to vaccination) . VaccineIn Chad, a sub-Saharan African country with about 14 million inhabitants , polio vThe Sustainable Development Goals (SDGs) target reduction of inequities in an interdisciplinary manner with universal policies considering the needs of disadvantaged and marginalized populations . AlthougDemand side barriers to vaccination among rural and hard-to-reach populations in Chad are not yet well understood. Based on anecdotal and non-structured analysis of people\u2019s beliefs and attitudes towards vaccination, managers of the Expanded Programme on Immunization (EPI) focused their efforts on providing information on the benefits of vaccines as a means to increase vaccination uptake. However, evidence from other West and Central African countries suggests that there can be other relevant factors that prevent caregivers from vaccinating their children, for instance, concerns about the potential harm of vaccines in Benin , fear ofThis study uses a qualitative approach to identify demand side barriers which hinder access to vaccination services among mobile pastoralist communities in Chad. Qualitative methods allow exploring the underlying issues underlying issues of vaccination hesitancy beyond the observed low utilization rates of vaccination services among mobile pastoralist communities. We hypothesized that Chadian mobile pastoralist communities face specific demand side barriers to access vaccination services. Understanding factors which caregivers in these communities might consider, explicitly or implicitly, in order to decide whether or not to vaccinate a child is an essential element to tailor vaccination programmes to increase vaccination acceptance and uptake. To our knowledge, the present study is the first to investigate factors that prevent mobile pastoralists from accessing vaccination services in Chad, providing an important opportunity to advance the understanding of why caregivers in hard to reach communities might decide not to vaccinate their children. The findings of this study will also inform the design and implementation of interventions to increase vaccination outcomes among mobile pastoralist communities. In this paper, the term \u201cnomadic communities\u201d is used interchangeably when referring to the same communities despite the fact that not all mobile pastoralists are necessarily nomads.Data was obtained from 12 individual semi-structured interviews and four focus group discussions (FGDs).Selection of participants was based on a convenience sampling approach designed to maximize demographic and functional diversity of the sample around the topic of vaccination. Interview participants were recruited based on their availability and included primary caregivers (mothers with at least one child under 5\u00a0years old), heads of families who were decision makers and resource controllers, local health authorities and civil and religious leaders Table\u00a0. ParticiFirst drafts of the interview and FGD guidelines were based on literature review and discussions with health experts in the Chadian context. The draft was field tested and further refined in a participatory process involving local health experts and representatives from the nomadic communities to compare and contrast views and opinions. Each FGD took approximately one hour and was facilitated by at least two people of the same sex as the participants. Individual interviews took between 40 and 60\u00a0minutes. Data from male participants was obtained in mobile pastoralists\u2019 camps, in a quit and private place away from distractions. To ensure confidentiality and a favorable atmosphere for discussions, interviews and FGDs with nomadic women were conducted in a protected environment, most often in a woman\u2019s home. Data collectors were trained anthropologists and sociologists from the University of N\u2019Djam\u00e9na holding at least a Master\u2019s degree. No relationship existed between researchers and study participants prior to study commencement.Face-to-face interviews and FGDs were audio recorded, transcribed and translated from Chadian Arabic into French. Data evaluation was done manually following a deductive approach. More specifically, the analysis of the transcripts was based on content analysis using a directed approach , 29 baseFirst, transcripts were carefully reviewed to highlight all text that appeared to describe vaccination concerns. Then, all highlighted text was coded using the pre-defined categories. Text that did not fit into one of the categories was assigned as \u201cother issues\u201d. Study findings were reported based on the incidence of codes that represent the pre-defined categories by comparing the overall rank order of the codes and the corresponding percentages within and between the population groups . EvidencEthical clearance was given by the National Bioethics Committee in Chad \u201cComit\u00e9 National de Bio\u00e9thique du Tchad (CNBT)\u201d and the WHO Research Ethics Committee Review (WHO ERC) .The study participants were given detailed information about the purpose of the study, the background of the data collectors and the extent of their involvement. Informed consent was obtained from all study participants before starting any interviews or FGDs. It was explained that participation was voluntary, without compensation, individuals could withdraw from the study at any time, statements would be anonymised so that attribution to individuals would not be possible, and participation was without negative consequences for them, their family or their community. All participants were adults and either signed or fingerprinted the consent form.A total of 94 coded quotes that reported concerns about hesitancy or barriers to access vaccination in Danamadji were extracted from the transcripts based on 12 individual interviews and four FGDs. In total, 35 men and women participated in the four FGDs. There were no refusals to participate in the study.The quotes were retrieved as follows: 73 from interviews, 15 from FGDs with male participants and 12 from FGDs with female participants. Most quotes were from caregivers, followed by health staff and community leaders. We present the results using the pre-defined categories to describe the results  issues wn\u2009=\u200994), followed by health system issues , and concerns related to potential harm of vaccines . The sub-categories with the five most frequently demand side barriers to vaccination are shown in Table The most frequently reported demand side barriers were related to issues with programme mistrust 53%, %, n\u2009=\u200994Concerns related to the potential harmful effects of vaccines or their side effects were the least reported category of demand side barriers to vaccination among mobile pastoralist communities in Danamadji. Among other concerns, participants reported the risk of sterility, fever, diarrhoea, inflammation of the throat and even death.In general, diseases are part of human daily life. It is not all the time that when a child is sick, then we should go immediately to a hospital. Diseases for children are somehow a necessary bad thing. By falling ill, they become immune. So we do not go to the hospital or health centre immediately for a given disease of the child\u201d .\u201cFor some individuals, the prevention of certain diseases by vaccines was not a desired outcome because diseases were opportunities for the body to get stronger and, since vaccines prevented them, they subsequently weakened the child\u2019s (immune) system. One father pointed out:Certainly the disease is a very bad thing, especially malaria and colds in children. In general, we do not want the children to get sick. (\u2026) But when the child is still in good health, there is fear the day it falls ill. I have in all 7 children, 2 of them died. One died unexpectedly because he was always healthy. One day he fell ill and the third day of his illness, he could not conquer the disease and died. Therefore, diseases in children are a sign of longevity. Do not regret too much that children fall ill\u201d .\u201cSome extreme views were reported by caregivers who believed that one of the reasons why children die unexpectedly was because they were consistently healthy: We cannot comment on the pros and cons of a thing until you know the thing. In the case of vaccination, we cannot say, because no one came to us to tell us against which disease the vaccination is. So we cannot know whether vaccination is a solution as described by the State or a problem as the rumours say\u201d .\u201cThe most frequently reported demand side barrier to vaccination were that caregivers did not have enough information to understand the benefits of vaccination and to know the process for getting their children vaccinated or they did not trust health workers coming to the camps during polio outreach vaccination days. It was widely acknowledged by most participants that nomadic communities received too little information about vaccines and their benefits: Yes we heard about the vaccination about polio. But also for this vaccination issue, we have not seen drugs that can cure or protect our children\u201d .\u201cThere was some confusion about the difference between vaccination days for polio vaccination and routine vaccination. Several participants referred only to polio vaccination when raising their arguments. They usually talked about \u201cdrops\u201d when they referred to vaccination in general. Benefits of vaccination were not clear, and there was some reluctance to believe that vaccines are effective: Vaccination, I heard about it in street talks from people who do not know more than me. So nobody really told me what it is\u201d .\u201cEven the most basic information about vaccinations did not reach some nomadic communities: \u201cThere are no communication channels between nomads and health professionals. In our camp here as elsewhere, we do not have a person who acts as an intermediary to convey information between us and the immunization services. There is a total lack of dialogue between us and the health services. They do not even have the phone number of the camp chief to call and deliver information\u201d .No communication channel was reported that brings pro-vaccination messages to nomadic communities. Some caregivers complained that instead of receiving more information they were intimidated by health authorities forcing them to vaccinate their children. A camp leader reported: Here we do not know that when a child is healthy, we can get him to the hospital to take the vaccine which protects him against a number of diseases that are disturbing and even killing our children\u201d .\u201cMobile pastoralist communities were usually reached less often with information than other communities, and they did not have regular contact with health facilities or authorities. There were only few opportunities when individuals had regular contact with conventional health services , and they only made use of health services during illness or in emergencies. A participant in a FGD was surprised that health services could be used preventively:  \u201cWhat we deplore is that when the vaccinators come here, they do not explain what they came to do. They only call the children and put the drops in their mouths. They are always in a hurry.\u201d .Even when health workers from the district health system moved to camps to provide health services, they did not use the opportunity to reduce the information gap with either local leaders or caregivers. A mother complained:It\u2019s true that I am the imam (religious leader) having a great influence on the community, but no one came to explain to me what the vaccination is about so that I may have the possibility to widely inform my congregation during the Friday prayer and when people meet. General health services and those related to vaccination in particular lack a method to inform or convey their message. For example in the case of polio, instead of explaining us the merits and inform us of the arrival of the team of vaccinators in our camps, we suddenly see them arriving and catching children within their reach and administering the drops of vaccines. We parents only accept this method against our will. Some prefer to hide their children and sometimes colour their fingers to show that the children were already vaccinated so that they would not swallow anything. All of this is the lack of information about polio\u201d (Religious leader).\u201cSome participants pointed out that it is understandable that parents do not have trust in something they do not know or have not been informed about. The way in which polio outreach vaccination days are organised, with teams moving from camp to camp during one day to vaccinate children, was inadequate to provide sufficient information and convince caregivers to vaccinate their children, specifically for routine immunization. A religious leader reported: a plan of God to train the child for the difficult moments\u201d , and they should not fight them. For others, diseases had a religious/divine origin, and they must be handled by traditional healers such as the Marabout. The services provided by traditional healers were considered to be more affordable, despite the fact that vaccination is offered free of charge in Chad. They were also considered more effective as compared with western medicine (including vaccination): When the children here become sick, I intervene in the first place to use religious incantations. And it is only when the disease persists that the child is brought to the hospital. There are also cases where the child is sent home from the hospital without being cured, and at this level too I am the last resort to pray for God to cure the sick child. I intervene, I use incantations for all kinds of diseases\u201d .\u201cReligious and cultural beliefs also played a role in the decision making process of whether to vaccinate infants living in nomadic camps. Some communities believed that diseases are \u201c(\u2026) When we go to the health centre to seek care for our sick children, we are very poorly received. In some situations, we are expelled by health workers. Hoping that a child would never be ill so that one would not have to wait at the hospital saying that we want to have medication, imagine what treatments can be reserved for us? We pastoralists, don\u2019t we have rights? Health workers consider us like our animals\u201d .\u201cConcerns about vaccination providers in health facilities being unpleasant were widely reported by participants in interviews and FGDs. Some participants considered health workers to be authoritarian and bad tempered. One informant pointed out: You see filthy agents who come to do this work. Some of them are drunkards, which we know. This does not inspire confidence. You end up saying this vaccination business is a way to get work for some, to make money for others and all this at the expense of the health of our children. Finally, I have a negative perception of the entire vaccination operation\u201d, .\u201cNomadic communities had a very poor opinion of health care workers in the district which was a major barrier to vaccination. Even acknowledging that vaccination is free of charge and could have some benefits for children, parents decided not to vaccinate because they did not trust the system that provides them: some participants believed that vaccination was not effective and vaccination campaigns were only conducted in the interest of district officials and health workers who receive per diem payments for the vaccination days: For me, polio is an organised business from the high hierarchy to the last vaccinators who administers the drops. Everyone finds his interest and that\u2019s it. This practice makes me doubt about the efficacy of poliomyelitis vaccine\u201d .\u201cIn line with this idea, They send us the dirty young people from the neighbourhood to come and vaccinate our children against poliomyelitis. They are young people who only seek money without further concerns. They do not know anything about health (\u2026..) People treat us like our animals and have no consideration for us. We have never seen a trained health worker or a doctor coming to vaccinate our children\u201d .\u201cIt was frequently reported that health professionals working in vaccination campaigns were not trained doctors or nurses, which raised concerns about their capacity to deliver vaccination activities. Some interviewees even saw this situation as a form of disrespect to nomadic communities: We want people to send us staff who know the health field. We prefer people close to our realities, who know our problems and who can transmit them to higher authorities to react. We want reliable people, who can educate us on vaccination\u201d .\u201cThe fact that the messages about vaccination  or the interventions themselves were not provided by staff who were considered as peers in terms of religious and cultural background prevented some parents from vaccinating their children. In addition to the language barrier between health professionals and nomadic communities, health workers seemed to ignore the basic cultural and religious norms in the camps, and there were few Muslim health workers. One camp chief criticised: The reality is that the vaccinators cannot make the trip to the camps at any time, when the head of household is absent following his herds, for example. This is a serious cultural breach in pastoral communities as a wife has to seek permission of her husband to decide on certain issues; such as exposing a child to strangers. This is also valid for the vaccination of children\u201d .\u201cOther examples of health system issues were the lack of cultural appropriateness of vaccination services and the timing of teams from the health centre for visiting the camps. The timing for the visits significantly interfered with daily activities and obligations for both men and women in the camps. As one of the administrative authorities in Danamadji recognised, We identified demand side barriers to vaccination among nomadic communities in Danamadji District in Chad. We conducted a study using qualitative research to identify factors or beliefs that prevent caregivers from vaccinating their children. Contrary to expectations, this study found that issues related to the health system itself, such as health staff being unpleasant or vaccination campaigns being poorly organised, were widely reported by nomadic communities. In comparison to previous studies on vaccine hesitancy in low and middle income countries (LMIC) , it is sThere is a significant body of literature on barriers to vaccination services which shows that concerns about the harmful effects of vaccination and lack of information are the most important (frequently reported) demand side barriers to vaccination , 15, 17.A limitation is that most participants referred primarily to the polio vaccination outreach days in their answers although the questions were designed to capture the perception of routine and outreach vaccination services. Issues related to lack of trust in the vaccination outreach days against polio and health system issues were the most frequently reported. Nomadic communities were reluctant to vaccinate their children because they did not have enough information about the benefit of vaccines or the location of vaccination services in their district. A substantial number of participants in our study complained that health staff were unpleasant or that they felt neglected or humiliated because they were nomads. They raised concerns about the qualification of vaccinators and their cultural distance from the nomadic community as one of the most important disincentives to get their children vaccinated. They sought interlocutors with knowledge on the daily life and culture between them and the health services.Communication channels between nomadic communities and the local health system does not seem to exist. It is well known that communication and social mobilisation is associated with high vaccination coverage and allows for reaching \u201csparsely covered groups\u201d when included as a key component of immunisation programmes, e.g. polio , 30. AltThe health system in Danamadji fails to provide vaccination services to nomadic communities, which translates into substantial immunisation inequities when compared to rural settled populations in the same district. To reduce health inequities in light of the SDGs, modern health system interventions must ensure that all population strata benefit from new policies. Barriers to existing vaccination services among mobile communities in Danamadji could be substantially reduced by improving the information exchanges between the provider  and the population. It has been previously shown that outreach campaigns combining veterinary and human health services are a promising and feasible strategy for increasing vaccination uptake among mobile communities . These cIn the past, we have made good experience with trans-disciplinary stakeholder meetings  between A limitation of this study is that during transcription interviews were translated from Chadian Arabic to French. Even though the translation was done by native Chadian Arabic speakers, there was still potential for lost meaning during the process.Nomadic pastoralist communities face specific demand side barriers to vaccination. Understanding these barriers is essential to reduce vaccine hesitancy and increase vaccination uptake. Local health systems must be sensitive to and act upon these specific needs, particularly the mistrust based on bad experiences of mobile pastoralist communities."}
{"text": "Objective: There is a lack of data relating to vaccination of children with special health care needs (CSHCN) and its influencing factors in China. We investigated the disease spectrum of CSHCN at the Vaccination Consultation Clinic in Zhejiang province as well as the underlying factors of vaccination recommendations of these children.Methods: In this study, we retrospectively analyzed the data of 4,525 CSHCN, who visited to our clinic for a vaccination consultation from January 1, 2016 to May 30, 2018. Descriptive data were presented as mean \u00b1 standard deviation (SD) and percentages. Multivariate analysis was performed with non-conditional bivariate logistic regression to identify the underlying factors of vaccination recommendations. Subsequent information regarding the following vaccination and the occurrence of AEFI were also collected and analyzed.Results: The main diseases consulted were those relating to the circulatory and nervous systems as well as neonatal diseases. The distribution of diseases varied by age: 53.6% infants under 12 months were counseled for circulatory system diseases, while 44.6% children aged 12~24 months and 54.7% children over 25 months were counseled for nervous system diseases. According to the evaluation reports issued by the consultation clinic, 75.0% of CSHCN were recommended to be vaccinated normally, 21.2% were recommended to defer specific vaccination, while only 3.8% were recommended to defer all vaccinations. In logistic regression analysis, age, history of adverse events following immunization (AEFI) and the number of diseases combined were all strong correlative factors for vaccination recommendations. Children who were aged over 25-month-old  or had a history of AEFI  or those who had numerous diseases combined  tended to have a higher rate of deferred vaccination recommendation. Among those CSHCN who received nationally-recommended vaccines, the estimated AEFI rate was 24.29/100 000. No uncommon or rare serious adverse reactions were detected.Conclusion: Age, history of AEFI, and the number of diseases combined were important factors that affected the vaccination recommendations of CSHCN. Most CSHCN can be safely vaccinated according to the nationally-recommended schedule. Vaccination is one of the most cost-effective interventions of preventing infectious disease and reducing the burden of disease . It makeChildren with special health care needs (CSHCN) are those who have or are at increased risk for physical, developmental, behavioral, or emotional disorders . They alThe vaccination coverage varies significantly among CSHCN in different countries. For example, from the national survey in the United States, it is reported that CSHCN have similar vaccination rates as normally developing children ; while iIn China, the vaccination coverage in recent years has been maintained at an optimal level for the general population , but theTo improve the safety of vaccination as well as to increase the vaccination coverage among CHSCN in Zhejiang, China, Health Commission of Zhejiang Province set up the Vaccination Consultation Clinic in our hospital in 2016. Specialists of the Consultation Clinic provide the vaccination recommendation to the group of children, who were denied vaccination at community health centers.We conducted the present study, a retrospectively analysis of the data of CSHCN who visited our Vaccination Consultation Clinic, in order to gain insight into the immunization status in CSHCN in Zhejiang province and to identify correlative factors that affect vaccination recommendations. The result of the study can contribute to the existing literature on the vaccination of CSHCN and help us to explore new strategies of improving clinicians' and providers' understanding of the contraindications and precautions of vaccination in China.The Vaccination Consultation Clinic was established in Children's hospital Zhejiang University School of Medicine in 2016. Pediatricians who were systematically trained in vaccinology and public health were responsible for the consulting work.CSHCN was defined as children who meet at least one of the following criteria resulting from a medical condition that lasted, or was expected to last \u226512 months: (1) ongoing need of prescription medications; (2) on going need of health care services above the average for a child the same age; (3) on going need of specialized treatments; (4) limitation in activities that most children the same age can perform; (5) presence of ongoing behavioral or developmental conditions requiring treatment or counseling .In this study, CSHCN who visited the clinic from January 1, 2016 to May 30, 2018 were enrolled. Medical records of treatments, disease history, family history, allergic history, vaccination status and AEFI history were collected from parents during the interview. Relevant laboratory tests were conducted if seen to be necessary.Children were evaluated according to their medical records and lab results. Specialists of the Consultation Clinic have a meeting once a week to conduct discussions on the vaccination plans for each CSHCN. Referring to \u201cChinese Immunization Program for Children Immunization Procedures and Instructions (2016), \u201cChinese Pharmacopeia\u201d and \u201cthe General Best Practice Guidelines for Immunization (2016) , 10, andThe vaccination recommendation included three options: (1) defer all vaccinations, which meant children should postpone all vaccinations due to the moderate to severe illness, or because they had an unstable chronic diseases; (2) defer specific vaccination, which meant children should postpone one or more specific vaccines due to their current disease, treatment or history of AEFI; (3) normal vaccination, which meant children could receive all vaccines according to the nationally-recommended schedule.Providers in community health centers carried out the vaccination in accordance with the vaccination recommendations. Local CDC monitored and recorded vaccination and uncommon/rare serious AEFI of those CSHCN. The following vaccination and the occurrence of AEFI were collected by telephone interview from parents at an interval of 6 months after the consultation.The data were extracted from the hospital information management system. All data were managed and analyzed by SPSS 20.0. Descriptive data were presented as mean \u00b1 standard deviation (SD) and percentages. The vaccination recommendations were categorized into two levels: The first level was \u201cnormal vaccination,\u201d and the other was \u201cdelayed vaccination,\u201d which combined \u201cdefer all vaccinations\u201d and \u201cdefer specific vaccination.\u201d Multivariate analysis was performed with non-conditional bivariate logistic regression to determine significant independent variables for predicting vaccination recommendations. All predictor variables were entered in the equation as dummy variables. The alpha level of significance for bivariate logistic analysis was set at 0.05 for a two-tailed test.The study was approved by the ethics committee of the Children's Hospital Zhejiang University School of Medicine. The need for informed consent was waived by the Ethics Committee of the Children's Hospital Zhejiang University School of Medicine.A total of 4,525 children were included in our analysis. Participants ranged in age from 0 month to 15 years old; the mean age was 14.2 months (SD = 19.1). Almost half (50.7%) of the participants were under 6 months old; among them, 56.7% were male; 27.8% had a history of food or drug allergies; 4.7% had a history of AEFI; 20.9% had a family history of related disease; 61.2% were consulted for only one disease shown in The main diseases of those CSHCN for consultation were circulatory system diseases (43.1%), nervous system diseases (30.3%) and neonatal diseases (25.3%). The proportions of children with a history of AEFI and a family history of related disease were 1.3 and 0.9%, respectively .The distribution of diseases was different between CSHCN that were of different ages. Infants with 0~6 months and 7~12 months visiting the clinic were mostly for circulatory system diseases, especially the CHD (96.4 vs. 95.4%); children aged 12~24 months and over 25 months old mostly consulted for nervous system diseases, among which febrile convulsion (37.6 vs. 41.4%), developmental delay(20.7 vs. 15.1%) and epilepsy (16.5 vs. 20.7%) were the top 3 causes.According to the evaluation reports issued by the consultation clinic, 3,395(75.0%) of the evaluated CSHCN were recommended to receive vaccines normally according to the nationally-recommended schedule, and 958(21.2%) were recommended to defer specific vaccination, while only 171(3.8%) were recommended to defer all vaccinations.Of the CSHCN with the recommendation of \u201cdefer specific vaccination\u201d or \u201cdefer all vaccination\u201d, most had a history of AEFI , tumors , infectious disease , hematological disease  or immune, and allergic disease  .Binominal regression analysis indicated that age, history of AEFI and the number of combined diseases were important factors of vaccination recommendations . SubjectIn our study, 3,395 enrolled CSHCN were given vaccines normally according to the nationally-recommended schedule after consultation, among which, 2,976 continued follow-up, while 417(12.29%) children dropped-out for a variety of reasons, such as changing telephone number, unwilling to give information or forgetting specific information. Among the 2,976 valid cases, a total of 20,587 vaccine doses were administered and only five cases experienced adverse reactions , two experienced low-grade fevers, one experienced a rash and two presented with local redness at the injection site. These reactions were mild and self-limiting, and did not require medical treatment. No uncommon or rare serious adverse reactions were reported.To our knowledge, this was the first study on the vaccination and its correlative factors among CSHCN in Zhejiang, China. The main diseases consulted were circulatory and nervous system diseases as well as neonatal diseases. Age, history of AEFI and the number of combined disease were correlative factors of vaccination recommendations. Most CSHCN who visited the consultation clinic were safely vaccinated according to the nationally-recommended schedule after consultation.In the present study, we found that nearly 50% of the children visiting the consultation clinic were under 6 months old. The probable reason for this was that most vaccinations were scheduled under 12 months of age, with 1~3 doses per month in average . CliniciIn this CSHCN group, circulatory system diseases, especially CHD, were the most frequently consulted diseases for infants under 12 months old. Routine physical examinations during the first year of life and the use of ultrasound made the diagnosis of CHD sensitive and accurate in younger infants. It was estimated that the incidence of CHD at birth was about 0.8% . About aThe second cause of consultation was neurological diseases, most of which was convulsions. Convulsions were clinically unpredictable. In some cases, children experienced febrile convulsion or seizures for a short period of time after receiving the vaccine , 16, whiAccording to the vaccination evaluation, the majority of CSHCN enrolled can receive vaccines following the nationally-recommended schedule. However, their vaccine schedules were usually delayed before they visited the consultation clinic. We inferred that the possible reasons are as follows: Firstly, it was due to the unclear description for contraindications in the instructions of some vaccines, as well as the lack of evidence regarding the safety and efficacy for CSHCN. Secondly, most vaccination providers at community health centers were majoring in Public Health rather than Clinical Medicine. They do not receive systematic training for vaccinology and lack clinical experience, which prevents them from making the correct judgment for the precautions and contraindications of vaccination for CSHCN \u201324. In aIn order to explore new strategies of improving the vaccination coverage of CSHCN, it was important to identify the main correlative factors that affect vaccination of this population. In the United States, demographic characteristics such as age, gender, insurance status are considered to be associated with vaccination coverage in youths with special health care , 26. In In this study, the incidence of AEFI among the follow-up children was low  and no uncommon or rare serious adverse reactions were observed. It was consistent with the results from the similar analyses at national level . Our resAltogether, the results of our study increase the awareness of primary healthcare workers/providers on vaccination for CSHCN. It is urgent to identify the barriers of vaccination from patients, families, providers and vaccination delivery systems. Innovative strategies should be implemented to improve the vaccination coverage and reduce missed opportunities for CSHCN, such as strengthening the training of providers in the community health center to help them to fully understand the contraindications and precautions of vaccination and to increase parents' awareness of vaccines.The limitation of the present study is mainly related to its reliance on parent-reported immunization status and the occurrence of AEFI. Specifically, some parents could not accurately recall the mild side effects of vaccination. Furthermore, our vaccination evaluation objects mainly come from Zhejiang province, which did not represent the situation of CSHCN in the entire country. Future longitudinal multicenter studies with larger sample sizes are needed to monitor vaccination coverage, efficacy and the incidence of AEFI in such population. It is hoped that the vaccination rate of CSHCN in Zhejiang, China will be improved through further data accumulation and research.The majority of CSHCN can be vaccinated according to nationally- recommended schedule, especially the children suffering from CHD, febrile convulsion and developmental delay. It is very necessary to conduct intensive training on vaccinology and public health among clinicians and vaccination providers, so they can have a better understanding of the contraindications and precautions of vaccination, and provide correct and appropriate advice to CSHCN. Additionally, children with a history of AEFI or multiple diseases should be screened more carefully before receiving vaccines.The study was approved by the ethics committee of the Children's Hospital Zhejiang University School of Medicine. The need for informed consent was waived by the Ethics Committee of the Children's Hospital Zhejiang University School of Medicine.CJ designed the research. DY, XW, and YZ interviewed respondents and entered data. ML and BW analyzed the data and performed the statistical analyses. ML, CJ, and JS wrote and revised the manuscript. All authors approved the final content of the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest."}
{"text": "Progress Toward Poliomyelitis Eradication \u2014 Afghanistan, January 2017\u2013May 2018,\u201d multiple incorrect spellings occurred because of a spell-check error. The errors are corrected online.In the report \u201c1; Hemant Shukla, MD2; Meiland Ahmadi, MD3; Joanna Inulin, MD2; Mufti Sabari Widodo, MBBS2; Jamal Ahmed, MD2; Chukwuma Mbaeyi, DDS1; Jaime Jabra, PhD4; Derek Gerhardt, MPH1\u201dThe listing of authors originally read \u201cMaureen Martinez, MPH1; Hemant Shukla, MD2; Maiwand Ahmadzai, MD3; Joanna Nikulin, MD2; Mufti Zubair Wadood, MBBS2; Jamal Ahmed, MD2; Chukwuma Mbaeyi, DDS1; Jaume Jorba, PhD4; Derek Ehrhardt, MPH1\u201dThe listing of authors should have read \u201cMaureen Martinez, MPHThe first paragraph of text under Immunization Activities on page 833 beginning with the third sentence originally read \u201cAdministrative OPV3 coverage  in 2017 ranged from 100% in the central provinces of Kapitsa and Panjsher to 24% and 9% in the southern provinces of Helmand and Kabul, respectively. The proportion of children aged 6\u201323 months nationally with NPAFP who never received OPV through routine immunization services or SIAs  was approximately 1% during 2016\u20132017. High proportions of zero-dose children were reported in 2017 in Kabul (9%) and Kandahar (4%) provinces in the southern region, Kunar (8%) province in the eastern region, and Paktika (7%) province in the southeastern region.\u201dKapisa and Panjsher to 24% and 9% in the southern provinces of Helmand and Zabul, respectively. The proportion of children aged 6\u201323 months nationally with NPAFP who never received OPV through routine immunization services or SIAs  was approximately 1% during 2016\u20132017. High proportions of zero-dose children were reported in 2017 in Zabul (9%) and Kandahar (4%) provinces in the southern region, Kunar (8%) province in the eastern region, and Paktika (7%) province in the southeastern region.\u201dThe sentences should have read \u201cAdministrative OPV3 coverage  in 2017 ranged from 100% in the central provinces of"}
