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This brief commentary adds to the recent study by paper by Yokomitsu, Kono and Takada (2022). Their study examined social presence in gambling by experimentally investigating the effects of the presence of other people on risky betting among high-risk gamblers. This commentary argues that the paper by Yokomitsu et al. provided a highly selective review on available studies and omitted many of the key studies in the area of social presence and social facilitation in which their findings could have been compared. The commentary also briefly outlines a number of studies that have I co-authored in this area over the past three decades using a variety of different methodologies (e.g., non-participant observation studies, experiments, data mining of account-based tracking data), none of which were mentioned by Yokomitsu et al. despite their clear relevance to this area. |
Purpose:The aim was to investigate the feasibility and optimal stimulation parameters for supramaximal stimulation of muscle recorded transcranial electrical stimulation motor evoked potentials (mTc-MEP).Methods:Forty-seven consecutive patients that underwent scoliosis surgery were included. First, the feasibility of supramaximal stimulation was assessed for two settings (setting 1: pulse duration 0.075ms, interstimulus interval (ISI) 1.5ms; setting 2: pulse duration 0.300ms, ISI 3ms). Thereafter, three mTc-MEP parameters were considered for both settings; (1) elicitability, (2) amplitude, and (3) if supramaximal stimulation was achieved with ≥ 20 V below maximum output. Finally, ISIs (1ms–4ms) were optimized for setting 1.Results:Nine patients (19.15%) were excluded. Of the remaining patients, supramaximal stimulation was achieved in all patients for setting 1, and in 26 (68.42%) for setting 2. In one patient, mTc-MEPs were elicitable in more muscles for setting (1) Amplitudes were not significantly different. Stimulation voltage could be increased ≥ 20 V in all 38 patients for setting 1 and in 10 (38.46%) for setting (2) Optimal ISI’s differed widely.Conclusion:We recommend using setting 1 when monitoring mTc-MEPs with supramaximal stimulation, after which an individualized ISI optimization can be performed. Moreover, when using supramaximal stimulation, short ISI’s (i.e. 1ms or 1.5ms) can be the optimal ISI for obtaining the highest mTc-MEP amplitude.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10877-022-00972-5. |
Vertical transmission of the herpes simplex virus (HSV) in the preclinical phase of the disease progression is rare. Here, we present a case of perinatal-acquired herpes from an asymptomatic mother. Our findings suggest that clinicians should consider screening predisposed mothers for HSV as part of prenatal care to identify asymptomatic primary genital HSV infections. |
PurposeThoracic trauma accounts for 25–50% of posttraumatic mortality. Data on epidemiology of thoracic trauma in Scandinavia and risk factors for mortality are scarce. This study aims to provide an overview of epidemiology, clinical events and risk factors for mortality of patients with severe thoracic injuries.MethodsA retrospective study including adult thoracic trauma patients with abbreviated injury scale ≥ 3, between 2009 and 2018 at Haukeland University Hospital was performed. Subgroup analyses were performed for specific patient groups: (1) isolated thoracic trauma, (2) polytrauma without Traumatic Brain Injury (TBI) and (3) polytrauma with TBI. Logistic regression analyses were applied to find risk factors for 30-days mortality. Age, sex, comorbidity polypharmacy score (CPS), trauma and injury severity score (TRISS) and comprehensive complication index (CI) were included in the final model.ResultsData of 514 patients were analyzed, of which 60 (12%) patients died. Median (IQR) injury severity score (ISS) was 17 (13–27). Data of 463 patients, of which 39 patients died (8%), were included in multivariate analyses. Female sex odds ratio (OR) (2.7,p= 0.04), CPS > 9 (OR 4.8;p= 0.01), TRISS ≤ 50% (OR 44;p< 0.001) and CI ≥ 30 (OR 12.5,p< 0.001) were significant risk factors for mortality. Subgroup analyses did not demonstrate other risk factors.ConclusionComorbidities and associated pharmacotherapies, TRISS, female sex, and complications during admission predict in-hospital mortality after thoracic trauma. Current findings might help to recognize patients at risk of an adverse outcome, and thereby prevent complications.Trial registration: retrospectively registeredThe regional committees for medical and health research ethics file number is 2017/293.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00068-022-02177-6. |
Introduction:Endoscopic retrograde cholangiopancreatography (ERCP) for asymptomatic common bile duct stones (CBDS) has been associated with an increased risk of post-ERCP pancreatitis (PEP). Patients with asymptomatic CBDS at the time of ERCP include those with incidentally discovered CBDS (group A) and previously symptomatic patients with CBDS who became asymptomatic after conservative treatment for symptomatic CBDS, including obstructive jaundice or acute cholangitis (group B). In this study, we aimed to examine PEP risk in group B by comparing PEP risks between groups A, B, and currently symptomatic patients (group C).Methods:In this multicenter retrospective study, we examined 77 patients in group A, 41 patients in group B, and 1225 patients in group C who had native papillae. PEP incidence rates between asymptomatic patients at the time of ERCP (groups A and B) and symptomatic patients (group C) were compared using one-to-one propensity score matching. Bonferroni’s correction analysis was also performed to compare PEP incidence rates among the three groups.Results:As per our findings, PEP incidence rate in propensity score-matched groups A and B was significantly higher than that of propensity score-matched group C (13.2% [15/114] versus 4.4% [5/114], respectively, P = 0.033). In groups A and B, PEP incidence rates were 11.7% (9/77) and 14.6% (6/41), respectively. PEP risk in group B was similar to that in group A (P = 1.0). PEP incidence in group B was significantly higher than PEP incidence in group C (14.6% (6/41)) vs. 2.9% (35/1225)) (P = 0.005)).Conclusions:ERCP for previously symptomatic patients with CBDS who became asymptomatic after conservative treatment for symptomatic CBDS may increase the risk of PEP compared with ERCP for currently symptomatic patients. Thus, ERCP should be performed before patients become asymptomatic using conservative treatments if patients can tolerate ERCP procedures. |
ObjectiveTo investigate the effects of ultrasound-guided erector spinae plane block (ESPB) on acute and chronic post-surgical pain in patients underwent video-assisted thoracoscopic lobectomy.MethodsA total of 94 patients, who underwent elective unilateral video-assisted thoracoscopic lobotomy from August 2021 to December 2021 were randomly divided into general anesthesia group (group A,n= 46) and ESPB combined with general anesthesia group (group B,n= 48) by computer. Patient controlled intravenous analgesia(PCIA) was performed in both groups after operation. The numerical rating scale(NRS) of rest and cough pain at post anesthesia care unit(PACU), 2 h, 6 h, 12 h, 24 and 48 h after operation, frequency of PCIA in 24 h after operation, frequency of rescue analgesia, patient satisfaction, adverse reactions and complications were recorded in the two groups. Incidence of chronic pain at 3 months and 6 months after operation, the effect of daily life and rating of chronic pain management measures were recorded in the two groups.ResultsCompared with group A, rest and cough NRS score at 2 h, 6 h, 12 h, 24 and 48 h after surgery, frequency of PCIA use at 24 h after surgery, frequency of rescue analgesia were significantly decreased in group B (P< 0.05). There was no significant difference in NRS scores of rest and cough at PACU after operation between 2 groups after surgery at post anesthesia care unit (P> 0.05). There were no significant differences in the incidence of postoperative chronic pain between the 2 groups(P> 0.05);The effect of postoperative chronic pain on daily life and pain management measures in group B were significantly lower than those in group A(P< 0.05). Compared with group A, patients in group B had higher satisfaction degree, lower incidence of postoperative nausea and vomiting(PONV), and lower incidence of agitation during anesthesia recovery (P< 0.05). There were no pneumothorax, hematoma and toxicity of local anesthetic in the 2 groups.ConclusionUltrasound-guided erector spinae plane block can significantly reduce acute post-surgical pain, can not reduce the incidence of chronic post-surgical pain, but can significantly reduce the severity of chronic pain in patients underwent video-assisted thoracoscopic lobectomy.Trial registrationChiCTR2100050313,date of registration:26/08/2021 |
BackgroundPrognositic nutritional index (PNI), monocyte-to-lymphocyte ratio (MLR) and platelet (PLT) are associated with tumor survival in many human malignancies. Whereas, no study combined PNI-MLR-PLT score and indicated its predictive significance on the prognosis of patients with non-metastatic clear cell renal cell carcinoma (ccRCC).MethodsIn this study, we retrospectively collected the clinicopathological characteristics and prognostic data from 164 cases of non-metastatic ccRCC and aimed to determine the clinical significance of PNI-MLR-PLT score on patients’ outcomes after surgery. The optimal cut-off values of PNI (PNI > 47.40 vs PNI < 47.40), MLR (MLR > 0.31 vs MLR < 0.31) and PLT (PLT > 245 vs PLT < 245) were identified with relative operating characteristic (ROC) curve analysis. The PNI-MLR-PLT score system was established by the value of three indexes, each indication was assigned a score of 0 or 1. Overall survival (OS) and metastasis-free survival (MFS) were analyzed using Kaplan–Meier estimate and Cox regression models.ResultsThe mean follow-up period was 85.67 months. Eight (5.0%) patients died, 4 (2.0%) relapsed, and 7 (4.0%) developed metastasis after surgery. The 3-year OS and MFS rates were 98.2% and 97.6%, and the 5-year OS and MFS rates were both 90.2%. Our results suggested that PNI-MLR-PLT score negatively correlated with pathological T stage and tumor grade. Survival outcomes revealed that lower PNI-MLR-PLT score is associated with inferior OS (P< 0.001) and MFS (P< 0.001) after surgery. Subgroup analysis regarding pathological T stage, tumor grade and surgical modalities obtained consistent results. univariable and multivariable Cox analysis showed that high PNI-MLR-PLT score was the independent protective factor of tumor survival in non-metastatic ccRCC patients.ConclusionsOur data suggested that PNI-MLR-PLT score could serve as a promising independent prognostic factor in patients with non-metastatic ccRCC. |
The public’s trust in the science of avoiding unhealthy weight depends on a radical reform of the design and execution of weight loss programmes and their clinical trials. This Perspective reiterates the longstanding argument for measuring the effectiveness of each component of an intervention on obesity. Body energy content change results from a difference in rates between input and output. These rates are determined by the frequencies of specific patterns of dietary behaviour, physical activity and thermal comfort, plus the cost of resting metabolism. Since fat-free mass changes alongside fat mass, the amount of change in weight from a change in the frequency of a behaviour pattern comes to an asymptote. That step change in weight per unit of behaviour change is measured by regression from the change in frequency of the behaviour that has been maintained from baseline to follow-up. For hard evidence, weight loss programme participants’ own words must be used to specify behaviour. In RCTs of multiple-component programmes, sequences of the behaviour patterns to be changed are randomised among groups. The resulting evidence on effective slimming practices can be delivered directly into therapeutic services and public health interventions for the culture investigated. |
AimStudent’ engagement is a predictor of various educational outcomes, and it is a key factor in perceived learning. This study aims to investigate the psychometric properties of University Student Engagement Inventory (USEI) among students of Arab universities.MethodsIn this cross-sectional methodological study 525 Arab university students participated. Data was collected from December 2020 to January 2021. The confirmatory factor analysis used for construct validity, reliability and Invariance analysis for Sex were evaluated.ResultsConfirmatory factor analysis indices confirmed the good model fit to the data (CFIscl=0.977, NFIscl=0.974, TLIscl=0.972, SRMR = 0.036, RMSEAscl=0.111, n = 525). All tested models showed strong invariance of the USEI between male and females. There was also evidence of convergent (AVE > 0.7 for all the scales) and discriminant validity (HTMT > 0.75 for all scales). Reliability evidence for the USEI measures in the sample of Arabic students was high (αordinaland ω above 0.86).ConclusionThe results of this study support the validity and reliability of the USEI with 15 items and 3 factors and demonstrate the importance of students’ engagement in the learning process, academic progress, and self-directed learning.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12912-023-01318-5. |