{"text": "Objectives: To study the effects of a self-powered Fontan circulation in both idealized Fontan models and patient-specific models. Methods: In silico, a conduit with a nozzle was introduced from ascending aorta into the anastomosis of superior vena cava and pulmonary artery. Computational fluid dynamics (CFD) simulation was applied to calculate the fluid fields of models. Three 3-dimentional idealized models with different offsets were reconstructed by computer-aided design to evaluate the effects of the self-powered conduit. Furthermore, to validate the effects in patient-specific models, the conduit was introduced to three reconstructed models with different offsets. Results: The pressures at superior venae cavae and inferior venae cavae were decreased in both idealized models (0.4\u2009mmHg) and patient-specific models (0.7\u2009mmHg). In idealized models, the flows to left lungs were decreased (70%) by the jets from the conduits. However, in patient-specific models, the reductions of blood to the left lungs were relatively limited (30%) comparing to idealized models. Conclusions: CFD simulation was applied to analyze the effectiveness of the Fontan self-powered conduit. This self-powered conduit may help to decrease the venae cavae pressures and increase the flow to pulmonary arteries. Total cavopulmonary connection (TCPC) has been the most widely adopted Fontan procedure, in which an intra-atrial lateral tunnel or an extracardiac conduit is constructed to reroute blood from the inferior vena cava (IVC) to the pulmonary arteries2. Despite the accepted early survival rate following the Fontan procedure, bypass of the subpulmonary ventricle may inevitably result in long-term complications including protein-losing enteropathy3 and Fontan-associated liver disease5 in some survivors, which are partly due to increased systemic venous pressure6.The Fontan procedure has evolved over the decades since its first introduction in 19717, tissue engineering/regenerative medicine devices8) or mechanical assist devices . Moreover, though several reports were previously published, in which patients had focused on the use of the Berlin Heart12, the assist devices were large in size and complex in structure. This reflects the great barrier to translating these experimental studies into clinical practice. Thus, pursuit of a desirable, sustainable, and clinically feasible solution to improve late prognosis in the Fontan population is urgently required.Multiple groups have attempted to provide an adequate preload to optimize the Fontan circulation using biological  pressure16. Ni and colleagues designed a self-powered Fontan circulation17. However, they did not assess the influence of offsets and different insert positions of the conduit and did not apply the conduit to patient-specific models. Thus, its clinical application requires further investigation. In the present study, we report a feasible and simplified Fontan self-powered conduit based on the Venturi effect and evaluate its role in reducing vena cava pressures and increasing pulmonary flow.Several studies performed computational fluid dynamics (CFD) and aimed to achieve an ideal cavopulmonary connectionThe Ethics Committee of the Shanghai Children\u2019s Medical Center reviewed and approved this study. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was obtained from the patients\u2019 parents (patients were under 18 years old).17, a conduit with a 2-mm nozzle has clinical usability. Therefore, our conduit consists of 3 sections: inflow, constricted, and outflow sections, whose diameters were 4\u2009mm, 2\u2009mm, and 4\u2009mm, respectively  toward point P (midpoint of the entrance of RPA) Fig.\u00a0. In an iAccording to our clinical experience, the longer the conduit is, the easier it is to bend. Thus, the assist conduit was assumed to introduce the blood from ascending aorta to reduce the risk of bending. Considering the anatomies after the Fontan procedure, we select three insert positions for each Fontan model. The rules for inserting the conduit were formulated as follows:In this computer simulation analysis, we collected the clinical data of three patients who had underwent the extracardiac Fontan procedure at the age of 5. In the three patients, the offsets between the SVCs and IVCs were 0, 0.5, and 1 IVC diameters, respectively. The datasets for CFD simulations were collected before their discharge. The three-dimensional (3D) geometries of the Fontan pathway were reconstructed in Mimics 19.0 . Then, we used Mimics to draw the centerlines of these models. All TCPC vessels were cut proximal to the closest branching points. The selection rules of insert positions were the same as the idealized models, but owing to the specific 3D geometries, not all the insert positions were suitable for the future operations. Thus, we deleted some insert positions that were impossible to apply intraoperatively.19. A tetrahedral mesh was generated in the central connection area with a base mesh size of 0.6\u2009mm and three boundary-fitted prism layers were generated at the near-wall regions to improve the resolution of the relevant scales in fluid motion. Mesh density function in the ANSYS-ICEM was used to increase the density of the grids. Each model grid was refined at the anastomosis between the conduit and vessel wall. The cell count for each model consisted of approximately 9 million cells.All geometries were imported into ANSYS-ICEM 17.0  to generate unstructured meshes. All inlets and outlets were extruded over a sufficient distance to reduce the impact of the uncertainty of the boundary conditions on the region of interest and to increase the stability of the solver at the outflows\u22125. The conservation target was set as 1\u2009\u00d7\u200910\u22124. In idealized models, the flow rates of the venae cavae was 2.1\u2009L/min, which are reasonable estimates of TCPC flow in children22. The static pressure at the inlets of the self-powered conduit was mean arterial pressure of patients, while outlets of the extruded LPA and RPA was set as 10\u2009mmHg (1333\u2009Pa). In patient-specific models, the boundary conditions of patients were from their clinical data. After induction of general anesthesia, mean SVC pressure, mean IVC pressure, and pulmonary arterial pressures were measured using a catheter inserted via the jugular vein into the pulmonary arteries. Time average flow rates of venae cavae were measured by cardiac MRI. The pressures at the SVC and IVC were measured by the average pressure of their cross sections. The cross sections locate at the closest branching points of each vessels. Pressure drop describes the pressure difference between two points. In current study, we used pressure drop to describe changes of the relative pressures between venae cavae and pulmonary arteries. Hepatic flow distribution (HFD) was quantified by examining the percentage of IVC flow entering the LPA and RPA in each patient-specific model.CFD simulations were performed on Ansys-CFX 17.0. Convergence of simulations was based on the residual mean square (RMS) and the residual target was set as 1\u2009\u00d7\u200910The pressures at SVCs and IVCs, the pressure drops between the venae cavae and RPAs, and pulmonary flow rates are shown in Fig.\u00a0The pulmonary flow distribution data of the pulmonary arteries are shown in Fig.\u00a0The geometries of the patient-specific models are shown in Fig.\u00a0Generally, in all patient-specific models, the conduits could drop approximately 0.5\u2009mmHg at the venae cavae Fig.\u00a0. The preIn patient A, the conduits inserted from three points could decrease 0.49~0.74\u2009mmHg. In the case of insertion point B, a good result is that the pressure of the vena cava is reduced by 0.7\u2009mmHg, and the effect on the LPA blood flow is relatively limited. The HFD of patient A was slightly changed in self-powered models.In patients B and C, the offsets of these two patients were 0.5 D and 1 D, respectively, which accounts for the majority of clinical Fontan patients. In these two patients, the effects of the conduits were consistent and the pressure drops between the SVCs and RPAs were approximately 0.7\u20130.85\u2009mmHg. Moreover, the effects of the conduits on the blood flows to the LPAs were also limited, which were different from the idealized models. The baseline HFDs of patient B (LPA:RPA\u2009=\u200932%:68%) and patient C (LPA:RPA\u2009=\u200921%:79%) were imbalance, but after adding the self-powered conduit, HFD were balanced .In this study, we designed a conduit to provide a self-powered circulation in extracardiac Fontan, which may help to alleviate the chronic elevation in systemic venous pressure following the Fontan procedure. We performed CFD analysis to evaluate different insert position of the shunt graft and calculate the fluid fields under physiological conditions to determine the optimal position. The features of this study include the following: (1) extracardiac Fontan with different offsets were included; (2) different insert positions were simulated; (3) the conduit could provide kinetic energy for the circulation, reducing the pressure of the venae cavae, which could increase the flow of pulmonary arteries without increasing pressures at the venae cavae; (4) both the spatial structures and feasibility of inserting a single conduit were taken into account, which makes the self-powered Fontan procedure applicable in clinical practice.The decreased pressure in the venae cavae can vary from 0.3\u2009mmHg to 0.8\u2009mmHg according to different models. Given that the original pressure differences exist between the venae cavae and pulmonary arteries, the conduit can provide sufficient energy for the venous blood despite the limited reduction in pressure. Jet from the conduit significantly changed the flow pattern around it Fig.\u00a0. The jet24. However, in patient-specific models, there is relatively less influence on the LPA flows caused by the conduits, which may be due to patients\u2019 individualized anatomical morphology. The angles of IVCs and LPAs in idealized models are 90\u00b0, whereas those in patient-specific models are larger than 90\u00b0  pressure16. The conduit in that study was connected to SVC rather than the anastomosis of SVC and RPA, which result in increasing pressure of SVC. Ni and colleagues designed a self-powered Fontan circulation17. However, the nozzles were extended into pulmonary arteries without supporting structures, where displacement would occur. And they did not assess the influence of offsets and different insert positions of the conduit and did not apply the conduit to patient-specific models. Our study selected another connection area and assessed effects of different positions. Although our design is a shunt pointing to RPA, this structure is a clinically feasible structure and 4\u2009mm diameter conduit is easy for anastomosing.While there are several publications quantifying outcomes use similar device to improve single ventricular circulation, these studies have had inappropriate insert positions28. But most clinical measurement cannot provide parameters of cardiac function and loading conditions. Liang and colleagues provide a method of patient-specific assessment to overcome these difficulties29. Therefore, patient-specific multiscale modeling of Fontan circulation could provide global hemodynamic profile. In our further study, Fontan patient-specific 3D models will be coupled with a reduced-dimensional model to address the interaction between local and global hemodynamics.In this 3D model study, we mainly focused on hemodynamic phenomena in local vascular regions. However, 3D model cannot sufficiently account for the influence of the downstream vascular systems. Meanwhile, the hemodynamic performance of Fontan circulation is influenced by cardiovascular properties, such as pulmonary vascular resistance and left ventricular function30. Therefore, thromboembolic events may be the greatest challenge for application of this pipeline in vivo. The use of aggressive anticoagulation measures and biocompatible materials could reduce the risk of thromboembolic events. To say the least, the circulation could still maintain a normal Fontan circulation irrespective of thrombosis occurring within the inserted conduit. Clinical application of this conduit-assisted Fontan requires further technical refinements and investigations ; however, it provides an alternative clinically feasible solution to help the subset of survivors overcome the unavoidable sequelae of Fontan circulation and have improved quality of life and longevity.The most notable challenge for the application of the conduit is the prevention of thromboembolism. In this study, we considered blood as a homogeneous fluid, with fixed values for density and dynamic viscosity, and the destruction of blood cells was not considered. Disturbed flows occur in the regions of RPAs near the IVCs in both idealized models and patient-specific models, which may be caused by the rapid blood flow near these areas Fig.\u00a0. FurtherThe small sample size in this study is one of the limitations; more patient-specific models are needed to verify the results. Another limitation is that steady inflow rates were imposed on the inlets, which means that the effects of respiration and exercise were not included. Moreover, outflow boundary conditions were imposed at the outlets in the CFD models, modeling the immediate perioperative status in the TCPC, and not the longer-term adaptation of the single ventricle physiology using resistances or lumped parameter networks in the boundary conditions. Finally, we assumed that the vessel walls were rigid and impermeable, with no-slip boundary conditions. A fluid-structure-interaction analysis is required in future studies.Using CFD simulation, we analyzed the effectiveness of a Fontan self-powered conduit. This conduit is a feasible, economical, and effective solution that could decrease vena cava pressures and increase the flow to the pulmonary arteries."}
{"text": "Virtually any malignancy can metastasize to the liver. Large solitary metastases are rare and can be difficult to distinguish from primary tumors. Malignant mesothelioma is often considered as a locally invasive cancer but tumor dissemination to extra-thoracic sites is possible, and the liver can be involved. Herein, we present a rare case of pleural mesothelioma with a solitary large liver metastasis diagnosed postmortem in a ninety-two-year-old man with 35 years of exposure to asbestos. Results of immunohistochemical staining of the pleural and liver tumor were similar, both positive for low-molecular weight keratins, calretinin, vimentin, and podoplanin, and negative for Claudin-4, TTF1, CEA, BerEP4, CK7, CK19, CK20, BAP1, Hep Par1, p40, and WT1. Fluorescent in-situ hybridization (FISH) for p16/CDKN2A was also performed and a homozygous deletion was detected in both tumors, supporting the diagnosis of mesothelioma. Reporting this case, we would like to point out that extra-thoracic dissemination from pleural mesothelioma, even if exceptional, can occur. In cases where differential diagnoses are challenging, the value of ancillary techniques and a practical approach to diagnostic work-up is of primary importance."}
{"text": "To evaluate the effect of vitamin D supplementation on C-reactive protein (CRP) through a systematic review and meta-analysis of randomized control trials (RCTs).PubMed-Medline, SCOPUS, Google Scholar and Web of Science databases were searched (up until April 2016) to identify RCTs evaluating the impact of vitamin D supplementation on CRP. We used random effects models (using DerSimonian-Laird method) as well as the generic inverse variance methods for quantitative data synthesis. For sensitivity analysis, we applied leave-one-out approach. To examine the heterogeneity we used I2 index. Registration code: CRD42016036932., 24 studies met the inclusion criteria in the final evaluation. Pooling the data together indicated a non-significant decrease in CRP level following administration of vitamin D (weighted mean difference [WMD] -0.26(mg/l), . The WMDs for IL6 was 0.67\u00a0pg/ml, , 0.43\u00a0pg/ml, , for IL10, and \u22120.11\u00a0pg/ml,  for TNF-\u03b1, 4.03\u00a0pg/ml,  for adiponectin. Sensitivity analyses confirmed the robustness of the findings.Among 1274 search itemsThis study provided evidence that vitamin D supplementation had no impact on serum CRP, IL10, and TNF-\u03b1, while significantly increased serum IL6. We recommend RCTs with longer period of follow-up time (12\u00a0months) for future studies to provide explicit results.The online version of this article (10.1186/s40795-017-0207-6) contains supplementary material, which is available to authorized users. Historically, vitamin D is recognised for its important role for bone health. However, recent studies suggest extra-skeletal effects of vitamin D through autocrine and paracrine systems. Low vitamin D concentrations are related with several diseases with inflammatory nature including rheumatoid arthritis, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and some types of cancer . Low vitThe potential effect of of vitamin D supplementation in decearsing chronic inflammation, if proven, is of public health interest given the disproportionate prevalence of vitamin D deficiency and insufficiency across the globe. A number of recent clinical trials have assessed vitamin D supplementation in different populations for its impact on circulating concentrations of several pro- and anti-inflammatory factors. However, such studies have had limitations such as small sample size, poor research design and subject traits , and underpowered to achieve a comprehensive and reliable conclusion. Therfore there is substantial uncertainty about the net effect of vitamin D supplementation on CRP levels. Asystematic study which has addressed this issue dates back to 2014 inlcuding only a few studies . TherefoWe conducted his systematic review based on the international referred Reporting Items for Systematic Reviews and Meta- Analyses (PRISMA) Guidelines , 14. We In litrature search we considred the effect of vitamin D supplementation on plasma CRP concentration as the primary exposure of interest. The secondary exposure was the effect of vitamin D supplementation on inflammatory and anti-inflammatory markers and cytokines. We considred multiple databases including PUBMED/ Medline, Cochrane Central Register of Controlled Trials (CCTR), Cochrane Database of Systematic Reviews (CDSR), Web of Science and Google Scholar, until April 2016 for litrature search. Weapplied relevant search terms to find a published and unpublished studies for our interested outcome . We resolved the disagreements at a meeting between reviewers prior to selected articles being retrieved.We selected published randomized control trials (RCTs) assessing the impact of vitamin D administration on the infmlamatory parametres. Criteria for selecting studies: (i) clinical trial with single-arm, parallel or cross-over designs; (ii) RCTs of participants received vitamin D supplement compared to control group (either no vitamin D or placebo); and (iii) studies with information on primary outcome at the baseline and the endpoint in each group or the net change values. Exclusion criteria were: (i) non-clinical trials including those with case\u2013control, cross-sectional or cohort designs; and (ii) studies missing to report mean (or median) plasma concentrations of our measures of interest at the baseline and/or at the endpoint. We carried out the selection by removing the of duplicates followed by titles and abstracts screening by two reviewers. The agreement between the reviewers was conisderable  retrieved the full text of studies the met the inclusion criteria, and screened to determine the eligibility. After assessment of methodological quality, the two reviewers extracted data onto a purpose-designed data extraction form. The same reviewers independently summarised the most significant results of each study f. We compared the summaries and any variations of ideas resolved through a discussion with the third reviewer (HV). Details information from selected RCTs is summarized in Table\u00a0We used the Cochrane criteria to assess potential bias .n), where n is the number of subjects. We sued the GetData Graph Digitizer 2.24 [According to Cochrane Handbook recommendations, the mean change from baseline in the level of variables of interest and standard deviation (SD) for both groups were collected and used to compute the effect size . The folzer 2.24  to extra2 index, where values of 25%, 50%, and 75% reflect low, medium and high heterogeneity, respectively. We expressed the effect sizes as the weighted mean differences (WMD) and 95% confidence interval (CI). Sensetivity analysis was applied to assess the effct of each RCT on the overall effect size [We applied random effects model (using the DerSimonian\u2013 Laird method) and the generic inverse variance method to take to account the heterogeneity of studies in terms of demographic characteristics of populations .A quantiect size \u201320.To determine potential publication bias we used Begg\u2019s rank correlation, and Egger\u2019s weighted regression tests /The fill\u2019 and \u2018fail-safe N\u2019 and Duval & Tweedie \u2018trim methods were applied to adjust for the potential effects of publication bias , 22. Then\u2009=\u20094); editorial or review articles (n\u2009=\u20093); incomplete data (2); Fig.\u00a0From searches in different search engines overall 1273 single citations recognized, of these, 126 were duplicates. From 1147 items, 35 left after assessment based on titles and abstracts, of which, 11 were not selected due to fact that: genetic, non-human studies, or molecular studies  across all studies  and \u22120.22(mg/l),  in more than six months and \u22646\u00a0months accordingly. We have divided our data based on mean age of the participants (>50 and 50\u2264), pooled estimate for >50 group was \u22120.75(mg/l),  and 50\u2009\u2264\u2009\u22120.22(mg/l), . In terms of the sex, we ran the analysis for studies which included just females \u22120.34(mg/l), .The pooled estimate (weighted mean difference) of the effect of vitamin D supplementation on C-reactive protein was \u22120.26(mg/l),  across all studies  of the impact of vitamin D supplementation on IL-6 was 0.67\u00a0pg/ml,  across all studies.The pooled estimate (weighted mean difference) of the impact of vitamin D supplementation on IL-10 was 0.43\u00a0pg/ml,  across all studies.The pooled estimate (weighted mean difference) of the impact of vitamin D supplementation on TNF-\u03b1 was \u22120.11\u00a0pg/ml,  across all studies.The pooled estimate (weighted mean difference) of the impact of vitamin D supplementation on Adiponectin was 4.03\u00a0pg/ml,  across all studies.The pooled estimate (weighted mean difference) of the impact of of vitamin D supplementation on ICAM-1 was \u22120.79\u00a0pg/ml,  across all studies.The pooled estimate (weighted mean difference) of the impact of vitamin D supplementation on IL-7 was \u22122.32\u00a0pg/ml,  across all studies.The pooled estimate (weighted mean difference) of the impact of vitamin D supplementation on IL-2 was \u22120.111\u00a0pg/ml,  across all studies.The pooled estimate (weighted mean difference) of theimpact of vitamin D supplementation on IL-4 was 0.027\u00a0pg/ml,  across all studies.The pooled estimate (weighted mean difference) of theimpact of vitamin D supplementation on IL-5 was 0.631\u00a0pg/ml,  across all studies.The pooled estimate (weighted mean difference) of theimpact of vitamin D supplementation on IL-12 was 0.045\u00a0pg/ml,  across all studies.The pooled estimate (weighted mean difference) of the impact of vitamin D supplementation on IL-13 was \u22120.15\u00a0pg/ml,  and Begg\u2019s rank correlation test . After adjustment of effect size for potential publication bias using the \u2018trim and fill\u2019 correction, no potentially missing studies were imputed in funnel plots. Hence no difference in effect size than the initial estimate (WMD \u22120.26(mg/l), 95% CI -0.75 to 0.22)  value.The visual inspection of funnel plot asymmetry declared no potential publication bias for the comparison of CRP levels between vitamin D supplementation and placebo groups Fig.\u00a0. MoreoveIn the current meta-analysis of randomized trials, we investigated the impact of high-dose vitamin D supplementation on circulating inflammatory and anti-inflammatory indexes. We detected no effect of vitamin D supplementation on circulating CRP. However our analysis revealed that vitamin D supplementation significantly increased IL-6 level by 0.67(pg/dl), while no significant effect was found on serum IL10 and TNF-\u03b1.From a theoretical point of view, there are several possible mechanisms that may explain vitamin D may affect serum CRP and IL-6. The physiological impact of vitamin D is not limited to the homeostasis of calcium and phosphate. For instance, vitamin D receptors (VDR) play role in the decreased activation of the pro-inflammatory transcription factor nuclear factor kappa B (NF-\u03baB). This suggests that VDR has an intrinsic inhibitory role in inflammation , 36. Onen\u2009=\u20091381) [According to our results, existing studies report mixed results regarding the impact of vitamin D supplementation on CRP. The Framingham Offspring Study cohort reported no significant association was found between vitamin D and CRP \u2009=\u20091381) . While, 81 . Whil\u2009=\u20091381) . It has In the study by Forman et al.(2008) in a 1484 young women (aged 32 to 52\u00a0years)found that although vitamin D supplementation did not lower CRP specifically, it did lead to improvements in other inflammatory markers, for example IL-10 and TNF-\u03b1 . In addiIL-6 is a multi-potential inflammatory cytokine that has a fundamental role in host defence including the immune responses, acute phase reactions and haematopoiesis . Our anaOur study has some potential limitations. Internal validity of our results relies on the quality of individual studies as it is seen in all meta-analsyes. Several limitations can be named in this regard. Firstly, most studies in this meta-analysis had medium sample sizes. This may lead to overestimation of vitamin D supplementaion effects. Smaller trials might be methodologically less robust and more prone to report larger effect sizes , 49. TheThe current study revealed that vitamin D supplementation significantly increase level of IL6, while having no effect on CRP, IL10, and TNF-\u03b1 concentration. RCTs with larger sample size and longer follow-up period (12\u00a0months) should be considered for future investigations to provide an unequivocal answer.Additional file 1: Table S1.Table S2. Quality of bias assessment of the included studies according to the Cochrane guidelines. (DOCX 26 kb)Full search terms and strategy for the databases."}
{"text": "A pixel-based approach for extracting structure factors from X-ray free-electron laser crystal diffraction measurements is presented. 4\u2212106) of exposures. Although sufficient for generating biological insights, this approach converges slowly, and using it to accurately measure anomalous differences has proved difficult. This report presents a novel approach for increasing the accuracy of structure factors obtained from SFX data. A physical model describing all observed pixels is defined to a degree of complexity such that it can decouple the various contributions to the pixel intensities. Model dependencies include lattice orientation, unit-cell dimensions, mosaic structure, incident photon spectra and structure factor amplitudes. Maximum likelihood estimation is used to optimize all model parameters. The application of prior knowledge that structure factor amplitudes are positive quantities is included in the form of a reparameterization. The method is tested using a synthesized SFX dataset of ytterbium(III) lysozyme, where each X-ray laser pulse energy is centered at 9034\u2005eV. This energy is 100\u2005eV above the Yb3+L-III absorption edge, so the anomalous difference signal is stable at 10 electrons despite the inherent energy jitter of each femtosecond X-ray laser pulse. This work demonstrates that this approach allows the determination of anomalous structure factors with very high accuracy while requiring an order-of-magnitude fewer shots than conventional integration-based methods would require to achieve similar results.Most crystallographic data processing methods use pixel integration. In serial femtosecond crystallography (SFX), the intricate interaction between the reciprocal lattice point and the Ewald sphere is integrated out by averaging symmetrically equivalent observations recorded across a large number (10 Several programs have emerged to treat the problem of partiality, with cxi.merge  of 10 electrons . The crystal mosaic spread was computed by averaging scattering contributions from 100 equivalent mosaic domains. The misorientation of each mosaic domain with respect to the nominal orientation was taken from a normal distribution with a mean of 0\u00b0 and standard deviation of 0.01\u00b0 degrees, forming a mosaic texture. The mosaic texture was the same for all synthetic crystals, and the value 0.01\u00b0 was assumed to be a typically observed value in real crystals  was computational expediency. Random variation in the scale factor for each crystal was used to mimic variation in exposed crystal volume expected during each shot at the XFEL. The value 1150 was chosen by hand such that the contrast between low- and high-resolution spots was typical. We represented the crystal using a standard matrix convention  where panel is the CSPAD panel ID (0\u201331), fast is the panel fast-scan pixel coordinate (0\u2013184) and slow is the panel slow-scan pixel coordinate (0\u2013387). The CSPAD was placed 124\u2005mm from the interaction region, giving a corner resolution of 1.7\u2005\u00c5; however, we only analyzed scattering out to 2.1\u2005\u00c5. For each synthesized diffraction event we used a unique SASE input spectrum that was a scaled and shifted version of real spectra recorded during an LCLS experiment  using an upstream spectrometer  as set up at CXI  is the fluence in photons per area at wavelength \u03bb, sZ is the crystal scale factor randomly sampled for each shot from a normal distribution Fh| is the structure factor amplitude of the protein in each unit cell and I0 is the interference factor arising from the periodicity in the crystal lattice. The term \u0394hi,j,s is the Ewald offset at the pixel determined from the orientation of mosaic block j, and m3 is the total number of unit cells in the mosaic domain. jN is the number of orientations used to form a mosaic texture, the scattering power of which is then normalized by jN and scaled up by sZ for total scattering equivalent to a crystal that is made up of sZ mosaic blocks. For the synthetic data used here, the expected Bragg scattering was computed according toI0 should be maximal when the pixel is exactly probing the diffraction condition , and it should fall off rapidly as \u0394hi,j,s increases. We let I0 take the Gaussian formC was chosen such that the full width at half-maximum of the principal peaks in I0 would be equal to that arising from a parallelepiped mosaic block [see Appendix AC = 3.175]. The dimensionless Ewald offset \u0394hi,j,s is simply the residual between the fractional Miller index at each pixel with the nearest integer Miller indexqi(\u03bb) is the momentum transfer from incident beam unit vector UB in equation (5)B are what define the lattice translation vectors. Note the dependence of I0 on m; a larger mosaic domain parameter yields a brighter maximum with a more rapid falloff. For the synthetic data, we let m = 10 and jN = 100. For real data, we expect the true shape of the Bragg peak profiles to be well approximated by Gaussians, or a sum of Gaussians. The parameters describing the synthetic Bragg scattering data are summarized in Table 1To compute the Bragg scattering measured by each pixel, 2.2.2.nanoBragg computed the expected scattering for liquid water:VH2O, \u03c1H2O and uH2O are the volume, density and molecular weight of water, respectively, NA is Avogadro\u2019s constant, and |FH2O(qi)| is the isotropic structure factor amplitude per molecule of liquid water which depends on the scattering angle of the pixel, 2\u03b8i = sin\u22121(qi\u03bb/2). |FH2O(qi)| was measured independently at the Advanced Light Source beamline 8.3.1 . Here, the photon gain for each pixel was assigned by randomly selecting numbers from a normal distribution with a mean of 28 ADUs per photon and standard deviation equivalent to 3% of the mean, or 0.84 ADUs. These per-pixel gain values are typical for the CSPAD, and once selected they are fixed for all shots. Note that this type of calibration error assumes all pixels are the same physical size; pixel-to-pixel non-uniformity could be computed by adjusting the expected number of photons before computing the Poisson deviates above. Lastly, there is noise associated with detector readout due to electronic switching during the readout event itself and dark-charge accumulation during the exposure. CSPADs are dominated by dark current noise, but here we make no distinction and lump all errors associated with readout into a single Gaussian process. We included readout noise of the detector by adding a random number to the final computed values, where that random number was drawn from a normal distribution with a mean of 0 and a standard deviation of 3 ADUs. We modeled dark-subtracted data, where an average dark signal had already been subtracted from each shot, hence why the readout error fluctuates about 0. Per-pixel readout and counting noise terms fluctuate across every pixel and every shot; however, pixel gain calibration errors, though different for each pixel, are constant for all shots. It is typical to divide the observed pixel values by a nominal gain value for the entire camera (28 in this case) so that a unit pixel increment is the same size as the signal from a single photon, hence we have for the pixel valueNi,s is randomly sampled from a Poisson distribution with the expectation value Ii,s,data + Ti,s,data, the pixel gains ig form a normal distribution ri,s is randomly sampled from a normal distribution nanoBragg, see the supplemental material from the work by Holton et al. . This per-shot variation in observations is what makes the analysis of XFEL still shots with conventional protocols subject to large uncertainties. By summing together neighboring Bragg spot pixels, one loses the intricate per-pixel intensity variations that encode the incident photon spectra and crystal morphology. This information could otherwise be used to constrain complicated physical models. Rather than integrate Bragg spots we seek to use their pixelated profiles to optimize a model, thereby disentangling the various contributions to the scattering, and obtaining a more accurate measure of the structure factor amplitudes |Fh|.Fig. 22.3.1.Xi,s within all the Bragg-spot shoeboxes  represent the probability of observing Xi,s given the full set of model parameters \u0398 needed to describe the observed pixel values. We will explicitly define \u0398 in Section 2.3.7ML that maximizes the likelihood of the data The goal was to treat our synthetic images as an experimental dataset, and then use the pixel values es Fig. 2 to optim2.3.2.p, the probability of observing Xi,s given a set of model parameters \u0398 describing the scattering. In this case we know the precise model that was used to generate Xi,s, but the arguments below are general and applicable to real data. In what follows, we let XR represent a random variable for a pixel measurement, where Xi,s is a sample from the distribution governing XR. We assume XR describes an observation after division by the nominal gain, and after subtraction of an average dark pedestal, as shown in equation (8)XR as an expression involving three independent random variables:nR represents randomness in photon counting, gR represents randomness in signal amplification and rR represents randomness in signal readout. The random variable nR is governed by a Poisson distribution n represents the expectation value for the number of photons captured by the pixel during the diffraction event. We can simplify the statistics by approximating XR. The random variable gR arises due to error in detector gain calibration; even though we divide through by the nominal gain value, we do not know the precise gain of each pixel. Therefore, we let g by recording flat illumination on the detector, e.g. scattering from a copper foil far upstream of the detector, but the result is never perfect. The product of the two normally distributed random variables nRgR is in general not a normal random variable, however in certain limits we can make that approximation. Specifically, if we assume that nR and gR are independent random variables, then for large \u03bcn/\u03c3n and \u03bcg/\u03c3g we can approximate  this occurs when \u03bcn = 1.1 \u00d7 10 3\u2005photons, and for the work presented here most pixels received far fewer photons. The random variable rR describes a random offset applied to each pixel measurement which is governed by the underlying electronics of the detector modules, and it follows a normal distribution rR. The value \u03c3r is easy to estimate by closing the X-ray shutter and observing the pixel values fluctuating in the absence of X-rays. We used a value of \u03c3r = 3/28 throughout the analysis in this paper, in line with equation (8)fRX governing XR. This distribution is the convolution of frR (true for the sum of any two random variables). In the case that both nRgRf and frR are normal, then fXR will also be normal: Xi,s photons asni,s(\u0398) to represent the model for the expected number of photons in pixel i during shot s. Note this is different from Ni,s used in equation (8)ni,s(\u0398). It is noteworthy that the probability model in equation (13)Xi,s to be negative, something mathematically forbidden when modeling the observations using Poisson statistics alone. In other words, a photon count by itself can never be negative, only when coupled with additional terms such as the readout noise can a pixel report a negative value. Negative pixel values occur in regions of weak scattering where readout noise dominates. This can easily happen and is indeed expected after dark current subtraction for in-vacuum low-background measurements at facilities like CXI 2.3.3.5 pixels per image. This made maximum-likelihood estimation approximately 17 times faster than it would be if including all pixels. Interestingly, we found that over-predicting shoeboxes  did not hurt the refinement. This is a key distinction from integration methods, where over-prediction can be problematic.In principle one can evaluate the likelihood shown in equation (9)2.3.4.ni,s(\u0398) as a sum of Bragg scattering Ii,s and background scattering Ti,s:We modeled 2.3.5.Us. The scale factor sG relates primarily to the crystal size variation, but other factors can also affect the scale during real measurement. One can use equation (4)supporting information). Also, given the relatively small mosaic domain size used for the synthetic data, we assumed mosaicity would dominate the spot profile shapes, as opposed to wavelength dispersion. Even though all crystals have the same mosaic parameter m and unit-cell matrix B, we modeled each crystal as having a unique mosaic parameter sm and unit-cell matrix Bs.We modeled the Bragg scattering similarly to that shown in equation (3):2.3.6.t = , where ix, iy are the fast-scan, slow-scan coordinates of the TN shoebox pixels selected for the tilt plane fit, and where iX are the observed values of those pixels. Rewriting equation (17)At = b, we can then write the solution as W is a diagonal matrix whose diagonal entries are the reciprocals of crude variance estimates for each pixel value in b. Given a pixel value iX, we approximated its variance (for tilt plane fitting purposes only) as r is the readout noise standard deviation (3/28 = 0.11 in the synthetic data), and we used this information to compute a signal-to-noise estimate for each Bragg reflection t, we modeled the background for pixels in the corresponding shoebox ast1, t2, t3] were initialized as the solutions to equation (17)ni,s(\u0398), especially for pixels at the shoebox periphery. This is a result of using a non-physical background model, and it poses a risk to violate equation (13)vi,s(\u0398) remain positive. To guard against this occurrence, we filtered all shoeboxes whose tilt planes dipped below 0 for any pixel in the shoebox. This resulted in the removal of an average of 2.3 out of 580 shoeboxes per shot.The measured background scattering arose from the solvent, and we did not model it using first principles. Instead, we fit a linear expression, or tilt plane, to the pixel measurements at the periphery of each Bragg spot shoebox CCTBX. L-BFGS requires the first derivative of the likelihood expression f(\u0398) in equation (9)nanoBragg (dubbed diffBragg) for computing the derivatives of the expected scattering ni,s with respect to each parameter. For example, when computing the derivative of the likelihood expression with respect to the structure factors, we used diffBragg to evaluateSolving for \u0398o is the initial value of the parameter and \u03c3\u03b8 represents the expected variation of the parameter during refinement 1/3. The initial estimates for |Fh| came from running the standard integration-based XFEL merging application in CCTBX (see Table 3supporting information for a comparison with post-refinement). The scale factors sG were each initially set to a very high number, in this case 106. This number was chosen to ensure that the model initially predicted finite Bragg scattering in most of the shoeboxes. The background tilt-planes for all shoeboxes were initialized by solving equation (17)Initial estimates of the orientation matrices  al. 1997. The out3.2.Once the parameters were initialized, maximum-likelihood parameter optimization was carried out in two main stages.3.2.1.sG and the mosaic parameter sm while keeping all other parameters fixed. We did this using only the low-resolution shoeboxes (less than 5\u2005\u00c5) with signal-to-noise ratio greater than 3. Second, using the optimized values for sG and sm, the unit cell matrix Bs and the crystal rotation matrix Us were refined while keeping all other parameters fixed. This was done for all spots with signal-to-noise ratio greater than 0.2 and resolution less than 2.1\u2005\u00c5. After this stage we identified images which refined poorly and removed them prior to the global stage 2 refinement. For the 2023 shot example, we removed 25 out of 2048 shots after stage 1 refinement by examining the resulting distributions for all sa, s, smc and sG . The results of stage 1 refinement are shown in Fig. 3Us = 0.001\u00b0, \u03c3Bs = 0.1\u2005\u00c5, \u03c3sG = 1 and \u03c3sm = 0.1 for all s, where \u03c3Us corresponds to the expected variation in the three angles defining the crystal rotation matrices Us and \u03c3sB corresponds to the expected variation in the unit-cell edge parameters. Timing statistics for this stage of refinement are shown in Table 4Here we refined shots one at a time in a series of two steps: first, for each shot, we refined the scale 3.2.2.Fh| and the scale factors sG as part of a global refinement over all images. All other parameters were kept fixed. At the start of this refinement stage, we set all sm equal to the median of the values obtained during stage 1 [see Fig. 3c)]. This was done because the per-shot scales sG and the per-shot mosaic domain parameters sm are correlated (both directly increase the number of expected photons in shot s). Also, at the start of this stage, all scale factors sG were set equal to the median of the results obtained for the scale factors during stage 1 refinement [see Fig. 3d)], but then they optimized to different values for each shot. Fig. 4hF = \u03c3sG = 1 for all Miller indices h and shots s.Here we refined the structure factor amplitudes |3.2.3.6 Bragg spot shoeboxes for a total of 2.7 \u00d7 108 pixels. For 2023 shots, stage 1 refinement (including input/output overhead) was completed in 12\u2005min, utilizing all 40 hardware threads. Stage 2 refinement ran at a rate of 23.5\u2005s per L-BFGS iteration using all 40 hardware threads (40 MPI ranks), though this number can be decreased by utilizing multiple compute nodes simultaneously. Future work will also utilize GPU-acceleration. The nanoBragg program used to compute the pixel values in equation (3)diffBragg to compute the log-likelihood and its derivatives have only been written for CPUs.Standard message passing interface (MPI) was used to accelerate the analysis, parallelizing over images; however, beyond that no attempt was made to optimize the runtime. Timing tests for stage 1 and stage 2 refinement were conducted on a single compute node at NERSC comprising two 2.4\u2005GHz Intel Xeon Gold processors for a total of 40 hardware threads. The complete set of data for all 2023 shots comprises 1.17 \u00d7 103.3.diffBragg maximum-likelihood estimation by comparing refined parameters with the ground truth parameters used to synthesize the data. In this section we discuss three metrics important for judging the success of the refinement, namely the per-shot lattice misorientation with respect to the ground truth, the ground truth R factor and the anomalous difference correlation with the ground truth.We judged the success of the 3.3.1.sU of the optimized crystal rotation matrices Us from the known crystal rotation matrices used to synthesize each shot. Fig. 3e) shows \u0394sU before and after stage 1 refinement. For 2023 exposures, starting with a median \u0394sU of 0.038\u00b0 (as given by the DIALS indexing results), we were able to refine the crystal orientations such that the median \u0394sU was 0.0028\u00b0 [Fig. 3e)].A useful metric to observe during optimization is the misorientation \u03943.3.2.R factor between the refined structure factor amplitudes and the ground truth (GT) structure factor amplitudes:k is a scale factor chosen to minimize RGT. Fig. 4RGT throughout stage 2 refinement for different resolution bins. At each point in refinement we computed a new k using the Adaptive Nelder\u2013Mead Simplex method , all of which can be detrimental in situations involving weak signals, such as anomalous difference amplitudes used for the spatial resolution of heavy atoms  and exascale systems at Argonne National Laboratory and Oak Ridge National Laboratory  will provide data processing at speeds to match the increased data collection rates expected for next-generation XFEL facilities (LCLS-II). The need for this level of computing (which includes GPU acceleration) becomes apparent by recalling equation (16)On a single compute node, refinement of 2023 shots took approximately 208\u2005min, including 12\u2005min for per-shot (stage 1) refinement and 196\u2005min for 500 iterations of global (stage 2) refinement running at 23.5\u2005s per iteration . We also assumed a detector with minimal pixel crosstalk and a well calibrated linear response, attributes that are realized in current-generation detectors like the ePix  . Sources of error we have not described include measurement parallax, per-image Debye\u2013Waller factors, intra-crystal unit-cell variation and multiple lattice scattering, all of which contribute to error in the determined structure factors. Thus far we have neglected any mention of structure factor errors, but we know proper error estimation can aid in solving real systems (Brewster, Bhowmick et al., 2019u and v are row and column indices. The variances of the parameters \u0398ML, including the structure factors {|Fh|}, are given by the diagonal elements of It is common to model the aggregate effect of energy-bandwidth and mosaicity in a single Gaussian equation (Parkhurst, 2020 al. 2012, we applnanoBragg to generate realistic XFEL diffraction images, which we analyzed using both the standard integration protocol and the new program, diffBragg. With diffBragg, we utilized all measured pixels simultaneously to estimate high-accuracy structure factors while requiring an order of magnitude fewer diffraction events compared with the conventional method. Reducing the number of required shots for a dataset can greatly benefit the general SFX experiment, with scarce beam time routinely plagued by unforeseen interruptions, limiting the amount of data one can realistically collect. Future work will aim to apply this method to real measurements and develop a user-friendly application for the general SFX researcher.In summary, we used the program 6.diffBragg refinement are included in CCTBX. Scripts for computing and processing the synthetic data are available at https://github.com/dermen/cxid9114.The tools used for 10.1107/S2052252520013007/zf5012sup1.pdfSupporting figures and tables detailing the effects of mosaic spread and geometry errors on the refinement. DOI:"}
{"text": "Correction to: Egypt J Bronchol (2021) 15:8https://doi.org/10.1186/s43168-021-00053-2After publication of the original article , the autThe incorrect author name is: Shohel Rana.The correct author name is: Sohel Rana.The original article has been corrected."}
{"text": "Enterobacterales, 111 of Pseudomonas aeruginosa, and 99 of Acinetobacter baumannii, all selected for carbapenem resistance and multidrug resistance to other agents. At 2 and 4\u2009\u03bcg/ml, cefiderocol inhibited 78.Cefiderocol is a parenteral siderophore cephalosporin with a catechol-containing 3\u2032 substituent. We evaluated its MICs against Gram-negative bacteria, using iron-depleted Mueller-Hinton broth. The panel comprised 305 isolates of  Enterobacterales, 111 of Pseudomonas aeruginosa, and 99 of Acinetobacter baumannii, all selected for carbapenem resistance and multidrug resistance to other agents. At 2 and 4\u2009\u03bcg/ml, cefiderocol inhibited 78.7 and 92.1%, respectively, of all Enterobacterales isolates tested, with rates of 80 to 100% for isolates with all modes of carbapenem resistance except NDM enzymes (41.0% inhibited at 2\u2009\u03bcg/ml and 72.1% at 4\u2009\u03bcg/ml) or combinations of extended-spectrum \u03b2-lactamase (ESBL) and porin loss (61.5% inhibited at 2\u2009\u03bcg/ml and 88.5% at 4\u2009\u03bcg/ml). Cefiderocol also inhibited 81.1 and 86.5% of all P. aeruginosa isolates at 2 and 4\u2009\u03bcg/ml, respectively, with rates of 80 to 100% for isolates with VIM, IMP, GES, or VEB \u03b2-lactamases and slightly lower rates for those with NDM (45.5% at 2\u2009\u03bcg/ml and 72.7% at 4\u2009\u03bcg/ml) and PER (66.7% at 2\u2009\u03bcg/ml and 73.3% at 4\u2009\u03bcg/ml) enzymes; 63.3% of P. aeruginosa isolates were inhibited at the FDA\u2019s 1-\u03bcg/ml breakpoint. Lastly, cefiderocol at 2 and 4\u2009\u03bcg/ml inhibited 80.8 and 88.9% of the A. baumannii isolates, respectively, with rates of >85% for isolates with OXA-51-like, -23, -24, or -58 enzymes and 50% at 2\u2009\u03bcg/ml and 80% at 4\u2009\u03bcg/ml for those with NDM carbapenemases. Dipicolinic acid and avibactam weakly potentiated cefiderocol against Enterobacterales isolates with metallo-\u03b2-lactamases (MBLs) and serine carbapenemase, respectively, indicating incomplete \u03b2-lactamase stability.Cefiderocol is a parenteral siderophore cephalosporin with a catechol-containing 3\u2032 substituent. We evaluated its MICs against Gram-negative bacteria, using iron-depleted Mueller-Hinton broth. The panel comprised 305 isolates of  Carbapenem-resistant Gram-negative bacteria have proliferated globally and are a growing problem, prioritized by the WHO . Their rMany carbapenemase producers are resistant to multiple antibiotics besides \u03b2-lactams, including fluoroquinolones, aminoglycosides, and antifolates . ConsequEnterobacterales isolates with KPC and OXA-48-like enzymes, while meropenem-vaborbactam and imipenem-relebactam inhibit those with KPC enzymes only , and in the European Union (EU) for the treatment of infections due to aerobic Gram-negative bacteria in adults with limited treatment options. It has a catechol moiety attached via its 3-position side chain, allowing uptake into Gram-negative bacteria via the ferric iron transporter system \u201313. We e\u2013Enterobacterales isolates based on the FDA 2-\u03bcg/ml breakpoint but only 42.0% based on the EUCAST 0.5-\u03bcg/ml value, which, strictly, is only applicable to Escherichia coli and Citrobacter koseri.The isolate panel was deliberately loaded with highly resistant organisms , as reflEnterobacterales, inhibiting 41.6% of isolates at its breakpoint of 8 \u03bcg/ml for\u2009ceftazidime plus\u20094 \u03bcg/ml for avibactam, essentially comprising almost all those without MBLs. Aztreonam was the most active \u03b2-lactam against the P. aeruginosa panel, inhibiting 46.8% of isolates\u2014mostly MBL producers\u2014at its 16-\u03bcg/ml breakpoint. Resistance to established \u03b2-lactams, including ceftazidime-avibactam, was nearly universal in the A. baumannii panel.Among comparator \u03b2-lactams, ceftazidime-avibactam was the most active combination against Enterobacterales isolates at 2\u2009\u03bcg/ml and 92.1% at 4\u2009\u03bcg/ml; corresponding proportions for the P. aeruginosa collection were 81.1 and 86.5%, respectively, although only 63.3% were inhibited at the FDA\u2019s 1-\u03bcg/ml breakpoint. The proportions of the Acinetobacter collection inhibited at 2 and 4\u2009\u03bcg/ml were 80.8 and 88.9%, respectively; neither CLSI nor the FDA has breakpoints for this genus.Cefiderocol inhibited 78.7% of Enterobacterales groups except those with NDM carbapenemases (41% inhibited) or combinations of extended-spectrum \u03b2-lactamases (ESBLs) and porin loss (61.5% inhibited)  those with NDM MBLs (72.1% inhibited) and (ii) those with combinations of ESBL and impermeability (88.5% inhibited).MICs of cefiderocol were widely scattered within enterobacterial species and had no obvious association with species . Accordihibited) . At 4\u2009\u03bcgEnterobacterales isolates with NDM enzymes was extended and elevated compared with those for isolates with other MBLs. This behavior was independent of aztreonam resistance, indicating that higher cefiderocol values, where seen, were not contingent upon coresident ESBL or AmpC enzymes , PER (66.7%), and NDM (45.5%) \u03b2-lactamases , PER (73.3%), or NDM enzymes (72.7%). Cefiderocol MICs of \u2265128\u2009\u03bcg/ml were recorded for two isolates: one with an NDM carbapenemase and one with a VIM carbapenemase.At 2\u2009\u03bcg/ml, cefiderocol inhibited 81.1% of ctamases . At 4\u2009\u03bcgEnterobacterales, cefiderocol MICs for P. aeruginosa isolates with NDM carbapenemases were elevated compared with those for isolates with other mechanisms, although it should be cautioned that (i) the behavior seemed less marked and (ii) only 11 P. aeruginosa isolates with NDM carbapenemases were tested\u2014far fewer than the 61 Enterobacterales isolates.As with A. baumannii isolates, with rates of \u226585% for all groups, except for those with NDM carbapenemases (50.0%); at 4\u2009\u03bcg/ml, it inhibited 88.9% , as an inhibitor of MBLs, and avibactam (4\u2009\u03bcg/ml), as an inhibitor of any coproduced serine \u03b2-lactamases, and with a combination of both these inhibitors. A panel of 40 chanisms .Enterobacterales isolates showed a >2-fold reduction in cefiderocol MIC. Dipicolinic acid, in contrast, achieved 4- to 32-fold reductions in MIC for 25/40 blaNDM-positive isolates, with combination MICs ranging from \u22640.03 to 16\u2009\u03bcg/ml and a mode of 1\u2009\u03bcg/ml, compared with 4\u2009\u03bcg/ml for cefiderocol alone. There was a greater effect when both inhibitors were tested together in combination with cefiderocol, with 4- to 64-fold MIC reductions for 36/40 blaNDM-positive isolates. Using this triple combination, all 40 NDM-positive isolates were inhibited by cefiderocol at \u22642\u2009\u03bcg/ml compared with 22.5% for cefiderocol alone.Avibactam alone had predictably little effect on the MICs of cefiderocol for the isolates with NDM enzymes: only 1/40 NDM-positive The control groups were small, reducing the strength of conclusions for individual enzyme types: nonetheless, MICs of cefiderocol for isolates with VIM enzymes generally showed 2- to 4-fold reductions when dipicolinic acid was added alone or together with avibactam, whereas no reductions were seen with only avibactam added. Conversely, the MICs of cefiderocol for isolates with KPC or OXA-like carbapenemases, or with combinations of ESBL and porin loss, mostly were reduced by the addition of avibactam alone or combined with dipicolinic acid, whereas dipicolinic acid alone had minimal effect.in vitro activity against otherwise extremely resistant Enterobacterales isolates and nonfermenters, at least under iron-deficient conditions. Thus, as found here and by others , meropenem-vaborbactam, and imipenem-relebactam  of those with VIM and IMP MBLs . This behavior was unrelated to aztreonam resistance or susceptibility, implying that the higher MICs reflected the NDM enzymes themselves and not coproduced ESBLs or AmpC enzymes. To explore this aspect further and to determine if NDM enzyme protected bacteria against cefiderocol, we undertook combination tests with \u03b2-lactamase inhibitors. The results supported the view that cefiderocol is not completely \u03b2-lactamase stable, as it was frequently, though weakly, potentiated by dipicolinic acid against the isolates with NDM (particularly) and VIM MBLs and by avibactam for isolates with KPC, OXA-48, ESBL, and AmpC enzymes. Additional synergy for Enterobacterales isolates with NDM enzymes when both dipicolinic acid and avibactam were added is surprising. It may be that avibactam inhibits coresident class A or D \u03b2-lactamases, but were this a significant factor, one would expect the MICs of unprotected cefiderocol to be higher for aztreonam-resistant, NDM-positive Enterobacterales isolates than for their aztreonam-susceptible counterparts lacking ESBLs or AmpC enzymes, and this was not the case  of the case .P. aeruginosa, unless OprD is lost, despite lability to the organism\u2019s chromosomal AmpC enzyme  111 isolates of P. aeruginosa, selected to represent producers of MBLs and GES carbapenemases, along with isolates that produced VEB or PER ESBLs and were carbapenem resistant via OprD loss; and (iii) 99 isolates of A. baumannii with NDM MBLs or various OXA carbapenemases.The test isolates  comprisePseudomonas aeruginosa with PER ESBLs, which were collected in Turkey in the early 1990s  Reference Unit collections for inclusion, we favored organisms with phenotypes for other \u03b2-lactams (cefiderocol had not previously been tested), typical of their mechanisms but including susceptible and resistant representatives for antibiotics that divide isolates within groups. Thus, for example, groups with metallo-\u03b2-lactamases were selected to include both aztreonam-resistant organisms  and those that were aztreonam susceptible (inferred to lack ESBLs or AmpC enzymes). We ensured that the isolates were from diverse hospitals and excluded multiple isolates from single patients. Almost all of the organisms were submitted by hospital laboratories in the United Kingdom between 2008 and 2018 for investigation of unusual resistance phenotypes and/or susceptibility testing for therapeutic guidance. Exceptions were 3 isolates referred to the PHE-AMRHAI Reference Unit from hospitals in the Republic of Ireland and 11 isolates of ly 1990s .Carbapenemases and VEB and PER enzymes were identified by PCR of their encoding genes or by whole-genome sequencing (WGS). Carbapenem resistance due to porin loss combined with ESBL or AmpC activity was inferred from previous susceptibility results and the absence of carbapenemase, as confirmed by PCR or WGS. Species identification was by matrix-assisted laser desorption ionization\u2013time of flight (MALDI-TOF) mass spectroscopy.2+, Ca2+, and Zn2+ ions at concentrations of 20 to 25, 10 to 12.5, and 0.5 to 1.0\u2009\u03bcg/ml, respectively. The comparator antibiotics were meropenem, ceftazidime, ceftazidime-avibactam (4\u2009\u03bcg/ml), cefepime, ceftolozane-tazobactam (4\u2009\u03bcg/ml), aztreonam, colistin, amikacin, ciprofloxacin, and tigecycline, all sourced by IHMA.MICs were determined using preprepared broth microdilution plates  with antibiotic dilutions in cation-adjusted Mueller-Hinton broth (CAMHB) . Iron-deEnterobacterales isolates was similarly tested on a second broth microdilution plate that included cefiderocol alone, cefiderocol-avibactam (4\u2009\u03bcg/ml), cefiderocol-dipicolinic acid (100\u2009\u03bcg/ml), and cefiderocol plus both avibactam (4\u2009\u03bcg/ml) and dipicolinic acid (100\u2009\u03bcg/ml). ID-CAMHB was used.A subpanel of 64 Enterobacterales and P. aeruginosa; the FDA has values of S \u2264 2\u2009\u03bcg/ml and R > 4\u2009\u03bcg/ml for Enterobacterales and S \u2264 1\u2009\u03bcg/ml and R > 2\u2009\u03bcg/ml for P. aeruginosa; CSLI still has values under review, but previously, when cefiderocol was in trial, had investigational values of S \u2264 4\u2009\u03bcg/ml and R > 8\u2009\u03bcg/ml. MICs of comparator antibiotics were interpreted using EUCAST guidelines where available, the exceptions being ceftazidime and cefepime for Acinetobacter spp., for which only CLSI breakpoints are available.We reviewed results against published breakpoints: EUCAST has values of S \u2264 2 \u03bcg/ml and R > 2\u2009\u03bcg/ml for"}
{"text": "The results showed that excess NO increased the inflammation marker levels in T2DM, which is activated by the PPAR\u03b3/eNOS pathway. These findings will strengthen the understanding of NO in T2DM and provide a new target for the treatment of T2DM.Inflammation accounts for the process of type II diabetes mellitus (T2DM), the specific mechanism of which is still to be elucidated yet. Nitric oxide (NO), a critical inflammation regulator, the role of which is the inflammation of T2DM, is rarely reported. Therefore, our study is aimed at exploring the effect of NO on the inflammation in T2DM and the corresponding mechanism. We analyzed the NO levels in plasma samples from T2DM patients and paired healthy adults by Nitric Oxide Analyzer then measured the expression of inflammatory cytokines (C-reactive protein, heptoglobin, IL-1 The high prevalence of T2DM is a serious public health event over the world [\u03b2-cell dysfunction, which adds the risk of developing T2DM [\u03b1, IL-1\u03b2, and IL-6 have been clarified to cause insulin resistance by inhibiting insulin signaling [Type II diabetes mellitus T2DM) is a common chronic metabolic and endocrine disease characterized by insulin resistance and he world . AccordiDM is a che world , 4, and ing T2DM , 6. C-reing T2DM , 7. Hapting T2DM , 9. Inflignaling , 11. The\u03b3 belongs to a family of peroxisome proliferator-activated nuclear receptors that regulate the expression of multiple genes involved in the regulation of lipid/glucose/amino acid metabolism, cell proliferation/differentiation, and inflammation, suggesting that it may play important roles in many diseases [\u03b3, has potent insulin-sensitizing effects and is used to treat T2DM, but the drug will produce side effects such as weight gain, liver damage, and cardiovascular risk and is gradually declining in clinical use [\u03b3 in T2DM. In recent years, studies have told that PPAR\u03b3 regulates the expression of inflammatory pathways. For example, GMG-43AC antagonist can be applied to treat acne because it activates PPAR\u03b3 to inhibit inflammation [\u03b3-mediated upregulation of CD36 is involved in the regulation of microglial activation and phenotype and promotes phagocyte-cell proliferation of apoptotic cells, thereby promoting the recovery of postischemic inflammation [\u03b3 activation is essential in the suppression of intestinal inflammatory response [\u03b3 regulates inflammation remains to be refined.PPARdiseases . Thiazolical use , 14. Thuammation . PPAR\u03b3-mammation . Moreoveresponse . In T2DM\u03b3/eNOS pathway regulates hypertension [\u03b3/eNOS pathway mediates the inflammatory process in T2DM.Nitric oxide (NO), a free radical molecule with pathophysiological functions, is extensively studied in inflammation. NO has anti-inflammatory and proinflammatory effects, which are correlated with its concentration . Excess rtension , ischemirtension , steatohrtension , ischemirtension , and so \u03b3/eNOS pathway and validated in the present study. Our findings may provide a new treatment target for T2DM.Therefore, we put forward the hypothesis that NO may regulate inflammation in T2DM through the PPARThe study was approved by the ethics committee of Huai'an Second People's Hospital and Hospital of Chengdu University of Traditional Chinese Medicine. Fifty-five T2DM patients and fifty healthy adults in this study signed informed consent forms and began to sample blood at 8:30\u2009am in the morning under a fasting state (no food and water absorption for at least 8\u2009h before sampling). The whole blood samples were collected and placed in a heparin anticoagulation tube , then centrifuged at 3500 g at 4\u00b0C for 10\u2009min. The achieved uppermost layer is the plasma layer, which should be stored at -80\u00b0C for subsequent testing.\u22126\u2009mol/L. 200\u2009\u03bcL of insulin preparation solution was added to each well in the model group, and an equal amount of RPMI1640 complete medium was added to each well in the control group; all cells were cultured for 48\u2009h [2).HepG2 cells were purchased from the Cell Bank of the Chinese Academy of Sciences ; they were cultured in 96-well plates in RPMI1640 medium  with 10% fetal bovine serum  and 1% penicillin-streptomycin  and allowed to grow to logarithmic growth phase for subsequent studies after a successful recovery. To construct a cell model of T2DM, insulin  was first diluted in RPMI1640 complete medium to a final concentration of 10for 48\u2009h . In the \u03b3siRNA  by using the Amaxa Lonza Cell Line Nucleofector\u00ae Kit  according to the manufacturer's instructions, and an equal amount of nonspecific siRNA  was transfected with HepG2 cells as a negative control. After incubation for 24\u2009h, they were used for western blot analysis.HepG2 cells were transfected with 100\u2009pmol PPARDue to the fact that NO has a short half-life and is not easy to directly detect, the concentration of its stable metabolites nitrite and nitrate can represent the levels of NO . In the \u03b2, TNF-\u03b1, and IL-6 in HepG2 cells were detected using an ELISA kit , and each experiment was performed 3 times according to the manufacturer's instructions.The levels of IL-1\u03b3. The expression levels were analyzed by the -\u0394\u03942Ct method, and GADPH (5\u2032-AGGTCGGAGTCAACGGATTT-3\u2032 (forward) and 5\u2032-TAGTTGAGGTCAATGAAGGG-3\u2032 (reverse)) expression levels were used as the reference standard.Total RNA was isolated from cells using TRIzol reagent  then reverse transcribed into single-stranded cDNA using a Prime ScriptTMRT kit . Real-time PCR equipment  was to detect the expression of C-reactive protein, haptoglobin, eNOS, and PPAR\u03bcg of total protein was isolated on 12% SDS-PAGE and transferred to PVDF membranes. Membrane blotting was first blocked with 5% bovine serum albumin  for 1\u2009h then incubated with primary antibody  overnight at 4\u00b0C, followed by incubation with horseradish peroxidase for 2\u2009h at room temperature. The relative protein expression levels were normalized to GAPDH.After HepG2 cells were treated with RIPA lysis buffer , 30\u2009t-test analysis. And p < 0.05 indicates statistical significance.All statistics were analyzed using GraphPad Prism 7.0 software (USA), and all experimental data were expressed as mean \u00b1 SD. Whether the expression of nitrite, nitrate, and NO differed between the different groups was obtained by To evaluate the effect of NO in the T2DM, we firstly examined the levels of nitrite and nitrate in plasma between 55 T2DM patients and paired 50 healthy adults (control group). The clinical data of volunteers in the study is shown in p < 0.0001), and the plasma nitrate levels between the T2DM group and control group were evidently different (p < 0.0001), which was found in Figures The concentration of plasma nitrite in the T2DM group was significantly higher than the concentration of plasma nitrate in the control group  and NO scavenger 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide , respectively. The concentration of IL-1\u03b3 can modulate the level of diabetic inflammation, the PPAR\u03b3/eNOS pathway plays an important role in several diseases. In the present study, insulin-induced HepG2 cells transfected with PPAR\u03b3 siRNA were found to significantly decrease the expression of PPAR\u03b3, eNOS, and NO in Figures \u03b3 expression in HepG2 cells prompted a significant decrease in the expression levels of IL-1\u03b2, TNF-\u03b1, IL-6, C-reactive protein, and heptoglobin. These results suggest that inflammation in T2DM may be associated with the PPAR\u03b3/eNOS/NO pathway.To investigate the mechanism of the development of inflammation in T2DM, we detected the expression of eNOS and NO in vitro. As shown in Figures The inflammatory response can drive the pathological process of T2DM by leading to deleterious effects on tissue function and insulin resistance , 29, so \u03b2, TNF-\u03b1, IL-6) was significantly increased in insulin-induced HepG2 cells after NO donor treatment, while the levels of inflammatory factors were decreased in insulin-induced HepG2 cells stimulated with NO scavenger. The results support that NO may take part in the inflammatory process in T2DM patients. To investigate the mechanism of NO on inflammation in T2DM, we investigated and conducted further studies. Previous studies have shown that PPAR\u03b3 hyperglycosylation modification induces endothelial insulin resistance and dysfunction associated with diabetic vascular complications by regulating the eNOS-NO pathway [\u03b3 provides assistance to the expression of eNOS [\u03b3-eNOS signaling pathway is currently unclear.In vitro experiment revealed that the concentration of inflammatory factors (C-reactive protein, heptoglobin, IL-1 pathway . PPAR\u03b3 p of eNOS , which i\u03b3 in vitro and found that the expression of eNOS and NO decreased after the treatment of insulin-induced HepG2 cells with NOS inhibitor. Inhibiting the expression of PPAR\u03b3 in insulin-induced HepG2 cells significantly decreased the levels of PPAR\u03b3, eNOS, and NO, and the levels of C-reactive protein, heptoglobin, IL-1\u03b2, TNF-\u03b1, and IL-6 were significantly reduced. Therefore, the expression of T2DM inflammation may be regulated through the PPAR\u03b3/eNOS pathway-mediated expression of NO.To test the hypothesis, this study detected the expression of eNOS and PPARIn summary, this study explored the link between NO and inflammation through insulin-induced HepG2 cells, which provides a potential therapeutic target for the possible treatment of T2DM."}
{"text": "A sample of 20,000 genotyped animals were used to predict ungenotyped using animal model. Prediction accuracies for ungenotyped animals for SRh and SRl were 0.60 and 0.54, and for allele content were from 0.41 to 0.71, respectively. Response to selection on SRh and SRl increased SR by 0.52 and 0.28, and on allele content from 0.13 to 0.50, respectively. In addition, the selected animals had large proportion of homozygous for the favorable haplotypes. Thus, pre-selection prior to genotyping could reduce genotyping costs for breeding programs. Using a linear animal model to predict SR makes better use of available information for the breeding programs.Selection based on scrapie genotypes could improve the genetic resistance for scrapie in sheep. However, in practice, few animals are genotyped. The objectives were to define numerical values of scrapie resistance genotypes and adjust for their non-additive genetic effect; evaluate prediction accuracy of ungenotyped animals using linear animal model; and predict and assess selection response based on estimated breeding values (EBV) of ungenotyped animals. The scrapie resistance (SR) was defined by ranking scrapie genotypes from low (0) to high (4) resistance based on genotype risk groups and was also adjusted for non-additive genetic effect of the haplotypes. Genotypes were simulated for 1,671,890 animals from pedigree. The simulated alleles were assigned to scrapie haplotypes in two scenarios of high (SR PrP gene [In the typical form of scrapie, the risk of infection is determined by variation in amino acid sequence encoded in the PrP gene ,2,3,4. TPrP gene ,6,7. OthPrP gene . A totalPrP gene ,9. Due tPrP gene ,8,10,11.PrP gene  proposedSelection based on risk group of the genotypes could be practiced ,5,8,9. HThe objectives of this research were to: (1) define numeric values of scrapie resistance genotypes and adjust them for their non-additive genetic effect; (2) evaluate the accuracy of using BLUP for prediction of scrapie resistance and allele content of ungenotyped animals; and (3) predict selection response and assess the change of genetic merit of selected ungenotyped animals based on estimated breeding value. The hypothesis of this research was that it is possible use a linear animal model for genetic evaluation and selection of ungenotyped sheep for scrapie resistance based on a small proportion of genotyped animals.The numeric value of scrapie resistance genotypes was defined by ranking the scrapie genotypes from 0 (most susceptible) to 4 (most resistant), which were based on risk levels previously presented in literature ,8,9 see. The addwww.genovis.ca; Guelph, ON, Canada accessed on 9 June 2017) was used to simulate genotypes at a single locus with five alleles resulting in 15 possible common genotypes. The genotype frequencies resulting from the simulation are shown in h and SRl, respectively) and the allele content  for the haplotypes  are presented in n = 1,671,890) and the randomly chosen animals  that had their genotypic information available , respectively.A pedigree containing 1,671,890 sheep from the GenOvis database (h and SRl) and haplotype allele contents  where predicted for the ungenotyped animals using the observed records of the 20,000 genotyped animal using ASREML [ith animal for the trait being analyzed ; ith animal; and The scrapie resistance phenotypes , thus assuming a negligible residual. In order to estimate breeding values (EBV) for all animals (including the ungenotyped with no genotyped relatives) in the pedigree, unknown parents were assigned to genetic group based on sex and breed.The heritability was assumed to be almost complete ; 2 = 0.99 ) between selected  to assess: (1) the proportion of animals selected at different truncation point; (2) the proportion of recovered homozygous from ungenotyped animals among the selected animals  at different truncation point; (3) allele frequencies at different selection truncation points; and (4) homozygous genotype frequencies at different selection truncation points.h for ungenotyped individuals was high 0.60. In addition, the predicted SRh was positively correlated (r = 0.58) with the most favorable haplotype in this analysis ARR (H1), and negatively correlated with the other haplotypes . The correlation between predicted allele content for ARR (Hc1) with its true content and SRh was 0.71 and 0.47, respectively. This means that selection based on SRh is expected to increase SR and ARR allele content, while decreasing the allele content for other haplotypes . On the other hand, prediction of SRl was less accurate when predicting the true SRl (r = 0.54) compared to SRh, and was negatively associated with the least favorable allele in this scenario, i.e., H1 (VRQ), while positively correlated with the other haplotypes . This means that selection for SRl will increase SR by replacing ARR by the other haplotypes in the population.The Pearson\u2019s correlation coefficients between EBV and the trait true genetic value are shown in h, SRl and the haplotype allele contents  for ungenotyped animals . Selection of SRh EBV was predicted to increase scrapie resistance by 0.46 and ARR (Hc1) allele content by 0.36, and decrease the other haplotype allele contents . Selection for Hc1 EBV was predicted to increase the SRh by 0.36 and ARR (Hc1) allele content by 0.44, and decrease the other haplotypes allele contents. On the other hand, in the low resistance population (low-SR), direct selection for SRl EBV was predicted to increase SR by 0.33 and increase the allele content of haplotypes ARQ, ARH, AHQ, and ARR, while decreasing the allele content of the most unfavorable haplotype VRQ. Compared to VRQ, selection for the other haplotypes was predicted to be slower, reflecting their lower accuracies of prediction  and AHQ (Hc2) by 0.29 and 0.16, respectively. On the other hand, in a low-SR population, selection increased SRl by 0.71 accompanied of a decrease in allele content of VRQ (Hc1) by 0.74, while increasing haplotype allele contents for ARQ (Hc2), ARH (Hc3), AHQ (Hc4), and ARR (Hc5) by 0.33, 0.13, 0.15, and 0.13, respectively. As expected, when all animals were genotyped, there is a higher gain than when only a fraction of the animals was genotyped for scrapie , selection based on Hc1 EBV \u2265 mean EBV resulted in selecting 50.7% from the population and recovering a total of 87.7% of the target homozygous genotype (ARR/ARR). This means that by pre-selecting 50.7% of individuals based on EBV for allele content for genotyping, 87.7% of homozygous genotypes could be captured from the original population. Thus, this would reduce the number of animals required for genotyping. In the case of low ARR allele frequency , when pre-selecting based on EBV for allele content \u2265 mean EBV, the number of individuals required for genotype validation was reduced to 37.8% (As expected, as the selection truncation point increased, the proportion of selected  and the to 37.8% , while rto 37.8%  of homozmyostatin gene in Belgium blue cattle, with prediction accuracies between 0.47 and 0.50. In another study in Canadian Holstein cattle, the prediction accuracy for allele content was as high as 0.93 [genes, such as for maedi-visna [PrP gene underlying scrapie phenotypes is multi-allelic with different contributions from the different haplotypes to the level of scrapie resistance in sheep [The accuracy for prediction of haplotype allele contents ranged between 0.41 and 0.71 . Gengler as 0.93 . Legarra as 0.93  reporteddi-visna  and for di-visna . Applyindi-visna  is possiin sheep ,9. In thSelection response on SR and allele content was predicted for ungenotyped sheep . The selSelecting ungenotyped animals with EBV \u2265 mean resulted in reduction of number of animals compare to unselected population , while cBreeding programs can contribute to the reduction of prevalence of the typical form of scrapie in sheep. Arnold and Rajamyagam  estimateThis research proposed the use of a linear animal model as a practical method for genetic evaluation and selection for SR of ungenotyped sheep. Different scrapie eradication strategies used in breeding programs were described in previous studies. For instance, Arnold et al.  proposedModerate to highly accurate estimated breeding values for scrapie resistance and haplotype allele content for ungenotyped animals can be obtained from a linear animal model using genotype data from only a fraction of the total sheep population. Thus, selecting ungenotyped animals based on EBV could result in effective genetic gains for scrapie resistance and allele content. Individuals with EBV \u2265 mean were shown to carry a large proportion of homozygous genotypes. Thus, pre-selection prior to genotyping could reduce the number of animals needed to be genotyped to identify individuals with the favorable homozygous genotypes in the population and, consequently, reduce the genotyping cost. Therefore, a linear animal model could make better use of the available information for genetic improvement of scrapie resistance in sheep."}
{"text": "BackgroundThe use of acellular dermal matrix (ADM) for post-mastectomy reconstruction is considered by many surgeons to be an accepted component of surgical technique. Early clinical experience is described for SimpliDerm\u00ae - a novel human ADM , and AlloDerm\u00ae Ready-To-Use (RTU) - an established ADM .MethodsRecords were retrospectively reviewed from four sites between 2016 and 2021 of patients who underwent immediate, two-stage reconstruction with either SimpliDerm (n=38) or AlloDerm RTU (n=69) after mastectomy and were followed out to exchange to permanent implant(s), tissue expander(s) explant, or death.Results2. Significantly more patients in the SimpliDerm group were of Hispanic or Latino ethnicity . Reconstructions were predominantly prepectoral (82.3%). A total of 35 adverse events (AEs) occurred in 27 (25.2%) patients, with no difference in AE type, classification, or rates between ADM groups. No AEs were considered related to either ADM. The observed AE profiles and rates are similar to those published for other ADMs in immediate breast reconstruction.Immediate breast reconstruction with tissue expanders and ADM was performed on 107 patients (181 breasts). Overall mean patient age was 51.4 \u00b1 12.4 years, and mean BMI was 28.0 \u00b1 5.8 kg/mConclusionsThere continues to be a need for additional clinically equivalent ADMs to provide physicians with more availability and options for their practice. This retrospective, multisite study describes comparable clinical outcomes with SimpliDerm and AlloDerm RTU through a median of 133.5 days (~four months) following immediate two-stage breast reconstruction. Acellular dermal matrices (ADMs) are used in approximately 60% of all breast reconstructions performed every year in the United States (US) . In addiADMs are manufactured from decellularized biologic xenograft or allograft material. In addition to their basic clinical characteristics and species/tissue source , ADMs may be differentiated based on their processing methods during manufacturing. The different manufacturing processes required to remove immunogenic components and sterilize the matrix give rise to a variety of ADMs with differing physical and biological characteristics. Different processing methods may affect product handling, remodeling, and integration into native tissues, which could influence clinical performance and overall cost .Enhanced preservation of extracellular matrix (ECM) structure has been shown in clinical and pre-clinical studies to support the integration of ADM into native tissues by promoting constructive tissue remodeling processes such as neovascularization and inflammation , 14. SimA recent publication reports early (30-day) outcomes of a retrospective series using two ADMs (SimpliDerm and AlloDerm RTU) in immediate, two-stage breast reconstructions . HoweverEach participating site received approval from a review board  to perform a retrospective chart review of SimpliDerm and AlloDerm RTU used in consecutive patients undergoing immediate, two-stage breast reconstruction post-mastectomy between August 2016 and July 2021. Patients were excluded if they underwent delayed breast reconstruction, cosmetic or aesthetic breast augmentation or revision, or revision of a prior breast reconstruction.All treating surgeons were experienced with using both hADMs in ADM-based breast reconstruction, and their general surgical technique and postoperative protocol was similar between surgeons and hADM products. Both SimpliDerm and AlloDerm RTU were prepared based on the appropriate manufacturer\u2019s instructions and used to cover the tissue expander Figure . The choStandard patient-specific and procedural data were extracted from the medical records along with peri- and postoperative outcomes and complications. Complications related to surgical procedure or disease were reported during the perioperative period and recorded as requiring or not requiring explantation and/or surgical intervention. Adverse events were recorded as any untoward medical occurrence in a study subject that occurred at any time during follow-up and may or may not have been related to the study intervention. Serious adverse events were those considered to be life-threatening, resulting in death, requiring hospitalization, resulting in significant disability, or requiring intervention to prevent these outcomes. Major complications were defined as those requiring hospitalization and/or surgical intervention, and minor complications as those requiring outpatient clinic treatment only .Statistical analysisContinuous variables were assessed for normality. Independent samples t-tests were used to compare mean differences between cohorts. Medians were compared using Mann Whitney U test. Pearson chi-squares were reported for comparisons with expected cell counts of five or greater, and Fisher\u2019s exact tests were reported if a cell count was less than five. Statistical significance was set to P<.05. SPSS version 26  was used for statistical analysis.Records from four centers in the US totaling 107 patients (181 breasts) who underwent immediate, two-stage, tissue-expander-based breast reconstruction with the use of SimpliDerm  or AlloDerm RTU , followed by exchange to permanent implant(s), tissue expander(s) explant, or death were reviewed during the study period.Patient demographicsPatient demographics are listed in Table Relating to ADM types, there were no statistically significant differences between groups for patient age, race, BMI, smoking status, medical history, or pretreatment medications Table . RegardiProcedural detailsMastectomy indication was predominantly for the treatment of malignancy (87.3%) Table . The plaThe bilateral reconstruction rate did not differ by ADM type  Table . Use of Follow-up and complicationsFollow-up details and reported complications are listed in Table Median follow-up time was similar between groups , trending toward longer follow-up time in the AlloDerm RTU group . There were no differences between groups in the proportion of patients who reached their exchange procedure  or in the number of days from reconstruction to exchange. The proportion of patients with complications requiring surgical intervention or resulting in explantation also did not differ between groups - a total of six patients in each group had a complication that resulted in explantation . Final expander fill volumes and permanent implant volumes for patients who underwent an exchange procedure (N=162 breasts) also were comparable between groups  were reported in 27 (25.2%) patients  were similar to the number of patients in previously published analyses (10.6% - 33.3%) which described significant associations with postoperative complications , 23, 26.Ethnicity and outcomes of breast reconstructionIn general, ethnicity is under-reported in ADM-based breast reconstruction publications, and the relationship of ethnicity to access to care and clinical outcomes can be complex. Many studies have reported lower rates of breast reconstruction and higher rates of adverse events following reconstruction in Hispanic and Latino patients compared to non-Hispanic whites -30. The LimitationsThis study was limited by its retrospective and non-randomized design, the number of patients, mixed plane of expander/implant placement, and length of follow-up. The non-randomized design makes it difficult to understand if patient selection played a role in the over-representation of individuals with specific characteristics, such as pretreatment chemotherapy or Hispanic or Latino ethnicity, or how these characteristics may have affected outcomes. Also, since our ethnicity data were gathered retrospectively from existing patient charts, the accuracy of this data is unknown. The modest sample size may have prevented the identification of statistical significance in outcomes that showed numerical trends. Additional studies are warranted to determine clinical outcomes between sub- and pre-pectoral placement in patients receiving these ADMs, as this was not possible with our small cohort. Studies reporting long-term clinical outcomes will further our understanding of these ADMs and their long-term complication profiles. These limitations, while frequent in recently published studies due to intrinsic challenges related to studying ADMs in post-mastectomy breast reconstruction, nevertheless limit the interpretability of study findings. The longer-term (post-exchange procedure) consequences of post-mastectomy breast reconstruction remain an additional clinical concern and need to be addressed in future investigations.Implant-based breast reconstruction will continue to be performed in conjunction with ADM, as more studies continue to demonstrate the safety and clinical and aesthetic benefits in this setting. Our findings support that SimpliDerm is a clinically equivalent ADM to AlloDerm RTU that is safe and effective for two-stage breast reconstructions through over four months of follow-up."}
{"text": "Parkrun has grown to be one of the most popular. The present study identifies the motives of residents in the Western Cape Province to join parkrun and how their involvement influences future physical activity levels. Participants (N = 1787) completed a survey consisting of demographic history, parkrun participation history, motivations for participation, and physical activity-related behaviour changes associated with parkrun participation. The majority of participants were female (n = 952) and over 50 years of age . Along with health-related benefits, the provision of a safe and organised event was reported as a key motive to participate. The social connectedness developed by parkrun encouraged continued participation and promoted uptake of more physical activity. Close to half the participants reported increases in physical activity levels after joining parkrun, which demonstrates the benefit obtained from participation in structured mass participation events. With the large diversity in socioeconomic status in South Africa related to physical activity levels, parkrun provides a protected and engaging environment that provides opportunity for increased physical activity and potentially reducing the burden on the healthcare system.Mass participation events are promoted in South Africa as a positive public health initiative.  South Africa is a low- to middle-income country (LMIC) with diverse cultures and people of different socioeconomic strata . Physicaparkrun. Parkrun is a weekly free mass participation event held in parks and other free open areas [Mass participation physical activity events have been used to increase positive health behaviour among participants . These aen areas . In Soutparkrun to be associated with positive improvements in both physical and mental health and well-being [parkrun was important in engaging physically inactive participants; low socioeconomic communities were more likely to participate, and non-active runners used the events as an easy access starting point. Each event also creates a sense of belonging and social connectedness, which is a strong motivation for continued participation [parkrun as a mass participation physical fitness event.Research has identified participation in ll-being ,12,13. Scipation . A sensecipation . When apcipation . Thus, aparkrun seeks to address as a mass participation event to encourage physical activity [parkrun, and to ascertain the physical activity-related behavioural changes among registered parkrun participants in the Western Cape Province of South Africa.However, the majority of this research has been conducted in Australia and the UK ,17, and activity . The aimparkrun Global and parkrun South Africa, all registered members of the 37 parkrun South Africa sites in the Western Cape were contacted via email with details about the study, a plain language statement and a link to complete the online survey. Face-to-face collection was also conducted to include participants at three sites  who may not have had access to data or electronic resources required to complete the online questionnaire. Participants at these sites were recruited through short announcements made by parkrun organisers before the start of each event. After each race, interested participants completed informed consent and the survey in hard copy. Participants who completed the online questionnaire were not included in the face-to-face survey to prevent duplication of results and vice versa. To be eligible in either format, participants had to be over 18 years of age, registered with one of the regions of Parkrun sites, and to have completed a minimum of two parkrun events in the preceding six months.Following formal permission from parkrun study in Australia [parkrun participation history, motivations for participation, and physical activity-related behaviour changes associated with parkrun participation. Minor adaptations were made to improve the contextual relevance of the questionnaire to South African parkrun, and included information on Discovery Health Vitality points. Discovery Health is South Africa\u2019s biggest private medical aid covering healthcare costs. It rewards members who are registered in their Vitality Programme with points when they engage in health-/fitness-related activities, e.g., gym attendance, health screening, participating in parkrun, total daily step count, etc. For each parkrun event completed, members get 300 points. Once accrued, points can be redeemed for discounts on services and purchases. In an effort to improve response rates, the survey was compressed into the smallest functional size, and took on average four minutes to complete.A survey, adapted from a previous ustralia , was useparkrun. The online version of the survey was completed over a two-week period in August 2019. Face-to-face data collection, using a paper-based survey that was identical to the online version, was completed at eight parkrun events over a five-week period in August and September of the same year. The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the University of Cape Town, Faculty of Health Sciences Human Research Ethics Committee (HREC REF 119/2019 and HREC REF 142/2019). A certificate of approval was also granted by the parkrun research board.Initially the survey was forwarded to experts in physical activity and wellness in public health for assessment of the content and construct validity related to the adaption of the original survey to a South African audience. Three experts gave feedback on the clarity and relevance of the questions and recommended the inclusion of socialisation as a motivation for participation and including comments for participants regarding motivation and physical activity before and after joining parkrun. Independent variables used for this analysis include gender, education level, and gym membership. For all statistical analyses, a p-value less than 0.05 was accepted as statistically significant.All face-to-face data collected were manually coded and saved for analysis. Informed consent was not provided by 627 participants and they were excluded, along with 169 who did not meet the inclusion criteria and 222 who had incomplete data. Statistical analyses were performed using TIBCO Software\u2019s STATISTICA application version 13.5.0.17 and Graphpad Prism software version 8.3.0. The Shapiro\u2013Wilk test was used to assess for normality among continuous variables of age, height, weight, and body mass index (BMI). All data were found to be not normally distributed. Categorical data were analysed based on frequency and grouped in relation to gender, educational level, level of physical activity, and motivation for participation. Associations between categorical variables were assessed using the Chi-square test of association. The Kruskal\u2013Wallis H test was used to determine differences between at least three independent groups on total activity times (dependent variable). The Wilcoxon signed rank test and the Mann\u2013Whitney U test were used to compare physical activity levels before and after joining A final sample consisted of complete data for 1787 participants. The majority of participants were female, aged 50 years or over, and had a BMI in the overweight category. Most participants were married, had completed higher education, were employed, reported to be in very good personal health, and were regular exercisers see .parkrun were compared, using Chi-square, according to sex. Women favoured a safe environment, stress relief, and cost as their main motivations, whereas men recognized competition with others as a key motivator  or increased their weekly physical activity levels (n = 429) after joining parkrun. All participants who reported increasing their physical activity levels after joining parkrun were grouped according to demographic characteristics  took up new activities  and over the age of 50, which is comparable with parkrun participation globally [parkrun in Australia and the UK [The aim of this study was to identify the motives for participant in globally ,17. Partd the UK . This isd the UK , which md the UK . Educatid the UK  and may parkrun. There are considerable health and fitness benefits, including positive changes in weight, increases in cardiorespiratory fitness, and improvements in mental health [parkrun and initiate new physical activity practices, which is common within exercise motivation literature [Multiple motives exist for initiating participation in l health ,24. Evenl health . An additerature .parkrun as a safe environment for exercise participation. Over 79% of households in South Africa feel unsafe in their neighbourhoods [Parkrun is a community event manned by community members and volunteers to ensure safety for participants. Women in particular identified this as a motive for participation. This is a consistent barrier to participation globally [Parkrun addresses these issues and provides a safe space for exercise for all groups. It is not just a safer physical environment that is provided, but also a family-orientated nature [parkrun is on fun, enjoyment, and personal development, which can break down recognised barriers to women\u2019s participation in physical activity [Many people chose ourhoods . Parkrunglobally . Parkrund nature . The focactivity . Furtheractivity .parkrun is of great importance to continued participation. Parkrun creates a community and provides a sense of belonging. Over half the respondents in the present study reported socialisation to be influential to their participation. Similar findings have been attributed to parkrun globally [Parkrun also promotes a system that encourages participants to volunteer in the organisation and running of each event. This approach supports more social interaction, with group identification and participation known to have a reciprocal relationship [parkrun participants are able to gain a sense of autonomy. Competence is also developed and supported by the recognition of achieving personal goals and reaching milestones of 50/100/150/etc. runs [The socialisation that is provided by globally . Parkruntionship . Consisttionship . Applyintc. runs .parkrun. Only a small percentage, much lower than the national average [parkrun, with women most likely to incorporate more regular exercise and increased physical activity into their lifestyle. A similar finding has been reported in both Australia [parkrun, almost three quarters now integrated regular exercise into their daily life. This increased physical activity has the potential to reduce incidence of NCDs [parkrun, appears to be an important strategy to encourage less physically inactive lifestyles.The large majority (83.4%) of participants were physically active  prior to joining  average , classif average . The lowustralia  and the ustralia . Further of NCDs . In LMICparkrun participants in the country due to the diversity of South African socioeconomic demographics. A logical first step would be to replicate this study in a greater proportion of the South African population to ascertain a more complete overview and minimize any selection bias. Furthermore, only active and registered parkrun participants were recruited and the results may not be applicable to non-parkrunners and those who had previously participated in parkrun and since withdrawn. The current study used a cross-sectional design and therefore, it is not possible to determine a cause-and-effect relationship in describing the various variables in the study. Although there were instances where people reported losing weight after parkrun, this could be as a result of other factors and not due to parkrun alone. A longitudinal prospective study is advised to evaluate health-related behaviour changes and motivations of parkrun participants.The Western Cape Province is one of the most economically active provinces of South Africa, contributing over 13% to the national gross domestic product and providing 23.6% of the country\u2019s employment in 2018 . As suchparkrun for physical and mental health benefits. The provision of a safe environment for physical activity by parkrun is an important factor, particularly in LMICs, and encourages greater participation from women and older people. The added dimension of social connectedness from an organised, regular mass participation event appears to increase self-determined behaviours and encourage persistence and continued physical activity. This may contribute to better health and reduce the load on the national health system. Almost half of all respondents reported increased physical activity since joining the parkrun community, demonstrating an opportunity for mass participation events to become an efficient method for improving the health and well-being of the general population.In general, residents in the Western Cape Province of South Africa reported in this study that they participated in"}