AbstractOperons are transcriptional modules that allow bacteria to adapt to environmental changes by coordinately expressing the relevant set of genes. In humans, biological pathways and their regulation are more complex. If and how human cells coordinate the expression of entire biological processes is unclear. Here, we capture 31 higher‐order co‐regulation modules, which we term progulons, by help of supervised machine‐learning on proteomics data. Progulons consist of dozens to hundreds of proteins that together mediate core cellular functions. They are not restricted to physical interactions or co‐localisation. Progulon abundance changes are primarily controlled at the level of protein synthesis and degradation. Implemented as a web app atwww.proteomehd.net/progulonFinder, our approach enables the targeted search for progulons of specific cellular processes. We use it to identify a DNA replication progulon and reveal multiple new replication factors, validated by extensive phenotyping of siRNA‐induced knockdowns. Progulons provide a new entry point into the molecular understanding of biological processes. |
Acute kidney injury could occasionally complicate wasp stings. We describe two such cases. The first one developed acute kidney injury as a result of rhabdomyolysis and hemolysis, whereas the other patient developed acute kidney injury as part of multiorgan dysfunction syndrome resulting from shock and rhabdomyolysis. Both remained dependent on intermittent hemodialysis for a short period of time before recovering spontaneously. These cases highlight different pathophysiological processes leading to acute kidney injury, and the importance of timely diagnosis to achieve favourable clinical outcomes. |
AbstractA 35‐year‐old female who suffered from recurrent pancreatitis was admitted to our hospital. Her magnetic resonance cholangiopancreatography revealed ansa pancreatica. And during endoscopic retrograde cholangiopancreatography, a major duodenal papilla adenoma was identified. Hybrid endoscopic mucosal resection of this lesion was performed with pancreatic stent placement through the minor papilla to prevent recurrent pancreatitis. To our knowledge, this is the first report of a major papilla adenoma associated with ansa pancreatica. These minimally invasive endoscopic treatments solved a difficult clinical problem and avoided traumatic surgery. |
BackgroundRapid conversion from prediabetes to diabetes and frequent postprandial hyperglycemia (PPHG) is seen in Asian Indians. These should be the target of dietary strategies.ObjectivesWe hypothesized that dietary intervention of preloading major meals with almonds in participants with prediabetes will decrease overall glycemia and PPHG.DesignThe study included two phases: (1) an oral glucose tolerance test (OGTT)-based crossover randomized control study, the effect of a single premeal almond load (20 g) given before OGTT was evaluated (n= 60, 30 each period). (2) The continuous glucose monitoring system (CGMS)-based study for 3 days including premeal almond load before three major meals was a free-living, open-labeled, crossover randomized control trial, where control and premeal almond load diets were compared for glycaemic control (n= 60, 30 in each period). The study was registered at clinicaltrials.gov (registration no. NCT04769726).ResultsIn the OGTT-based study phase, the overall AUC for blood glucose, serum insulin, C-peptide, and plasma glucagon post-75 g oral glucose load was significantly lower for treatment vs. control diet (p< 0.001). Specifically, with the former diet, PPHG was significantly lower (18.05% in AUC on OGTT, 24.8% at 1-h, 28.9% at 2-h post OGTT, and 10.07% during CGMS). The CGMS data showed that premeal almond load significantly improved 24-glucose variability; SD of mean glucose concentration and mean of daily differences. Daily glycaemic control improved significantly as per the following: mean 24-h blood glucose concentration (M), time spent above 7.8 mmol/L of blood glucose, together with the corresponding AUC values. Premeal almond load significantly decreased following: overall hyperglycemia (glucose AUC), PPHG, peak 24-h glycaemia, and minimum glucose level during night.ConclusionIncorporation of 20 g of almonds, 30 min before each major meal led to a significant decrease in PPHG (as revealed in OGTT-based study phase) and also improved insulin, C-peptide, glucagon levels, and improved glucose variability and glycemic parameters on CGMS in participants with prediabetes.Clinical trial registryThe study was registered at clinicaltrials.gov (registration no. NCT04769726). |
Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin’s lymphoma and can rarely present as a primary gastrointestinal malignancy. Primary gastrointestinal lymphoma (PGIL) is associated with a significant risk of perforation and peritonitis, with high rates of mortality. Here we describe a case of a newly diagnosed PGIL in a previously healthy 22-year-old male presenting for new-onset abdominal pain with diarrhea. Early hospital course was characterized by peritonitis and severe septic shock. Despite multiple surgical interventions and resuscitative efforts, the patient’s condition continued to deteriorate until cardiac arrest and death on hospital day five. A diagnosis of DLBCL of the terminal ileum and cecum was made by pathology post-mortem. The prognosis for these patients can be improved through early intervention with chemotherapy regimens and surgical resection of the malignant tissue. This report highlights DLBCL as a rare cause of gastrointestinal perforation that can culminate in precipitous multiorgan failure and death. |
AbstractThe field of geriatric oncology has made significant progress in recent decades, but there are still missed opportunities in important areas of research. One issue is the underrepresentation of older patients, especially those aged 75 years and older, in clinical trials. This has resulted in a lack of high-quality data for the care of this population, and the American Society of Clinical Oncology has called for an increase in the evidence base for older patients with cancer. The second missed opportunity is the chance to gather important knowledge from older patients participating in clinical trials, such as medications, social support, insurance, and financial information. These data can be easily collected and incorporated into the trial design to enhance the information available to researchers and clinicians. The third missed opportunity is the chance to robustly analyze and report clinical trial data for the benefit of geriatric oncology research. Many trials only report a median age and range, which is a disservice to both the participants and the patients who will be treated based on the study results. To advance geriatric oncology research, the necessary data need to be collected, analyzed, and reported through appropriate representation of older patients, collection of essential information, and thorough analysis and communication of results. Clinical trial design needs to include geriatric baseline parameters, and Cancer Therapy Evaluation Program (CTEP) has modified its template to include these parameters. |
ObjectiveTo examine the prognostic value of HRV measurements during anesthesia for postoperative clinical outcomes prediction using machine learning models.Data sourcesVitalDB, a comprehensive database of 6388 surgical patients admitted to Seoul National University Hospital.Eligibility criteria for study selectionCases with ECG lead II recording duration of less than one hour were excluded. Cases with more than 20% of missing HRV measurements were also excluded. A total of 5641 cases were eligible for the analyses.MethodsSix machine learning models including Logistic Regression (LR), Support Vector Machine (SVM), Random Forest (RF), Gradient Boosting Decision Trees (GBT), Extreme Gradient Boosting (XGB), and an ensemble of the five baseline models were developed to predict postoperative clinical outcomes. The prediction models were trained using only clinical information, and using both clinical information and HRV features, respectively. Feature importance based on the SHAP method was used to assess the contribution of the HRV measurements to the outcome predictions. Subgroup analysis was also performed to evaluate the risk association between postoperative ICU stay and various HRV measurements such as heart rate, low-frequency power (LFP), and short-term fluctuation DFA\documentclass[12pt]{minimal}
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\begin{document}$${\alpha }_{1}$$\end{document}α1.ResultThe final cohort included 5641 unique cases, among whom 4678 (83.0%) cases had ages over 40, 2877 (51.0%) were male, 1073 (19.0%) stayed in ICU after surgery, 52 (0.9%) suffered in-hospital death, and 3167(56.1%) had a total length of hospital stay longer than 7 days. In the final test set, the highest AUROC performance with only clinical information was 0.79 for postoperative ICU stay, 0.58 for in-hospital mortality, and 0.76 for the total length of hospital stay prediction. Importantly, using both clinical information and HRV features, the AUROC performance was 0.83, 0.70, and 0.76 for the three clinical outcome predictions, respectively. Subgroup analysis found that patients with an average heart rate higher than 70, low-frequency power (LFP) < 33, and short-term fluctuation DFA\documentclass[12pt]{minimal}
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\begin{document}$${\alpha }_{1}$$\end{document}α1< 0.95 during anesthesia, had a significantly higher risk of entering the ICU after surgery.ConclusionThis study suggested that HRV measurements during anesthesia are feasible and effective for predicting postoperative clinical outcomes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12871-023-02118-9. |
The microbiome is known to play a role in many human diseases, but identifying key microbes and their functions generally requires large studies due to the vast number of species and genes, and the high levels of intra-individual and inter-individual variation. 16S amplicon sequencing of the rRNA gene is commonly used for large studies due to its comparatively low sequencing cost, but it has poor taxonomic and functional resolution. Deep shotgun sequencing is a more accurate and comprehensive alternative for small studies, but can be cost-prohibitive for biomarker discovery in large populations. Shallow or moderate-depth shotgun metagenomics may serve as a viable alternative to 16S sequencing for large-scale and/or dense longitudinal studies, but only if resolution and reproducibility are comparable. Here we applied both 16S and shallow shotgun stool microbiome sequencing to a cohort of 5 subjects sampled twice daily and weekly, with technical replication at the DNA extraction and the library preparation/sequencing steps, for a total of 80 16S samples and 80 shallow shotgun sequencing samples. We found that shallow shotgun sequencing produced lower technical variation and higher taxonomic resolution than 16S sequencing, at a much lower cost than deep shotgun sequencing. These findings suggest that shallow shotgun sequencing provides a more specific and more reproducible alternative to 16S sequencing for large-scale microbiome studies where costs prohibit deep shotgun sequencing and where bacterial species are expected to have good coverage in whole-genome reference databases. |
This meta-analysis examined the associations between five-factor personality model traits and problem gambling. To be eligible for inclusion in the meta-analysis, studies had to provide effect size data that quantified the magnitude of the association between all five personality traits and problem gambling. Studies also had to use psychometrically sound measures. The meta-analysis included 20 separate samples from 19 studies and 32,222 total participants. The results showed that problem gambling was significantly correlated with the five-factor model of personality. The strongest personality correlate of problem gambling was neuroticismr= .31,p= < 0.001, 95%CI[0.17, 0.44], followed by conscientiousnessr= − .28,p= < 0.001, 95%CI[-0.38,-0.17] ), agreeablenessr= − .22,p= < 0.001, 95%CI[-0.34, − 0.10], opennessr= − .17,p= < 0.001, 95%CI[-0.22,-0.12], and extraversionr= − .11,p= .024, 95%CI[-0.20,-0.01]. These results suggest problem gamblers tend to share a common personality profile – one that could provide clues as to the most effective ways to prevent and to treat problem gambling. |
Human sterile α motif and HD domain-containing protein 1 (SAMHD1) has deoxyribonucleoside triphosphohydrolase (dNTPase) activity that allows it to defend against human immunodeficiency virus type I (HIV-1) infections and regulate the cell cycle. Although SAMHD1 mutations have been identified in various cancer types, their role in cancer is unclear. Here, we aimed to investigate the oncogenic role of SAMHD1 in human clear cell renal cell carcinoma (ccRCC), particularly as a core molecule promoting cancer cell migration. We found that SAMHD1 participated in endocytosis and lamellipodia formation. Mechanistically, SAMHD1 contributed to the formation of the endosomal complex by binding to cortactin. Thereafter, SAMHD1-stimulated endosomal focal adhesion kinase (FAK) signaling activated Rac1, which promoted lamellipodia formation on the plasma membrane and enhanced the motility of ccRCC cells. Finally, we observed a strong correlation between SAMHD1 expression and the activation of FAK and cortactin in tumor tissues obtained from patients with ccRCC. In brief, these findings reveal that SAMHD1 is an oncogene that plays a pivotal role in ccRCC cell migration through the endosomal FAK-Rac1 signaling pathway. |