{"text": "Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features.st 2020 and August 6th, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. \u201ctraditional\u201d vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset.We searched PubMed and EMBASE covering the period between January 1Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18\u201327%) of subjects after the first dose of vaccine and in 29% (95% CI 23\u201335%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10\u201312% of cases. No differences were detected across different vaccines or by mRNA-based vs. \u201ctraditional\u201d ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown.Our results show that vaccines are associated to a two-fold risk of developing headache within 7\u00a0days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24\u00a0h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40\u201360% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.The online version contains supplementary material available at 10.1186/s10194-022-01400-4. In late 2019, SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2), the etiologic agent of Coronavirus Disease 2019 (COVID-19) spread rapidly into the human population causing a global pandemic, with a relevant impact on mortality but also on a multi-organ morbidity  and COVIAccording to recent data published by the U.S Centre for Disease Control, referred to 13 jurisdictions and to the period April 4 \u2013 July 17 2021, 92% of infections, 92% of hospitalizations and 91% of deaths were observed among not fully vaccinated (i.e. one dose of two-doses products) or unvaccinated people compared to fully vaccinated (i.e. two doses or one dose of one-shot products) . Data puThe first vaccines against COVID-19 were introduced in some countries in the second half of 2020 . Since tHeadache is one of the most frequently reported adverse events (AEs) after vaccination, with some differences in term of incidence related to different vaccine type and dose. In some recent meta-analyses , 14, datWe will probably have to deal with COVID-19 prevention treatments for the next years, and the definition and incidence of possible side effects is crucial. In addition to being a common post-vaccination AEs, headache constitutes the cardinal symptom of primary headache disorders, which are among the most prevalent and disabling conditions , and oneWe conducted a literature review with meta-analysis and reported results according to the \u2018Preferred Reporting Items for Systematic Reviews and Meta-Analyses\u2019 (PRISMA) .Search terms had to combine information three main terms, i.e. COVID-19/SARS-CoV-2 AND Vaccination AND headache/adverse events. For each of three main terms, PubMed and EMBASE were searched using either free text and MeSH and EMTREE terms. The PubMed search was synthetically organized in this way: [COVID-19 (MeSH) OR COVID (free search in ti/abs)] AND [COVID-19 Vaccines (MeSH) OR Vaccin* (free search in ti/abs)] AND [headache (MeSH) OR headache (free search in ti/abs) OR trial OR side effect (free search in ti/abs)]. Similarly, the EMBASE search was synthetically organized in this way: [Coronarvirus OR SARS-CoV2 (emtree) OR COVID (free search in ti/abs)] AND [SARS-CoV2 Vaccine (emtree) OR Vaccin* (free search in ti/abs)] AND [headache (emtree) OR headache (free search in ti/abs) OR trial OR side effect (free search in ti/abs)].st 2020 and August 6th, 2021, looking for record in English and with an abstract. The full search strings are reported in the PubMed and EMBASE were searched covering the period between January 1Retrieved references were exported as.csv files and imported to Rayyan QRCI  for duplRetrieved references were equally and randomly assigned to the authors who screened titles and abstracts for eligibility. Nine authors  performed the double check about titles and abstracts eligibility of 20% randomly selected references.To be eligible and be evaluated in full texts, records had to be referred to primary research and to report, in titles and abstracts, information on headache incidence following vaccination against SARS-CoV-2. Authors were instructed to select records if they: a) referred to vaccine for SARS-CoV-2, or similar terms; b) were primary research articles; c) mentioned safety profile/adverse events; d) mentioned headache post-vaccination. Conversely, authors were instructed to exclude records if they: a) were published before 2020; b) did not have an abstract; c) were not in English; d) were letters, editorials, conference material, book chapters, case reports, literature reviews or meta-analyses; e) were clearly out of topic ; f) referred to pediatric populations (aged below 12) exclusively.In this phase, the agreement among the judgements of the raters (inter-rater reliability) was estimated with Krippendorff's alpha coefficient (\u03b1) ranging from 0  to 1 . In case of disagreement, the record was retained for full-text evaluation. In case \u03b1 was below 0.70, a second 20% set of reference was submitted to double check.Eligible references were equally and randomly assigned to the authors who screened full texts for inclusion. For full texts evaluation, studies were excluded if: a) were not available in full text; b) were not in English or published before 2020; c) did not refer primary research on COVID vaccine trials ; d) were not based on adult humans ; e) did not report data on safety issues and adverse events derived from a systematic evaluation, i.e. we excluded studies in which a case report form (CRF), either self-reported or based on structured interview with a health professional, was not used.Five authors  performed a double check on 50% of the full texts with regard to their eligibility and Krippendorff's \u03b1 was calculated: the choice for such a high rate is due to the large set of co-authors.Data extraction was performed through an ad hoc electronic spreadsheet of Microsoft Excel for Windows. Included studies were equally and randomly assigned to the authors who extracted information on the sample considering the whole sample, the sub-sample receiving placebo (where applicable), the sub-sample receiving each vaccine (for studies reporting information on more than one vaccine type), as well as for all subjects receiving any kind of vaccine.Extracted information included basic information, such as total number of participants, number of females, and average age, as well as the core information, i.e. the number of subjects who developed headache after vaccine or placebo inoculation. Additional information was: the number of subject developing migraine-like headache; the number of subject developing TTH-like headache; the number of subject with history of any headache; the number of subject with any chronic medical condition; the rank position of headache among reported AEs; the average days between injection and headache onset. With the exclusion of the last variables (which had to be reported directly), if the information was not directly available , it had to be calculated. Finally, authors were asked to refer whether the trial was in Phase II, III or IV, and whether the sample was entirely composed of subjects with specific health conditions .A final control measure was made on extracted data: five authors  double checked 100% of extracted data. Such a choice was again made in consideration of the large amount of authors selecting full-texts and extracting data.We descriptively summarized data reported to provide an overview of the included studies and samples in the studies, using medians and interquartile ranges (IQR) for raw data. The measure of interest was the proportion of subjects who developed headache among those who received vaccination of any kind, or placebo.2-test, and significant heterogeneity was defined when P-value was below 0.10. Inconsistency was quantified using the I2 statistic [2 below 40% indicates no or not relevant heterogeneity; I2 comprised between 30 and 60% indicates moderate heterogeneity: I2 comprised between 50 and 90% indicates substantial heterogeneity; I2 higher than 75% indicates considerable heterogeneity [The 95% Confidence Intervals (95%CI) were based on Wilson\u2019s procedure . Due to tatistic : I2 beloogeneity . MS exceSub-analyses included: analysis of headache development by single vaccines, for those vaccine type in which there were at least three studies; comparison between vaccine recipients (taken as a whole) and placebo recipients; comparison between first and second doses in terms of headache onset ; comparison between newly-developed mRNA-based vaccines and traditional vaccines (inactivated and vector-based vaccines) recipients.Finally, to address the impact of age and sex on headache development, a meta-regression analysis was performed. Mean participants\u2019 age and percentage of females in each single study were entered as moderators for the effect of vaccination or placebo on headache development. Meta-regression can be performed only if at least 6 effect size estimates with corresponding data for moderators are available: thus, it was run only for a portion of compounds and placebo .Once duplicate were removed, a total of 9338 records were selected for abstract check. Of them, 298 records were retained (double check agreement 98.1%) for full-text evaluation, which resulted in 84 papers included in the review (double check agreement 98.0%) \u2013110  of subjects developed headache after the first dose of vaccine and 29% (95% CI 23\u201335%) after the second, and that these rates were two-fold higher compared to those receiving placebo (10\u201312%). Headache was generally reported as the third most common AE, the first usually being pain at injection site. No significant differences could be observed between vaccines based on the new mRNA technology and \u201ctraditional\u201d  ones, together with a minor impact of age, which enables presuming that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction.After almost two years since the beginning of the COVID-19 pandemic, the SARS-CoV-2 is still causing a large number of deaths worldwide, and vaccination campaign is the most promising and safe way to reduce its spreading: this in fact means to reduce the impact of COVID-19 on the health of citizens\u00a0, by reduFirst, included studies report largely heterogeneous results on onset of post-vaccination headache, with no information about pre-existing headache disorders, which might act as risk factors for post-vaccination headache development. Moreover, no information on headache features, time to onset, duration and response to acute treatment could be derived by included studies. So, our literature review cannot provide direct evidence on pre-existing headache and features of post-vaccination headache, which is fundamental to determine if headache occurring after vaccination against SARS-CoV-2 can be considered as one of the usual headaches (for those with previous history of headache), or a totally new headache.The main reason for such a poor description of headache features lies in the selection criteria we applied, i.e. that we selected studies focused on vaccine efficacy, in which headache was addressed within solicited AEs, i.e. using structured CRFs. In most cases, such AEs were collected within 7\u00a0days from injection: this clearly leaves poor data to present the features of such headache, and thus such data do not enable to distinguish reversible, common and non-severe cases from those that should be considered as red flags for life threatening conditions, like cerebral venous thrombosis (CVT). Some reports specifically address headache as a premonitory symptom of CVT in non-replicant adenovirus vector based COVID-19 vaccine recipients\u00a0, 118. SuHowever, in most cases, headache occurring after vaccination from SARS-CoV-2 is reversible, with onset few hours after vaccine receipt and a few hours to few days\u2019 duration. Two manuscripts showed differences between first and second dose: our results show headache is more common after the second dose, but one study by Perrotta and colleagues showed the opposite (29.2% after the first and 22.1% after the second)\u00a0. The sevFinally, with regard to the features of headache occurring after SARS-CoV-2 vaccines, some inputs were available in four different studies\u00a0, 121, anWith regard to treatment for post-vaccination headache, available literature provides little information. The aforementioned studies\u00a0, 121 shoThe possible mechanism of post-vaccination headache is currently unknown and, in order to make some hypotheses, a step back to the mechanisms that have been hypothesized for SARS-CoV-2 to spread and impact on human body is needed. Several possible routes for SARS-CoV-2 virus spread in the human body are currently postulated: use of the bloodstream with subsequent neuronal dissemination, infection of endothelial cells within the blood\u2013brain barrier (BBB) or blood-cerebrospinal fluid barrier, use of transsynaptic pathways after infection of the endings nerves (forward or retrograde transport) mainly in the olfactory bulb, crossing the BBB as a result of leukocyte infection (Trojan horse mechanism) or through the use of the glymphatic system , 123. HoSARS-CoV-2 has been shown to be a neurotropic virus that has the ability to infect and replicate in cultures of neuronal cells and brains . It seemCOVID-19 related headache is frequently accompanied by osmophobia, phonophobia, and photophobia, which are less frequently reported in post-vaccination headache. In addition, other clinical features may present with some differences: post-vaccination headache is in fact mostly bilateral, less intensity and shorter duration than COVID-19 related headache\u00a0. Post-vaProbably the only common denominator for all of the analysed vaccine types is SARS-CoV-2 spike protein (SP). SP binds with ACE2 and leads to diverse biological, and potentially pain-related reactions . PresentThere exists an alternative to above described rationale. It attributes this symptom to disorder of homoeostasis. Vaccines are designed to induce humoral and cellular immunity. These reactions include diverse mechanisms, some of which possibly may provoke headache. Adaptive immune reaction takes days or weeks to develop, and hence would not provoke headache occurring hours after vaccination. However, innate immunity has been proven to begin within hours after vaccine administration , 138. ThThe attribution of headache to immune reaction is a compelling idea. It could be hypothesised that in this situation a more robust immune reaction could translate to more headache cases, but also more effective immunogenicity. Alas the studies from our meta-analysis did not try to find an association between post-vaccination headache and vaccine effectiveness. A post-hoc analysis could solve this conundrum. Finally, it should be mentioned that both of above-described mechanisms (SP and innate immune reaction) could explain many similarities between headache characteristics after COVID-19 vaccination\u00a0, 121 andWhen discussing the possible mechanism of post-vaccination headache, one might wonder if, in the case of viral vector COVID-19 vaccines, the headache is not a consequence of systemic infection. Then the headache could be identified using ICHD-3 code 9.9.2.1 \u2013 Acute headache attributed to systemic viral infection. However, in such a case, one would expect a higher incidence of headaches from this type of vaccination, which was not observed in this meta-analysis. That is naturally a completely theoretical situation, since adenoviruses in vector-based vaccines are unable to replicate. Hence their spread is limited to the muscle where they were administered via injection.It should also be remembered that in very rare cases the headache following vaccination may be a consequence of a complication of the COVID-19 vaccination. Cases of cerebral venous thrombosis or ischemic stroke in unusual locations associated with vaccine-induced immune thrombotic thrombocytopenia (VITT) have been reported following ChAdOx1-S and Ad26.COV2S vaccine , 142. ThSome limitations have to be taken into consideration. First, we were unable to locate eight studies. Second, there was a considerable heterogeneity across studies and two very large studies account for approximately 85% of the studies\u2019 sample . Third, there is a mixture of\u00a0phase-II/III and phase-IV studies, and therefore comparison against placebo is not always reported. Fourth, we were unable to report information on headache type and duration, and on presence of headache before vaccination, as this kind of information was not reported among selected studies: the information reported in this manuscript referred to headache features and higher likelihood to develop it among patients with history of headache was in fact derived from descriptive studies which did not meet our inclusion criteria. Finally, we have no information at all whether being on a migraine-specific prophylaxis might have a positive effect on post-vaccine headache development.In conclusion, headache is the third most common AE associated to vaccination against SARS-CoV-2, and it occurred in 22% (95% CI: 18\u201327%) after the first and in 29% (95% CI: 23\u201335%) after the second dose over a 7-day period, and such rates are higher compared to those receiving placebo (10\u201312%) as well as compared to population studies showing 6\u201317% likelihood to have headache on the previous day. The features of such headache, in approximately one-third of the cases, resemble that of migraine with pulsating quality, phono and photophobia, whereas aggravation with activity is more common . Its onset is generally within the first 24\u00a0h and the majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.Our meta-analysis showed no significant difference in the frequency of headaches observed with different vaccine types, which differ essentially in composition. Given the various mechanisms possibly implicated in the onset of post-vaccination headache, it seems most likely to be related to the systemic inflammatory response with a still unclear mechanism.Additional file 1."}
{"text": "Brassica juncea is a crucial cultivated mustard species and principal oilseed crop of India and Madhya Pradesh, grown for diverse vegetables, condiments, and oilseeds. Somaclonal variation was explored as a probable source of additional variability for the manipulation of fatty acids, especially low erucic acid contents that may be valuable for this commercially important plant species. The plantlets regenerated from tissue cultures (R0), their R1 generation and respective parental lines were compared for morpho-physiological traits and fatty acid profile for the probable existence of somaclonal variations. The first putative somaclone derived from genotype CS54 contained 5.48% and 5.52% erucic acid in R0 and R1 regenerants, respectively, compared to the mother plant (41.36%). In comparison, the second somaclone acquired from PM30 exhibited a complete absence of erucic acid corresponding to its mother plant (1.07%). These putative somaclones present a source of variation for exploitation in the development of future mustard crops with low erucic acid content. Brassica juncea L.) displays an immense polymorphism and is the basis of diverse types of vegetables, condiments, and oilseeds. It is an important oilseed crop globally, nutritionally affluent in fat, carbohydrate, vitamins, minerals, and water. As a result, its oil is expansively exercised in the medicinal, cosmetic and leather industries. It is an oilseed in high demand proving an increasing trend by fulfilling demand and supply with desired qualitative traits. The occurrence of erucic acid (C22:1) in elevated concentration (35\u201350%) is a significant drawback to mustard oil [Indian mustard  in further exploitation in conventional and/or molecular breeding programs. In vitro selection employing pathotoxins as a selection mediator for ca napus . Anuradhca napus  evaluated Chopra . Ahmad [d Chopra  attempten et al. . Roy andn et al.  identifin et al.  cultureda et al.  for engia et al.  to manips narrow , especias narrow , soybeans narrow ,23,24,25s narrow ,27,28, os narrow , and Witomnifera  with varIn the current investigation, an effort has been made to investigate the existence of somaclonal variation for low erucic acid content that can further be utilized as a source of added variability for the improvement of Indian mustard. To accomplish this, two genotypes viz., CS54 and PM30, were selected for the present research based on erucic acid content, whether higher or low, with two explants viz., immature cotyledons and seeds, to establish callus and subsequently to raise cell suspension cultures followed by an efficient and reproducible plantlet regeneration. However, the selection of genotypes with low erucic acid content with higher yield is hampered by various aspects, including plant species, genotypes, explant sources, nutritional requirements, and environmental behavior. Thus, the procedure and conditions for callus induction and shoot differentiation followed by plantlet regeneration were optimized for generating somaclones via callus and cell suspension cultures.The potential and limitations of the tissue culture technique for creating new genotype(s) with desired characteristics of agricultural importance have been documented in a considerable number of crop plants, including Brassica. Attempts to select lines with low and high erucic acid content are based on the assumption that depending on the cultivation protocol, the level and content of specific metabolites in tissue culture can be influenced to some extent. Certain metabolic pathways of a particular plant species lead to the synthesis of a specific metabolite . Their production also operates in cells and cell lines selected based on particular metabolite yield, and these lines were derived from the regenerant.In contrast, regenerants derived from these lines may have altered levels of certain metabolites of interest. \u20131 2,4 dichlorophenoxyacitic acid performed superior among all the combinations tested  medium amended with 3.0 mg Ls tested A\u2013E from m et al.  and Nasrm et al.  were in m et al.  in soybe\u22121 2,4-D in combination with 0.5 mg L\u22121 6-Benzylaminopurine(BAP) facilitated higher growth rates  regeneration medium for shoot organogenesis  was induced on modified MS media supplemented with a higher intensity of cytokinin viz., kinetin or zeatin, in combination with lower indole-3-acetic acid (IAA). Cytokinin BAP alone or in combination with auxins IAA or \u03b1-naphthalene acetic acid (NAA) did not support plantlet regeneration [1 generation was obtained from the growing Ro generation.The response to callus induction applying 2,4-D was more pronounced in terms of type, nature, and color of callus proliferated. However, plant regeneration has not been obtained on a medium amended with 2,4-D alone from cultured immature seeds in optimum frequencies. Therefore, consecutively to augment shoot regeneration efficiency, callus cultures were subsequently inoculated on MS media fortified with BAP. Well growing callus cell lines of genotypes CS54 and PM30 were subjected to MS.5B  per plant, number(s) of seed per siliqua and plant, seed yield per plant, and biological yield when compared to mother plants. However, the number(s) of primary branches and days to 50% flowering were not significantly varied. The number(s) of secondary branches per plant increased in both putative somaclones significantly compared to the mother plant at a 5% probability level of significance. No statistically significant difference was recorded between the performance of R0 and R1 plants for different morphological parameters investigated except number(s) of silique per plant for somaclone derived from cell lines of genotype CS54 where R1 regenerants showed more number(s) of silique per plant as compared to R0 regenerants. Perhaps this happened due to the mutations of genes and induction of somaclonal variation and the activation of recessive genes that reduced expression of most morpho-physiological traits, as stated earlier by D\u2019Amato [1 generation. Some of the plants showed significantly higher yield and/or other improved characteristics than the control. In addition, a dwarf plant type was also identified. Several plants were selected from this generation and carried forward to R2 generation, and most of these lines bred true in the R2 generation.The data of different morpho-physiological traits are presented in  D\u2019Amato . They di D\u2019Amato  also eva0 and R1 generations of putative somaclones regenerated from cell lines of genotypes CS54, it was interesting to note that plantlets regenerated in vitro, the erucic acid content recorded was 5.48% and 5.52%, respectively, in R0 and R1 regenerants as compared to mother plants (41.36%) of genotype CS54 . The percent value ranged between 2.88% and 10.90%. The highest content (10.90%) was recorded for Ethyl 9,12,15-octadecatrienoate, 9,12,15-Octadecatrienoic acid, methyl ester, -, and n-Propy1 9,12,15-octadecatrienoate at RT 10.4 on given conditions, whereas the lowest value (2.88%) was recorded for Ethyl 9, 12, 15-octadecatrienoate, 9, 12, 15-Octadecatrienoic acid, methyl ester, -, and n-Propyl 9,12,15-octadecatrienoate at 11.4 RT . These fype CS54 . However0 and R1 generations regenerated from callus and cell suspension cultures of genotype PM30 despite its presence (1.07%) in the mother plant. Although palmitic and oleic acid ratios considerably increased in R0 and R1 generations of putative somaclones compared to mother plants. Conforming findings have also been reported by Jagannath et al. [7 generation by Priyamedha et al. [B. junceia and B. napus had a fatty acid profile different from parental values, mainly for oleic and erucic acids. The low oleic acid (13%) in B. juncea increased to 23\u201326% in hybrids, and high erucic acid in B. juncea (41%) declined to 21\u201323% among hybrids. Linoleic and linolenic acids showed slight variation from parental values. The fatty acid profile of F1 hybrids shifted towards that of canola quality. The F2 seeds had zero erucic acid and high oleic acid, similar to or exceeding the canola parent. Successful interspecific hybridization of B. juncea and B. napus was confirmed by altered FAP and molecular markers [B. juncea showed an increase in oleic and linoleic acid content, while double zero varieties of B. napus showed a proportional increase in oleic acid content and reduced erucic acid content [0 and R1 generations of putative somaclones of both genotypes. It occurred perhaps due to the metabolic pathway of erucic acid synthesis, as immature cotyledons and seeds have taken as explants sources, and plantlets were regenerated from cell lines derived from these explants.Fatty acid profile analysis of somaclones derived from callus cultures of genotype PM30  also revh et al. , who obsh et al.  reporteda et al. . Amongst markers . Low eru content . In the After hardening, seven plants of genotype CS54 and eight of genotype PM30 were subjected to molecular confirmation. A total of twenty-three RAPD markers  were useFAE1) gene that translates the enzyme \u03b2-ketoacyl-CoA synthase (KCS) in erucic acid biosynthesis alleyway and catalyzes the first four enzymatic reactions in the synthesis of very-long-chain monounsaturated fatty acids (VLCMFAs) [FAE1 gene primes the forfeiture of occupation in enzymatic action and diminishes the gathering of VLCMFAs in seeds [0 and R1 generations of putative somaclones raised from both the genotypes compared to mother plants, possibly due to mutations.It has been proven that erucic acid content is governed by the fatty acid elongase 1 (VLCMFAs) ,46,47,48in seeds ,49,50. IBrassica juncea. The conventional breeding scheme reports, limited success in procuring low erucic acid content variants. In an earlier attempt, Roy and Saha [2 generation. In the transgenic approach conducted by Sinha et al. [Brassica [The present study is a probable first of its kind, regenerating low-erucic acid-containing variants employing a suspension culture for and Saha  screeneda et al. , the fata et al.  and showa et al.  offered Brassica ,16.Brassica, the in vitro regeneration capabilities have been genotype-specific [B. juncea, Hachey et al. [B. campestris, and by Zhang and Bhalla [B. napus.Further, the environmental and nutritional conditions can be controlled uniformly and precisely under tissue culture conditions, and at a given time large number(s) of somatic cell lines could be screened swiftly to regenerate variants. In genus specific ,51. Levespecific  in B. juy et al.  in B. cad Bhalla  in B. naTwo genotypes were selected based on different morpho-physiological, biochemical, and SSR molecular characterizations of Indian mustard genotypes ,5,6,7. T\u22121 sugar and 7.5 g L\u22121 agar, was supplemented to establish callus cultures from immature cotyledons and seeds, in turn, raising embryogenic cell suspension cultures. The culture media was prepared by making the final volume 1 liter, pH was adjusted to 5.8 \u00b1 0.1 with 1N NaOH/HCl, and 7.5 g L\u22121 agar was added as a gelling agent. However, in liquid media for cell suspension culture, agar was not incorporated. The warm media in liquid state were dispensed into culture bottles (50\u201370 mL/bottle) and culture tubes (20\u201320 mL/tube) followed by sterilization at 121 \u00b0C and 15 psi pressure for 25\u201330 min in an automatic autoclave. Pre-sterilized 100 \u00d7 17 mm glass Petri dishes were used for the culture. Media combinations and other ingredients were shortlisted during preliminary experiments carried out in our laboratory. Basal media, PGR\u2019s and other supplements were procured from Hi-Media\u00ae Laboratories, Mumbai, India.MS  was emplw/v) Carbendazim for 2 min followed by a rinsing with deionized water. The silique was further exposed to 70% ethyl alcohol for 2 min followed by surface sterilization by immersing in 0.1% mercuric chloride (HgCl2) for 1\u20132 min and finally three times with sterilized distilled water. Immature cotyledon (0.1 cm) and 1 to 2 mm sized immature seeds were excised from siliquae and cultured on pre-sterilized 100 \u00d7 17 mm glass Petri dishes containing 25\u201330 mL/dish media. All the cultures were incubated in racks inside a culture room exposed to a photoperiodic cycle of 16 h, at an intensity of 1600 lux luminance provided with cool white fluorescent light and 8h darkness at 25 \u00b1 2 \u00b0C and 70% RH.Silique containing immature seeds were acquired and treated with Tween-20 for 10 min following cleaning with double distilled water followed by treatment with 0.25%  and were disquieted on a horizontal shaker (120 rpm) at 25 \u00b1 2 \u00b0C in the absolute dark. After two weeks, cultures were subjected, under a photoperiod regime, each of 12 h light and dark at an intensity of 1200 lux luminance provided by white, fluorescent light. After two weeks, the cultures were sieved aseptically to eliminate large clumps, and 10 mL filtrate was appended with 40 mL of a fresh medium. The leftover filtrate was subcultured to establish new suspension cultures and for regeneration.\u22121 BAP) for regeneration and on non-selective media MS.5D.5B  or MSN.5B (MS +1.0 mg L\u22121 NAA + 0.5 mg L\u22121 BAP) for the continuation of organogenetic calli growth. After one month of incubation on the selection medium, callus portions with green shoot primordia were separated and transferred into shoot regeneration medium MS.5B (MS + 0.5 mg L\u22121 BAP). Well-developed cultures with regenerated shootlets were divided into pieces after 45 days and subcultured once again on regeneration media in glass jars to obtain multiple shoots and growth. The shootlets were allowed to grow under growth room conditions at 25 \u00b1 2 \u00b0C, RH 75% and 1600 lux for 16 h light and 8 h dark cycles. Well-developed normal-looking shootlets of appropriate length (<7.5 cm) were then transferred to the rooting MS medium amended with 0.5 mg L\u22121 indole-3-butyric acid (IBA), 15.0 g L\u22121 sucrose, and 7.5 g L\u22121 agar in line with the suggestion of Tripathi et al. [Callus cultures/somatic embryoids of two genotypes viz., CS54 and PM30, were obtained from callus cultures. They sustained through continuous sub-culturing and were cut into small pieces. Five pieces of callus and 10\u201320 cell clumps acquired from liquid culture were picked arbitrarily and inoculated in a Petri dish containing selective media MS.5B  and sand (1:1:1) for 30 days, maintaining the light, humidity, and temperature at greenhouse conditions. After 30 days, well-developed regenerants were placed in a net house for 45 days before being transferred to field conditions, where they were grown till maturity and seed set.0 and R1 generations were compared with their respective mother plants for different morpho-physiological parameters viz., plant height, number(s) of primary and secondary branches, days to 50% flowering and maturity, number(s) of siliqua per plant, siliqua length, number(s) of seed per siliqua, seed yield per plant, and biological yield during field evaluation.Regenerants were assumed as putative somaclones, and RThe plantlets regenerated from in vitro cultures subjected to fatty acids analysis to characterize and quantify different fatty acids, including erucic acid content.\u00d7 150 mm), and 5 mL methanol was added to each tube, followed by two drops of concentrated H2SO4. Tubes containing oil\u2013methanol\u2013acid blends were kept in a water bath at 65 \u00b0C for an hour. Then tubes were cooled to room temperature, followed by the addition of 2.0 mL hexane into each tube. The tubes were vortexed and held till the hexane layer was settled out that contains methyl esters. The hexane layer (1.0\u20131.5 mL) was removed carefully using a micropipette and subjected to a 2 mL screw-capped tube. A small amount of hydrous sodium sulfate was added to each tube to seize moisture. A total of 1 mL of the hexane layer holding methyl esters was injected into a pre-conditioned gas chromatograph (GC).Five grams of Brassica seeds of both the genotypes were ground with a pestle and mortar to obtain a fine powder. The powder was shifted to a completely dry test tube  fitted with a mega bore column (30 m long and 0.53 mm \u00d8) assembled with OV-101, methyl silicone polymer, and applying a FID (flame ionization detector). The column temperature (150\u2013270 \u00b0C), injector temperature (250 \u00b0C), and detector temperature (250 \u00b0C) were maintained. GLC was set to 10 \u00b0C per minute increment, and at the end, it was kept at 270 \u00b0C.Taq DNA polymerase with PCR buffer  added. The cycling parameters were: 45 cycles at 94 \u00b0C of 1 min, 1 min at 36 \u00b0C, 2 min at 72 \u00b0C with a final extension time of 7 min at 72 \u00b0C. Amplicons were separated by electrophoresis on 1.4% agarose gel and envisaged under a gel documentation system after staining with ethidium bromide.DNA was extracted from the young leaves of genotypes, viz., CS54 and PM30, and selected putative somaclone plants using the Qiagen DNA extraction kit. Extracted DNA samples were quantified with the help of a nanodrop spectrophotometer and diluted up to 25 ng/\u00b5L. For PCR amplification, a total of 23 random decamer primers  were empp < 0.05. The same letters in one treatment represent non-significant differences at p < 0.05.Experiments on in vitro culture, cell suspension culture, and plantlet regeneration were conducted in CRD (completely randomized design) with two replications for each treatment. For each replication, around 200 explants/cell clumps/embryoids were plated per culture media treatment. Fatty acid profiling was also conducted in CRD in two replications. While morpho-physiological data were analyzed in a randomized block design (RBD) with three replications and the data were analyzed as suggested by Snedecor and Cochran . The sigIn conclusion, two putative somaclones with low erucic acid derived from the cell lines of genotypes CS54 and PM30 have been developed during in vitro culturing, providing a reliable source of variability. Future studies must understand the mechanism of variable erucic acid content in somaclones derived from in vitro cultures, especially suspension cultures. It will help decide the selection strategy for developing low-erucic acid varieties of Indian mustard toward breeding and biotechnological prospects. These putative somaclones may be used in molecular breeding programs, considering them as a parent in the crop improvement program."}