AbstractDNA methylation comprises a cumulative record of lifetime exposures superimposed on genetically determined markers. Little is known about methylation dynamics in humans following an acute perturbation, such as infection. We characterized the temporal trajectory of blood epigenetic remodeling in 133 participants in a prospective study of young adults before, during, and after asymptomatic and mildly symptomatic SARS‐CoV‐2 infection. The differential methylation caused by asymptomatic or mildly symptomatic infections was indistinguishable. While differential gene expression largely returned to baseline levels after the virus became undetectable, some differentially methylated sites persisted for months of follow‐up, with a pattern resembling autoimmune or inflammatory disease. We leveraged these responses to construct methylation‐based machine learning models that distinguished samples from pre‐, during‐, and postinfection time periods, and quantitatively predicted the time since infection. The clinical trajectory in the young adults and in a diverse cohort with more severe outcomes was predicted by the similarity of methylation before or early after SARS‐CoV‐2 infection to the model‐defined postinfection state. Unlike the phenomenon of trained immunity, the postacute SARS‐CoV‐2 epigenetic landscape we identify is antiprotective. |
AbstractNiraparib (NIRA) is a highly selective inhibitor of poly (adenosine diphosphate-ribose) polymerase, PARP1 and PARP2, which play a role in DNA repair. The phase II QUEST study evaluated NIRA combinations in patients with metastatic castration-resistant prostate cancer who were positive for homologous recombination repair gene alterations and had progressed on 1 prior line of novel androgen receptor-targeted therapy. Results from the combination of NIRA with abiraterone acetate plus prednisone, which disrupts androgen axis signaling through inhibition of CYP17, showed promising efficacy and a manageable safety profile in this patient population. |
In this population-based study, we aimed to characterize and compare subgroups of therapy-related Myelodysplastic syndromes (t-MDS) and define the implications of type of previous treatment and primary disease. We combined data from MDS patients, diagnosed between 2009 and 2017 (n= 2705), in the nationwide Swedish MDS register, with several health registers. Furthermore, using matched population controls, we investigated the prevalence of antecedent malignancies in MDS patients in comparison with the general population. This first ever nationwide study on t-MDS confirms a shorter median survival for t-MDS compared to de novo MDS (15.8 months vs 31.1 months,p< 0.001). T-MDS patients previously treated with radiation only had disease characteristics with a striking resemblance to de novo-MDS, in sharp contrast to patients treated with chemotherapy who had a significantly higher risk profile. IPSS-R and the WHO classification differentiated t-MDS into different risk groups. As compared with controls, MDS patients had a six-fold increased prevalence of a previous hematological malignancy but only a 34% increased prevalence of a previous solid tumor. T-MDS patients with a previous hematological malignancy had a dismal prognosis, due both to mortality related to their primary disease and to high-risk MDS. |
AbstractBackgroundNicotine receptor partial agonists may help people to stop smoking by a combination of maintaining moderate levels of dopamine to counteract withdrawal symptoms (acting as an agonist) and reducing smoking satisfaction (acting as an antagonist). This is an update of a Cochrane Review first published in 2007.ObjectivesTo assess the effectiveness of nicotine receptor partial agonists, including varenicline and cytisine, for smoking cessation.Search methodsWe searched the Cochrane Tobacco Addiction Group's Specialised Register in April 2022 for trials, using relevant terms in the title or abstract, or as keywords. The register is compiled from searches of CENTRAL, MEDLINE, Embase, and PsycINFO.Selection criteriaWe included randomised controlled trials that compared the treatment drug with placebo, another smoking cessation drug, e‐cigarettes, or no medication. We excluded trials that did not report a minimum follow‐up period of six months from baseline.Data collection and analysisWe followed standard Cochrane methods. Our main outcome was abstinence from smoking at longest follow‐up using the most rigorous definition of abstinence, preferring biochemically validated rates where reported. We pooled risk ratios (RRs), using the Mantel‐Haenszel fixed‐effect model. We also reported the number of people reporting serious adverse events (SAEs).Main resultsWe included 75 trials of 45,049 people; 45 were new for this update. We rated 22 at low risk of bias, 18 at high risk, and 35 at unclear risk.We found moderate‐certainty evidence (limited by heterogeneity) that cytisine helps more people to quit smoking than placebo (RR 1.30, 95% confidence interval (CI) 1.15 to 1.47; I2= 83%; 4 studies, 4623 participants), and no evidence of a difference in the number reporting SAEs (RR 1.04, 95% CI 0.78 to 1.37; I2= 0%; 3 studies, 3781 participants; low‐certainty evidence). SAE evidence was limited by imprecision. We found no data on neuropsychiatric or cardiac SAEs.We found high‐certainty evidence that varenicline helps more people to quit than placebo (RR 2.32, 95% CI 2.15 to 2.51; I2= 60%, 41 studies, 17,395 participants), and moderate‐certainty evidence that people taking varenicline are more likely to report SAEs than those not taking it (RR 1.23, 95% CI 1.01 to 1.48; I2= 0%; 26 studies, 14,356 participants). While point estimates suggested increased risk of cardiac SAEs (RR 1.20, 95% CI 0.79 to 1.84; I2= 0%; 18 studies, 7151 participants; low‐certainty evidence), and decreased risk of neuropsychiatric SAEs (RR 0.89, 95% CI 0.61 to 1.29; I2= 0%; 22 studies, 7846 participants; low‐certainty evidence), in both cases evidence was limited by imprecision, and confidence intervals were compatible with both benefit and harm.Pooled results from studies that randomised people to receive cytisine or varenicline showed that more people in the varenicline arm quit smoking (RR 0.83, 95% CI 0.66 to 1.05; I2= 0%; 2 studies, 2131 participants; moderate‐certainty evidence) and reported SAEs (RR 0.67, 95% CI 0.44 to 1.03; I2= 45%; 2 studies, 2017 participants; low‐certainty evidence). However, the evidence was limited by imprecision, and confidence intervals incorporated the potential for benefit from either cytisine or varenicline. We found no data on neuropsychiatric or cardiac SAEs.We found high‐certainty evidence that varenicline helps more people to quit than bupropion (RR 1.36, 95% CI 1.25 to 1.49; I2= 0%; 9 studies, 7560 participants), and no clear evidence of difference in rates of SAEs (RR 0.89, 95% CI 0.61 to 1.31; I2= 0%; 5 studies, 5317 participants), neuropsychiatric SAEs (RR 1.05, 95% CI 0.16 to 7.04; I2= 10%; 2 studies, 866 participants), or cardiac SAEs (RR 3.17, 95% CI 0.33 to 30.18; I2= 0%; 2 studies, 866 participants). Evidence of harms was of low certainty, limited by imprecision.We found high‐certainty evidence that varenicline helps more people to quit than a single form of nicotine replacement therapy (NRT) (RR 1.25, 95% CI 1.14 to 1.37; I2= 28%; 11 studies, 7572 participants), and low‐certainty evidence, limited by imprecision, of fewer reported SAEs (RR 0.70, 95% CI 0.50 to 0.99; I2= 24%; 6 studies, 6535 participants). We found no data on neuropsychiatric or cardiac SAEs.We found no clear evidence of a difference in quit rates between varenicline and dual‐form NRT (RR 1.02, 95% CI 0.87 to 1.20; I2= 0%; 5 studies, 2344 participants; low‐certainty evidence, downgraded because of imprecision). While pooled point estimates suggested increased risk of SAEs (RR 2.15, 95% CI 0.49 to 9.46; I2= 0%; 4 studies, 1852 participants) and neuropsychiatric SAEs (RR 4.69, 95% CI 0.23 to 96.50; I2not estimable as events only in 1 study; 2 studies, 764 participants), and reduced risk of cardiac SAEs (RR 0.32, 95% CI 0.01 to 7.88; I2not estimable as events only in 1 study; 2 studies, 819 participants), in all three cases evidence was of low certainty and confidence intervals were very wide, encompassing both substantial harm and benefit.Authors' conclusionsCytisine and varenicline both help more people to quit smoking than placebo or no medication. Varenicline is more effective at helping people to quit smoking than bupropion, or a single form of NRT, and may be as or more effective than dual‐form NRT. People taking varenicline are probably more likely to experience SAEs than those not taking it, and while there may be increased risk of cardiac SAEs and decreased risk of neuropsychiatric SAEs, evidence was compatible with both benefit and harm. Cytisine may lead to fewer people reporting SAEs than varenicline. Based on studies that directly compared cytisine and varenicline, there may be a benefit from varenicline for quitting smoking, however further evidence could strengthen this finding or demonstrate a benefit from cytisine.Future trials should test the effectiveness and safety of cytisine compared with varenicline and other pharmacotherapies, and should also test variations in dose and duration. There is limited benefit to be gained from more trials testing the effect of standard‐dose varenicline compared with placebo for smoking cessation. Further trials on varenicline should test variations in dose and duration, and compare varenicline with e‐cigarettes for smoking cessation. |
The ABO blood group (BG) system is of great importance for blood transfusion and organ transplantation. Since the same transcription factors (TFs) and microRNAs (miRNAs) govern the expression of ABO BG antigens and regulate erythropoiesis, we hypothesized functional connections between both processes. We found significantly higher hemoglobin and hematocrit values in BG B blood donors compared to BG A. Furthermore, we observed that erythropoiesis in BG B hematopoietic stem/progenitor cells (HSPCs) was accelerated compared to BG A HSPCs. Specifically, BG B HSPCs yielded more lineage-specific progenitors in a shorter time (B: 31.3 ± 2.2% vs. A: 22.5 ± 3.0%). Moreover, non-BG A individuals exhibited more terminally differentiated RBCs with higher enucleation rates containing more hemoglobin compared to BG A. Additionally, we detected increased levels of miRNA-215-5p and -182-5p and decreased expression of their target TFs RUNX1 and HES-1 mRNAs in erythroid BG B precursor cells compared to BG A. This highlights the important roles of these factors for the disappearance of differentiation-specific glycan antigens and the appearance of cancer-specific glycan antigens. Our work contributes to a deeper understanding of erythropoiesis gene regulatory networks and identifies its interference with BG-specific gene expression regulations particularly in diseases, where ABO BGs determine treatment susceptibility and disease progression. |
Hypoparathyroidism is a relatively rare human and veterinary disease characterized by deficient or absent production of parathyroid hormone (PTH). PTH is known as a classical regulator of calcium and phosphorus homeostasis. Nevertheless, the hormone also appears to modulate immune functions. For example, increased CD4:CD8 T-cell ratios and elevated interleukin (IL)-6 and IL-17A levels were observed in patients with hyperparathyroidism, whereas gene expression of tumor necrosis factor-α (TNF-α) and granulocyte macrophage-colony stimulating factor (GM-CSF) was decreased in patients with chronic postsurgical hypoparathyroidism. Various immune cell populations are affected differently. So, there is a need for validated animal models for the further characterization of this disease for identifying targeted immune-modulatory therapies. In addition to genetically modified mouse models of hypoparathyroidism, there are surgical rodent models. Parathyroidectomy (PTX) can be well performed in rats—for pharmacological and associated osteoimmunological research and bone mechanical studies, a large animal model could be preferable, however. A major drawback for successfully performing total PTX in large animal species (pigs and sheep) is the presence of accessory glands, thus demanding to develop new approaches for real-time detection of all parathyroid tissues. |