{"text": "A number of studies have investigated the effectiveness of dance in older adults in the context of healthy aging. Analysing results across studies is important to understand whether dance in older adults is an effective adjunctive intervention for the healthy aging. To summarize the current research results about the effectiveness of dance in older adults in the context of healthy aging, and to identify key areas for future research. The search was conducted in Web of Science, PubMed and Google Scholar databases, using the following search string and Boolean logic  locating studies published between database inception and September 2018: Dance OR contemporary dance OR ballroom dance OR Latin dance OR standard dance OR hip-hop dance OR tango AND Cardiovascular OR circulation AND Emotion OR well-being OR blood pressure OR disease OR thrombosis OR vascular OR glucose OR blood OR cardiac OR mental OR heart rate. Two reviewers independently extracted studies data. Eight suitable publications were included. The results showed that dance promote improvements in cognitive parameters when compared to other types of exercise or no-exercise. Significant effects were found on some physiological parameters, even after a short intervention period. Dance proved to be able to assist older adults in the context of healthy aging. The improvements in the cognitive, physiological and motor control parameters are very relevant for this population, due to the impact in a better quality of life. During aging process, the pharmacological treatment in certain cases if necessary is indispensable and this fact is indisputable. However, any non-pharmacological procedures, interventions and programmes that does not disrupt correct bodily function regardless of age group but especially for the older adults is of interest, and even enthusiasm, provided it can be effective in the prevention of certain disease or simply improving well-being. This is especially true when positive effects are elicited on the cardiorespiratory fitness, psycho-motor skills , nervousOne prominent example is dancing, which represents one of the best physical activity (PA) especially recommended for older adults \u226560 y)  and bett0 y  and Despite the fact that exercise is recommended by the World Health Organization (WHO) to maintain health and prevent disease  and presPhysical inactivity is widely observed among individuals aged \u2265 60 years , althougIt seemed essential to investigate interventions designed to promote quality of life (QOL) and health for adults over age 60 years, helping them to ameliorate deterioration related with aging , 25 sincDifferent studies showed that PA could improve age-related changes and among different kind of PA dance is increasingly used as an intervention due to it combines many diverse features related to the physical and psychological aspects .Dancing is a social activity that comprises rhythmic, motor coordination, balance and memory, apart from its requirements for PA. These characteristics make dance a potentially powerful intervention for older adults , 28. HowA number of studies have investigated the effectiveness of dance in older adults in the context of healthy aging. Analysing results across studies is important to understand whether dance in older adults is an effective adjunctive treatment for the healthy aging. This review aimed to summarize the current research results on this topic, and to identify key areas for future research.The search for this narrative review was conducted in Web of Science, PubMed and Google Scholar databases, using the following search string and Boolean logic  to locate studies published between database inception and September 2018: Dance OR contemporary dance OR ballroom dance OR Latin dance OR standard dance OR hip-hop dance OR tango AND Cardiovascular OR circulation AND Emotion OR well-being OR blood pressure OR disease OR thrombosis OR vascular OR glucose OR blood OR cardiac OR mental OR heart rate.Coding of papers only allowed for studies that included at least one typology of dance, including but not limited to: contemporary, ballroom, Latin, standard, hip-hop, tango. The articles must refer to some cardiovascular or circulatory component; and must report a physiological or cognitive variable(s), in participants \u226550 years old. Studies of varying designs were acceptable for the purposes of this review however, technical reports, review articles, non-human based studies, or studies that did not report a physiological or cognitive output were not considered further.We conducted multiple searches in each selected databases and additional searches for relevant references and citations linked to the studies obtained during this primary search. The selection process sought to identify studies, of varying design, with no age restriction, that investigated multiple typologies of dance, cardiovascular and circulatory considerations and physiological and cognitive impact, and were published in English between database inception and September 2018. Two reviewers assessed all titles and abstracts and all full-text articles; decisions to accept or reject a paper were agreed between the first and second reviewer, and a third, independent reviewer helped achieve consensus if the first and second could not agree.Eight studies were included, which were in accordance to the eligibility criteria of this research and presented the best quality. The included studies were subdivided into three topics: 1) cognition, 2) physiological aspects, 3) motor control.et al. [Coubard et al.  examinedet al. [Kattenstroth et al.  investiget al. [In the prospective pilot study, Kim et al.  analysedet al. [Serrano-Guzman et al.  tested tet al. [2peak (L/min). Twenty-five older adults were attended the dance classes called Agilando for 1h/week for 24 weeks (intervention group), and 10 were not (control group). In neither of the groups, significant changes in cardio-respiratory performance were observed.Kattenstroth et al.  tested cet al. [2peak) and maximum heart rate (HRmax) were assessed during spiroergometric cardiopulmonary exercise testing on a treadmill. Before the dance training the mean results of VO2peak (mL\u22c5kg-1\u22c5min-1) and HRmax (bpm) were 24.3 \u00b1 2.9 and 161.8 \u00b1 15.5, and after the intervention 23.9 \u00b1 3.2 and 164.5 \u00b1 17.0, respectively. Neither VO2peak nor HRmax parameter changes were significant.Rossmeissl et al.  assessedet al. [2max (p<0.05) suggesting a significant increase in aerobic capacity post-intervention in comparison to pre-intervention. Authors described physical activity measure as the number of steps taken in each session: there was a significant increase in the number of steps recorded between the first and last training session  = 29.342, p<0.01). The number of steps increased from 761.4 \u00b1 401.82 on the first session to 1679.9 \u00b1 496.98 steps recorded at the tenth session.Sampaio et al.  evaluateet al. [Serrano-Guzman et al.  evaluateet al. [Wu et al.  analysedet al. [2peak), first and second ventilatory thresholds (VT1 and VT2) among ten women from 60 to 75 years old. The results of VO2 (mL\u22c5kg-1\u22c5min-1) are: VO2peak (23.3 \u00b1 4.3), VT1 (17.2 \u00b1 3.5) and VT2 (20.9 \u00b1 3.4). Dancing: warm-up , across-the-floor (14.2 \u00b1 2.4 ~62%VO2peak), choreography (14.6 \u00b1 3.2 ~63%VO2peak) and show . Since cardiorespiratory demands of a dance class for older women are at low aerobic intensity, authors concluded that a dance class may be modulated to improve aerobic fitness, at least at initial stages of training.Rodrigues-Krause et al.  assessedet al. [Kattenstroth et al.  performeChoice reaction and visual analysis of processing time were performed using the standardized Reaction Time Analysis (RA) implemented in the Viennese test system , which is based on a model assuming additivity of factors of the perception, cognitive processing and motor response. Posture and balance were analysed using a force platform. The performance of small hand and arm movements was evaluated using a commercial, computer-based test-battery for clinical neuropsychological research. This test assesses the degree of ataxia and the speed of movement by the ability of making rapid repeated aimed movements. Touch threshold was evaluated by probing the fingertips with von Frey filaments . Spatial 2-point discrimination (2pd) thresholds were assessed on the tips of the left (LID) and right (RID) index fingers by using the method of constant stimuli.p-value 0.073). For the domain of tactile performance, subjects in the dance group showed lower touch and 2pd thresholds, made fewer mistakes, and were faster in the haptic object recognition task. Postural performance improved significantly among subjects in the dance group. No differences were ascertained for subjects in the control group.In all tests contributing to reaction times, significant improvements were found for the dance group while no differences were found in the control group. In the domain Hand/Motor performance, subjects in the dance group showed a significant reduction of the number of errors for steadiness and a speeding up for aiming and pin plugging  and gain in performance after the intervention showed that subjects characterized by a low performance at the baseline attained higher individual gains. Significant correlations were found for reaction times , hand/motor performance , the tactile domain , and posture .This review aimed to summarize the current research on the effectiveness of dance in older adults in the context of healthy aging and to identify research gaps that need to be addressed in the future.In total, we found 8 suitable publications that investigated the specific effects of dance in older adults on cognitive, physiological, and motor control parameters related with aging. The small number of included publications on this review, as well as the fact that the oldest publication was published in 2011, indicates that dance for older adults as a potential intervention to enhance healthy aging is a relatively new area of research. However, various outcomes have been investigated as cognitive, physiological, kinaesthetic, motor and non-motor symptoms.It seems to be obvious that not all symptoms of aging can be reduced in the same way with different kinaesthetic, physiotherapeutic and physical activity approaches. However, this review, after analysed results across studies, aimed to indicate that these aging symptoms might be reduced due to participation in dance interventions.Furthermore, the study results showed especially promoting aspects of dance intervention in cognitive parameters what seems to be interesting in context of WHO principles and modern approach there is \u201cno health without mental health\u201d . Since aet al. [Cognition is a general term that refers to the mental abilities, which includes the short- and long-term memory, working memory, verbal fluency, and the ability to feel, to think, to reason, to form complex structures of thought and to respond to external stimuli , 45. Coget al.  outlinedet al. [2peak, lower body muscle power and static balance. Interestingly, we have observed non-significant changes in blood pressure [2peak and HRmax [et al. [In the cardiorespiratory parameters we found different results. Rodrigues-Krause et al.  indicatepressure , VO2peaknd HRmax . Kattens [et al.  found noTo create positive changes in cardiorespiratory system, increasing aerobic capacity, aerobic endurance, maximal oxygen uptake and other physiological parameters, there is needed appropriate adjustment to age and health status bout of appropriate intensity, volume and weekly frequency of exercise. During aging aerobic and anaerobic capacity and power decline -49. Howe2max [It is particularly interesting that significant effects were found on some physiological parameters, as VO2max  and mobi2max , even af2max , 31, 34.max). In addition, muscle mass plays a particularly important role in the elderly since muscle metabolism, and the associated myocyte oxygen, stimulates the cardiovascular system to produce more intense functioning. In the group of older adults, this is one of the main reasons for the decrease in the exercise capacity, especially after exceeding 60 years old and in women in the postmenopausal period.For older adults, it is also possible to observe training adaptation in terms of cardiorespiratory parameters. However, in their case, physiological processes look much different than young people. Among others, in older adults appears a natural decrease in aerobic and anaerobic capacity resulting from the reduction of the body's tolerance to training, lowering the maximum values of the oxygen uptake, which reduces the maximal cardiac output  it provides up-to-date summary of dance studies in relation to cognitive and physical health status in older adults, (2) our inclusion and exclusion criteria did not negate studies with symptomatic samples and this potentially prevented the results bias. Although this review provides some evidence of the beneficial effects of regular dance activities on cognitive functions, physiological markers and multiple physical fitness components (mainly cardiorespiratory fitness), future studies are needed to validate the hypothesis that dancing could simultaneously improve cognition functions, physiological status and physical fitness of elderly populations. Moreover, future research should also move beyond investigating effectiveness and begin to refine the prescription of training to promote the greatest benefits in terms of healthy aging concept.Dance proved to be able to assist older adults in the context of healthy aging. The improvements in the cognitive, physiological and motor control parameters are very relevant for this population, due to the impact in better quality of life.We identified a lack of studies and scientific information in the area of dance and older adults, indicating that this area of research is relatively new. It is suggested that another research conducted in this field, should include different outcomes and should be studied with greater and better scientific accuracy, as clinical trials."}
{"text": "Parkinson\u2019s disease is a neurodegenerative disorder impacting patients\u2019 movement, causing a variety of movement abnormalities. It has been the focus of research studies for early detection based on wearable technologies. The benefit of wearable technologies in the domain rises by continuous monitoring of this population\u2019s movement patterns over time. The ubiquity of wrist-worn accelerometry and the fact that the wrist is the most common and acceptable body location to wear the accelerometer for continuous monitoring suggests that wrist-worn accelerometers are the best choice for early detection of the disease and also tracking the severity of it over time. In this study, we use a dataset consisting of one-week wrist-worn accelerometry data collected from individuals with Parkinson\u2019s disease and healthy elderlies for early detection of the disease. Two feature engineering methods, including epoch-based statistical feature engineering and the document-of-words method, were used. Using various machine learning classifiers, the impact of different windowing strategies, using the document-of-words method versus the statistical method, and the amount of data in terms of number of days were investigated. Based on our results, PD was detected with the highest average accuracy value (85% \u00b1 15%) across 100 runs of SVM classifier using a set of features containing features from every and all windowing strategies. We also found that the document-of-words method significantly improves the classification performance compared to the statistical feature engineering model. Although the best performance of the classification task between PD and healthy elderlies was obtained using seven days of data collection, the results indicated that with three days of data collection, we can reach a classification performance that is not significantly different from a model built using seven days of data collection. Parkinson\u2019s disease (PD) is a neurological disorder that occurs due to a decrease in the brain dopamine level, impacting patients\u2019 movement. Symptoms of PD include movement abnormalities such as tremor, dysfunction of magnitude, and symmetry of arm swing, and gait characterized by shorter strides and slower movements compared to healthy individuals ,2. TheseThe wrist is the most common and acceptable body location for people to wear sensors on . AdvanceThe contributions of this study are listed as follows: (1) Early detection of PD using wrist accelerometer and passive monitoring, (2) using the document-of-word feature engineering approach to improve the performance over the traditional statistical feature engineering method, (3) identifying the best window size for segmentation of the wrist accelerometer data so that it increases the accuracy of the early detection of PD, and (4) identifying the optimal amount of monitoring time for the early detection of PD. Each of these goals that lead to our contributions in this paper are explained in the following paragraphs.Passive monitoring of individuals over time using an easy-to-wear and comfortable sensor on the wrist could provide us with initial information on whether a person is likely to be in the early stages of a disease with movement disorder. This is the case for patients with PD, because PD is a progressive neurodegenerative disorder of the brain and central nervous system, affecting patients\u2019 motor system, causing reduced movement, tremor, postural instability, and postural rigidity . FatigueThe standard statistical feature engineering method has been the most common feature extraction method in this domain ,21. In tOur third contribution is to test different window size values and identify the best one for data segmentation so that it leads to a classification model with the best performance for the early detection of PD. Choosing the right window size from which features are calculated has been shown to have a significant impact on detecting bradykinesia in patients with PD . ChoosinThe last contribution of this paper is to provide information on what could be the optimal amount of data needed for the early detection of PD when passive monitoring participants using a wrist accelerometer. The inertial sensors\u2019 battery life depends on factors such as the number of sensors utilized, sampling frequency, and recording time, and even in the best-case scenario, when just accelerometer is utilized, there is a constraint on long-term data recording due to these devices\u2019 limited battery lives . TherefoOur main aim in this study is the early detection of PD in a free-living environment using wrist accelerometers. Many research studies have been conducted on PD clinical test automation using wearable technologies in the clinical setting ,27,28,29Our second aim is to investigate the impact of using two feature engineering methods on the early detection of PD: the statistical and document-of-words feature engineering methods. There are only a few research studies in which document-of-words feature engineering was performed. Kheirkhahan et al.  used theFor related work, we consider studies in which a wrist sensor was used to collect data on individuals in free-living conditions, because the mean value of features calculated from data captured in a free-living environment has been shown to be different from that captured in a controlled environment ,39.Monitoring PD patients using wearable sensors and in a free-living environment has been attracting attention recently ,41. MoniIn a research study by San Segundo et al., wrist accelerometry was used to detect tremor in PD both using annotated laboratory data and free-living data . Their rIn a study conducted by Lipsmeier et al., individuals with PD and their healthy age-matched counterparts were monitored in free-living conditions using smartphones to investigate differences in features among participants . Active Zhan et al. conducted a longitudinal study on PD subjects over a period of 6 months in which data were collected actively through five smartphone activities and used to develop a mobile PD score . The scoThe authors of the Parkinson@Home validation study  used accHabets J.G. conducted a study to monitor bradykinesia in patients with PD using a wrist accelerometer . Their dThe study of Williamson et al. on PD  is the mThe following five subsections of this section explain this study data collection\u2019s protocol and methodology. The data were collected from two groups of subjects: (1) healthy elderlies (64.2 \u00b1 7 years and no movement deficiencies) and (2) individuals with various stages of PD (71 \u00b1 6.2). PD patients reported no other illnesses impacting their gait and movement. The Hoehn and Yahr (H&Y) score used in our study is one of the commonly used measures of progression of PD and has been shown to correlate with motor decline happening in PD patients. The data were collected from participants while they had an Actigraph triaxial accelerometer on their non-dominant wrist for seven consecutive days. To be more specific, we used ActiGraph GT3X with ActiLife v6.13.3 Firmware v1.7.1 at 100 Hz. The sensor could be taken off while taking a shower or swimming. The dataset includes three phases of data collection with 6\u201312 months between each two consecutive phases. The Actigraph device was recorded at 100 Hz with a range of \u00b18 g. In each phase, the H&R score and relevant clinical measures were recorded for each participant. The data from the first phase of the data collection is used for our analysis in this paper. In this study, an epoch-based segmentation approach was used in which we converted each subject\u2019s wrist movement signal into subsequences of a predefined length. Since a passive data collection was performed without labeling the data, each segment may represent both activities of daily living and symptoms of PD in the case of PD patients, which should be informative when it comes to distinguishing between the PD population and their healthy counterparts. Feature window size has been shown to significantly impact identifying symptoms of PD, including bradykinesia, resting tremor, and freezing of gait ,16,43,44The window lengths considered in this study were as follows: . Each individual time series was split into smaller subsequences using a sliding window of S\u2014second with overlapping windows of size ter data ,16, whilter data . A studyter data . A windoter data . We alsoUsing the epoch-based segmentation approach explained in To be able to compare the statistical feature engineering approach with the document-of-words method, a set of statistical features was used to create the epoch-based statistical features. Below is a list of features included in the analysis:Signal vector magnitude: For the segments of each segmentation strategy, we calculated signal vector magnitude as \u221a(X2 + Y2+ Z2) in which x, y, and z represent the accelerometers\u2019 axes. This measure is dependent from the accelerometer\u2019s orientation. This feature is used by researchers both for identifying PD symptoms [symptoms  and earlsymptoms  to identRMS of acceleration in the anterior posterior (AP), mediolateral (ML), and vertical (Ver) directions: Root mean square (RMS) of acceleration is a time domain feature used in many studies focusing on PD symptom detection or early diagnosis of the disease [RMS values in each direction:  disease ,16,44. Udir represents each of the following directions: {AP, ML, Ver}.The denominator is signal vector magnitude and Movement dispersion feature: this feature is introduced in [z-score values (zi(t) represents z-score of data point, t, in axis i within the nth segment). Then, we removed the outliers, defined as the points for which the standard deviation of either of the axes is greater than two. Then, using the valid points (non-outlier points) of each segment, dispersion in axis i can be calculated as follows in Equations (2) and (3):V(n) represents a set of valid points within the nth segment, Zi(t) represents the z-score of data point t in axis I, and S(n) is the number of the pairs of valid points within the nth frame. Therefore, the vector of dispersion features for each segment looks like {Dx(n), Dy(n), Dz(n)}.duced in  and onlyduced in . First, Acceleration range: This feature is reported among the features used for identifying tremor in PD patients [patients ,23. To cThe average of these features across all subsequences was calculated in the statistical feature engineering method and considered for classification model development. The document-of-words feature representation approach mainly includes three steps: data segmentation, vocabulary generation, and feature calculation, as described in . Every sti denotes the duration of data collection and s is the window size. Data segmentation was performed using the method explained in In the second step, we generated a vocabulary set in which each subsequence was considered as a word. Since it is unlikely to find two identical subsequences with the same feature descriptors, we put all the segments obtained from all subjects together and grouped them using K-medoid clustering . TherefoD = {d0, d1, \u2026, dk} per subject\u2019s data, in which di is a normalized value of word frequency based on the total number of words per individual (Equation (5)):In the last step, every segment was assigned a word, which was assigned to its cluster centroid. Using these words, we could convert every subject\u2019s wrist data into a document of words and construct a vector Feature selection is mainly performed in the analytics domain so that relevant features are selected for model development while irrelevant and redundant features are removed to reduce the model complexity and avoid overfitting. Since genetic algorithm (GA) has been shown to be one of the best algorithms for optimizing the classification of movement data in the healthcare domain, it was used for feature selection in our work. GA is a method inspired by natural selection to solve optimization problems by taking a population of individuals and trying to produce better approximations. The function to optimize here is the performance of our classification models. Each individual was considered to be a binary representation of features. A total of 40 random individuals were generated as the initial population. Our fitness function was defined as a combination of the average accuracy of all classifiers in this study combined with the number of features. The best fitness score is the one with the highest accuracy and the lowest number of features. We ran GA with 50 generations. In each generation, 20 individuals were selected for crossover, half of whom were the fittest and the other half random. This way, we avoided the issue of falling into a local optimum. Crossover was performed four times using random pairs, generating four feature sets. Using crossover, each feature set was generated by the features randomly selected from the parent feature sets. Then, each individual was given a 14% chance of being mutated, creating the new feature sets. More details on how genetic algorithm was applied to our feature set can be found in .To create a model that distinguishes between healthy subjects and patients with PD, we applied different classifiers, including support vector machine (SVM with an RBF kernel), decision tree (DT), random forest (RF), K nearest neighbors (KNN), AdaBoost (AB), and naive Bayes (NB). These classifiers have been used in the gait analysis and document classification literature ,23,48. To evaluate each classification, we performed 100 runs of that classifier with 10-fold cross-validation, such that in each run of cross validation, nine folds  were used for training and the remaining one fold (six subjects\u2019 data) was considered as the validation set. Reported results are based on the average accuracy values and standard deviation around the average. This validation strategy is performed to make sure that the results are robust enough. H0:\u00a0StatisticalFeatures \u2265 meanWordFeaturesmean.H0a:\u00a0StatisticalFeatures < meanWordFeaturesmean.in which meanStatisticalFeatures and meanWordFeatures are the average accuracy values across all classifiers in the case of using statistical features and word features, respectively. The feature set used for this hypothesis test was generated using the best windowing strategy/the best combination of windowing strategies identified prior to this step.To reach our second goal, in addition to the observations and results obtained from the classification models, we developed a hypothesis to compare the average performance of the two feature engineering methods. The following hypothesis was developed:Considering one set of features, 100 runs per classifier, and six classifiers, we must have 600 accuracy values per method. H0:\u00a0Combination_of_Aall \u2264 Performance3 SecondsPerformance.H0a:\u00a0Combination_of_All > Performance3 SecondsPerformance.in which PerformanceCombination_of_All represents the average accuracy obtained using the features calculated from all data granularity levels, and Performance3 Seconds represents the average accuracy of obtained using features calculated out of subsequences of 3 s length. Similar hypotheses were developed for the comparison of each pair of best performing window size/sizes and for the comparison of them with the baseline windowing strategies.To investigate the impact of window size on classification performance, we applied different classification methods using features calculated from subsequences of each windowing strategy , different combinations of all features together, and a reduced feature set selected from the combination of all. The performance of the classifiers based on each single window strategy was considered as baseline. Considering 100 runs of each classifier and 10-fold cross-validation, firstly, all authors investigated the results by observation and identified windowing strategy/strategies that seemed to provide the best performance values. Then, we took the best ones and statistically checked for any significant difference between them and baseline windowing strategies. Here is an example of one hypothesis test developed:To identify the optimal number of days for data collection for early detection of PD, we selected the best windowing strategy/strategies and the best set of features . ClassifH0:\u00a0performance_1 Day = performance_2 Days = performance_3 Days = performance_4 Days = performance_5 Days = performance_6 Day = performance_7 Day.H0a:\u00a0not all the performance values from different amounts of data are the same.The null hypothesis states that the classification performance values are not significantly different across different numbers of days from which the data were collected. Using the epoch-based statistical feature representation, the average value of each feature across all subsequences was calculated. First, all possible combinations of the statistical features were investigated by running the classifiers. The best results were obtained using SDS = {RMSX, RMSY, RMSZ, Vector Magnitude, RangeAP, RangeML, RangeVER, DX, DY, DZ}. Then, using this SDS, each classifier was run 100 times using features from various subsequence lengths. The best results were obtained using a reduced set of features containing at least one feature from each windowing strategy. As it appears, the best classification performance was obtained using a reduced set of features containing features from all windowing strategies. This set includes the following features: {DispersionAP_10 s, DispresionAP _60 s, RMSRAP-300, RMSRML-300, signal_vector_magnitude_300 s, signal_vector_magnitude_900 s, RMSRAP-3 s, ARML_3 s, ARAp_3 s, ARVer _3 s}.th person\u2019s wrist data when the signal is split into subsequences of 3 s, 10 s, 1 min, 5 min, and 15 min, respectively. Combining all the words, each individual\u2019s wrist data could be represented by a document of 100 words as follows:To create the features using the document-of-words method, we used the same SDS introduced in the statistical feature method. Various values of subsequence lengths and various numbers of clusters were investigated. The optimum number of clusters/values of k were selected based on the elbow method for each and all windowing strategies. This number ranged between 4 and 32 for each window size. The value of k determines the number of words needed to represent all individuals. After investigating different values of k , the optimum number of clusters for subsequences of 3 s, 10 s, 60 s, 300 s, and 900 s were found to be 22, 22, 20, 20, and 16, respectively. Therefore, each subject\u2019s wrist movement signal could be represented as follows:F = 4.07, p = 0.022. Tukey\u2019s HSD test for multiple comparisons found that the mean accuracy value from the reduced feature set containing features from all granularity levels was significantly higher than that of all other features sets obtained from the other windowing strategies , except for the one containing the combination of all features.For each hypothesis test, we first checked the normality, and since our data were normally distributed, we used ANOVA to compare the average accuracy values based on the different windowing strategies listed in In general, if we look at the results in t = 6.85, df = 4797.8, p-value = 1.27 \u00d7 10\u22126).The normality test was demonstrated that the distribution of accuracy values per group was normal. Therefore, a paired-sample t-test was performed. The test outcome indicates that the average accuracy value of the classification using word features is significantly greater that the average accuracy value of the classification using statistical features  and homogeneity (constant variance) check, we could not use parametric test. Thus, the Kruskal\u2013Wallis non-parametric test was selected and performed, which resulted in a chi-squared = 40.951, with df = 6, and p-value = 2.96 \u00d7 10\u22127. There is enough evidence that the classification performance considering different amounts of data (day-wise) is significantly different.Upon the result of the normality  Early detection of patients with PD using accelerometers worn on the most common and accepted body location, the wrist. Our results indicate that PD can be detected using wrist-worn accelerometry and passive monitoring of individuals with good accuracy values. (2) Application of the document-of-words feature engineering method, which is novel for PD detection using data collected from wrist sensors. Although this method was used for PD detection using data collected from participants\u2019 ankles , the datAP, RMSRML, RMSRVer, DispersionAP, DispresionML, DispersionVer, ARAp, ARML, ARVer}. This set was selected as the best-performing set of statistical features. Various classification models were applied to our dataset using 10-fold cross-validation, and the results were reported per 100 runs of each classifier.In this study, we used two feature engineering methods: epoch-based traditional statistical feature engineering method and the document-of-words approach. Our statistical feature set, which was also used as the subsequence descriptor set in the document-of-words approach, included the following set of ten features: {signal vector magnitude, RMSRAP_10 s, DispresionAP _60 s, RMSRAP-300, RMSRML-300, signal_vector_magnitude_300 s, signal_vector_magnitude_900 s, RMSRAP-3 s, ARML_3 s, ARAp_3 s, ARVer _3 s}. The reason why AR in all three directions using a window size of three is included in the selected feature set could be because of its importance in identifying tremor and bradykinesia [AP from 3 s window sizes could be explained using the same rationale. Dispersion features using a window size of 10 has been shown to contribute positively to the diagnosis of PD [AP_10 s appeared as one of the important features in our reduced statistical feature set. Vector magnitude features from windows of sizes 300 and 900, and RMSRAP-300 and RMSRML-300, can be also seen in the selected subset of features, which could be indicating the amount of hand movement over longer periods of time. Using the document-of-words features, the best performance was obtained using a reduced set of 20 words while the set had words generated from all windowing strategies. This indicates that considering data from each granularity level reveals some useful information about the populations in the study, and that contributes to a better performance of classification tasks.Based on our results, the document-of-words method significantly improves the classification performance compared to the statistical method. Interestingly, our results indicate that the highest performance of both the epoch-based statistical approach and the document-of-words method was obtained when we used a combination of features from all windowing strategies . This set of features was a reduced feature set out of all possible features generated from each windowing strategy. The statistical set of features that contributed to the best classification results is as follows: {Dispersionykinesia . The exiis of PD , and thaThis study is a step towards the early diagnosis of Parkinson\u2019s disease using wrist-worn accelerometry in a real-life setting and would benefit patients and healthcare providers. The document-of-words feature engineering method eliminates the need for precise step/stride segmentation, which is a challenging task specifically for populations with a health condition.It is not easy to compare our work and the results of this study with those from other studies because there has not been a great number of works that have attempted the early detection of PD using wrist-worn sensors and passive monitoring. Moreover, no study has reported on the impact of window size on PD diagnosis. The methods and dataset used in this study have strengths and limitations. One of the strengths of the dataset is that it was passively collected from the most common and acceptable body location of individuals in a free-living condition. Moreover, our methodology does not require participants to wear the sensor on the most-affected wrist. Another strength of this work is that PD can be detected without explicit labeling of the data, e.g., symptoms detection and labeling. We did not have to label the data for activities of daily living and the symptoms of the disease. Furthermore, we had a balanced dataset in terms of the number of patients with PD and healthy elderlies. The other strength of our approach is that we had a set of features that was independent from sensor orientation.Our dataset\u2019s limitations are as follows: a limited number of participants and lack of additional information from each subject .There are several opportunities for future work with the same dataset. Since we have three phases of data collection with 6\u201312 months in between, we should be able to test our results by combining participants from all three phases and see how that improves the results. Another possible task would be to select our test sets completely independently from the training set by selecting individuals for our test set from the other phase of the study. Another promising next step would be to conduct a longitudinal study and predict each individual\u2019s health status in the third phase based on the first two phases of data. Another next step would be to develop models based on more sophisticated machine learning models to distinguish PD patients with different disease severities.As mentioned in , wrist-wThis research study had four aims, including the early diagnosis of Parkinson\u2019s disease in a free-living environment using wrist accelerometry, investigating the impact of two feature engineering methods on classification models\u2019 performance, investigating the impact of different windowing strategies and their associated features on models\u2019 performance, and investigating the impact of the amount of data on classification models\u2019 performance. Our results indicate the feasibility of using data from wrist-worn accelerometry collected in free-living conditions for the early diagnosis of PD. The performance of our PD diagnosis models were improved using the document-of-words feature engineering method, and a subset of features including at least one feature from each windowing strategy was included. This indicates that including data from different granularity levels adds to our model performance. By comparing our models\u2019 performance values using different amounts of data in terms of days, we noticed an increase in the model performance as the amount of data increased. However, our models\u2019 performance values using three, four, five, and six days of data collection were not significantly different from that of seven days, suggesting the possibility of using three days of data collection for the diagnosis of PD without compromising the diagnosis model performance."}
{"text": "We thank profs. Deng and Zhang for their comment on our manuscript.First, profs. Deng and Zhang mentioned that it was unknown why we selected randomized controlled trials (RCTs) and observational studies simultaneously in the same meta\u2010analysis. A high\u00a0quality meta\u2010analysis based on RCTs is regarded as the highest level of evidence\u2010based medical evidence, and the formulation of many clinical guidelines also follows this standard, but this does not mean that we should unconditionally believe in RCT\u2010based meta\u2010analysis, especially when the results of RCTs are different from those of observational efficacy comparison trials. The implementation of RCTs is limited by the scale of funds and usually can only ensure the statistical efficiency of the primary outcome indicators. Considering the operability and other factors, the included population is often different from that in clinical practice, the external applicability of evidence is limited, and the direct application to clinical practice sometimes cannot achieve the expected effect. The population included in the observational efficacy comparison study is closer to clinical practice, but since there is no randomization, there are many factors that may interfere with the final results. When answering a clinical question, do not just believe in RCTs. Observational efficacy comparative studies also need to be included in the evaluation. Moreover,\u00a0if the results of RCTs are inconsistent with those of observational studies, it is more necessary to carefully evaluate the reasons for the differences. Sometimes the conclusions of observational studies are more credible.p\u2009<\u2009.0001 and stroke . However, that difference was not found in nonfatal myocardial infarction , cardiovascular\u2010related mortality , and all\u2010cause mortality .Second, both profs. Deng and Zhang have noted that two eligible published studies were missed in our meta\u2010analysis. One of the missed studies compares major cardiovascular events in patients with gout and concurrent cardiovascular disease\u00a0and chronic kidney disease who receive febuxostat or allopurinol.n Figure\u00a0  Nonfatal stroke; (B) nonfatal myocardial infarction; (C) cardiovascular death; and (D) death from any cause.Third, we agree with profs.\u00a0Deng and Zhang that another probably missing critical point is the quality assessment of the included studies. Study quality was independently assessed (by Gao L. G. and Cheng R.) according to a tool that was specifically developed for the randomized studies based on the Delphi Consensus.The Newcastle Ottawa Scale (NOS) was used to assess the quality of the included nonrandomised studies.We have benefited a lot from this discussion. This meta\u2010analysis was updated and supplemented according to valuable opinions, which further makes up for the shortcomings of this analysis. We appreciate the authors' comments on our study. Your valuable suggestions will be of great help to our future scientific research work.The authors declare no conflict of interest."}