This explorative study provides insights into how civil protection organizations can learn, be innovative, and develop their capabilities toward achieving greater organizational resilience. After the enormous impact of the COVID-19 pandemic, civil protection organizations had to actively shape crisis-related learning processes, particularly concerning workflows and organizational structures, collaboration with stakeholders, preparedness, risk analysis, digitalization, and the political framework. Empirical findings collected in Europe during and between the main pandemic peaks of 2020 and 2021 were analyzed for implications for policymakers and civil protection organizations. Key findings illustrate how important it is for civil protection organizations to respond quickly and adapt flexibly in times of crisis. In interviews with civil protection experts, respondents highlight the benefits of a partner network and the need for digital capabilities and data infrastructure. Other relevant factors in dealing with a crisis were found to be self-evaluation and the ability to recover from a previous wave while preparing for and responding to the next.Supplementary InformationThe online version contains supplementary material available at 10.1007/s41125-023-00090-6. |
IntroductionThis article aimed to compare the prevalence of dyslipidemia and determine risk factors associated with lipid levels in a cohort of HIV-infected patients receiving two different antiretroviral therapy (ART) regimens, nucleoside reverse transcriptase inhibitor/non-nucleoside reverse transcriptase inhibitor (NRTI/NNRTI) and nucleoside reverse transcriptase inhibitor/integrase strand transfer inhibitor (NRTI/INSTI).MethodsThis longitudinal study analyzed 633 HIV-infected patients with complete blood lipid profile records for at least 1 year at the ART clinic of Zhongnan Hospital of Wuhan University, China, from June 2018 to March 2021. Demographic and clinical data, including age, gender, body weight, height, current/former/non-smoker, current drinker, diabetes mellitus, hypertension, were extracted from electronic medical records. Laboratory tests included hematology, total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), Lipoprotein(a) and CD4 cell count. The observation duration of this study was a maximum of 33 months. Data comparisons were performed using the Chi-square test, Student’st-test and Mann–WhitneyUtest. Generalized linear mixed-effects model (GLMM) andvalue of p< 0.05 were used to determine factors associated with serum lipid profiles.ResultsIn this study, the effect of the NNRTIs group on the lipid profile over time was mainly an increase in TC and HDL-C, while a decrease in TC/HDL-C and LDL/HDL-C. However, the INSTIs group had higher mean TC and lower HDL-C compared to the NNRTIs group, with significantly increased levels of TC, TG, HDL-C, and LDL-C. In the analysis of dyslipidemia rates, there were significant differences in the prevalence of abnormal TG and TC/HDL-C in HIV-infected patients receiving two different ART regimen groups during different follow-up periods. Dyslipidemia, defined as hypercholesterolemia, hypertriglyceridemia, and low HDL-C, was more prevalent in the INSTIs group, with a higher risk of developing hypertriglyceridemia and a higher TC/HDL-C ratio compared to the NNRTIs group. GLMM analysis suggested significantly higher TG values in the INSTIs group (estimated 0.36[0.10, 0.63], SE 0.14,p= 0.008) compared to the NNRTIs group, even after adjusting for other covariates. In addition, GLMM analysis also showed that age, gender, BMI, CD4 count, and ART duration were associated with dyslipidemia.ConclusionIn conclusion, treatment with both commonly-used ART regimens can increase the mean values of lipid profiles and the risk of dyslipidemia. The findings indicated that TG values were significantly higher in the INSTIs group than in HIV-infected patients receiving the NNRTIs regimens. Longitudinal TG values are independently associated with the clinical types of ART regimens.Clinical Trial Number: ChiCTR2200059861. |
Colorectal surgery is a treatment for colorectal lesions. Technological advancements have given the rise to robotic colorectal surgery, a procedure that limits excessive blood loss via 3D pin-point precision capabilities during surgeries. The aim of this study is to review robotic surgery in colorectal treatment procedures in order to dictate its ultimate merits. This is a literature review utilising PubMed and Google Scholar; it only includes case studies and case reviews related to robotic colorectal surgeries. Literature reviews are excluded. We incorporated abstracts from all articles and full publications were examined to compare the benefits of robotic surgery in colorectal treatments. The number of articles reviewed was 41 literature spanning from 2003 to 2022. We found that robotic surgeries yielded finer marginal resections, greater amounts of lymph node resections and earlier recovery of bowel functions. The patients also spent less time in hospital after surgery. The obstacles on the other hand are it costs longer operative hours and further training, which is expensive. Studies show robotic approach is a choice for treating rectal cancer. However further studies would be needed to conclude the best approach. This is especially true with patients treated for anterior colorectal resections. Based on the evidence it's safe to say that the upsides outweigh the downsides, but advancements and further research in robotic colorectal surgeries are still necessary to reduce operative hours and cost. Surgical societies should also take the initiative and set up effective training programmes for colorectal robotic surgeries, as trained physicians result in better treatment outcomes. |
ObjectivesThe purpose of this study was to analyze mid- to long-term outcomes of total hip arthroplasty (THA) following failed internal fixation of femoral neck fracture.MethodsThis study retrospectively analyzed 345 patients with femoral neck fracture who underwent THA after failure of internal fixation at our hospital between January, 2003 and December, 2019. Patients older than 55 years (n = 175) and patients no older than 55 years (n = 170) were compared in terms of complications and survival rates during follow-up, which lasted a mean of 6 years.ResultsThe two age groups showed similarly low incidence of complications and similarly long periods of survival without revision surgery. Only three younger patients and two older patients underwent revision surgery during follow-up. The two groups showed similarly high survival rates at the end of follow-up (> 93%). Younger patients showed significantly bettter Harris hip score at last follow-up (90.2 vs. 88.1 points, p < 0.001) without clinically significant difference, but they required THA significantly earlier after internal fixation (4.4 vs. 6.8 years, p < 0.001).ConclusionsTHA after failed internal fixation of femoral neck fracture is a well tolerated and effective procedure in older and younger patients. |
BackgroundAdenoid cystic carcinoma (ACC) is a rare type of cancer commonly occurring in salivary glands. It is characterized by slow but infiltrative growth, nerve infiltration and overall poor prognosis, with late recurrence and distant metastasis. The treatment of ACC is still limited to surgery and/or (adjuvant) radiotherapy. Till now no promising systemic therapy option exists. However, various studies deliver promising results after treatment with anti-angiogenetic agents, such as anti-EGFR-antibody Cetuximab or Tyrosinkinase inhibitor Lenvatinib.MethodsBy using of immunohistological methods we analyzed and compared the macrophage and lymphocyte populations, vascularization, and PD-L1-status in 12 ACC of the salivary glands.ResultsAll cases showed a significant elevation of macrophages with M2 polarization and a higher vascularization in ACC compared to normal salivary gland tissue. The CD4/CD8 quotient was heterogenous. ACC does not show relevant PD-L1 expression.ConclusionsThe predominant M2 polarization of macrophages in ACC could be responsible for elevated vascularization, as already been proved in other cancer types, that M2 macrophages promote angiogenesis. |
BackgroundSepsis-associated encephalopathy (SAE) is frequent in septic patients. Electroencephalography (EEG) is very sensitive to detect early epileptic abnormalities, such as seizures and periodic discharges (PDs), and to quantify their duration (the so-called burden). However, the prevalence of these EEG abnormalities in septic patients, as well as their effect on morbidity and mortality, are still unclear. The aims of this study were to assess whether the presence of electrographic abnormalities (i.e. the absence of reactivity, the presence and burden of seizures and PDs) was associated with functional outcome and mortality in septic patients and whether these abnormalities were associated with sepsis-associated encephalopathy (SAE).MethodsWe prospectively included septic patients, without known chronic or acute intracranial disease or pre-existing acute encephalopathy, requiring ICU admission in a tertiary academic centre. Continuous EEG monitoring was started within 72 h after inclusion and performed for up to 7 days. A comprehensive assessment of consciousness and delirium was performed twice daily by a trained neuropsychologist. Primary endpoints were unfavourable functional outcome (UO, defined as a Glasgow Outcome Scale-Extended—GOSE—score < 5), and mortality collected at hospital discharge and secondary endpoint was the association of PDs with SAE. Mann–Whitney, Fisher’s exact andχ2tests were used to assess differences in variables between groups, as appropriate. Multivariable logistic regression analysis with in-hospital mortality, functional outcome, SAE or PDs as the dependent variables were performed.ResultsWe included 92 patients. No seizures were identified. Nearly 25% of patients had PDs. The presence of PDs and PDs burden was associated with UO in univariate (n= 15 [41%],p= 0.005 andp= 0.008, respectively) and, for PDs presence, also in multivariate analysis after correcting for disease severity (OR 3.82, IC 95% [1.27–11.49],p= 0.02). The PDs burden negatively correlated with GOSE (Spearman’s coefficientρ= − 0.2,p= 0.047). The presence of PDs was also independently associated with SAE (OR 8.98 [1.11–72.8],p= 0.04). Reactivity was observed in the majority of patients and was associated with outcomes (p= 0.044 for both functional outcome and mortality).ConclusionOur findings suggest that PDs and PDs burden are associated with SAE and might affect outcome in septic patients.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13054-023-04475-w. |
ObjectiveThe aim of this prospective cross sectional study was to evaluate the cranial structure and condylar asymmetry of adult patients with rheumatoid arthritis (RA) diagnosed after 25 years of age compared to a healthy adult control group.MethodsEighteen adult patients (57.4 ± 11.4 years) with RA were compared with a control group. Cephalometric analysis and the Habets method for the calculation of the condylar asymmetry were used. The main cephalometric data investigated were focused on the diagnosis of hyperdivergent cranial structure (NSL/ML, NL/ML), backwards rotation of the mandible (Fh/ML), short vertical ramus (Ar:Go), steep mandibular plane (ML/Oc).ResultsThe cephalometric data considered were not significantly different in the RA vs controls except for the steepness of the occlusal plane (NL/Oc), which was steeper in the patients group (P< 0.02) and the ramus of the mandible which was greater in patients. The asymmetry of the condyles was significant (P< 0.003) and different from the control group, but that of the ramus was not.ConclusionsIn this study, RA patients diagnosed after 25 years of age did not show a different pattern of growth with respect to the control group. As expected, the condyles showed a difference being asymmetrical in RA patients due to the high turnover of this joint reacting to severe systemic inflammation in conditions of continuous functional work, load and forces. This study follows a previous study with the same research plan conducted on young JIA patients who showed a different pattern of growth of the skull leading to a severe hyperdivergent cranial structure with backward rotation of the mandible; this is mainly due to the insufficient growth of the condylar site exposed to the inflammatory process during development. Unlike JIA patients, this study showed that RA patients follow an individual growth pattern not affected by inflammation, even if they show joint asymmetry. |
Dispatching of the EMS crews (ambulances) to awaiting patients and then directing the patients, that are already onboard, to appropriate Emergency Departments (ED), is a nontrivial decision problem. In many emergency medical systems it is handled by the Medical Dispatcher using various strategies—sometimes preferring the closest unit. However, applying a wrong strategy may result in transferring acute-state patients, who require very specialised medical aid, to low-speciality EDs with insufficient treatment capabilities. Then, they would need to be re-transferred to referential units, prolonging substantially the time to receive treatment. In some cases such a delay might make the treatment less effective or even impossible. In this work we propose two multi-criteria mathematical optimisation problems—the first one allows us to calculate the ambulance-to-patient assignment, the second one—to establish the patient-to-hospital assignment. These problems not only take the time-to-support criterion into consideration but also optimise for the speciality of care received by each patient. The ED dispatching problem proposed allows both for direct transfers of patients to referential units and for re-transferring them from non-referential EDs. The performance of the proposed approach is tested in simulations with real-life emergency cases from the NEMSIS data set and compared with classic assignment strategies. The tests showed the proposed approach is able to produce better and more fit-for-purpose dispatching results than other strategies tested. Additionally, we propose a framework for embedding the proposed optimisation problems in the current EMS/ED dispatching process. |
Colon adenocarcinoma (COAD) is one of the tumors with the highest mortality rates. It is of the utmost significance to make an accurate prognostic assessment and to tailor one's treatment to the specific needs of the patient. Multiple lines of evidence point to the possibility that genetic variables and clinicopathological traits are connected to the onset and development of cancer. In the past, a number of studies have revealed that gamma-aminobutyric acid type A receptor subunit delta (GABRD) plays a role in the advancement of a number of different cancers. However, its function in COAD was rarely reported. In this study, we analyzed TCGA datasets and identified 29 survival-related differentially expressed genes (DEGs) in COAD patients. In particular, GABRD expression was noticeably elevated in COAD specimens. There was a correlation between high GABRD expression and an advanced clinical stage. According to the results of the survival tests, patients whose GABRD expression was high had a lower overall survival time and progression-free survival time than those whose GABRD expression was low. GABRD expression was found to be an independent predictive predictor for overall survival, as determined by multivariate COX regression analysis. Additionally, the predictive nomogram model can accurately predict the fate of individuals with COAD. In addition, we observed that GABRD expressions were positively associated with the expression of T cells regulatory (Tregs), macrophages M0, while negatively associated with the expression of T cells CD8, T cells follicular helper, macrophages M1, dendritic cells activated, eosinophils, and T cells CD4 memory activated. The IC50 of BI-2536, bleomycin, embelin, FR-180204, GW843682X, LY317615, NSC-207895, rTRAIL, and VX-11e was higher in the GABRD high-expression group. In conclusion, we have shown evidence that GABRD is a novel biomarker that is connected with immune cell infiltration in COAD and may be utilized to predict the prognosis of COAD patients. |
Melatonin (MT) and methyl jasmonate (MeJA) play important roles in the adaptation of plants to different stress factors by modulating stress tolerance mechanisms. The present study reports the involvement of MT (100 µM) in MeJA (10 µM)-induced photosynthetic performance and heat stress acclimation through regulation of the antioxidant metabolism and ethylene production in wheat (Triticum aestivumL.) plants. Plants exposed to 40 °C for 6 h per day for 15 days and allowed to retrieve at 28 °C showed enhanced oxidative stress and antioxidant metabolism, increased 1-aminocyclopropane-1-carboxylic acid (ACC) synthase (ACS) activity and ethylene production, and decreased photosynthetic performance. In contrast, the exogenously applied MT and MeJA reduced oxidative stress through improved S-assimilation (+ 73.6% S content), antioxidant defense system (+ 70.9% SOD, + 115.8% APX and + 104.2% GR, and + 49.5% GSH), optimized ethylene level to 58.4% resulting in improved photosynthesis by 75%. The use ofp-chlorophenyl alanine, a MT biosynthesis inhibitor along with MeJA in the presence of heat stress reduced the photosynthetic performance, ATP-S activity and GSH content, substantiated the requirement of MT in the MeJA-induced photosynthetic response of plants under heat stress. These findings suggest that MeJA evoked the plant’s ability to withstand heat stress by regulating the S-assimilation, antioxidant defense system, and ethylene production, and improving photosynthetic performance was dependent on MT. |
IntroductionLower cognitive functioning in old age has been associated with personality traits or systemic inflammatory markers. Associations have also been found between personality traits and inflammatory markers. However, no study has explored the inter-relationships between these three components simultaneously. The present study aims to better understand the inter-relationships among personality traits, inflammatory markers, and cognitive performance in elderly individuals without dementia.MethodsThis study utilizes a network analysis approach, a statistical method that allows visualization of the data’s unique pairwise associations. We performed a cross-sectional analysis on 720 elderly individuals without dementia, using data from Colaus|PsyColaus, a population-based study conducted in Lausanne, Switzerland. The Revised NEO Five-Factor Inventory (NEO-FFI-R) was used to assess personality traits, and interleukin (IL)-1β, IL-6, tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were used as peripheral inflammatory markers. Cognitive domains were investigated using the Mini-Mental State Examination (MMSE), the Verbal Fluency Test, the Stroop Test, the DO40, and the Free and Cued Selective Reminding (FCSR) test.ResultsOpenness was associated with verbal fluency and Agreeableness with immediate free recall. In contrast, no association between inflammatory markers and personality traits or cognition was identified.DiscussionIn elderly individuals without dementia, a high level of Openness or Agreeableness was associated with executive functioning/semantic memory and episodic memory, respectively. |
BackgroundMultiple imputation (MI) is an established technique for handling missing data in observational studies. Joint modelling (JM) and fully conditional specification (FCS) are commonly used methods for imputing multilevel data. However, MI methods for multilevel ordinal outcome variables have not been well studied, especially when cluster size is informative on the outcome. The purpose of this study is to describe and compare different MI strategies for dealing with multilevel ordinal outcomes when informative cluster size (ICS) exists.MethodsWe conducted comprehensive Monte Carlo simulation studies to compare the performance of five strategies: complete case analysis (CCA), FCS, FCS+CS (including cluster size (CS) in the imputation model), JM, and JM+CS under various scenarios. We evaluated their performance using a proportional odds logistic regression model estimated with cluster weighted generalized estimating equations (CWGEE).ResultsThe simulation results showed that including CS in the imputation model can significantly improve estimation accuracy when ICS exists. FCS provided more accurate and robust estimation than JM, followed by CCA for multilevel ordinal outcomes. We further applied these strategies to a real dental study to assess the association between metabolic syndrome and clinical attachment loss scores. The results based on FCS + CS indicated that the power of the analysis would increase after carrying out the appropriate MI strategy.ConclusionsMI is an effective tool to increase the accuracy and power of the downstream statistical analysis for missing ordinal outcomes. FCS slightly outperforms JM when imputing multilevel ordinal outcomes. When there is plausible ICS, we recommend including CS in the imputation phase.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12874-023-01909-5. |
gapless is a new tool for combined execution of correction, scaffolding and gap filling using PacBio or Oxford Nanopore reads. |
BackgroundVaccination is one of the most cost-effective global public health interventions to reduce childhood morbidity and mortality. Defaulters to full vaccination can put children at greater risk of acquiring vaccine-preventable disease outbreaks. The reason for not receiving full vaccination is not well explored, and hence, there is limited evidence about defaulters of vaccination in Ethiopia.ObjectivesTo identify determinants of defaulter to full vaccination among children aged 12–23 months in Siraro District, West Arsi Zone, Oromia Region, Ethiopia.MethodsA community-based unmatched case-control study was conducted among children aged 12–23 months from March 20 to April 30, 2022, with a total sample size of 444 (148 cases and 296 controls). Cases were children aged 12–23 months who had missed at least one routine vaccination dose, while controls were children who had received all of the recommended routine vaccinations. Consecutive sampling and simple random sampling techniques were used to select representative cases and controls respectively. Data were collected using a structured questionnaire, entered into Epi-data version 4.6, and exported to Statistical Package for Social Sciences version 26 for analysis. Logistic regression was used to identify determinants of the defaulter to full vaccination and the variables with p-value < 0.25 were recruited for multivariable analysis, and an adjusted odds ratio with a 95% confidence interval and a p-value of ≤ 0.05 was used to declare the statistical significance of the association.ResultOf the assessed determinants of the defaulter to full vaccination; inadequate knowledge of mothers/caretakers (AOR = 4.32, 95% CI:2.78–6.70), educational status of a father unable to read and write (AOR = 3.66, 95% CI:1.29–10.39), time to reach health facility ≥ 30 minutes (AOR = 2.45, 95% CI:1.51–3.97), not told about the type of vaccine received (AOR = 2.37, 95% CI;1.27–4.45), no parents discussion on vaccination (AOR = 2.16, 95% CI:1.24–3.79), home delivery (AOR = 2.43, 95% CI:1.39–4.25) and not participated in pregnant mother conference (AOR = 2.47, 95% CI = 1.35–4.49) were the identified determinants of the defaulter to full vaccination.ConclusionMother’s’ knowledge, father’s education, place of delivery, time to reach a health facility, health workers who told the type of vaccine received, participation in pregnant mother conference, and parents’ discussion on vaccination were the determinants of the defaulter to full vaccination status. Thus, the district health office should work on defaulters of vaccination by strengthening immunization service delivery and improving maternal knowledge on vaccination through pregnant mother conference participation. |
PurposeThe combination of cyclin-dependent kinase 4/6 inhibitors and endocrine therapy is a standard treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC); however, their toxicities and financial burden are major issues, especially for prolonged treatment. We investigated fulvestrant plus palbociclib in patients with HR-positive MBC resistant to fulvestrant monotherapy.MethodsPatients who initially received fulvestrant as their first- or second-line endocrine therapy were assigned to group A. Patients with disease progression during fulvestrant monotherapy who subsequently received fulvestrant plus palbociclib were assigned to group B. The primary endpoint was progression-free survival (PFS1) in group B. We set the threshold median PFS of 5 months (null hypothesis).ResultsBetween January 2018 and February 2020 we enrolled 167 patients in group A (January 2018–February 2020) from 55 institutions, of whom 72 subsequently received fulvestrant plus palbociclib and were enrolled in group B. The median follow-up was 23.8 and 8.9 months in groups A and B, respectively. The median PFS in group B (combination therapy) was 9.4 (90% confidence interval [CI]: 6.9–11.2) months (p< 0.001). This was 25.7 (90% CI: 21.2–30.3) months in group A (fulvestrant monotherapy). The TTF in group B was 7.2 (90% CI: 5.5–10.4) months. In thepost-hocanalysis, the median PFS1 in group B among patients with longer-duration fulvestrant monotherapy (> 1 year) was longer than that of patients with shorter-duration monotherapy (≤ 1 year) (11.3 vs. 7.6 months). No new toxicities were observed.ConclusionOur findings suggest that palbociclib plus fulvestrant after disease progression despite fulvestrant monotherapy is potentially safe and effective in patients with HR-positive/HER2-negative advanced MBC.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10549-023-06911-5. |
The epidermal growth factor receptor (EGFR) is a central regulator of cell physiology. EGFR is activated by ligand binding, triggering receptor dimerization, activation of kinase activity, and intracellular signaling. EGFR is transiently confined within various plasma membrane nanodomains, yet how this may contribute to regulation of EGFR ligand binding is poorly understood. To resolve how EGFR nanoscale compartmentalization gates ligand binding, we developed single-particle tracking methods to track the mobility of ligand-bound and total EGFR, in combination with modeling of EGFR ligand binding. In comparison to unliganded EGFR, ligand-bound EGFR is more confined and distinctly regulated by clathrin and tetraspanin nanodomains. Ligand binding to unliganded EGFR occurs preferentially in tetraspanin nanodomains, and disruption of tetraspanin nanodomains impairs EGFR ligand binding and alters the conformation of the receptor’s ectodomain. We thus reveal a mechanism by which EGFR confinement within tetraspanin nanodomains regulates receptor signaling at the level of ligand binding. |