{"text": "The prevalence of smoking among young adults aged 19\u201328 years old in the United States persists at rates of 14.3%. Young adults underutilize pharmacotherapy for smoking cessation, and the use of e-cigarettes has increased. We analyzed comments from online smoking-cessation support groups to understand young-adult smokers\u2019 views of pharmacotherapy and e-cigarettes, to provide a more in-depth insight into the underutilization of pharmacotherapy. A qualitative analysis was performed on comments about pharmacotherapy and e-cigarettes from participants enrolled in online smoking-cessation support groups in 2016\u20132020. A codebook was developed with a deductive approach to code the comments, followed by thematic analysis. Eighteen themes were identified, with four dominant themes: interest, benefit, knowledge, and flavor. Participants expressed less interest in both nicotine-replacement therapy and e-cigarettes; moreover, they expressed unfamiliarity with and misconceptions about pharmacotherapy, and recognized the enticing flavors of e-cigarettes. Participants often felt e-cigarettes were not useful for smoking cessation, but the flavors of e-cigarettes were appealing for use. Participants had mixed opinions about the use of e-cigarettes for smoking cessation, but predominantly felt e-cigarettes were not useful for smoking cessation. The use of social media may be an effective way to address misconceptions about pharmacotherapy for smoking cessation and increase willingness to accept assistance. Though the prevalence of cigarette smoking among young adults has been decreasing over the past several years, as many as 14.2% of young adults age 19-28 in the United States (USA) still currently smoke cigarettes . Early sWatkins et al. found that young adults are 3.6 times more likely to use electronic cigarettes (e-cigarettes) or \u201cvapes\u201d, also known as electronic nicotine-delivery systems (ENDS), than evidence-based pharmacotherapy . One posCommune Smokefree Social was implemented utilizing the online social-media platform, Facebook. Commune Smokefree Social was an adaptation of the Tobacco Status Project, which had shown short-term efficacy in a randomized trial , but since nicotine dependence isn\u2019t my main issue with quitting, I don\u2019t know that it would be right for me.\u201dDespite more participants expressing the higher frequency of disinterest in NRT, there were some participants that expressed a willingness to consider using NRT, with the highest interest being in nicotine lozenges.\u201cHaven\u2019t tried any over the counter method but it [lozenge] does seem effective because you really just miss the feeling of a cigarette in your mouth too.\u201dPosts about ENDS revealed the concern about the safety and health risks of ENDS use, which contributed to overall disinterest. Conversations about ENDS differed from those regarding NRT, in that participants were particularly focused on safety when discussing ENDS. Several individuals shared their skepticism about joining the ENDS trend and concerns over the potential occurrence of \u201cpopcorn lung\u201d . Comments about ENDS and NRT were similar in that many individuals were less interested because of doubts regarding efficacy for quitting. In general, more participants expressed disinterest towards ENDS than interest. Individuals who expressed interest shared that ENDS were an appealing alternative compared to more foul-smelling cigarettes. There was an association between a sense of shame with smoking cigarettes and the general notion that ENDS were a more socially acceptable way to mask a nicotine addiction.\u201cI\u2019d probably grab the e-cig. It\u2019s easier to hide and some of the flavors are good.\u201dParticipants who had personal experience with NRT, bupropion, or varenicline tended to report beneficial outcomes with their use compared to participants with no experience. Participants expressed mixed impressions of nicotine patches and nicotine gum; many expressed that these forms of pharmacotherapy were useful, while others expressed that they were not beneficial. Individuals found the nicotine patch and gum to be helpful in preventing nicotine cravings. Those who stated that nicotine gum was useful had personal experience with utilizing gum to help them quit, particularly to help satisfy the hand\u2013mouth action, preventing further cravings for more cigarettes.\u201cI like gum because it also satisfies my mouth\u2019s need to be active without shoving a bunch of food into it.\u201dSome participants stated that the nicotine patch was not effective in keeping their hands distracted from reaching another cigarette. Individuals also expressed that nicotine patches were not effective often, because their use was limited by the side effects and inability to keep patches on for a longer duration. Participants who stated that nicotine gum was not useful often expressed an aversion to the peppery taste. \u201cI did but it [nicotine patch] made me sick and gave me a rash that would last for weeks each time I used one. I\u2019ve known it [nicotine patch] to work for other people though.\u201dThe attitudes and perceptions around ENDS shared many similarities with those around NRT. There was a strong correlation with friend and family influences that led participants to believe ENDS were an ineffective aid to quit smoking cigarettes. Participants also mentioned that ENDS helped curb their craving for a cigarette, similar to their thoughts about certain NRTs. Other individuals expressed that ENDS were ineffective as an alternative due to the throat burn and overall feeling of being unsatisfied. In contrast, many participants mentioned that they tried ENDS, but expressed concerns over them perpetuating the dependence due to their similarity to cigarettes. \u201cE-cigs don\u2019t work for me, they\u2019re too similar and its [sic] too easy to spend all day vaping.\u201dParticipants expressed more familiarity with nicotine patches and gums and less familiarity with other forms of NRT, such as nicotine inhalers and nasal sprays. Many of those who lacked knowledge about NRT and medications expressed less interest in utilizing these options to aid in smoking cessation. There were many misconceptions about NRT or medication use, such as the belief that NRT would cause more dependence on nicotine or cause a new dependence. Some participants expressed distaste for the utilization of smoking-cessation medications because they viewed it as a replacement rather than an aid to quit smoking. There was a common belief that nicotine is a harmful substance and that utilizing NRT would be counterintuitive to quitting smoking. \u201cNot interested in replacing the intake method... I don\u2019t want nicotine in any form to rule my life, and I am afraid I will simply just use the patch or the gum or the lozenge indefinitely.\u201dThe co-occurrence of knowledge and cost appeared, which suggested that participants were unaware of options that would help NRT and medications become more affordable, such as insurance coverage. Many individuals did not know that certain smoking-cessation pharmacotherapy options are covered under insurance plans.\u201cJust didn\u2019t like the fact it [nicotine gum] was $60 per box and I didn\u2019t know it [nicotine gum] was covered by insurance at the time.\u201dIn contrast, there was an even mixture of participants who were aware of ENDS and those who were unaware of this nicotine-delivery system. Many individuals who knew about ENDS were those who had prior experience with them. Participants believed that the use of candy or fruit flavors was a smart marketing strategy and were enticing, and expressed that the ENDS flavors made their smoking experience more palatable and enjoyable than smoking cigarettes. Many shared that their utilization of ENDS was not for purposes of smoking cessation and felt that ENDS were harmless. \u201cI enjoy the flavors and love how not stinky it is compared to cigs. I hope to gradually reduce my use but I enjoy it.\u201dHowever, there were a few participants who expressed disgust towards the flavors used in the ENDS juices and their potential for harm.To our knowledge, this is the only qualitative analysis, to date, that describes perceptions surrounding smoking-cessation pharmacotherapy and ENDS in young adults attempting to quit smoking on social media. Our data analysis identified gaps in knowledge, which were mainly misconceptions about NRT and smoking-cessation medications. Our findings were similar to Duarte et al.\u2019s focus-group study with non-college-educated young adults, which revealed an overall negative perception about cessation treatments due to side effects, and a misunderstanding of how these pharmacologic therapies work . Our anaParticipants expressed interest in ENDS as an alternative to tobacco cigarettes because of the enticing and customizable flavors of ENDS. This was consistent with a survey conducted by Farsalinos et al., which found that the most important factor for the maintenance of ENDS use was the variety of flavorings, which assisted with reduction of tobacco cigarette use . HoweverIn addition, non-pharmacological methods may help decrease young-adult smoking, including motivational cognitive behavioral therapy or social-media campaigns that de-normalize the tobacco industry ,39,40,41This qualitative analysis of Facebook posts is subject to inherent limitations. The themes identified were based on the content of the posts, and the coders may have brought biases in determining the themes; however, this was mitigated by blinded coding and having a third reviewer. Additionally, this intervention was limited to the young-adult population in the Bay Area. We cannot generalize our findings to other populations. Lastly, engagement among participants varied, so it is possible that the common themes that we identified may have been based on the more active participants. Many young-adult smokers ready to quit in online support groups expressed a lack of interest and knowledge in and about smoking-cessation pharmacotherapy. This was mainly driven by misconceptions about its use, side-effect concerns, a preference to quit without assistance (\u201ccold turkey\u201d), and a lack of recognition of nicotine dependence. In general, there were mixed opinions about ENDS, but more participants ready to quit expressed that ENDS would not be beneficial in smoking cessation. Social-media-based approaches for smoking cessation have been found to be an effective intervention, and their use may serve as a vehicle to deliver educational information regarding smoking-cessation pharmacotherapy to young adults. It is pertinent to identify effective methods to decrease smoking rates in young adults through online support groups. This may be achieved by integrating information for available smoking-cessation strategies to encourage tobacco abstinence, to prevent further risks of tobacco-related conditions and mortality. Social-media-based approaches should also address the barriers or misconceptions about pharmacologic agents that have been identified in our study and other literature, which may be significant barriers to young adults quitting smoking. As smoking among young adults is a major public-health issue across the world, efforts to use social media to mitigate incorrect, pre-perceived notions about smoking-cessation pharmacotherapy, and to promote the effectiveness of evidence-based smoking-cessation pharmacotherapy methods, are needed."}
{"text": "This meta-analysis aimed to determine the prognostic impact of microscopically positive margins (R1) on primary gastrointestinal stromal tumors.A literature search was performed using PubMed, Embase, Web of Science, and Cochrane Library for studies up to 23 November 2020. The pooled disease-free survival (DFS) and overall survival (OS) between R1 and negative margins (R0) were estimated using a random-effects model.2 = 0%; reference: R0). This negative impact of R1 disappeared with the use of adjuvant Imatinib . R1 was related to poor DFS in gastric GISTs , which was attenuated in the subgroup of adjuvant Imatinib . Rectal GIST with R1 margin who even received adjuvant Imatinib still had poor DFS . Patients who underwent R1 resection had similar OS compared with those underwent R0 resection regardless of the use of adjuvant Imatinib.Twenty studies with 6,465 patients were included. Compared with R0 resection, R1 was associated with poor DFS in patients who did not receive adjuvant Imatinib (HR: 1.62, 95% CI: 1.26\u20132.09; P = 0.48, IR1 was associated with poor DFS for primary GISTs, which was attenuated by adjuvant therapy with Imatinib. Similar result was observed in the gastric GISTs subgroup. Rectal GIST patients with R1 resection had poor DFS even when they received adjuvant Imatinib. The R1 margin did not influence the OS of GISTs. Gastrointestinal stromal tumors (GISTs) are one of the most common mesenchymal tumors, accounting for 80% of tumors that arise from the gastrointestinal tract . The rarpost hoc study based on the EORTC 62024 randomized trial suggested that tumor rupture rather than R1 margin significantly influenced the overall survival (OS) of GIST regardless of the acceptance of adjuvant Imatinib  through PubMed, Embase, Web of Science, and Cochrane Library to identify studies that reported the relationship between the status of surgical margins and prognosis of gastrointestinal stromal tumor. The search included studies up to 23 November 2020. Attempts have been made to obtain additional eligible studies by searching the references of relevant studies. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines .Eligible studies were identified by two investigators (ZL and HY) according to the following criteria: (1) Participants (P): The patients were diagnosed pathologically and immunohistochemically as primary GISTs without metastasis or other cancers; (2) Interventions (I) and comparisons (C): All the patients underwent surgery and outcomes between R1 and R0 resection margin were compared; (4) Outcomes (O): DFS and/or OS were available or able to be calculated by sufficient data in the studies. When duplicate studies based on similar populations were identified, only the newest or largest study was included. Any discrepancies were resolved by discussion with a third investigator (XG).The name of the first author, year of publication, country, sample size, tumor site, recurrence events, adjuvant therapy, follow-up, DFS, disease-specific survival, and OS were extracted independently by two investigators (SL and JZ). If the hazard ratio (HR) and 95% confidence interval (CI) were not provided in the studies, we calculated these data from available data or from the Kaplan\u2013Meier survival curves using the methods reported by Tierney et\u00a0al. . A thirdTwo authors (ZL and ZZ) independently assessed the quality of all included studies using the Newcastle\u2013Ottawa Quality Assessment Scale (NOS) with the highest score of nine , and any2 statistics. Subgroup analysis was conducted to identify the source of heterogeneity. The random-effects model was used by default because of the nature of the included studies. The estimated results of the fixed-effects model are also provided for reference. Sensitivity analysis was performed to validate the stability of the model by sequentially omitting each study. Potential publication bias was assessed using the Begg\u2019s and Egger\u2019s tests. Statistical analyses were performed using R software 3.6.1  with the meta package (4.13-0) . Statistical heterogeneity was evaluated using the chi-square test and Iackage 4.-0 (13). (4.13-0) .As shown in 2 = 8%). Sensitivity analysis was performed by omitting each study sequentially, and the estimated results did not differ significantly, indicating the stability of the model  but not in subgroup of RCT . However, patients of two series of the three in the subgroup analyzing data from RCTs received adjuvant Imatinib.Two of the 17 studies (three series) analyzed data from randomized controlled trials (RCT) and the remaining 15 were observational studies. Thus, subgroup analysis according to the type of study  in the subgroup without adjuvant Imatinib, while the status of resection margin had no significant impact on DFS in the adjuvant Imatinib subgroup .Thus, another subgroup analysis was performed according to the use of adjuvant Imatinib .Tumor site is another key prognostic factor for GISTs. The eligible studies were categorized into three subgroups: stomach, rectum, and mixed sites. The mixed sites included studies that analyzed more than one tumor site. The results of this subgroup analysis . However, a relatively high heterogeneity was observed in the gastric subgroup without adjuvant Imatinib , which made the result of this subgroup less reliable. Notably, rectal GIST patients with R1 resection had poor DFS even when they received adjuvant Imatinib . In the mixed sites group, R1 resection was correlated with poor DFS compared with R0 resection  for patients without adjuvant Imatinib, while the status of resection margin did not impact DFS for patients receiving adjuvant Imatinib .The results differed when tumor site and Imatinib use were both taken into consideration (2 = 0%), regardless of whether they received adjuvant Imatinib  or not   Figure\u00a04As shown in The present study found that R1 resection was associated with poor DFS for primary GISTs. Subgroup analysis was performed according to study type, use of adjuvant Imatinib, and tumor site. DFS did not worsen for patients who underwent R1 resection in the subgroup of RCT. However, patients of two of the three series in the RCT subgroup received adjuvant Imatinib. To illustrate this point, in the subgroup analysis of the use of adjuvant Imatinib, the negative influence of R1 resection on DFS was attenuated by adjuvant Imatinib. Similar effect of adjuvant Imatinib in DFS was observed in the subgroup of gastric GISTs. Rectal GIST patients who underwent R1 resection had poor DFS even when they received adjuvant Imatinib. Patients who underwent R1 resection had similar OS compared with those underwent R0 resection regardless of the use of adjuvant Imatinib.Although surgical margin was removed from the 2014 edition of the European Society for Medical Oncology (ESMO) guidelines  as a proHowever, the Imatinib in these studies was not specifically given to those who had R1 margins, and the mechanism by which Imatinib attenuated the negative survival impact of R1 requires further exploration. Interestingly, Shannon et\u00a0al.  in theirFurther subgroup analysis of this meta-analysis according to tumor site and use of adjuvant Imatinib showed that gastric GISTs with R1 margin had poor DFS which was attenuated in the subgroup of adjuvant Imatinib. Notably, R1 margin was associated with poor DFS of rectal GISTs that even received adjuvant Imatinib. The relatively lower malignancy of GISTs in the stomach  and high2 = 50%), which makes the result of this subgroup less reliable and requires further exploration. Fourth, risk factors that are collinear with the R1 margin were not analyzed in the current study. In summary, further high-quality case-controlled observational trials with a balanced baseline are needed.The current study has some limitations. First, the majority of the included studies were retrospectively designed such that bias was inevitable in the process of this meta-analysis. Second, adjuvant Imatinib was not given specifically to those who experienced R1 margin, so the mechanism of Imatinib attenuating the negative survival impact of R1 needs further exploration. Third, a relatively high heterogeneity was observed in the gastric subgroup without adjuvant Imatinib ; 2. CAMS Innovation Fund for Medical Sciences (2020-I2M-C&T-B-027); 3. Beijing Bethune Charitable Foundation (WCJZL202106); 4. Beijing Xisike Clinical Oncology Research Foundation (Y-HS2019-43).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."}
{"text": "This study supplies a comprehensive strategy for discovering potential serum biomarkers of RA and provides a different perspective for comprehending the pathological mechanism of RA, identifying potential therapeutic targets, and disease management.Rheumatoid arthritis (RA) causes serious disability and productivity loss, and there is an urgent need for appropriate biomarkers for diagnosis, treatment assessment, and prognosis evaluation. To identify serum markers of RA, we performed mass spectrometry (MS)-based proteomics, and we obtained 24 important markers in normal and RA patient samples using a random forest machine learning model and 11 protein\u2013protein interaction (PPI) network topological analysis methods. Markers were reanalyzed using additional proteomics datasets, immune infiltration status, tissue specificity, subcellular localization, correlation analysis with disease activity-based diagnostic indications, and diagnostic receiver-operating characteristic analysis. We discovered that ORM1 in serum is significantly differentially expressed in normal and RA patient samples, which is positively correlated with disease activity, and is closely related to CD56dim natural killer cell, effector memory CD8 Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic erosive arthritis, which affects 1% of the world\u2019s population and usually occurs in middle-aged and elderly women , 3.Current common laboratory indicators are rheumatoid factor (RF), anti-cyclic citrullinated peptide antibody (ACPA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) . HoweverIt is known that proteins have an important role in RA pathogenesis with the formation of a new epitope; compared with other techniques such as transcription, proteomics can study the posttranscriptional modification of proteins and their interactions in cells and tissues . PreviouIn this study, our comprehensive analysis of serum proteins in RA from multiple perspectives is shown Figure\u00a01Human serum specimens were collected from the First Affiliated Hospital of Guangzhou University of Chinese Medicine . The study was approved by the Chinese Clinical Trial Registry (ChiCTR), and the registration number is ChiCTR2100043294. This study was approved by the local research ethics committee; the approval document number of the ethics committee is NO. JY[2020]264. All subjects in this study were asked for consent. Human serum samples included 8 healthy control and 7 patients at different time points of 0 and 6 after administration. All samples were frozen and stored at \u221280\u00b0C in aliquots of polyethylene tubes until use.Bicinchoninic acid (BCA) assay was used for protein quantification, taking 500 \u03bcg of protein and using High Select\u2122 Top14 Abundant Protein Depletion Resin to remove high-abundance proteins. After adding the supernatant obtained in the previous step to dithiothreitol (DTT) at a final concentration of 10 mM, polypeptide samples were prepared using the filter-aided sample preparation (FASP) method from previous literatures , 12. In p-values were obtained by using the t-test, and the p-values of comparisons were adjusted for multiple comparisons to preserve an error rate of 5%. To identify the significant pair(s), we used multiple comparisons. The Benjamini\u2013Hochberg method was used for the multiple comparisons.Tryptic peptides were separated using a 60-min total data collection for peptide separation, with the Easy-nLC 1200 system connected online to an Orbitrap Eclipse mass spectrometer equipped with FAIMS Pro (Thermo). Scans were collected in data-dependent top-speed mode with dynamic exclusion at 90 s. Raw data were analyzed using MaxQuant version 1.6.17.0 search against the Human Fasta database, with label-free quantification and match-between-run functions enabled. The identification of proteins that were differentially expressed between patients with RA and HCs was conducted based on the empirical Bayes method using the limma R package. The Machine learning was combined with PPI network analysis to screen differential proteins. The random forest classifier (RFC) was used to perform feature extraction on protein sample expression data, screen out the top 30 key proteins based on classification features, and use MeanDecreaseGini to plot. 11 topological analysis methods, including Degree, Edge Percolated Component (EPC), Maximum Neighborhood Component (MNC), Density of Maximum Neighborhood Component (DMNC), Maximal Clique Centrality (MCC), and six centralities  based on shortest paths were used to measure the true efficiency of nodes in the PPI network to evaluate their importance.R (version 3.6.3)\u2019s ggplot2 package and clusterProfiler package were used to analyze the enrichment analysis of 24 differential proteins, including KEGG pathway, biological process (BP), cell component (CC), and molecular function (MF).https://pubmed.ncbi.nlm.nih.gov/) was used to search, and clinical samples with healthy people were selected as the control group. A total of 5 datasets were collected, including 155 healthy controls and 183 RA patients. The differentially expressed proteins were summarized in each dataset, and candidate proteins with the number of repetitions greater than 2 were selected. An NCBI gene ID was assigned to each protein based on gene symbol, and we kept proteins with the NCBI gene IDs for subsequent analysis.\u201crheumatoid arthritis\u201d and \u201cproteomics\u201d were used as keywords, PubMed  ssGSEA method was used for immune cell infiltration analysis, the degree of infiltration of 28 immune cells was calculated, and https://gtexportal.org/). GTEx is a tissue-specific database of gene expression and regulation derived from simultaneous transcriptome sequencing and genetic analysis of samples from multiple human tissues and organs.Tissue specificity data were obtained from GTEx (https://compartments.jensenlab.org/). COMPARTMENTS is a powerful website for predicting the subcellular localization of proteins, helping us to better understand candidate proteins.Subcellular localization was performed through COMPARTMENTS (R (version 3.6.3) was used for statistical analysis and visualization, the ggplot2 package (version 3.3.3) was used for visualization, and the statistical method used was Spearman. A heatmap was used to display the pairwise correlation (spearman correlation) of all elements between the two tables (protein expression table and diagnostic index change table). Statistical significance was marked on the heatmap.We used the pROC package for diagnostic ROC analysis and used the ggplot2 package for visualization. The value of the area under the curve (AUC) is between 0.5 and 1. The closer the AUC is to 1, the better the diagnostic effect. The AUC has a low accuracy when it is 0.5\u20130.7, it has a certain accuracy when it is 0.7\u20130.9, and it has a high accuracy when it is above 0.9; key proteins were further screened based on an AUC greater than 0.7.http://www.r-project.org/). Data visualization was generated by the clusterProfiler package (version3.14.3) of R and Microsoft Office 2019.The statistical analysis in this study was performed by the differential enrichment test of R platforms . The differential enrichment test of R software was used to study the differential expression of proteins. Test-diff was used to perform a differential enrichment test based on protein-wise linear models and empirical Bayes statistics using limma. False discovery rates were estimated using the fdrtool package (version 1.2.17). Analyzing 262 candidate proteins, according to the RFC machine learning method and 11 topological analysis methods , cell composition (CC), and molecular function (MF) and arrange them in ascending order of p-value<0.001); Cholesterol metabolism ; Vitamin digestion and absorption .\u201d The first 3 BPs with the smallest p-value were extracellular structure organization \u201c; platelet degranulation ; chylomicron assembly .\u201d The first 3 CCs with the smallest p-value were \u201cblood microparticle ; cytoplasmic vesicle lumen ; vesicle lumen .\u201d The first 3 MFs with the smallest p-value were \u201clipoprotein particle receptor binding ; cholesterol transporter activity ; intermembrane cholesterol transfer activity \u201d.24 proteins overlapping the reference datasets were analyzed. The first 3 KEGG pathways with the smallest p-value were \u201cComplement and coagulation cascades , and To further confirm the underlying function of potential targets, we used Fisher\u2019s exact test to calculate the enrichment significance of each term in KEGG, biological process (BP), cell composition (CC), and molecular function (MF) and arrange them in ascending order of p-value were \u201cComplement and coagulation cascades ; Staphylococcus aureus infection ; ECM-receptor interaction .\u201d The first 3 BPs with the smallest p-value were \u201cacute inflammatory response ; complement activation ; regulation of protein processing .\u201d The first 3 CCs with the smallest p-value were \u201cblood microparticle ; cytoplasmic vesicle lumen ; vesicle lumen \u201d. The first 3 MF with the smallest p-value were \u201clipoprotein particle binding ; protein-lipid complex binding ; antioxidant activity \u201d.The 30 proteins overlapping the reference datasets were analyzed. The first 3 KEGG pathways with the smallest +T cell, activated dendritic cell, CD56bright natural killer cell, CD56dim natural killer cell, central memory CD4+T cell, central memory CD8+T cell, effector memory CD8+T cell, eosinophil, gamma delta T cell, immature B cell, macrophage, mast cell, myeloid-derived suppressor cell, monocyte, natural killer cell, natural killer T cell, plasmacytoid dendritic cell, regulatory T cell, follicular helper cell, type 1 T helper cell, type 17 T helper cell, and type 2 T helper cell. As shown in +T cell, and natural killer cell was significantly different between HC and RA . Through Spearman correlation analysis, we found that 13 of the 24 differential genes were significantly related to the degree of immune cell infiltration, which are ORM1, HP, TTR, CRP, FGB, FN1, APOA2, APOC3, SAA1, FGG, FGA, APOB, and VWF; we believe that these 13 genes are potential biomarkers for the treatment of RA and related to immune cell infiltration, as shown in We found that the degree of immune cell infiltration in RA patients is generally lower than that in normal people. We analyzed 28 types of immune cells and obtained data on 23 types of immune cells, which are activated B cell, activated CD4As shown in As shown in p<0.001). After using Spearman correlation analysis between 24 proteins and 13 diagnostic indicators , the correlation analysis between CP and 11 diagnostic indicators except CRP and GH was statistically significant, as shown in In terms of predicting disease activity, CP (AUC=0.837), TTR (AUC=0.776), ORM1 (AUC=0.796), HP (AUC=0.816), SERPINA1 (AUC=0.796). They have a certain accuracy in the diagnosis and prediction of disease activity, but they are not statistically significant compared with other diagnosis results.As shown in p = 3.25 * 10-32, Fisher test) and dataset iii . Collectively, we showed the reliability and accuracy of our protein list, and it is in accordance with previous publication. We will upload this information together. The above evidence demonstrates the reliability and accuracy of our analysis.Through diverse-perspective analysis, our study provides novel insights into RA-related proteomics research. Using random forest machine learning methods and analysis of 11 other topological analysis methods, our proteomics data selected 24 potential differential proteins in normal and RA patient samples. When searching the PubMed database for 24 potential proteins, at least 19 (79.17%) were found in RA-related reports Table\u00a03.FN1, a multidomain extracellular matrix (ECM) protein, binds to multiple compounds on the cell surface, including collagen , fibrin In addition, our research reevaluated the importance of 24 candidate proteins in terms of immune infiltration, disease activity, experimental diagnosis correlation analysis, and diagnostic ROC analysis. After a comprehensive analysis, both HP and ORM1 exceled in this aspect.+T cells, and natural killer cells.HP has many physiological functions. It can combine with free hemoglobin to prevent oxidative damage to various organs  and acti+T cells, and natural killer cells. ORM has many activities including, but not limited to, acting as an acute-phase reactant and disease marker, modulating immunity, binding and carrying drugs, maintaining the barrier function of the capillary, and mediating the sphingolipid metabolism (Orosomucoid 1 (ORM1) is different from HP in that it has less research. When we searched in PubMed, there were only 3,555 related articles Table\u00a03,tabolism . In RA ptabolism . Althougtabolism . Based otabolism . In geneHowever, one of the disadvantages in this experiment design is that proteins are the performers of functions; it is necessary to consider combining the results of transcriptome and metabolomics for multidimensional research. Also, the serum proteome has its limitations, and the perspective of synovial proteomics is worth further studying. If possible, the systematic research on the differentially expressed proteins should be screened out, combined with animal experiments, clinical trials, etc., using molecular biology techniques to verify and enrich the rationality of high-throughput screening results.The innovation of this study is that we refer to the results of other RA proteomic studies to make our findings more convincing. Our analysis of differential proteins, combined with disease activity, is more clinically meaningful and valuable. In general, these rich data are expected to stimulate subsequent hypothesis-driven research, deepen our understanding of the pathogenesis of RA, provide potential biomarkers, and provide new strategies to facilitate the diagnosis and treatment of this harmful disease.The data presented in the study are deposited in the PRIDE and ProteomeXchange repository. ProteomeXchange accession number PXD032912.The studies involving human participants were reviewed and approved by the First Affiliated Hospital of Guangzhou University of Chinese Medicine Ethics Committee.[2020]264. The patients/participants provided their written informed consent to participate in this study. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.GC, LW, and CH conceived and designed the experiments. ZD and JX conducted the experiments and wrote the manuscript. LiZ, YX, ML, JY, LuZ, and HD provided some of the data. LL, MZ, JH, LW, and GC reviewed and revised the manuscript. CH and ZD have contributed equally to this work. All authors contributed to the article and approved the submitted version.This study was funded by the Guangzhou Science Technology and Innovation Commission Technology Research Projects (No. 201904010336) and the Innovative and Strong Hospital Project of The First Affiliated Hospital of Guangzhou University of Chinese Medicine (No. 211010010705).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher."}
{"text": "While e-cigarettes usually contain nicotine, their addictive potential is not yet fully understood. We hypothesized that if e-cigarettes are addictive, users will experience typical symptoms of addiction.The aim of our study was to investigate whether and how e-cigarette users report signs of addiction.We identified 3 large German-language e-cigarette online forums via a systematic Google search. Based on a netnographic approach, we used deductive content analysis to investigate relevant posts in these forums. Netnography has the advantage of limiting the social desirability bias that prevails in face-to-face research, such as focus groups. The data were coded according to the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) criteria for tobacco use disorder, adapted for e-cigarettes. The DSM-5 criteria were used to portray a broad spectrum of possible experiences of addiction.Overall, 5337 threads in 3 forums were screened, and 451 threads containing relevant information were included in the analysis. Users reported experiences consistent with the DSM-5 criteria, such as craving e-cigarettes, excessive time spent vaping, and health issues related to e-cigarette use. However, our analysis also showed that users reported the absence of typical tobacco use disorder criteria, such as successful attempts to reduce the nicotine dosage. For most themes, reports of their absence were more frequent than of their presence. The absence of perceived addiction was mostly reported in contrast to prior tobacco smoking.This is the first study to use a netnographic approach to explore unfiltered self-reports of experiences of e-cigarette addiction by users in online forums. As hypothesized, some but not all users reported subjective experiences that corresponded to the criteria of tobacco use disorder as defined by the DSM-5. Nevertheless, subjective reports also indicated that many e-cigarette users felt in control of their behavior, especially in contrast to their prior use of tobacco cigarettes. The finding that some e-cigarette users subjectively experience addiction highlights the need for effective cessation programs to support users who experience their e-cigarette use as burdensome. This research can guide the refinement of instruments to assess e-cigarette addiction and guide cessation programs.RR2-10.1186/s40359-021-00682-8 Electronic cigarettes, or e-cigarettes, are handheld electronic devices that heat a liquid to create vapor that users inhale . AlthougAlthough e-cigarettes are often marketed as a less harmful alternative to tobacco -11, schoFor this paper, substance-related addiction was defined as a \u201crecurring desire to continue taking the drug despite harmful consequences\u201d . CurrentPrevious studies provide some evidence for e-cigarettes\u2019 addictive potential. Browne and Todd  found thGiven this research gap, we hypothesized that if e-cigarette consumption led to addiction, users would report signs of tobacco use disorder. Thus, the aim of our study was to shed light on whether and how e-cigarette users subjectively perceive typical signs of addiction according to the DSM-5 criteria for tobacco use disorder. To answer this question within the Evaluation of the Addictive Potential of e-Cigarettes (EVAPE) project, we used a netnographic approach  and analThe study design was based on a netnographic approach, which applies ethnographic techniques to online social interactions. This approach was first developed and applied in a sociological research context and is increasingly used in epidemiology and health research .Previous research has shown that online forums are important spaces for e-cigarette users to communicate about relevant topics with like-minded people ,25. WithWe used a 3-step procedure to collect the data for this study. First, 1 study team member (DS) conducted a search for the relevant online forums via Google search using different combinations of the German versions of the keywords \u201ce-cigarette\u201d AND \u201c(online) forum\u201d . A searcIn the second step, we searched the identified forums for previously defined keywords. For each criterion, we defined 1 to 3 keywords that described the respective theme as accurately as possible . The iniIn the third step, 2 team members (DS and TG) screened all the threads, which were posted between April 9 and June 18, 2021. To assess whether a thread was relevant to the theme, we viewed short threads in their entirety. For long threads (\u22655 pages), we based the content assessment on the title of the thread and the post in which the keyword was mentioned. Threads without posts on relevant themes were excluded at this stage. We excluded posts from users who explicitly reported also smoking conventional cigarettes  from our analysis.We chose a deductive thematic approach, as described by Mayring , as the After data piloting, we decided to use positive  and negative  coding for each theme. For example, a forum user could report a craving for e-cigarettes (a positive code), or an absence of craving (a negative code). The program Maxqda  was used to code the data. According to the research standards for our deductive thematic approach , we desiQuotes chosen as examples for this paper were paraphrased and translated to English by 1 author (MA) and checked for accuracy by 2 authors (DS and SS).In addition to the qualitative analysis, we collected quantitative data on the frequency of reported signs.Specific ethical aspects need to be considered when researching online communities . Since wFrequently discussed topics in the forums were e-cigarette types and setups, different kinds of liquids and flavors, and general lifestyle. The forums were active, with the biggest forum having 1,458,441 posts and approximately 400 daily new posts by 14,751 users (forum statistics at time of data extraction in February 2021). The users\u2019 nicknames, as well as their posts, indicated that the majority were male and had smoked tobacco cigarettes before their e-cigarette use. As described above, we excluded posts from users who explicitly reported being current dual users from our analysis.Of the 5337 threads initially screened in the 3 forums, 451 contained relevant information regarding addiction and were included in the data analysis . We idenAttempts to reduce the nicotine dosage were frequently discussed in the forums. User #12 described their unsuccessful attempt: \u201cI started off with a lower nicotine dosage but I did not get a buzz from it. So now I vape a higher dosage and don\u2019t want to go back.\u201d On the other hand, more users related successful attempts to reduce the amount they consume. User #398 reported, \u201cI was a heavy smoker but when I started vaping I was able to reduce from 18mg to 7mg and have been vaping this mix for some years now.\u201dMany users reported almost uninterrupted e-cigarette use throughout the day. This behavior was often subjectively perceived as being deliberately chosen. For instance, user #137 wrote, \u201cI vape incessantly, in the morning, when I work, on the way to work, and when I go out in the evening.\u201d Other users stated that they spent a great deal of time consuming in specific situations, such as while drinking alcohol.We did not code a negative code for this theme, because the only relevant post mentioning a low time expenditure fitted the theme \u201closs of control\u201d more accurately.Different posts showed that even though users experienced health problems, they continued to use e-cigarettes. User #10 wrote, \u201cI get a swelling under my eyes whenever I vape more than usual. A few days after that I can still feel the swelling in my cheeks as well as under the eyes.\u201d Other symptoms described by users were headaches, inflammation, rash, swelling, dizziness, and digestive problems. Moreover, problems were reported to be associated with specific liquids and nicotine dosages. The ingredients propylene glycol and vegetable glycerin were prominently discussed as reasons for allergic reactions and other health issues.In contrast, other users perceived that their physical health improved after they switched from tobacco to e-cigarettes. User #71 reported, \u201cMy quality of life really improved when I stopped normal  smoking. When working out I breathe more easily and I can taste and smell much better.\u201d Moreover, improvements in mental health were also described. User #85 said that their panic attacks had stopped (\u201cI used to get panic attacks and was super nervous but not anymore!\u201d) since switching to an e-cigarette, and user #36 related that they slept better: \u201cI wake up before my alarm clock.\u201d No user reported improvements in health due to e-cigarette use without describing a contrast with tobacco.Some users reported explicit cravings for e-cigarettes, such as frequent thoughts about e-cigarettes or seeking out favorable opportunities to use e-cigarettes. Descriptions of craving in the context of specific situations or habits were also found. For example, user #54 reported, \u201cThere are specific moments where I feel craving for my e-cigarette. Mostly when I\u2019m alone or when I had a really exhausting day I want to reward myself with vaping.\u201d Another user stated, \u201cHonestly, I am addicted to vaping. Wherever I go, be it my office or in my free time, I instantly look for a place where I can vape.\u201dOn the other hand, more users described a weak or missing desire for e-cigarette use. For these users, it seemed easy to abstain, regardless of the situation. User #282 explained, \u201cWhen I still smoked I would always go for a smoke after lunch. But now I can sit and relax after lunch and enjoy the time.\u201dUsers described withdrawal symptoms when they could not use e-cigarettes for a long time or when the nicotine dosage was subjectively too low. Withdrawal symptoms such as physical unrest, nervousness, irritability, and difficulty concentrating were specified. For instance, user #57 reported, \u201cI was using a 18mg dosage. I was very confused why I was becoming more aggressive and hyperactive. And then I realized it was because I was vaping nicotine-free for half the day.\u201dOn the other hand, users also reported the absence of withdrawal symptoms, even when it was not possible to use e-cigarettes for a long time or when they used a lower nicotine dosage. For example, user #7 said, \u201cWhile I work, I cannot vape for the whole day. But that\u2019s fine by me.\u201dUsers reported (1) breaking off contact with people in whose presence e-cigarette use was undesired, (2) experiencing negative reactions from people in their immediate environment  to e-cigarettes, and (3) experiencing situations that escalated due to personal e-cigarette use. For example, user #493 wrote, \u201cOnce I started vaping, my circle of friends changed. I broke off contact with those who do not tolerate vaping when we meet.\u201dEspecially in contrast to when they used tobacco cigarettes, some users reported that reactions within their social environment to their e-cigarette use were positive. For example, user #41 related, \u201cIn the beginning my friends and family were worried. But now they see how much better my health is, they don\u2019t see it as a problem.\u201d Users also frequently reported being complimented on certain liquid flavors by their friends or colleagues.When discussing their dosage and liquid mixtures, some users recounted the development of tolerance. This means that their \u201cbuzz\u201d or nicotine high ceased, causing them to increase their dosage. For example, user #89 admitted, \u201cI have really become increasingly tolerant.\u201d Another user (user #11) asked the forum, \u201cI don\u2019t miss cigarettes but lately I have been vaping much more than usual and I do not get a buzz anymore. Am I the only one who gets more craving after vaping for some months?\u201dOnly one user (user #51) described negative physical reactions to the usual nicotine dose: \u201cI am realizing the effects of more nicotine...I have trouble sleeping, higher blood pressure, palpitations and so on.\u201dDauernuckler, the German word for someone who is constantly sucking on their e-cigarette, and admitted, \u201cI\u2019m actually very annoyed by it but I can\u2019t stop.\u201dA few users revealed that they used their e-cigarettes almost continuously, even though they did not intend to. As a consequence, they subjectively perceived this behavior as a problem or burden. For example, user #355 described themselves as a In contrast, only one user reported that they managed to control the amount they vaped by keeping a constant nicotine level: \u201cI vape 18mg just to avoid vaping constantly.\u201dOne user (user #243) reported they had to give up an activity because of e-cigarette use: \u201cSince I spend some money on my setup, I had to stop my hobby for the time being.\u201d We did not code a negative code for criterion 7 in cases when users saw e-cigarette use as their new hobby, since we did not interpret substance consumption as a new social activity.This study is the first to show that e-cigarette users report subjective experiences of addiction based on the DSM-5 criteria for tobacco use disorder. This was the result of a netnographic analysis of 451 threads from 3 large German-language online forums. In summary, some but not all users reported subjective experiences that corresponded to the criteria of a tobacco use disorder as defined by the DSM-5. Our aim was not to diagnose forum members but to use the DSM criteria to explore subjective experiences of addiction. Our chosen method of accessing the field allowed us to take an unfiltered look at user reports. Our findings are consistent with previous qualitative and quantitative research on e-cigarette addiction, as discussed below.The criterion we coded positively most often was \u201cexpenditure of time.\u201d While using any substance involves a certain amount of time, an excessive preoccupation with the consumption process is an important aspect of the definition of addiction. Indeed, specific questions regarding time are included in instruments such as the Fagerstr\u00f6m test of e-cigarette dependence .Furthermore, our analysis showed that many users continued their e-cigarette use despite experiencing health problems such as chest pain, skin swelling, or gastrointestinal symptoms. This reflects clinical observations of e-cigarette users\u2019 health . SimilarMoreover, we found that users reported experiencing cravings and withdrawal when they were not able to use e-cigarettes. This result confirms longitudinal studies conducted in the United States ,35. LikeIn the forums we investigated, some users described unsuccessful attempts to reduce the amount of nicotine they consumed. Indeed, they reported increasing their nicotine dosage over time. As of yet, only one study exists on nicotine dosing patterns in e-cigarette users over time, by Browne and Todd , who shoNevertheless, we also found that the absence of signs of addiction according to the DSM-5 criteria was frequently reported by users. This especially applied to the theme \u201cattempts to reduce.\u201d The majority of posts coded for this theme described successful attempts to reduce either e-cigarette use or nicotine dosage. One reason for this could be that in the forums, experienced members recommended starting with a high nicotine dosage when switching from tobacco to e-cigarettes, in order to avoid relapse. Furthermore, more posts discussed an absence of craving for e-cigarettes than its presence. The same was true for the themes \u201chealth problems,\u201d \u201csocial problems related to use\u201d and \u201cwithdrawal\u201d but with less pronounced differences in frequencies. Importantly, we found that an absence of these experiences was mostly reported in contrast to the previous use of tobacco cigarettes. Likewise, Schilling et al  reportedRegarding social acceptability, our analysis showed that while some users did experience social problems related to use, e-cigarette use was mostly accepted in their environments, especially in contrast to smoking. Users also reported using their e-cigarettes in different locations, such as their offices. This reflects previous research indicating that e-cigarette use is seen as more socially acceptable than smoking and is therefore possible in spaces in which smoking is restricted or undesirable .Finally, we did not find any posts corresponding to the DSM-5 criteria \u201cneglecting responsibilities\u201d or \u201chazardous use.\u201d This finding is in line with an ongoing debate on the appropriateness of the DSM-5 criteria for tobacco use disorder. Sokya and Baumg\u00e4rtner  criticizIn sum, our study offers a comprehensive and broad overview of subjective experiences of addiction, adding to the existing literature, which so far has mostly focused on specific symptoms. Our results indicate that some users perceive e-cigarettes to be highly addictive and reflect on their incessant use and craving. Since our research indicates which experiences are perceived as burdensome by users, this knowledge could be a starting point for the refinement of instruments to measure e-cigarette addiction, as well as tools to identify users who are at risk for e-cigarette addiction. Even though e-cigarettes are perceived as less addictive or harmful than tobacco cigarettes by users, our study clearly demonstrates that users do experience addiction. Hence, more research on effective strategies for e-cigarette cessation and efforts to support users with effective cessation programs are required.The evidence that there are users who experience signs of addiction is a piece of the overall puzzle of e-cigarette dependence. The interdisciplinary EVAPE project aims to provide further valuable insights based on neurobiological and longitudinal epidemiological data, as well as focus groups with e-cigarette users .This study has some limitations. First, we relied on user self-reports. A systematic review demonstrated that self-reports of smoking are less accurate than biological measures, as smokers underreport their behavior . FurtherAnother limitation is the possibility that the analysis included posts by users who use e-cigarettes in addition to tobacco . While we excluded posts containing explicit mentions of dual use, we could not exclude all posts by dual users. Since dual users have reported higher levels of addiction than exclusive e-cigarette users in previous research , this shThis study is the first to use a netnographic approach to explore self-reported signs of dependence in e-cigarette users. In contrast to other forms of qualitative research, such as interviews or focus group discussions, netnography approaches in the context of research on online forums have had to rely on limited responses, with no opportunity to clarify meanings, and hence bear the risk of misinterpreting responses. On the other hand, this approach avoids biases related to personal or group interviews, such as interviewer bias or social desirability bias . HoweverThe netnographic approach used in this study allowed us to explore unfiltered self-reports of addiction by e-cigarette users in online forums. Some but not all users reported subjective experiences that corresponded with the DSM-5 tobacco use disorder criteria. Nevertheless, we also found that users discussed the absence of such signs, and in most cases, reports of absence were more frequent than reports of presence. While it is not possible to derive a clinically reliable diagnosis of tobacco use disorder from such self-reports, our study clearly showed that some users reported signs that were comparable to the criteria for tobacco use disorder in the DSM-5."}