Neuronal TDP-43-positive inclusions are neuropathological hallmark lesions in frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). Pathogenic missense variants inTARDBP, the gene encoding TDP-43, can cause ALS and cluster in the C-terminal prion-like domain (PrLD), where they modulate the liquid condensation and aggregation properties of the protein. TDP-43-positive inclusions are also found in rimmed vacuole myopathies, including sporadic inclusion body myositis, but myopathy-causing TDP-43 variants have not been reported. Using genome-wide linkage analysis and whole exome sequencing in an extended five-generation family with an autosomal dominant rimmed vacuole myopathy, we identified a conclusively linked frameshift mutation in TDP-43 producing a C-terminally altered PrLD (TDP-43p.Trp385IlefsTer10) (maximum multipoint LOD-score 3.61). Patient-derived muscle biopsies showed TDP-43-positive sarcoplasmic inclusions, accumulation of autophagosomes and transcriptomes with abnormally spliced sarcomeric genes (includingTTNandNEB) and increased expression of muscle regeneration genes. In vitro phase separation assays demonstrated that TDP-43Trp385IlefsTer10does not form liquid-like condensates and readily forms solid-like fibrils indicating increased aggregation propensity compared to wild-type TDP-43. InDrosophilaTDP-43p.Trp385IlefsTer10behaved as a partial loss-of-function allele as it was able to rescue theTBPH(fly ortholog ofTARDBP) neurodevelopmental lethal null phenotype while showing strongly reduced toxic gain-of-function properties upon overexpression. Accordingly, TDP-43p.Trp385IlefsTer10showed reduced toxicity in a primary rat neuron disease model. Together, these genetic, pathological, in vitro and in vivo results demonstrate that TDP-43p.Trp385IlefsTer10is an aggregation-prone partial loss-of-function variant that causes autosomal dominant vacuolar myopathy but not ALS/FTD. Our study genetically links TDP-43 proteinopathy to myodegeneration, and reveals a tissue-specific role of the PrLD in directing pathology.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00401-023-02565-1. |
Clonal myeloproliferation and development of bone marrow (BM) fibrosis are the major pathogenetic events in myelofibrosis (MF). The identification of novel antifibrotic strategies is of utmost importance since the effectiveness of current therapies in reverting BM fibrosis is debated. We previously demonstrated that osteopontin (OPN) has a profibrotic role in MF by promoting mesenchymal stromal cells proliferation and collagen production. Moreover, increased plasma OPN correlated with higher BM fibrosis grade and inferior overall survival in MF patients. To understand whether OPN is a druggable target in MF, we assessed putative inhibitors of OPN expression in vitro and identified ERK1/2 as a major regulator of OPN production. Increased OPN plasma levels were associated with BM fibrosis development in the Romiplostim-induced MF mouse model. Moreover, ERK1/2 inhibition led to a remarkable reduction of OPN production and BM fibrosis in Romiplostim-treated mice. Strikingly, the antifibrotic effect of ERK1/2 inhibition can be mainly ascribed to the reduced OPN production since it could be recapitulated through the administration of anti-OPN neutralizing antibody. Our results demonstrate that OPN is a novel druggable target in MF and pave the way to antifibrotic therapies based on the inhibition of ERK1/2-driven OPN production or the neutralization of OPN activity. |
BackgroundMobile Health (“mHealth”) interventions have shown promise in improving HIV treatment outcomes for stigmatized populations. This paper presents the findings from a randomized controlled trial to assess the efficacy, participant-level feasibility and acceptability of a theory-informed mHealth intervention,Motivation Matters!, designed to improve viral suppression and ART adherence among HIV-seropositive women who engage in sex work in Mombasa, Kenya.MethodsA total of 119 women were randomized between the intervention and standard of care control. The primary outcome examined viral suppression (≤30 copies/mL) six months following ART initiation. ART adherence was assessed monthly using a visual analogue scale. Participant-level feasibility was measured through response rates to study text messages. Acceptability was assessed through qualitative exit interviews.ResultsSix months following treatment initiation, 69% of intervention and 63% of control participants were virally suppressed (Risk Ratio [RR] = 1.09, 95% Confidence Interval [95% CI] (0.83, 1.44). Among women who were viremic at baseline and endorsed engagement in sex work, 74% of women in the intervention arm compared with 46% of women in the control arm achieved viral suppression at month six RR = 1.61, 95% CI (1.02, 2.55). Adherence was higher in intervention versus control participants every month. All participants responded to at least one message, and there was a 55% overall response rate to intervention text messages. Qualitative exit interviews suggested high acceptability and perceived impact of the intervention.ConclusionThe improvements in ART adherence and viral suppression, combined with encouraging data on feasibility and acceptability, provides preliminary evidence thatMotivation Matters!could support ART adherence and viral suppression in women who engage in sex work.Trial registrationThis trial was registered with ClinicalTrials.gov (NCT02627365, 10/12/2015;http://clinicaltrials.gov). |
ObjectivePast vegetarians research has often found that they have lower blood pressure (BP). Effects may include their lower BMI and higher intake levels of fruit and vegetables. Besides, the study pursues to extend this evidence in a diverse population containing vegans, lacto-ovo vegetarians and omnivores.DesignThe study analyzed data on five hundred vigorous individuals aged 20 years or older from a standard medical screening program and provided validated questionnaire. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns.SettingHealth screening programs were conducted at a standard medical screening program in Taiwan between 2006 and 2017. Dietary data were gathered by self-administered questionnaire.SubjectsFive hundred Taiwanese subjects representing the cohort.ResultsMultiple regression analyses confirmed that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Taiwanese (β = − 6.8,p< 0.05 and β = − 6.9,p< 0.001). Findings for lacto-ovo vegetarians (β = − 9.1,p< 0.001 and β = − 5.8,p< 0.001) were similar. The vegetarians were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or routine of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0.37 (95% CI = 0.19–0.74), 0.57 (95% CI = 0.36–0.92) and 0.92 (95% CI = 0.50–1.70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Results were reduced after adjustment for BMI.ConclusionsThe study concludes from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores. |
BackgroundThe shaping of an accurate and stable microcatheter plays a vital role in the successful embolization of intracranial aneurysms. Our study aimed to investigate the application and the role of AneuShape™ software in microcatheter shaping for intracranial aneurysm embolization.MethodsFrom January 2021 to June 2022, 105 patients with single unruptured intracranial aneurysms were retrospectively analyzed with or without AneuShape™ software to assist in microcatheter shaping. The rates of microcatheter accessibility, accurate positioning, and stability for shaping were analyzed. During the operation, fluoroscopy duration, radiation dose, immediate postoperative angiography, and procedure-related complications were evaluated.ResultsCompared to the manual group, aneurysm-coiling procedures involving the AneuShape™ software exhibited superior results. The use of the software resulted in a lower rate of reshaping microcatheters (21.82 vs. 44.00%,p= 0.015) and higher rates of accessibility (81.82 vs. 58.00%,p= 0.008), better positioning (85.45 vs. 64.00%,p= 0.011), and higher stability (83.64 vs. 62.00%,p= 0.012). The software group also required more coils for both small (<7 mm) and large (≥7 mm) aneurysms compared to the manual group (3.50 ± 0.19 vs. 2.78 ± 0.11,p= 0.008 and 8.22 ± 0.36 vs. 6.00 ± 1.00,p= 0.081, respectively). In addition, the software group achieved better complete or approximately complete aneurysm obliteration (87.27 vs. 66.00%,p= 0.010) and had a lower procedure-related complication rate (3.60 vs. 12.00%,p= 0.107). Without this software, the operation had a longer intervention duration (34.31 ± 6.51 vs. 23.87 ± 6.98 min,p< 0.001) and a higher radiation dose (750.50 ± 177.81 vs. 563.53 ± 195.46 mGy,p< 0.001).ConclusionsSoftware-based microcatheter shaping techniques can assist in the precise shaping of microcatheters, reduce operating time and radiation dose, improve embolization density, and facilitate more stable and efficient intracranial aneurysm embolization. |
BackgroundCentral pontine myelinolysis (CPM) is a rare demyelinating disorder caused by the loss of myelin in the center of the basis pontis. CPM typically occurs with rapid correction of severe chronic hyponatremia and subsequent disturbances in serum osmolality. Although hyperglycaemia is recognized as a pathogenetic factor in serum osmolality fluctuations, CPM is rarely seen in the context of diabetes.Case presentationA 66-year-old Chinese male presented with a history of gait imbalance, mild slurred speech and dysphagia for two weeks. MRI showed the mass lesions in the brainstem, and laboratory examinations showed high blood glucose and HbA1c, as well as increased serum osmolality. The patient was diagnosed with CPM secondary to hyperosmolar hyperglyceamia and received insulin treatment as well as supportive therapy. After six weeks of followup, the patient had fully recovered to a normal state.ConclusionCPM is a potentially fatal neurological condition and can occur in uncontrolled diabetes mellitus. Early diagnosis and timely treatment are crucial for improving the prognosis. |
AbstractBackgroundLittle is known about the impact of spiritual caregivers, psychologists, and social workers on desired end-of-life (EoL) medical outcomes, such as reduced use of aggressive care in the final 2 weeks of life, having more time between the last active oncological treatment and death, and increased hospice use.Patients and MethodsWe conducted a prospective study of 180 patients with cancer and their families, their interactions with social work, psychology, and spiritual care, and the above three treatment outcomes.ResultsWe found that having one or more spiritual care visits (adjusted odds ratio (AOR) = 2.02;P= .04), having more quality visits with the psychologist (P= .01), and speaking with someone about one’s inner resources (AOR = 2.25;P= .03) all correlated with reduced EoL aggressive care. The key interventions correlating with increased time after final treatment were more visits with the spiritual caregiver or the social worker (AOR = 1.30;P< .001), and speaking about the medical treatment (AOR = 1.54;P< .001) and about interpersonal relationships (AOR = 2.28;P< .001). A subjectively good-quality connection with the spiritual caregiver correlated with increased hospice use (AOR = 10.00;P= .01).ConclusionsPatients with cancer who availed themselves of the spiritual care, psychology, and social work services, each profession in distinct ways, had significantly different outcomes in their EoL medical treatment, including undergoing fewer futile aggressive measures, having more time after their last active treatment, and using hospice services more. These outcomes directly bear on improved quality of life and reduced costs. |
AbstractBackgroundThoracolumbar intervertebral disc extrusions (TL‐IVDEs) are a common spinal disorder in dogs, especially within chondrodystrophic breeds. Loss of deep pain perception is a well‐documented negative prognostic indicator in dogs with TL‐IVDE. The objectives of this study were to report the rate of return of deep pain perception and independent ambulation in surgically treated, paraplegic, deep pain perception negative French bulldogs with TL‐IVDEs.MethodsA retrospective case series of deep pain perception negative dogs with TL‐IVDE presenting to two referral centres between 2015 and 2020 was conducted. Medical and MRI records were reviewed, including the following quantitative MRI changes: lesion length, extent of spinal cord swelling and severity of spinal cord compression.ResultsThirty‐seven French bulldogs met the inclusion criteria, with 14 of 37 (38%) regaining deep pain perception by the time of discharge (median hospitalisation 10.0 days [interquartile range 7.0–15.5 days]) with two dogs independently ambulatory (6%). Ten of the 37 dogs were euthanased during hospitalisation. Significantly fewer dogs (3/16, 19%) with L4‐S3 lesions regained deep pain perception compared to 11 of 21 (52%) of dogs with T3‐L3 lesions (p= 0.048). Quantitative MRI changes were not associated with the return of deep pain perception. After discharge, with a median 1‐month follow‐up period, an additional three dogs regained deep pain perception and five dogs became independently ambulatory (17/37 [46%] and 7/37 [19%], respectively).Conclusions and clinical importanceThis study adds support to the contention that the recovery of French bulldogs with TL‐IVDE from surgery is poor compared with other breeds; further prospective, breed‐controlled studies are indicated. |