{"text": "Mobile mapping technologies, based on techniques such as simultaneous localization and mapping (SLAM) and surface-from-motion (SfM), are being vigorously developed both in the scientific community and in industry. They are crucial concepts for automated 3D surveying and autonomous vehicles. For various applications, rotating multiline scanners, manufactured, for example, by Velodyne and Ouster, are utilized as the main sensor of the mapping hardware system. However, their principle of operation has a substantial drawback, as their scanning pattern creates natural gaps between the scanning lines. In some models, the vertical lidar field of view can also be severely limited. To overcome these issues, more sensors could be employed, which would significantly increase the cost of the mapping system. Instead, some investigators have added a tilting or rotating motor to the lidar. Although the effectiveness of such a solution is usually clearly visible, its impact on the quality of the acquired 3D data has not yet been investigated. This paper presents an adjustable mapping system, which allows for switching between a stable, tilting or fully rotating lidar position. A simple experiment in a building corridor was performed, simulating the conditions of a mobile robot passing through a narrow tunnel: a common setting for applications, such as mining surveying or industrial facility inspection. A SLAM algorithm is utilized to create a coherent 3D point cloud of the mapped corridor for three settings of the sensor movement. The extent of improvement in the 3D data quality when using the tilting and rotating lidar, compared to keeping a stable position, is quantified. Different metrics are proposed to account for different aspects of the 3D data quality, such as completeness, density and geometry coherence. The ability of SLAM algorithms to faithfully represent selected objects appearing in the mapped scene is also examined. The results show that the fully rotating solution is optimal in terms of most of the metrics analyzed. However, the improvement observed from a horizontally mounted sensor to a tilting sensor was the most significant. Simultaneous localization and mapping (SLAM) represents one of the most significant computational problems for any 3D reconstruction. It can be applied to autonomous cars and robotics inspection missions to solve specific tasks, in particular map generation and obstacle detection. The most promising data source for performing these tasks is application of the lidar distance measurement method. Although many 3D-mapping lidar systems have been developed and are used in various applications, the quality and accuracy of the generated 3D point clouds and 3D geometries often remain insufficient, particularly in complex or unstable environments. However, one of the most rapidly growing fields of application for mobile mapping systems is underground mining, as the speed and possible automation of performing such measurements enables the rapid acquisition of dense 3D data for vast underground structures. For these reasons, constant improvement is needed in measurement system construction and point cloud data processing. New approaches to the analysis and methodological assessment of the 3D data quality are also required. One promising solution, improving the hardware side of the mapping system, is the design of a spinning lidar sensor with an additional module that rotates the sensor around another axis. This actuated lidar design, in which a scanner is combined with an actuation mechanism to scan a 3D volume rather than a single line, has already been used in numerous mobile robot SLAM applications .Therefore, the main objective of our study was to quantitatively and qualitatively assess the influence of a well-known approach using lidar rotation on the accuracy and value of a 3D point cloud using an inspection robot in a test environment mimicking an underground mine tunnel. The paper is structured as follows: first, in The data acquisition strategy for autonomous vehicles and inspection robots using the lidar system needs to be based on an understanding of specific environmental parameters, such as the presence of a variety of dynamic or static obstacles, ensuring the highest possible level of accuracy in the scanned data. Measurement systems with rotating lidar sensors enable the capture of dense and close-to-spherical data about the surrounding environment . Thus, nThe design of a dual 2D/3D lidar mapping system and a six-degrees-of-freedom (DOF) interpolated odometry, where 2D lidar is used to enhance 3D solid-state lidar performance used on a ground vehicle platform, can be found in . The desConstruction of the scanning actuation mechanism can have an impact on different positions of the rotation center of the lidar mirror and construction itself; thus, sufficient calibration methods are needed. The description of an automatic calibration method for the actuated lidar can be found in . An extePoint cloud accuracy and data-quality assessment are amongst the most important factors for the creation of reliable, error-free methods used in laser scanning. To tackle the recurrent problems of misregistration, outlier detection and over-completeness, a comparison of several methods is needed. In , the useWith regard to the underground mining environment being investigated in the present study, SLAM solutions and applications in real or artificial spaces need to be considered. Underground workings are characterized by significant irregularities in the surrounding geometries and by dustiness that can affect the performance of the mobile system and the quality of measurements obtained. The results presented in the studies referred to below confirm that SLAM-enabled laser scanning represents a promising method for underground mining tunnel mapping and examination. One of the first studies that indicated the potential for high-resolution 3D-mapping of an underground mine involved a cart-mounted 3D-laser-scanner setup and an automatic 3D-modeling method . SimilarThe authors in  proposedThe literature review highlighted that there are still gaps to be filled with respect to evaluation methods for comparing the results  produced with different SLAM systems, with respect to both the hardware and the software used. Developing such methods would assist in choosing suitable solutions for selected use-case environments, optimizing the cost of scanning, system complexity and data size and quality. This study aims to tackle this challenge.The purpose of developing an adjustable mapping system for this study was to enable additional, controlled rotation of the lidar device around its longitudinal axis. In consequence, the effective field of view (FoV) of the sensor can be gradually increased, almost up to the point of a full-spherical FoV (excluding occlusions caused by the sensor mounting and the robot). The adjustability of the proposed system is controlled by the operator, who can easily change the range of lidar rotation using control software options on the remotely connected tablet. In this research, we utilized these options to emulate three different strategies for lidar head mounting, which have been used in various commercial solutions and research prototypes. The details of the system configuration are presented in the following paragraphs.In this study, a 16-line Velodyne VLP-16 lidar is used. The sensor is mounted on a rotating module, mounted above the set of sensors designed for inspection purposes A block diagram of the data-acquisition system with the actuator module is shown in In this study, several steps of point cloud acquisition are taken to obtain coherent and noise-free global point clouds. The aim is to ensure the highest quality of results from the different methods tested so that the comparison outcomes would not be affected by external factors or imperfect execution and repetition of the experiment. The parameter values in each step are universally chosen and kept consistent for each case. Although their method-specific tuning could potentially improve the accuracy of results, it might significantly influence the data density and, thus, introduce bias into one of the most important aspects of the analysis.tf broadcaster [First, the robot trajectory is estimated in real time with the SLAM system, consisting of A-LOAM lidar odometry , scan coadcaster , which radcaster ,29, withAn important part of the applied SLAM algorithm is correction for motion distortion of point clouds. The lidar used in the study acquires 360\u00b0 3D point clouds in constant motion, revolving internally around its z-axis. One revolution (a sweep) takes 0.1 s and an aggregated set of point coordinates is sent by the sensor to the PC. However, when the scanner is in motion, the points acquired between the start and the end of the sweep have a slightly different frame of reference. This results in aggregating in each point cloud points acquired from slightly different positions, introducing a systematic error into the measurements . Since tLidar odometry provides a quick and constant, but preliminary, sensor pose estimate. It is susceptible to long-term drift, especially with respect to orientation in the 3D space. With a rotating sensor, such as that used in the study, this could cause unacceptable mapping results, with common errors occurring, such as double walls or rotated corridors. To prevent this, loop closure detection and pose-graph optimization are included in the software system. In our test measurements, we did not have explicit loop closures in terms of returning to the same place the robot visited earlier. Therefore, Scan Context++ was used to additionally bind the trajectory after each full resolution of the actuator. The point clouds acquired at the same actuator inclination angle are/were similar due to the low speed of the robot. The resulting matches between scans are added as a constraint to the pose graph and optimized with GTSAM, reducing the drift of the odometry algorithm.Then, clusters of points representing dynamic objects are removed in post-processing using removert . This stEvaluating the quality of 3D point cloud data acquired with a mobile mapping system is not a straightforward task. Many metrics have been proposed and used to assess the accuracy of SLAM measurements, such as the absolute trajectory error (ATE), the relative trajectory error (RTE) and the relative position error (RPE) ,36. HoweN\u2014number of neighboring points in the radius R around the analyzed point.One of the metrics that can be used to estimate the local quality of a point cloud is its density. This simply describes the number of measured points per chosen unit of reference: a volume or a surface. For this study, since the mapped area primarily contains approximately planar surfaces, surface density was calculated with respect to Equation  and analData density provides information about the spatial distribution of points and their number, characterizing the redundancy of the measured geometry. However, this metric does not convey information on the noise level of the analyzed point cloud. To address this, another component was introduced to the analysis, namely, object reconstruction quality, that is, how accurate the measured geometry is of a single object in the scanned scene.For evaluating the object reconstruction quality, i.e., the local consistency of a point cloud, several objects were chosen as samples. They were manually identified in each point cloud and compared between different tested lidar SLAM configurations. For planar objects, such as walls, doors or floor, surface variation ,39 also. This meIn the cases of two distinctive objects in the study area, namely a ceiling lamp and a trashcan, such analysis would not be meaningful since their geometry is more complex than a plane. To account for this, for all objects, point cloud resolution was additionally compared by listing the number of points per object.The last analyzed aspect of the point clouds acquired with SLAM is their completeness. Since the raw number of points is heavily influenced by noise and redundant measurements, other metrics need to be utilized for this purpose. Such a metric should describe a unique volume of space, containing any measured points. Two data structures commonly used in 3D-data processing have this property: a voxelgrid and an octree. Both divide a 3D space into a regular volumetric grid of boxes. For the voxelgrid, the size of a single voxel is fixed, and an octree contains a multiresolutional representation of the scene, sequentially dividing cells at each level into octants ,43. To aSensor in fixed horizontal position, i.e., horizontal lidar;Sensor rotating in the full range from \u221290\u00b0 to 90\u00b0, i.e., rotating lidar;Sensor rotating in the limited range from \u221245\u00b0 to 45\u00b0, i.e., tilting lidar.Several experimental data acquisitions were performed with a wheeled mobile robot  to (f), in To begin with, the reconstruction quality of objects (a), (c), (e), and (f) was investigated, since they consist mostly of planar objects. Consecutively, they are: a vertical surface located high, a vertical surface at the same level as the measurement system, an area of the floor at the mid-section of the measurement area and a door at the side wall in the corridor. Their point clouds, colored by the calculated surface variation per point, are presented in Local accuracy of the final point clouds was assessed using a least-squares plane fit for objects (a), (c) and (e). The results are listed in Objects (b) and (d), which had more complex geometries, were analyzed only in a simplified context. Their point clouds are shown in The completeness of 3D data in the context of object reconstruction, as well as the point cloud density, can be additionally summed up with a simple metric\u2014the point count per object. Such an overview is presented in Different aspects of the 3D-data quality of three common hardware solutions utilizing a 3D lidar scanner for the SLAM problem were investigated. Multi-metric comparison was conducted to analyze factors such as local surface density and variation, plane reconstruction accuracy and numbers of octree cells, voxels and points per mapped object. This analysis enabled us to obtain insights into the behavior of SLAM in tunnel-like conditions, especially with respect to key aspects of inspection and mapping robotic missions in constrained, underground environments. Similarly to the method described in , in the Increasing the complexity of the system through introduction of an actuator to rotate the spinning lidar around another axis greatly increased the data density and completeness, and did not negatively impact the point cloud local coherence. Although the sensor rotating in its full range generally obtained the best results, a tilting sensor achieved results that were not much worse and provided significant improvement over the static, horizontal placement of the lidar. Depending on the metrics analyzed, generally, the performance of the rotating lidar was from 35% to almost 50% better than that of the tilting lidar. The tilting lidar obtained a smoother data density distribution and almost 200% better completeness (based on voxelgrid and octree cell counts) than the horizontal lidar, while still maintaining comparable plane fit accuracy and mean data density. Choosing the right tool for the selected measurement site will depend on the dimensions of the structure, notably its height and width. The presence of objects causing numerous occlusions, common for underground mining environments, would also favor the selection of one of the actuated lidar mounts.During inspection missions in underground mines, a massive amount of 3D data is collected with SLAM to be used for both navigation and 3D analysis. In the case of the latter, completeness of different object representations in the point cloud is crucial to enable machine learning algorithms to perform classification successfully and to correctly distinguish different objects of interest, which can then be processed with specialized, use-case-targeted algorithms. Therefore, given the results presented in"}
{"text": "As the number of children and young people (CYP) presenting to Emergency Departments (ED) with acute mental health (MH) presentations has been steadily increasing over the years and further accelerated by the pandemic, there is an urgent need to develop and evaluate innovative solutions to respond to this growing challenge.The evaluation of the Safeguards Teams Program (STP) aims to ascertain the impact, implementation and economic analysis of this acute rapid response recovery-focused, trauma-informed assessment and brief intervention for CYP (aged 0\u201317 years) presenting in acute MH crisis and their families/caregivers.The STP will support consumers (patients) and their families/caregivers to navigate the complex and often fragmented child and adolescent MH services (CAMHS) landscape, thereby avoiding unnecessary ED presentations or hospitalisations, and facilitating comprehensive assessment and appropriate care pathways for those who present in crisis.The STP is expected to provide CYP in MH crisis and their support networks with early access to evidence-based specialist care at the right place and time.Implementation of the STP will assist with identifying and addressing gaps in acute care for CYP and provide the necessary evidence for service redesign in collaboration with consumers, service providers and other stakeholders. Around one in seven 15%) children and adolescents globally are diagnosed with mental health (MH) conditions 5% childr3. MH conAs the number of children and young people (CYP) presenting to ED with acute MH presentations increases, there has been an attempt to find alternative solutions to manage crises within the community setting for vulnerable children and young people (CYP). The literature reports varied approaches to specific interventions, such as Multisystemic Therapy for behaviour disorders (4), Assertive Community Treatment for high-risk and difficult to engage adolescents who have a severe mental illness (5), and \u2018one-stop shops\u2019 of Integrated Community-Based Youth Service (C-BYS) Hubs that aim to cater for psychosocial, educational, physical and MH needs in an early intervention model (6). However, these models require specific funding, strong collaboration, and integration of services.The approach to acute crisis presentation requires accessibility and availability outside of usual business hours, outreach into the community, and individually tailored care that is specific for CYP and their families while also ensuring that appropriate referrals and linkages with other relevant services are in place to support CYP consumers following a crisis intervention. Without appropriate post-intervention support, CYP with MH conditions are highly likely to have poor health and social outcomes and high ongoing service user needs. Failing to support CYP during the crisis and adequately supporting them thereafter is expected to have a significant adverse impact on their long-term trajectory that may include poor adult MH, low school engagement and performance, unemployment, high dependence on welfare, unstable housing conditions, involvement with the child protection system, criminal activity, drug and alcohol dependency, and premature death .A recent systematic review found evidence for the effectiveness of crisis interventions for CYP who are in acute MH distress via reducing ED presentations and hospitalisations and reducing health system costs, but the review also highlighted the scarcity of studies in this area and called for further studies to bridge this knowledge gap . Here weThe Safeguards Teams Program aims to improve access to timely, evidence-based, recovery-focused, and trauma-informed assessment and brief intervention for children and adolescents presenting in acute MH crisis and their families/caregivers.The STP will reduce the rates of CYP re-presenting to the ED with acute MH concerns including the use of emergency services and/or necessitating re-hospitalisations and result in better engagement with services (primary outcome), and leading to better mental health outcomes, thereby minimising school (better school attendance) and psychosocial (better engagement and participation) disruption (secondary outcomes).An additional hypothesis is that the implementation of the STP program will be feasible, acceptable, and accessible and will result in effective referrals and linkages to relevant services post-intervention with the uptake of these recommendations and service satisfaction for consumers (CYP and their families), service providers  and other stakeholders . An economic evaluation will also be undertaken to ascertain the value for money by comparing the incremental cost and benefit based on child and family outcomes and service experiences. Return on investment, associated with wide-scale implementation, will be modelled based on the trial outcomes.The study will utilise a pre- (Time 1/baseline) and post-intervention (Time 2) design to compare outcomes of individuals who receive STP at entry into the program and then on exit from the STP followed by data collection at 3 months post-intervention (Time 3) for re-presentation to ED or in-patient wards including the use of emergency services  and engagement with referred services and uptake of recommendations. In addition to questionnaire/survey data collected at the three-time points, EMR data will be collated for those who participated in the STP program and from another CAMHS service site where CYP presenting in acute crisis received care as usual. Further qualitative study using focus groups and in-depth interviews, and ethnographic approaches, such as observations and reflections will be completed with consumers (CYP and their parents/caregivers), service providers and relevant stakeholders. An implementation evaluation of the overall impact, implementation process and economic analysis will also be carried out.The sample for the STP will include children and adolescents 0\u201317 years who are experiencing an acute MH crisis, who are not currently undertaking MH treatment and would benefit from a rapid response MH service. Services will be provided for both CYP and their parents/caregivers.Children and adolescents aged 0\u201317 years presenting in an acute mental health crisis , for an urgent or immediate response)  index).Mental health outcomes will be ascertained using pre- (at admission) and post- (at discharge) questionnaire surveys completed by clinicians, CYP and their parents/caregivers . QualitaA semi-structured questionnaire has been developed to gather not only baseline demographic data but also information regarding how CYP functions  relative to mental health service access; attendance, participation and performance at school; participation in sports or other physical or social activities; and the current relationship between the CYP and parent(s), other family members , friends, and social support network connections.Data will be collected at each time point.NSW Mental Health Carer Experience Survey provides a better understanding of the experiences, needs and outcomes of carers. The measure consists of 37-items.Children\u2019s Global Assessment Scale (CGAS) scale is a clinician-rated scale used to rate the functioning of children and young people aged 6\u201317 years old related to their psychological and social functioning. It is a brief- 10-item observer-rated scale.Clinical Global Impression \u2013 Severity scale (CGI-S) and Improvement scale (CGI-I) comprise a brief- 3-item observer-rated scale that requires the clinician to assess the overall severity of the individual\u2019s illness and overall improvement in the individual\u2019s illness relative to a baseline state.Health of the Nation Outcome Scales for Children and Adolescents (HoNOSCA) is a clinician-rated measure. The first section consists of questions related to the different types of problems that a child or adolescent might be experiencing; the second part of the survey relates to the parent/caregiver\u2019s knowledge of the nature of their child\u2019s difficulties and information about MH services available to support the child and the family.Kessler Psychological Distress Scale (K10) explores questions about depressive symptoms that CYP may have experienced. The survey is a 10-item measure and explores distress based on questions about anxiety and depressive symptoms that a person with a MH disorder may experience within a 4-week period.Pediatric Symptom Checklist\u2014Youth Report (Y-PSC) is a 17-item measurement psychosocial screen designed to facilitate the recognition of cognitive, emotional, and behavioural problems completed by youth aged 12\u201317 years and up. Similarly, the parent-completed Pediatric Symptom Checklist is also a 17-item measurement tool and provides a measure of their children\u2019s psychosocial functioning.Pictorial Pediatric Symptom Checklist (PPSC) is a pictorial psychosocial screen designed to facilitate the recognition of cognitive, emotional, learning, and behavioural problems completed by children and youth aged 6\u201311 years and up. It is a brief 35-item measurement tool.Your Experience of Service (YES) questionnaire explores the experiences of consumers about both their current and previous use of MH services.A mix of qualitative, quantitative, and ethnographic approaches will be used to examine the effectiveness of the implementation of the STP with a focus on key implementation outcome metrics including acceptability, appropriateness, fidelity, feasibility, coverage, cost, and sustainability as detailed in The STP processes of how care pathways, practices and agreements have been established and developed from ED, mental health services and community-managed organisations for children and adolescents with acute mental health crises will also be evaluated using a mixed-methods approach. This includes exploring how clinical practice changes have occurred within ED, mental health, and community-based organisations to prevent or decrease avoidable hospital ED presentations and hospital admissions . The data collection source will include interviews and focus groups with mental health clinicians, primary care clinicians, hospital clinicians, government agency representatives, community-managed organisations/stakeholders, and ethnographic observations in STP multidisciplinary meetings and stakeholders/steering committee meetings.Quantitative analysis: The effectiveness of the Safeguards Teams program will be evaluated by examining the difference in outcomes on entry before participants enrol into the program, and on exit, following a Safeguards encounter, using appropriate statistical methods for different outcomes. Descriptive analyses will explore changes following Safeguards Team\u2019s service delivery. We will use paired samples t-test to compare pre- versus post-intervention outcomes as per measures outlined earlier. Additionally, percent change at entry and exit from the STP from baseline for efficacy variables, will be analysed using analysis of covariance (ANCOVA) with respective baseline value as covariate. Least-square means (LSM) and 95% confidence intervals will be evaluated from the ANCOVA. The data of percent changes will be assumed as normally distributed.Qualitative analysis: In-depth semi-structured interviews of consumers and service providers (peer-workers and clinicians) will be conducted using the Consolidated Framework for Implementation Research (CFIR) [h (CFIR)  frameworh (CFIR)  for datah (CFIR) .Economic Evaluation: The economic evaluation will aim to understand the cost-effectiveness of the Safeguards Program to inform future decision-making. Trial-based economic analyses will be conducted to ascertain value for money by comparing (i) the incremental cost associated with the STP, including implementation costs, and (ii) incremental benefit assessed according to patient-reported outcome and experience measures and clinical measures. Return-on-investment, associated with wide-scale implementation, will be modelled based on the trial outcomes. Dynamic Simulation Models (DSMs) will be used to identify optimal combinations of services and referral trajectories that will provide policymakers and clinicians with practice-specific information to inform clinical decisions and forecast the potential impacts of services on outcomes. The evaluation will consider the economic return on investment as well as social return on investment.The study has been approved by the University of New South Wales Human Research Ethics Committee, reference HC220192, and SWSLHD Human Research Ethics and Governance, reference 2022/ETH00808.In most cases, little is known about the relative effectiveness and efficiency of different CAMHS delivery models . One reaIt is expected that the STP will provide CYP with MH conditions and their support networks with early access to comprehensive assessment and evidence-based acute response and referral and linkages to appropriate care delivered by specialist clinicians and support services. Outcomes from the STP may also provide clinicians involved in CAMHS with: (1) a more robust approach to service redesign specifically tailored for the provision of MH care and services to CYP consumers and their families experiencing acute MH problems; (2) data to support an economic evaluation to determine the cost-effectiveness of the Safeguards program compared with treatment as usual to inform future decision-making; (3) a mixed methods approach to explore any improvements regarding engagement, access, and uptake/integration of care in mental MH with the inclusion of the Safeguards Teams within the CAMHS as well as clinical practice changes within ED, MH services and community-based settings to prevent or decrease avoidable hospital ED presentations and hospital admissions .Moreover, the Safeguards Program will draw on building connections with local stakeholders and improving service delivery across CYP. As a result of embedding the new Safeguards Teams into the existing CAMHS structures, it will also ensure that access to MH care is based on level of acuity, risk, complexity, and distress, and is not limited by diagnosis or co-morbidities.Outcomes associated with the impact, implementation, and economic evaluation of the STP are expected to assist with identifying gaps in acute care for children and adolescents in the community and provide an alternative model of care for CYP presenting in MH crisis."}
{"text": "Introduction: Ablation therapy is a commonly used tool in the management of hepatocellular carcinoma (HCC). After ablation, dying cancer cells release a variety of substances that trigger subsequent immune responses. Immunogenic cell death (ICD) has been a trending topic in recent years and has been discussed many times along with oncologic chemotherapy. However, the subject of ablative therapy and ICDs has been little discussed. The purpose of this study was to investigate whether ablation treatment induces ICD in HCC cells and whether different types of ICDs arise because of different ablation temperatures.Methods: Four different HCC cell lines  were cultured and treated under different temperatures . Cell Counting Kit-8 assay was performed to analyze the viability of different cell lines. Apoptosis was detected by flow cytometry assay, and a few ICD-related cytokines  were detected by immunofluorescence or enzyme-linked immunosorbent assay.Results: The apoptosis rate of all kinds of cells increased significantly in \u221280\u00b0C group (p < 0.01) and 60\u00b0C group (p < 0.01). The expression levels of ICD-related cytokines were mostly significantly different between the different groups. For calreticulin, Hepa1-6 cells and SMMC7221 cells showed significantly higher protein expression levels in 60\u00b0C group (p < 0.01) and significantly lower protein expression levels \u221280\u00b0C group (p < 0.01). The ATP, high mobility group box 1 and CXCL10 expression levels were significantly higher in 60\u00b0C, \u221280\u00b0C and \u221240\u00b0C group of all four cell lines (p < 0.01).Conclusion: Different ablative treatments could induce different types of ICDs in HCC cells, providing a promising track for the development of individualized cancer therapies. There ahibition  or promohibition  of a disTo unravel how the immune system deciphers the complex signals sent by dying cancer cells, considerable efforts have been devoted. Notably, a precise combination of damage-associated molecular patterns (DAMPs) presented in a spatiotemporally orchestrated sequence by dying cancer cells can bolster the immune reaction that drives specific T-cell immunity, thereby implementing durable tumor regression and facilitating immunologic memory .To distinguish the different forms of dying tumor cells, a novel concept of immunogenic cell death (ICD) was introduced. Through concerted expression and release of a broad array of DAMPs, this specific form of apoptosis can lead to a pro-inflammatory immune process in an immunocompetent host . Relatedin vitro cultured HCC cells, we aimed to answer these two questions: (1) whether heat ablation or cryoablation, sparks ICDs in HCC cells, (2) whether the different temperature sparks different ICDs. We cultured two murine HCC cell lines (H22 and Hepa-16), and two human HCC cell lines (HepG2 and SMMC7221). Then we subjected them to acute cryoablation or heat ablation at different temperatures , with 37\u00b0C serving as a control group. Cell apoptosis was measured by flow cytometry, and the expression levels of various ICD-related cytokines were detected by immunofluorescence or enzyme-linked immunosorbent assay. Our data suggested that in different HCC cell lines, different treatment induced different expression levels of ICD-related cytokines.In recent years, a series of articles have explored whether the commonly used oncologic chemotherapeutic agents in clinical practice carry the ability to trigger ICDs , while t2 atmosphere.The human HCC cell lines , and the mouse HCC cell lines (H22 and Hepa1-6) were kindly provided by Stem Cell Bank, Chinese Academy of Sciences. The cells were grown and maintained in RPMI-1640 medium  containing 10% fetal bovine serum  and antibiotics , and the culture was incubated at 37\u00b0C in a 5% COFor each cell line, cells were divided into five groups for different thermal-treatment, \u221280\u00b0C, \u221240\u00b0C, 0\u00b0C, 37\u00b0C, 60\u00b0C. For cryoablation group, cells were placed in a refrigerator at \u221280\u00b0C, \u221240\u00b0C, or 0\u00b0C for 30\u00a0min. For heat ablation group and control group, cells were heated in a 60\u00b0C or 37\u00b0C water bath at for 30\u00a0min.5/mL per well into 96-well culture plates. After 24\u00a0h of incubation, the cells were subjected to the above-mentioned cryoablation or heat ablation. Then, the plates were rinsed, added 10\u00a0\u03bcL of enhanced CCK-8 reagent  per well, and then incubated for 4\u00a0h. Lastly, the 96-well plates were scanned at a wavelength of 490\u00a0nm using a microplate reader, and cell survival rate was calculated.Viability of different HCC lines following freezing or heating was analyzed by CCK-8 assay according to the manufacturer\u2019s protocols. In brief, HCC cells were cultured at a concentration of 5 \u00d7 105 resuspended cells of each cell line were centrifugated and gently resuspended in 195\u00a0\u03bcL Annexin V-FITC binding buffer. Next, cells were stained with 5\u00a0\u03bcL Annexin V-FITC and 10\u00a0\u03bcL propidium iodide. After 20\u00a0min of incubation at 4\u00b0C in darkness, the percentage of apoptosis rate was determined using flow cytometry .Flow cytometry was performed using a FITC-Annexin V and PI Apoptosis kit  according to the instruction. In brief, cells were collected after the ablation treatment and resuspended with cold PBS buffer and counted. 1 \u00d7 10To evaluate whether cryoablation or heat ablation could induce the predicted emission of specific cytokines, the levels of CXCL10, HMGB-1, and ATP were quantified with commercial ELISA kits  in accordance with the manufacturer\u2019s instructions. For each cytokine, required number of microplate strips were taken out from the matching ELISA kit, and the rest were sealed and stored at 4\u00b0C. The set standard wells were spiked with different concentrations of standards, 50\u00a0\u03bcL each. In the set sample wells, 10\u00a0\u03bcL of the sample was added firstly, and then 40\u00a0\u03bcL of sample dilution. No reagents were added to the set blank wells. Next, 100\u00a0\u03bcL of horseradish peroxidase (HRP)-labeled detection antibody was added to each well, except for the blank wells. The top of the wells was covered firmly with a seal until the end of a 60-min incubation. Then the wells were washed for 5 times and treated with 50\u00a0\u03bcL of substrate. And after a 30-min incubation in the dark for color development, each well was applied with 50\u00a0\u03bcL stop solution. The optical density was read at 450\u00a0nm using a Multiskan\u2122 GO detector system.The expression of CRT was detected by immunofluorescence assay. Different HCC cells were grown in 24-well plates and underwent cryoablation or heat ablation. After 3 washings with PBS and a 10-min fixation with 4% paraformaldehyde, each well was permeabilized by 200\u00a0\u03bcL of 0.2% Triton X-100 for 10\u00a0min. Next, 5% BSA was added to each well for 1\u00a0h to block non-specific staining. Then the primary antibody (Sigma-Aldrich) at 1:400 dilution was applied to the wells, which were stored at 4\u00b0C overnight. Followed by 4 washings, the wells were applied with Alexa Fluor 488-labeled goat anti-rabbit IgG (H + L) antibody  at 1:400 dilution, incubated at room temperature for 1\u00a0h and washed 4 times. Finally, 150\u00a0\u03bcL of DAPI was added to each well. After a 4-min incubation at room temperature, the plates were washed with PBS for the last 4 times. The slides were examined under a fluorescence microscope, and the fluorescence intensity of each sample was recorded.p-value <0.05 was considered a statistically significant difference.Dates are presented as the mean \u00b1 standard\u2009deviation\u2009(SD). The statistical analyses were performed using SPSS 25.0 software  and figures were made by GraphPad Prism version 9 . Comparison between different groups was determined by one-way ANOVA with Turkey\u2019s multiple comparison test. in vitro cultured HCC cells to ablation at different temperature is concluded in p < 0.01) and 60\u00b0C groups (p < 0.01), while no difference was observed as between \u221280\u00b0C and 60\u00b0C groups. The viability of human HepG2 HCC cells decreased after treatment, but the viability of SMMC7721 cells decreased obviously only in \u221280\u00b0C group (p < 0.01), not in \u221240\u00b0C group. And the cell viability (SMMC7721 and HepG2) in \u221280\u00b0C group was much lower than 60\u00b0C group (p < 0.01).Cell viabilities of different HCC cell lines were measured by CCK-8 method. The response of p < 0.01) and 60\u00b0C group (p < 0.01). And for SMMC7721 and HepG2 cells, the apoptosis rate in \u221280\u00b0C group was much higher than 60\u00b0C group (p < 0.01).Furthermore, an apoptosis assay was performed by co-staining with annexin V and PI. Flow cytometry was utilized to measure the apoptosis rate of H22, Hepa1-6, SMMC7721, and HepG2 cells. As shown in p > 0.05). Hepa1-6 cells and SMMC7221 cells showed significantly higher protein expression levels in 60\u00b0C group (p < 0.01) and significantly lower protein expression levels in \u221280\u00b0C group (p < 0.01). HepG2 cells showed no significant changes in protein expression levels under 60\u00b0C conditions, but significantly lower protein expression levels in \u221280\u00b0C group (p < 0.01).The expression levels of CRT were detected by cellular immunofluorescence assay. The results are shown in p < 0.01). The increase in ATP concentration in Hepa1-6 cells was greater in \u221280\u00b0C group than in 60\u00b0C group (p < 0.01). The other three kinds of cells showed higher levels of ATP concentration in 60\u00b0C group than in \u221280\u00b0C group (p < 0.01).The ATP and HMGB1 expression levels were detected by commercial ELISA kits. As shown in p < 0.01), and the concentration was a little higher in 60\u00b0C group than in \u221280\u00b0C group.As shown in p < 0.01) and thermal treatment (p < 0.01). For H22 and Hepa1-6 cells, the concentrations of CXCL10 were comparable. For SMMC7221 and HepG2 cells, the concentration of CXCL10 was a little higher in 60\u00b0C group than in \u221280\u00b0C group.in situ, so as to boost the immunogenicity of the tumor by exposing a broad array of neoantigens. In addition, numerous intracellular components that act as co-stimulatory molecules for immune activation are released post-ablation. Increasingly, efforts are being made to integrate the immune system with thermal ablation , 50\u00b0C is essentially high enough to cause coagulative necrosis in no time. Cryoablation arrests viability of local cells by removing heat. It has been suggested by a number of studies that temperatures below \u221220\u00b0C can effectively destroy cancer cells. Researchers generally set the lethal temperature at \u221240\u00b0C, although cryoablation can reduce the interstitial temperatures to as low as \u2212160\u00b0C. The extent of cellular damage caused by heat-based ablative therapies depends on three factors: the amount of energy applied, the rate of energy delivery, and the target tissue\u2019s intrinsic thermal sensitivity . Our stuWithin the endoplasmic reticulum, CRT, a soluble protein, carries out several important tasks, which include regulating calcium homeostasis, and assisting in protein folding. When present on the surface of the cell membrane, CRT primarily involves in antigen presentation. CRTs translocated to the membrane of dying cells and distributed in clusters interact with CD91 receptors in phagocytes, which provoke phagocytosis of dying cells  and the in vitro evidence for that HMGB1 promotes HCC cell proliferation, migration, and invasion  and receptor for advanced glycation endproducts (RAGE) and promotes the release of more inflammatory cytokines through the activation of NF-\u03baB pathway . As confinvasion . In thisin vitro, however, normalizing the level of extracellular ATP to the percentage of dead cells helps to distinguish ICD from other types of cell death.It is well known that ATP is the most important energy supplier for all intracellular life activities. Normally, in addition to being present at high levels within the cell, ATP is present at a low level extracellularly. However, under certain stimuli, ATP would be released in excess extracellularly and trigger a series of responses, such as recruitment and transformation of myeloid cells, by binding to and activating purinergic receptor P2Y2 (P2RY2) on the myeloid cell surface . To put Chemokines are secreted proteins structurally similar to cytokines and play an important role in regulating the migration of immune cells and the proliferation of tumor cells, including CXCL10, which possess a strong pro-inflammation capacity. Two recent reports have shed light on the connection between CXCL10 and immunotherapy. One of them demonstrated that CXCL10 can be produced not only by immune cells but also by melanoma cells after the application of immunotherapy, which is a prognostic benefit for the tumor . The othin situ that could boost anti-tumor immunity. Solely inducing tumor cell ICDs to release specific antigens is not successful in triggering an effective immune response most of the time. Under immunosuppressive conditions, additional APCs need to be recruited and activated to counteract the relatively insufficient release of DAMPs (in vivo should accelerate the development of personalized anticancer therapies and identification the optimal combination of treatments for the clinical management of cancer.Given the current clinical treatments, the high risk of relapse and acute or chronic liver function impairment after HCC treatment can hardly be addressed. The development of a low-risk and long-term effective treatment for HCC that can fight against the intrinsic immune privilege of liver remains a great challenge, the fulfillment of which depends on further exploration of the immunological features in the tumor microenvironment. In this direction, one of our ultimate goals is to implement an effective vaccine of DAMPs . As thisin vitro level, and no in vivo experiments have been performed yet. This is mainly owing to the fact that we could not yet heat or cool the target tissue to a specific temperature in vivo. It requires further technological development to break through these limitations.Limitations of this study should be mentioned. Firstly, we used water baths and refrigerator storage to simulate heating and cryo-ablation at different temperatures, which did not fully comply with the specifications of clinical ablation operations. Ideally, we should use a needle antenna to deliver energy, and precisely control the temperature. Secondly, our experiments were limited to the"}