IntroductionAbnormal lncRNA expression can lead to the resistance of tumor cells to anticancer drugs, which is a crucial factor leading to high cancer mortality. Studying the relationship between lncRNA and drug resistance becomes necessary. Recently, deep learning has achieved promising results in predicting biomolecular associations. However, to our knowledge, deep learning-based lncRNA-drug resistance associations prediction has yet to be studied.MethodsHere, we proposed a new computational model, DeepLDA, which used deep neural networks and graph attention mechanisms to learn lncRNA and drug embeddings for predicting potential relationships between lncRNAs and drug resistance. DeepLDA first constructed similarity networks for lncRNAs and drugs using known association information. Subsequently, deep graph neural networks were utilized to automatically extract features from multiple attributes of lncRNAs and drugs. These features were fed into graph attention networks to learn lncRNA and drug embeddings. Finally, the embeddings were used to predict potential associations between lncRNAs and drug resistance.ResultsExperimental results on the given datasets show that DeepLDA outperforms other machine learning-related prediction methods, and the deep neural network and attention mechanism can improve model performance.DicsussionIn summary, this study proposes a powerful deep-learning model that can effectively predict lncRNA-drug resistance associations and facilitate the development of lncRNA-targeted drugs. DeepLDA is available athttps://github.com/meihonggao/DeepLDA. |
AbstractMetabolism is controlled to ensure organismal development and homeostasis. Several mechanisms regulate metabolism, including allosteric control and transcriptional regulation of metabolic enzymes and transporters. So far, metabolism regulation has mostly been described for individual genes and pathways, and the extent of transcriptional regulation of the entire metabolic network remains largely unknown. Here, we find that three‐quarters of all metabolic genes are transcriptionally regulated in the nematodeCaenorhabditis elegans. We find that many annotated metabolic pathways are coexpressed, and we use gene expression data and the iCEL1314 metabolic network model to define coregulated subpathways in an unbiased manner. Using a large gene expression compendium, we determine the conditions where subpathways exhibit strong coexpression. Finally, we develop “WormClust,” a web application that enables a gene‐by‐gene query of genes to view their association with metabolic (sub)‐pathways. Overall, this study sheds light on the ubiquity of transcriptional regulation of metabolism and provides a blueprint for similar studies in other organisms, including humans. |
AbstractBackgroundRecurrence and metastasis of bladder cancer are major factors affecting patient prognosis. Endoscopic cryoablation achieved a better clinical outcome among clinical patients and could be synergistic with ICIs. Thus, this study aimed to evaluate the immunological mechanism of cryoablation for bladder cancer to reveal the therapeutic mechanism.MethodsWe systematically reviewed the clinical prognosis of patients underwent cryoablation at Huashan Hospital in these first‐in‐human studies (ChiCTR‐INR‐17013060). Murine models were constructed to explore cryoablation‐induced tumour‐specific immunity, which was further confirmed by primary bladder tumour organoids and autologous lymphocytes cocultured system.ResultsCryoablation improved progression‐free survival and recurrence‐free survival respectively. Assessment of murine models after cryoablation confirmed microenvironment remodelling and tumour‐specific T cells expansion. Enhanced antitumour effects were found after coculture of organoids with autologous lymphocytes collected from post‐cryoablation. We also demonstrated cryoablation‐induced tumour elimination required IFNGR expression on tumour cells. In addition, a long‐lasting antitumour memory response is achieved by cryoablation and could be enhanced after combination with ICIs.ConclusionsThis study revealed endoscopic cryoablation is an efficient and safe therapy for bladder tumour treatment. The tumour‐specific immune responses induced by cryoablation could reduce tumour recurrence and metastasis. |
Solitary extramedullary plasmacytoma (SEP) is a rare tumor due to the monoclonal proliferation of plasma cells without bone marrow involvement. Plasmacytomas are frequently encountered in bone or soft tissue but rarely occur in the gastrointestinal (GI) tract. They can present with a multitude of symptoms depending on their site. This report describes a case of SEP diagnosed as a duodenal ulcer (DU) during esophagogastroduodenoscopy (EGD) for iron deficiency anemia. |
INTRODUCTIONA large number of people around the world are exposed to the risks of passive smoking. This prospective study aimed to examine the association between secondhand smoke exposure, exposure time, and the incidence of chronic kidney disease (CKD) and determine whether this association was influenced by genetic susceptibility.METHODSThe study included 214244 participants of the UK Biobank who were initially free of CKD. Cox proportional hazards model was used to estimate the associations between secondhand smoke exposure time and the risks of CKD in people who have never smoked. The genetic risk score for CKD was calculated by a weighted method. The likelihood ratio test comparing models was used to examine the cross-product term between secondhand smoke exposure and genetic susceptibility to CKD outcomes.RESULTSDuring a median of 11.9 years of follow-up, 6583 incidents of CKD were documented. Secondhand smoke exposure increased the risk of CKD (HR=1.09; 95% CI: 1.03–1.16, p<0.01), and a dose-response relationship between CKD prevalence and secondhand smoke exposure time was found (p for trend<0.01). Secondhand smoke exposure increases the risk of CKD even in people who never smoke and have a low genetic risk (HR=1.13; 95% CI: 1.02–1.26, p=0.02). There was no statistically significant interaction between secondhand smoke exposure and genetic susceptibility to CKD (p for interaction=0.80).CONCLUSIONSSecondhand smoke exposure is associated with higher risk of CKD, even in people with low genetic risk, and the relationship is dose dependent. These findings change the belief that people with low genetic susceptibility and without direct participation in smoking activities are not prone to CKD, emphasizing the need to avoid the harm of secondhand smoke in public places. |
BackgroundPatients with treatment-resistant depression (TRD) report significant deficits in physical and mental health, as well as severely impaired health-related quality of life (HRQoL) and functioning. Esketamine effectively enhances the daily functioning in these patients while also improving their depressive symptoms. This study assessed HRQoL and health status of patients with TRD, who were treated with esketamine nasal spray and an oral antidepressant (ESK + AD) vs. placebo nasal spray and an AD (AD + PBO).MethodsData from TRANSFORM-2, a phase 3, randomized, double-blind, short-term flexibly dosed study, were analyzed. Patients (aged 18–64 years) with TRD were included. The outcome assessments included the European Quality of Life Group, Five Dimension, Five Level (EQ-5D-5L), EQ-Visual Analogue Scale (EQ-VAS), and Sheehan Disability Scale (SDS). The health status index (HSI) was calculated using EQ-5D-5L scores.ResultsThe full analysis set included 223 patients (ESK + AD: 114; AD + PBO: 109; mean [SD] age: 45.7 [11.89]). At Day 28, a lower percentage of patients reported impairment in the ESK + AD vs. AD + PBO group in all five EQ-5D-5L dimensions: mobility (10.6% vs. 25.0%), self-care (13.5% vs. 32.0%), usual activities (51.9% vs. 72.0%), pain/discomfort (35.6% vs. 54.0%), and anxiety/depression (69.2% vs. 78.0%). The mean (SD) change from baseline in HSI at Day 28 was 0.310 (0.219) for ESK + AD and 0.235 (0.252) for AD + PBO, with a higher score reflecting better levels of health. The mean (SD) change from baseline in EQ-VAS score at Day 28 was greater in ESK + AD (31.1 [25.67]) vs. AD + PBO (22.1 [26.43]). The mean (SD) change in the SDS total score from baseline to Day 28 also favored ESK + AD (-13.6 [8.31]) vs. AD + PBO (-9.4 [8.43]).ConclusionsGreater improvements in HRQoL and health status were observed among patients with TRD treated with ESK + AD vs. AD + PBO.Trial registrationClinicalTrials.gov Identifier: NCT02418585.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12955-023-02113-1. |
AbstractPurposeThe total crude alkaloidal extract ofPicralima nitidaseeds (PNE) is known to possess anti‐inflammatory activity among other therapeutic benefits although its benefits in colitis has not been investigated. The current study therefore seeks to investigate the anti‐colitis potential of PNE using acetic acid‐induced colitis model in rats.MethodsSprague Dawley rats were treated with oral 500 mg/kg sulphasalazine or 30, 100, and 300 mg/kg of PNE daily for 8 days with induction of colitis on the fourth day with acetic acid. Rats were killed 24 h after the last treatment and whole blood was obtained from the jugular vein for hematological analysis and biochemical assays. Colons were extirpated for assessment of macroscopic and histological damage to the colon.ResultsTreatment with PNE protected against colonic injury induced with acetic acid by decreasing mucosal ulceration, epithelial erosion, inflammatory cell infiltration, and colonic edema. Thus, PNE preserved mucosal architecture and suppressed goblet cells depletion. Moreover, treatment with PNE was associated with improved hematological parameters and reductions in the expression of serum tumor necrosis factor‐alpha, interleukin‐1β, and p38 mitogen‐activated protein kinase. Also, PNE treatment exerted antioxidant effects by reducing nitric oxide production and increasing glutathione levels. In addition, PNE inhibited colonic lipid peroxidation by decreasing myeloperoxidase activity and malondialdehyde production.ConclusionIt can be concluded that PNE attenuates intestinal oxidative and inflammatory damages following intrarectal acetic acid challenge. Thus, demonstrates potential for use in chronic intestinal inflammatory diseases such as ulcerative colitis. |
Clinical algorithms used in the assessment of febrile children in the Paediatric Emergency Departments are commonly based on threshold values for vital signs, which in children with fever are often outside the normal range. Our aim was to assess the diagnostic value of heart and respiratory rate for serious bacterial infection (SBI) in children after temperature lowering following administration of antipyretics. A prospective cohort of children presenting with fever between June 2014 and March 2015 at the Paediatric Emergency Department of a large teaching hospital in London, UK, was performed. Seven hundred forty children aged 1 month–16 years presenting with a fever and ≥ 1 warning signs of SBI given antipyretics were included. Tachycardia or tachypnoea were defined by different threshold values: (a) APLS threshold values, (b) age-specific and temperature-adjusted centiles charts and (c) relative difference inz-score. SBI was defined by a composite reference standard (cultures from a sterile site, microbiology and virology results, radiological abnormalities, expert panel). Persistent tachypnoea after body temperature lowering was an important predictor of SBI (OR 1.92, 95% CI 1.15, 3.30). This effect was only observed for pneumonia but not other SBIs. Threshold values for tachypnoea > 97th centile at repeat measurement achieved high specificity (0.95 (0.93, 0.96)) and positive likelihood ratios (LR + 3.25 (1.73, 6.11)) and may be useful for ruling in SBI, specifically pneumonia. Persistent tachycardia was not an independent predictor of SBI and had limited value as a diagnostic test.Conclusion: Among children given antipyretics, tachypnoea at repeat measurement had some value in predicting SBI and was useful to rule in pneumonia. The diagnostic value of tachycardia was poor. Overreliance on heart rate as a diagnostic feature following body temperature lowering may not be justified to facilitate safe discharge.What is Known:• Abnormal vital signs at triage have limited value as a diagnostic test to identify children with SBI, and fever alters the specificity of commonly used threshold values for vital signs.• The observed temperature response after antipyretics is not a clinically useful indicator to differentiate the cause of febrile illness.What is New:• Persistent tachycardia following reduction in body temperature was not associated with an increased risk of SBI and of poor value as a diagnostic test, whilst persistent tachypnoea may indicate the presence of pneumonia.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00431-023-04884-7. |