{"text": "The importance of animal welfare is being recognized worldwide. Recently, the increasing demand for enhanced laboratory animal welfare has led to clinically featured transformations of animal research institutes. This study aims to describe the process and findings of veterinary medical check-ups and its influence on laboratory dogs and pigs welfare. Regular medical checkups were conducted by the attending veterinarian twice a year to ensure the health and welfare of dogs and pigs in our animal research institute. Based on the findings from the medical checkup, we assessed the current health of dogs and pigs,providing reasonable treatments to prevent the\u00a0risk of complications.Blood tests and physical examinations revealed clinically relevant findings. Some of these findings were due to insufficient postoperative care after invasive surgical experiments and the remaining were predictable side effects after surgical experiments. However, one finding involved severe gum bleeding due to retained deciduous teeth. This animal was euthanized because it was judged to reach the humane endpoint. Majority of the dogs and pigs at our animal research institute were considered to be healthy, based on the comprehensive results of the medical checkups.Regular medical checkups by the attending veterinarian established enhanced animal welfare, ensuring the accuracy and reproducibility of animal studies. This pioneering veterinary animal care program can serve as a potential advanced guideline for animal research institutes to improve dogs and pigs welfare.The online version contains supplementary material available at 10.1186/s42826-023-00170-7. With progress in the healthcare industry and advanced technologies for the development of new drugs or medical devices, the number of animal research institutes have also increased worldwide. Animal research aims to provide scientific evidence prior to early feasible testing in humans and human clinical trials to assure the safety and efficacy of novel medical device technologies and therapies for humans and animals . A well-Laboratory animals, once considered only a biological reagent, are now being raised in animal research institutes, owing to the emerging global importance of ethical considerations , 4.The welfare of laboratory animals in South Korea is regulated by the ANIMAL PROTECTION ACT with the principles of the 3Rs . The law emphasizes the importance of animal health by stating that \u201cAnimal testing shall be conducted in consideration of the enhancement of welfare of humankind and the dignity of lives of animals\u201d. In addition, all animal research institutes should configure an Institutional Animal Care and Use Committee (IACUC) to ensure lawful compliance with the 3Rs .Since physiological indicators of laboratory animals vary depending on their environmental and health conditions, psychological stress or physical distress is considered as a potential trigger to substantial scientific and humane implications for the use of laboratory animals . The staAttending veterinarians are regular employees in laboratory animal facilities and are generally familiar with all the laboratory animal species. They play a significant role in the accreditation of the International Association for the Control of Laboratory Animals (AAALAC-i) or the Korean Excellent Laboratory Animal Facility (KELAF) by the Ministry of Food and Drug Safety. In particular, attending veterinarians play an important role in ensuring the health and a conducive environment for the laboratory animals, which can minimize unexpected variables in well-designed animal studies .This study aimed to design and evaluate a method for improving laboratory dogs and pigs welfare through regular health screening programs conducted by attending veterinarians in an animal research institute. This program is expected to play a pioneering role in laboratory dogs and pigs welfare, which is being strengthened worldwide.Health checkup of the animals was performed according to K-MEDI hub's health checkup procedure until euthanasia at the end of the experiment Fig.\u00a0. ResearcIn first half of 2019 (1H 2019), the feed amount of dog-#29 increased from 150\u00a0g/day to 200\u00a0g/day due a body condition score (BCS) of 3/9. This BCS was 4/9 at the medical checkup in the second half of the year. Dog-#39 showed difficulty in feeding due to right upper deciduous canine tooth with bleeding gums. Considering animal welfare, this dog was euthanized with the early termination of experiments, to alleviate pain. In second half of 2019 (2H 2019), the BCSs of dog-#1 and dog-#28 were 6/9. To lose body weight, their feed amounts were decreased from 300 to 250\u00a0g. In contrast, since the BCS of dog-#22 was 3/9, the feed amount was increased from 200 to 300\u00a0g. Consequently, the BCSs of all the three dogs were 4/9 at the medical checkup in the second half of the year. Although the body weights significantly increased in 2H 2019 (11.51\u2009\u00b1\u20091.28) and first half of 2020 (1H 2020) (11.72\u2009\u00b1\u20091.32), compared to those in 1H 2019 (9.31\u2009\u00b1\u20091.61) (Table 3 cells/uL) decreased to 1.81\u2009\u00d7\u2009103 cells/uL, which was within the normal range  for 3\u00a0days; on re-examination after 3\u00a0weeks, the blood monocyte concentration  and blood biochemistry were performed after aseptic blood collection. In addition, BCSs were measured and specifications were recorded through auscultation, visual inspection, and palpation. BCS is a verified method of scoring animals by physical inspection , 20; theThe BCSs of 3/9 or 6/9 in 4 dogs were normalized to 4/9 or 5/9 by adjusting the feed amount. Optimal body weight is essential for the health and welfare of animals, since BCS\u2009\u2265\u20096/9 (overweight) or BCS\u2009\u2264\u20093/9 (underweight) may be associated with disease or could serve as a predictor of a clinical condition . Dogs wiThe reason BCS was unaffected despite weight gain among dogs in 2H 2019, compared to that in 1H 2019 could be attributed to age-dependent musculoskeletal growth. All the dogs in the present study were beagles, who continue to grow upto 18\u00a0months of age . The aveMoreover, ideal BCSs (4/9 or 5/9) were observed among all dogs in 1H 2020, contrary to those among 1H 2019 and 2H 2019 dogs. Therefore, the S.D value of 1H 2020 (4.67\u2009\u00b1\u20090.71) was smaller than that of 1H 2019 (5.46\u2009\u00b1\u20090.93) and 2H 2019 (4.53\u2009\u00b1\u20090.49). Although only one pig in 1H 2020 showed a BCS 2/5, there was no additional clinical symptom. We inferred that this was due to successful regular calibration of BCSs with control of amount of feed and veterinary treatment, including antibiotic use to treat clinical symptoms such as monocytosis and neutrophilia, which can be induced during animal experiments. Therefore, regular health checkups by the AV are imperative to derive reliable results, since because factors causing distress can affect the reproducibility and reliability of animal studies .Despite the commitment to ensure the ideal health of laboratory animals, there are limitations relative to companion animals. First, the dog with bleeding gums due to retained deciduous teeth was euthanized, considering the principle of \u2018refinement\u2019 among the 3Rs, since the dog was in severe pain, accompanied by excessive bleeding. Contrary to companion animals, laboratory animals have a wider \u201chumane endpoint\u201d\u2014the scientifically justified point for pain or distress . The humContrary to companion animals, laboratory animals are raised in limited space and are exposed to invasive surgical experiments. It is a methodological challenge for AV to overcome the detrimental environments. Therefore, further studies on regular medical checkups should evaluate the psychological satisfaction of animals according to the provided environmental enrichment and post-operative pain control methods.We introduced highly enhanced animal welfare methods, the history of regular medical checkup established in this study will develop a roadmap for improving welfare and standardization of laboratory dogs and pigs in animal research institute.In conclusion, this study introduced enhanced animal welfare methods; the study design of regular medical checkups established in this study will aid in developing a roadmap for improving the welfare of laboratory dogs and pigs in an animal research institute.K-MEDI hub is a high-tech medical industry cluster created to strategically cater to the global new drug and medical device industries and supports the optimization of new drug candidates, design of medical devices, prototyping, and efficacy evaluation. K-MEDI hub consists of centers for new drug development, medical device development, preclinical research, and clinical drug manufacturing. Among these, the preclinical research center (PRC), which harbors a breeding system for mice, rats, rabbits, dogs, pigs, and monkey is specialized for laboratory animal research such as efficacy/pre-biological stability assessment of new drugs and the performance of new medical devices.The PRC, K-MEDI hub, was certified by the Ministry of Food and Drug Safety in Korea as KELAF in 2016 and fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care International (AAALAC-i) in 2020. AAALAC-i certification is recognized as an organization for non-clinical studies that encourages the humane treatment of animals in scientific research and ensures optimum animal care and use . These cThe capacities for mice, rats, rabbits, dogs, pigs, and monkey at PRC were 18,000, 1800, 100, 45, 35, and 46 respectively. The K-MEDI hub conducted preclinical evaluations by importing approximately 10,000 mice, 3000 rats, 250 rabbits, 50 dogs, and 40 pigs annually. Moreover, in 2023, they aim to address unmet needs for non-human primate preclinical research by importing roughly 20 non-human primates.Rodent breeding rooms were maintained as specific pathogen free barrier colonies established by the AV and experts in microbiological monitoring. Large animals such as rabbits, dogs, and pigs were reared separately from rodents to prevent cross infection. The IACUC of K-MEDI hub reviews whether exploring alternatives, rationale for the proposed number of animals, minimizing animal discomfort, and humane endpoints are included in the protocol. K-MEDI hub employs one AV who is responsible for animal quarantine, veterinary management, post-approval monitoring, and serving as a member of the Institutional Animal Care and Use Committee (IACUC), with a critical role in ensuring the ethical use of animals in research and maintaining high standards of animal welfare.The post-approval monitoring process of IACUC with the AV semi-annually ensures that the study is being conducted in accordance with the approval and that the researchers protect animal welfare.In this study, to enhance the animal welfare for laboratory animals, PRC, K-MEDI hub itself conducted regular medical check-up programs for laboratory animals, including dogs and pigs, by the AV to ensure the health and welfare of animals and perform appropriate veterinary treatments and environmental management in the facilities.A medical examination was conducted for all the dogs and pigs in breeding. Dogs and pigs were selected as the target species, since blood collection was possible without sacrifice and research involves a relatively long study period, contrary to that in rodents.In 1H 2019, 45 dogs  and 4 pigs  were examined, and in 2H 2019, 24 dogs  and 7 pigs  were examined; 21 dogs  and 14 pigs  were examined in 1H 2020.Blood collected using a sterilized syringe was placed into a serum-separating tube (SST) and an ethylenediaminetetraacetic acid tube and separated from serum in the SST tube.White blood cells (WBC), red blood cells, hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration in blood, red blood cell distribution width, platelets, and WBC differential count were analyzed as CBC using a hematology system with an autoslide .The levels of aspartate aminotransferase, albumin, alanine aminotransferase, total bilirubin, triglyceride, blood urea nitrogen, calcium, creatinine, inorganic phosphorus, glucose, sodium, total cholesterol, potassium, total protein, chloride, and C-reactive protein were analyzed as blood biochemistry using a clinical chemistry analyzer .Along with visual inspection, the body weight, auscultation, and palpation were measured along with determining the BCSs of dogs and pigs. Dogs are scored out of 9 and pigs are scored out of 5 , 22. DogStatistical significance was determined using GraphPad Prism 8 . All data are presented as mean\u2009\u00b1\u2009standard deviation. In case of changes in the body weight of dogs, the normality test was passed and one-way analysis of variance with Tukey's multiple comparisons test was used. P\u2009<\u20090.05 was considered as statistically significant. In case of changes in the BCSs of dogs and the body weights of pigs, normality tests were not passed, and Kruskal\u2013Wallis tests were used.Additional file 1.\u00a0Supplementary Figure 1. Medical checkup postponement / exemption application form of K-MEDI hub.\u00a0Supplementary Figure 2. Individual medical record form of K-MEDI hub.Additional file 2.\u00a0Supplementary Table 1. The results for complete blood cell count in 1H 2019.\u00a0Supplementary Table 2. The results for blood biochemistry in 1H 2019.\u00a0Supplementary Table 3. The results for complete blood cell count in 2H 2019.\u00a0Supplementary Table 4. The results for blood biochemistry in 2H 2019.\u00a0Supplementary Table 5. The results for complete blood cell count in 1H 2020.\u00a0Supplementary Table 6. The results for blood biochemistry in 1H 2020."}
{"text": "Estimate the prevalence of chronic pain and its association with symptoms of anxiety, sleep disorders, and aspects of remote work in the context of the COVID-19 pandemic.A cross-sectional and descriptive study conducted with 328 adults engaged in remote work. Data was collected online from February 2021 to January 2022. For pain investigation and evaluations of sleep and anxiety, a structured questionnaire, the Pittsburgh Sleep Quality Index, and the Generalized Anxiety Disorder-7 were used, respectively.The prevalence of chronic pain was 47.9% (CI 95% = 42.5-53.3). Associations were identified between pain and anxiety, sleep disorders, and sitting time (p<0.01).The prevalence of chronic pain in remote work was found to be high, with pain being of moderate intensity and associated with anxiety, sleep disorders, and prolonged sitting time. This led to a reduction in interactions among individuals due to the adoption of remote work, decreased circulation of people in public spaces, closure of businesses, and other measures. However, full-time remote work can have certain drawbacks, including decreased social interaction, limited movement, excessive screen time, and blurred boundaries between professional and personal lives. All these factors can contribute to physical and mental fatigue, stress, anxiety, pain, and exhaustion.Globally, there was a significant push towards the remote work format, also known as teleworking, the emergence of new cases of chronic pain (CP), and the exacerbation of preexisting pain symptoms, 6, especially among those who made drastic changes to their work routines. Pain is known to be multifactorial and can be linked to psychosocial factors. Therefore, during a crisis like the pandemic, the negative effects can be even more pronounced on individuals\u2019 mental, social, and physical well-being.Everyone affected by the COVID-19 pandemic felt its impact due to changes in routine and continuous exposure to physical, psychological, and social stressors. These factors might have led to symptoms of anxiety and sleep disorders, 5, 6, 7 and given the lack of specific research on CP and its correlations with sleep, anxiety, and the nuances of remote work among Brazilians during the pandemic, there was a recognized need to expand knowledge in this unique period. As a result, this study sought to explore the prevalence of CP among remote workers during the COVID-19 pandemic and determine if CP correlated with sleep disorders, anxiety symptoms, and the nature of remote work in that context.Based on the data from studiesTo estimate the prevalence of chronic pain and its association with symptoms of anxiety, sleep disorders, and aspects of remote work during the COVID-19 pandemic in Brazil.The study adhered to both national and international ethical standards and received approval from the Human Research Ethics Committee of the Federal University of S\u00e3o Carlos. All participants provided their consent by clicking on the designated area of the Informed Consent form, which is displayed on the first page of the interview questionnaire.This research is based on a master\u2019s thesis titled \u201cPain and associated factors in adults working remotely during the COVID-19 pandemic in Brazil.\u201d The study was carried out under the Postgraduate Program in Nursing at the Federal University of S\u00e3o Carlos in 2022.Following the STROBE guidelines, this descriptive, cross-sectional study employed a quantitative methodology. Data was collected online between February 2021 and January 2022 using a structured questionnaire on the Google Forms\u00ae platform. Invitations to partake in the research were disseminated via email. Brazilian university graduate programs were asked to forward the invite to faculty and professors, and companies that transitioned to remote work were also targeted. The study was promoted through the Federal University of S\u00e3o Carlos\u2019 institutional network and on the Meta\u00ae group\u2019s social media channels, including Facebook, Instagram, and WhatsApp. that focused on the Brazilian populace. For all hypothetical sample sizes, a significance level of 5% was upheld. Variations in the absolute tolerable error ranged from 1 to 8 percentage points (p.p.). Thus, the final sample size for this research fluctuated between 368 to 387 participants, allowing for a 5 p.p. tolerable error.To determine the study\u2019s sample size, calculations were made with the goal of estimating the prevalence of CP in an open-ended population. The prevalence value used in the calculation was sourced from a studyThe inclusion criteria covered adults 18 years and older who were engaged in remote work, be it full-time or part-time, during Brazil\u2019s COVID-19 pandemic. The exclusion criteria ruled out individuals diagnosed with fibromyalgia, rheumatoid arthritis, or cancer, as well as frontline healthcare workers battling COVID-19.To characterize the sample, we designed an online questionnaire to identify sociodemographic and economic profiles, the characteristics of remote work, and lifestyle habits.. Pain intensity was categorized as: 1-4 for mild pain, 5-6 for moderate pain, and 7-10 for severe pain. Pain was defined as chronic if it persisted for a period of 6 months or more from the data collection date.For pain assessment, we structured a questionnaire to ascertain its presence, intensity, location, and duration. To evaluate pain intensity, participants were asked about the average pain they experienced during the pandemic, using an 11-point numerical pain scale ranging from 0 (indicating \u201cno pain\u201d) to 10 (representing the \u201cworst possible pain\u201d) and validated for Brazilian Portuguese by Bertolazi et al.. This instrument, which assesses sleep quality and disturbances, comprises 19 questions. The highest possible score is 21 points, with a higher score indicating poorer sleep quality. A score between 0-4 suggests good sleep quality, 5-10 indicates poor quality, and scores above 10 point to sleep disorders, 13.For sleep evaluation, we used the Pittsburgh Sleep Quality Index (PSQI) questionnaire, developed by Buysse et al., based on the DSM-IV criteria, and was validated by Kroenke et al.. Its translation into Portuguese was done by Pfizer  and subsequently validated in Brazil by Moreno et al.. Comprising 7 items, each is rated on a 4-point scale, ranging from 0  to 3 (nearly every day). The total score can range from 0 to 21, with scores of 10 or higher potentially indicating symptoms of an anxiety disorder.For the assessment of anxiety, we employed the Generalized Anxiety Disorder-7 (GAD-7). This tool gauges the frequency of anxiety signs and symptoms over the past two weeks. It was devised by Spitzer et al., both in simple and multiple forms. A significance level of 5% (p<0.05) was maintained for all analyses.Descriptive statistics were used to characterize the sample. Categorical variables were depicted in both raw and relative frequencies, while continuous variables were represented with means and standard deviations (SD). In the association analyses, we employed the Poisson regression model with robust varianceThe study included 328 participants, with an average age of 32.96 (SD=8) years, ranging between 20 to 61 years. The majority were females (55.2%), and individuals with a completed higher education made up 86.3% of the sample. Socioeconomic and demographic data are detailed in Regarding lifestyle habits, it\u2019s notable that 95.7% of the participants did not smoke, and 62.5% consumed alcohol only socially. Before the pandemic, 61.3% of the sample engaged in physical activity, but this percentage dropped to 52.7% during the pandemic.The prevalence of CP stood at 47.9% . Of the 157 people with CP, 53.50% (n=84) had already felt pain before the pandemic and continued to do so during this period, while 46.49% (n=73) began to experience CP after the pandemic began. The most affected areas of the body were the lumbar spine (62.4%), the cervical spine (47.1%), and the head (42.0%).The average pain intensity during the pandemic was rated at 5.8 (SD=2.0), categorizing it as moderate. Among the participants with CP (n=157), the majority exhibited symptoms of Generalized Anxiety Disorder (GAD) at 53.5%. More than half reported poor sleep quality (59.2%), and 29.9% had sleep disorders. Notably, among people without CP, these percentages were significantly lower: 31.6% with GAD and 11.7% with sleep disorders. The average score on the GAD-7 was 10.9 (SD=5.8), and on the PSQI, it was 8.8 (SD=3.7).Further observation revealed that CP is correlated with sleep disorders (p<0.01). Individuals with CP have a 156% higher prevalence of sleep disorders compared to those without CP .No sociodemographic, economic, or lifestyle characteristics were associated with CP. However, the duration of sitting during remote work correlated with CP. The longer the sitting duration, the higher the prevalence of C P. Individuals who sit for 12 hours a day have a prevalence 3.35 times higher of having C P, and those sitting between 6 and 8 hours have a prevalence 3.28 times higher, compared to those who sit up to 6 hours a day ., 21, 22. However, it should be noted that such studies did not focus on remote workers, which could help explain the elevated rate.The results of the current study revealed a prevalence of 47.9% (95% CI: 42.46%\u201353.27%) of individuals working remotely with C P, with this pain being of moderate intensity  and associated with symptoms of anxiety, sleep disorders, and prolonged sitting. It can be stated that a 47.9% prevalence of CP during the pandemic is a high figure, especially when considering studies that assessed pain in the general Brazilian population in the years prior to the pandemic. These studies reported rates ranging from 22% to 42% of CP. Another systematic review noted that both the prevalence (95% CI: 0.29 to 0.96) and intensity (95% CI: -2.18 to -0.63) of pain were significantly higher during the pandemic compared to the pre-pandemic period, but it did not specify if the focus was on CP.After the onset of the pandemic, a systematic review of the general population in Brazil (from April to August 2020) showed an average CP prevalence of 45.59%. However, observed CP prevalence in these studies ranged from 23.02% to 76.01%, with the lumbar region (41.96%) being the most affected. Other studies also highlighted significant increases in both pain intensity and prevalence, finding rates between 27.9% and 70.5% of CP in remote workers during the pandemic, 27, 28.Findings similar to our study were identified in a study of adults from Malta (n=388), where the majority were remote workers. 49% of them reported experiencing lumbar spine pain after the pandemic began, whereas 30% had experienced it prior to the pandemic produced different findings: remote work was associated with a reduction in migraine pain intensity during chronic episodes. Psychological symptoms have also been emphasized in the literature due to the shift in people\u2019s routines. For instance, recent studies indicate high levels of anxiety symptoms during the pandemic (47.2% to 56.3%), both in the general population, 31 and among new remote workers, with the latter showing 19.6% to 55.8% anxiety prevalence, 29, 32.In Italy, a study by Curro et al., which found rates between 18.5% and 25.6% of anxiety in migraine sufferers. Bilen and Kucukkepeci found a 66.4% anxiety prevalence in individuals with C P. Nonetheless, there\u2019s a gap in the literature concerning studies linking CP with anxiety symptoms among remote workers during the pandemic. This association between CP and anxiety (p<0.01) was observed in our research, indicating that workers with CP had a 69% higher prevalence ratio compared to those without C P.In our study, 53.5% of those with CP had symptoms of GAD \u2014 a high percentage, especially when compared to Curro et al., the authors found that poor sleep quality and increased workload were predictors of anxiety. Curro et al. reported that increased pain intensity was linked to high levels of anxiety and reduced sleep quality and duration. Our study also found an association between pain and sleep disturbances.In the study by Erman et al., 27, 35. Sagat et al. also found that individuals who moved more reported lower pain intensity. It\u2019s worth noting that while sitting posture appears to be a factor in pain, CP is influenced by multiple factors that should be considered.Regarding remote work, our study observed that prolonged sitting is associated with C P, meaning the longer an individual remains seated, the higher their likelihood of developing CP. This is consistent with other studies that found sitting posture to be related to pain intensityThe sample size, initially estimated between 368 and 387 (with a tolerable error of 5 percentage points), was not achieved. Therefore, an approximate tolerable error of 5.4 percentage points is admitted. According to stratification by regions of Brazil, the sample size was only achieved in the Central-West (67) and Southeast (196) regions. This represents a significant limitation of the study.The lack of investigation regarding the intensity of CP before the pandemic is also a limitation. This information could have been collected for a better understanding of the situation, although it would be a subjective data relying on the recollection of pain intensity perception. However, it would be useful for comparative purposes.Finally, the remote mode of data collection can also be considered a limitation, as it doesn\u2019t allow for a diverse sample and limits potential participants\u2019 access due to outreach issues .This study is relevant because it provides important information about remote work, a work arrangement that became more common during the pandemic. This work format has both positive and negative aspects, as identified during this period. Therefore, it is important to pay attention to the physical and mental health of remote workers to understand how changes in their routines might lead to pain and other comorbidities. This research can help develop strategies and interventions in both the public and private sectors to minimize the negative effects of remote work.This research provides valuable insights for health professionals and pain specialists by providing an overview of chronic pain, anxiety symptoms, and sleep disorders in remote workers in Brazil. Companies and health professionals must work together to establish preventive and therapeutic measures for these symptoms in this group, as many companies are likely to continue to adopt remote work.We identified CP prevalence in approximately half of the Brazilian remote workers sample during the COVID-19 pandemic. The pain intensity was moderate among them, with the lumbar spine being the most affected region. Moreover, about half of those reporting CP manifested this symptom during the pandemic. Most showed GAD symptoms, and nearly a third of those with CP experienced sleep disorders. In contrast, in those without chronic pain, these rates were significantly lower. CP pain was associated with GAD symptoms, sleep disorders, and prolonged sitting.0034-7167-reben-76-s1-e20230012-suppl01Click here for additional data file."}
{"text": "While numerous studies over the last decade have highlighted the important influence of environmental factors on mental health, globally applicable data on physical surroundings are still limited. Access to such data and the possibility to link them to epidemiological studies is critical to unlocking the relationship of environment, brain and behaviour and promoting positive future mental health outcomes. The Adolescent Brain Cognitive Development (ABCD) Study is the largest ongoing longitudinal and observational study exploring brain development and child health among children from 21 sites across the United States. Here we describe the linking of the ABCD study data with satellite-based \u201cUrban-Satellite\u201d (UrbanSat) variables consisting of 11 satellite-data derived environmental indicators associated with each subject\u2019s residential address at their baseline visit, including land cover and land use, nighttime lights, and population characteristics. We present these UrbanSat variables and provide a review of the current literature that links environmental indicators with mental health, as well as key aspects that must be considered when using satellite data for mental health research. We also highlight and discuss significant links of the satellite data variables to the default mode network clustering coefficient and cognition. This comprehensive dataset provides the foundation for large-scale environmental epidemiology research. RecenProjected to cause around 250,000 additional deaths annually between 2030 and 2050 , climateNewer satellites are enhancing remote sensing for global environmental monitoring . They pr\u2120 Study (ABCD Study\u00ae) the largest ongoing U.S. study on child brain development across 21 sites [We introduce \u201cUrban Satellite\u201d variables (UrbanSat) originally developed by Xu et al. , measuri21 sites  encompas21 sites .In the following sections, we review recent studies on UrbanSat attributes relating to mental health and neuroimaging data and describe our developed variables linking satellite imagery with a USA-wide longitudinal neuroimaging cohort of adolescents.2.2.5.The first studies to utilize satellite-based observations for public health applications looked at Aerosol Optical Depth (AOD) data to examine the relation between environmental pollution and autism spectrum disorder (ASD)  and impaWith the launch and availability of satellite data in ever improving spatial, spectral and temporal resolutions, studies have begun examining the relation between other measurable aspects of Earth and public health, such as land cover, land use, landscape structure, vegetation cover, water bodies , populat2.1.Remote spectral imaging began in the 1960s with the Television Infrared Observation Satellite (TIROS) series, initiating experimental weather satellites for systematic Earth imaging . AdvanceSome of the major satellites used in the field of mental health include Landsat, the Moderate Resolution Imaging Spectroradiometer (MODIS), Sentinel series of satellites, the Defense Meteorological Satellite Program Operational Line Scanner (DMSP/OLS) and high and very-high spatial resolution imagery collected by small satellites and satellite constellations  which have become available since the 2000\u2019s.2.1.1.The 1972 launch of Landsat-1, marking the onset of systematic, repetitive Earth observations, revolutionized the accessibility of multispectral satellite imagery and its use across many applications . To date2.1.2.The launch of the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor on Terra and Aqua satellites  marked another milestone in satellite records, offering a broad spectral range and field of view, with a spatial resolution of 250 m \u2013 1000 m and 1\u20132 day revisit periods. Numerous studies have leveraged MODIS data to explore mental health correlations, such as Aerosol Optical Depth (AOD) with schizophrenia  and depr2.1.3.The European Space Agency (ESA) and the European Commission \u2018s Sentinel program, comprises satellites like Sentinel-1 and Sentinel-2, launched in 2014 and 2015 respectively, equipped with radar and multispectral instruments for diverse environmental monitoring. These publicly accessible data have since been applied for public health, including mental health relations to AODs , COVID-12.1.4.Sensors like the Defense Meteorological Satellite Program Operational Line Scanner (DMSP/OLS) collect data to measure Earth\u2019s nighttime lights (NTL), widely used by the scientific community for various applications . The assThe Visible Infrared Imaging Radiometer Suite (VIIRS) on the Suomi National Polar-orbiting Partnership (S-NPP) satellite, launched in 2011, succeeds DMSP-OLS for low-light Earth imaging. VIIRS day/night band (DNB) offers higher spatial resolution, reduced city center \u201cover-saturation\u201d due to a wider radiometric range and onboard calibration enhancing data quality . These i2.1.5.Since the 2000\u2019s, there has been a significant advancement in the availability of high-resolution and very high-resolution Electro-Optical (EO) satellite imagery. Very high-resolution data collected by IKONOS, Quickbird and GeoEye, followed by the increasing availability of small satellites and satellite constellations  have become available since the 2000\u2019s, allowing access to cheaper and more frequent daily imagery . SeveralWe provide in the 3.Since satellite data\u2019s adoption in public health, studies examining its relation to environmental characteristics and mental health outcomes such as depression and anxiety  have ste3.1.While discussions surrounding the environmental determinants of physical health are well-established \u201359, the A major focus is on urbanization, which has been linked to a higher prevalence of mental health disorders , while cEvidence suggests that green spaces have a positive influence on development from an early age. For instance, Engemann et al (2019)  demonstrThese benefits extend beyond early development. A comparison of street view and satellite methods assessing green and blue spaces in Beijing revealed an inverse association with geriatric depression . FurtherEvidence shows protective effects of green spaces on mental health globally, yet it is only beginning to be exploredin rapidly urbanizing regions with economic disparities like sub-Saharan Africa. A study from South Africa showcased the role of green environments in mitigating depression, particularly among middle-income individuals and African populations, emphasizing the importance of incorporating environmental considerations into sustainable socioeconomic development efforts in such contexts . While dWhile numerous studies have highlighted the positive impacts of green spaces on mental health, it is essential to approach this subject with a nuanced perspective taking into account critical mediators of this relationship. A recent Dutch study delved into the long-term relationship between residential greenery exposure and adult suicide mortality, emphasizing individual level risk factors in this association . Likewis3.3Satellite-measured nighttime lights (NTL) acting as proxies for urbanization, economic and industrial activity, and population distribution, have demonstrated relationships with a variety of mental health outcomes. For instance, Ohayon et al. (2016)  relied oImportant research has highlighted the links between higher NTL and worse mental health outcomes. In South Korea, Min and Min (2018)  found si3.4Despite many opportunities, research exploring the relationship between satellite data, brain features and mental health remains scarce. A seminal stud by Xu et al.  providedIn addition, Dadvand et al. (2018)  demonstr4.4.1.http://dx.doi.org/10.15154/8873-zj65) and include satellite data values linked up to three concurrent addresses for each participant at the baseline study visit when the participants were 9\u201310 years-old [The ABCD Study\u2019s UrbanSat variables consist of 11 key environmental indicators representing land cover characteristics, nighttime lights, population estimates and remote sensing indices in 2017 see . The dat4.2.Various Urban-Satellite data sources were unified into new raster files with identical parameters  using a custom Python script, aggregated at approximately 1km grid covering the 48 contiguous US states, with detailed methodology available in the supplement.Input data for each dataset were obtained for the year 2017 to align with the baseline ABCD Study visit timing (October 2016 thru October 2018) and comprised LULC , NTL and4.3.The UrbanSat data in ABCD release 5.0 encompasses 11 variables across 3 baseline addresses, reflecting diverse regional environmental aspects see . A stron4.3.1\u00ae cognition battery [To demonstrate the influence of UrbanSat indicators on behavior, cognition and brain function, we examined associations with measures from the ABCD Study\u2019s baseline assessments at ages 9\u201310 and utilized the total problem count from the Child Behavior Checklist (CBCL)  and the  battery  for our 4.3.2.We extracted 53 intrinsic connectivity networks (ICNs) via a spatially constrained independent component analysis framework, organizing them into seven functional domains see . We comp4.3.3.We evaluated the correlation between SES  and UrbanSat indicators . The levWithout including SES, UrbanSat indicators were associated with cognition and DMN clustering (except for forest land), with NTL also being associated with problem behavior .As proof of concept our simple analyses lend support for the interrelation of environmental factors derived from satellite image with brain and cognitive development, and mental health, while also hinting at the need for careful modeling multicollinearity between UrbanSat indicators and SES indicators. Thereby, we provided evidence for NTL being linked to more dense clustering of DMN with the rest of brain, and NTL and NDBI negatively affecting cognitive ability when controlled for SES. However, the results presented here need to be understood with consideration of limitations. Indeed, the mechanisms linking environmental factors such as UrbanSat variables and mental health, and neurobiological correlates, remain unclear. These connections involve complex physiological, psychological, and social pathways, providing important avenues for future research. For instance, in terms of biologically plausible pathways, the strengthening of physiological systems, such as respiratory health and immune function may act as crucial players linking green space and less build-up to mental health . FurtherSupplement 1"