In recent years, a growing number of attachment-based studies have contributed to the understanding of both substance and behavioral addictions. Although gambling is a form of addictive behavior widespread all over the world, both among young people and adults, the evidence on the association between attachment-related phenomena and gambling has not yet been systematized in literature. The aim of the present study, therefore, is to provide a systematic literature review aimed at summarizing the empirical evidence on this topic. Following the updated 2020 PRISMA guidelines, a systematic search in four electronic scientific databases (Scopus, PubMed, PsycInfo and Web of Science) was conducted. After removing duplicates, 146 records were double-screened, with 12 articles meeting the inclusion criteria. Additionally, by means of a backward search a further article was selected. Altogether, 13 articles were selected for the present systematic review. With few exceptions, the results underline the significant role played by attachment-related phenomena in gambling behaviors, highlighting that specific attachment contexts have a different influence on gambling, also depending on whether gamblers are youths or adults. In particular, while secure attachment has proven to be a protective factor for the onset of gambling behavior, insecure attachment has emerged to be a vulnerability factor in two ways. On the one hand, it directly favors gambling behaviors; on the other, it affects coping strategies and the individual’s ability to identify and regulate emotions, which in turn predict gambling. Limitations, strengths, and implications of the present systematic review are discussed. |
ObjectiveThere is a bidirectional interaction between circulating testosterone and blood glucose levels. We aim to investigate the testosterone levels in men with early-onset type 2 diabetes (T2DM).MethodsA total of 153 drug naive men with T2DM were enrolled in the study. Early- (n= 63) and late-onset (n= 90) T2DM was classified according to age 40 years old. Clinical characteristics and plasma for biochemical criterions were collected. Gonadal hormones were measured using chemiluminescent immunometric assay. The concentrations of 3β- and 17β-HSD were determined using ELISA.ResultsCompared with men with late-onset T2DM, those with early-onset T2DM had lower serum total testosterone (TT), sex hormone-binding globulin (SHBG), and FSH, but higher dehydroepiandrosterone sulfate (DHEA-S) level (p< 0.05). The mediating effect analysis showed that the decreased TT levels in patients with early-onset T2DM were associated with the higher HbA1c, BMI, and triglyceride in these patients (bothp< 0.05). The early-onset of T2DM directly correlated with increased DHEA-S (bothp< 0.01). The 3β-HSD concentration in the early-onset T2DM group was lower than that in the late-onset T2DM group (11.07 ± 3.05 vs. 12.40 ± 2.72 pg/mL,p= 0.048) and was positively correlated with fasting C-peptide, while negatively correlated with HbA1c and fasting glucagon (pall < 0.05).ConclusionsPatients with early-onset T2DM showed inhibition of conversion from DHEA to testosterone, which may attribute to the low level of 3β-HSD and high blood glucose in these patients. |
The formalization of biological systems using computational modelling approaches as an alternative to mathematical-based methods has recently received much interest because computational models provide a deeper mechanistic understanding of biological systems. In particular, formal verification, complementary approach to standard computational techniques such as simulation, is used to validate the system correctness and obtain critical information about system behaviour. In this study, we survey the most frequently used computational modelling approaches and formal verification techniques for computational biology. We compare a number of verification tools and software suites used to analyse biological systems and biochemical networks, and to verify a wide range of biological properties. For users who have no expertise in formal verification, we present a novel methodology that allows them to easily apply formal verification techniques to analyse their biological or biochemical system of interest. |
BackgroundThere is a vast amount of evidence-based medicine research on the major depressive disorder (MDD) available in the literature, however, no studies on the overall performance, productivity and impact of such research have been published to date. This study explored and mapped the research outputs of MDD-related systematic reviews and meta-analyses (SR/MA) from a bibliometric perspective.MethodsRelevant data were retrieved with search terms on MDD, systematic review and meta-analysis.ResultsA total of 4,870 papers with 365,402 citations published from 1983 to 2022 were included in the analysis. The publication output has grown steadily over time with the most publications originating from the USA (1,020; 20.94%), the UK (516; 10.60%) and China (448; 9.20%). The research collaborations between countries were most frequent between the USA and UK (266; 5.46%). Journal of Affective Disorders (379; 7.78%) was the most productive journal, while Cuijpers P was the most productive author (121; 2.48%), and University of Toronto (569; 11.78%) was the most productive institution. The top 10 most cited articles on MDD-related SR/MA had citations ranging from 1,806 to 3,448. The high-frequency keywords were mainly clustered into four themes, including psychiatric comorbidities, clinical trials, treatment, and brain stimulation in MDD.ConclusionThe rapid increase in the number of SR/MA of MDD in recent years highlights the importance of this research field. Psychiatric comorbidities, clinical interventions, and treatment of MDD have been identified as hot topics, while biological mechanisms in MDD are likely to be an emerging research priority. |
There was a global shortage of nab-paclitaxel (AbraxaneⓇ), a major antineoplastic agent, for a long period (from October 2021 to June 2022) because of manufacturing problems. Japan was one of the first affected countries by the depletion, and the medical institutes started to save the use of the drug in August 2021; numerous patients with gastric, breast, and lung cancer who potentially could receive benefits failed to be treated with the antineoplastic agent; thus, they opted for alternative treatments. Meanwhile, the hospitals in the United States and some countries continued to consume nab-paclitaxel at a regular pace as usual and then the worldwide depletion occurred in October 2021. Early communications about the drug shortage between authorities worldwide might have soothed the depletion; effective platforms for global information sharing would be necessary in order to secure the access to anticancer agents. |
There are numerous contagious diseases caused by pathogenic microorganisms, including bacteria, viruses, fungi, and parasites, that have the propensity to culminate in fatal consequences. A communicable disease is an illness caused by a contagion agent or its toxins and spread directly or indirectly to a susceptible animal or human host by an infected person, animal, vector, or immaterial environment. Human immunodeficiency virus (HIV) infection, hepatitis A, B, and C, and measles are all examples of communicable diseases. Acquired immunodeficiency syndrome (AIDS) is a communicable disease caused by HIV infection that has become the most severe issue facing humanity. The research work in this paper is to numerically explore a mathematical model and demonstrate the dynamics of HIV/AIDS disease transmission using a continuous Galerkin–Petrov time discretization of a higher-order scheme, specifically the cGP(2)-scheme. Depict a graphical and tabular comparison between the outcomes of the mentioned scheme and those obtained through other classical schemes that exist in the literature. Further, a comparison is performed relative to the well-known fourth-order Ruge–Kutta (RK4) method with different step sizes. By contrast, the suggested approach provided more accurate results with a larger step size than RK4 with a smaller step size. After validation and confirmation of the suggested scheme and code, we implement the method to the extended model by introducing a treatment rate and show the impact of various non-linear source terms for the generation of new cells. We also determined the basic reproduction number and use the Routh-Hurwitz criterion to assess the stability of disease-free and unique endemic equilibrium states of the HIV model. |
The evolution of behaviour on islands is a pervasive phenomenon that contributed to Darwin's theory of natural selection. Island populations frequently show increased boldness and exploration compared with their mainland counterparts. Despite the generality of this pattern, the genetic basis of island-associated behaviours remains a mystery. To address this gap in knowledge, we genetically dissected behaviour in 613 F2s generated by crossing inbred mouse strains from Gough Island (where they live without predators or human commensals) and a mainland conspecific. We used open field and light/dark box tests to measure seven behaviours related to boldness and exploration in juveniles and adults. Across all assays, we identified a total of 41 quantitative trait loci (QTL) influencing boldness and exploration. QTL have moderate effects and are often unique to specific behaviours or ages. Function-valued trait mapping revealed changes in estimated effects of QTL during assays, providing a rare dynamic window into the genetics of behaviour often missed by standard approaches. The genomic locations of QTL are distinct from those found in laboratory strains of mice, indicating different genetic paths to the evolution of similar behaviours. We combine our mapping results with extensive phenotypic and genetic information available for laboratory mice to nominate candidate genes for the evolution of behaviour on islands. |
Intracranial germ cell tumors are uncommon brain tumors; germinoma is the most common tumor in children and young adults, and the most common regions affected are pineal gland and suprasellar region. Germinomas of the suprasellar region are accompanied by endocrine alterations, with adipsia being a rare presentation. Here, we present the case of a patient with an extensive intracranial germinoma whose initial presentation was adipsia, without any other endocrinological alteration, with development of severe hypernatremia and unusual manifestations derived from it, such as deep vein thrombosis, myopathy with rhabdomyolysis, and neurological axonal damage. |
BackgroundThis study aimed to develop a unique online infection prevention and control (IPC) training on Covid-19 for healthcare workers in psychiatric institutes in Japan and to examine its efficacy based on its impact on the knowledge, attitude, and confidence about IPC for Covid-19 among the healthcare workers.MethodThis quasi-experimental study was conducted using online training on Covid-19 IPC for healthcare workers in various psychiatric institutes from April 2021 to March 2022. An online training video on Covid-19 IPC was developed. Voluntary healthcare workers in psychiatric institutes located in five prefectures in Japan were recruited to participate in this training. The participants then completed 30 min of online training and surveys about knowledge, attitude, and confidence were conducted pre, post, and three months after the training. The video training and surveys were contextually validated by the experts, but not by any previous study.ResultsA total of 224 participants were included, of which 108 (54.0%) were men. The mean (standard deviation (SD)) age and the mean occupational experience were 47.4 (9.5) and 18.0 (12.6) years, respectively. Among the participants, 190 (84.8%) completed the post-training, and 131 (58.5%) completed the three-month-later training surveys. The total score on the quizzes in the post-training (+ 31.1%, SD 15.7, p-value < 0.01) and three-month-later training (+ 14.9%, SD 16.8, p-value < 0.01) surveys had significantly increased from that in the pre-training survey. In contrast, the total score in the three-month-later training had significantly decreased from that in the post-training survey (-16.1%, SD 16.7, p-value < 0.01).ConclusionThirty minutes of online training about IPC for Covid-19 had improved knowledge, confidence, and attitude among psychiatric healthcare workers. Regular online training would help in preventing the transmission or formation of clusters of Covid-19 in psychiatric healthcare institutes.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12888-023-04826-5. |
BackgroundRNA 5-methylcytosine (m5C) modification plays critical roles in the pathogenesis of various tumors. However, the function and molecular mechanism of RNA m5C modification in tumor drug resistance remain unclear.MethodsThe correlation between RNA m5C methylation, m5C writer NOP2/Sun RNA methyltransferase family member 2 (NSUN2) and EGFR-TKIs resistance was determined in non-small-cell lung cancer (NSCLC) cell lines and patient samples. The effects of NSUN2 on EGFR-TKIs resistance were investigated by gain- and loss-of-function assaysin vitroandin vivo. RNA-sequencing (RNA-seq), RNA bisulfite sequencing (RNA-BisSeq) and m5C methylated RNA immunoprecipitation-qPCR (MeRIP-qPCR) were performed to identify the target gene of NSUN2 involved in EGFR-TKIs resistance. Furthermore, the regulatory mechanism of NSUN2 modulating the target gene expression was investigated by functional rescue and puromycin incorporation assays.ResultsRNA m5C hypermethylation and NSUN2 were significantly correlated with intrinsic resistance to EGFR-TKIs. Overexpression of NSUN2 resulted in gefitinib resistance and tumor recurrence, while genetic inhibition of NSUN2 led to tumor regression and overcame intrinsic resistance to gefitinibin vitroandin vivo. Integrated RNA-seq and m5C-BisSeq analyses identified quiescin sulfhydryl oxidase 1 (QSOX1) as a potential target of aberrant m5C modification. NSUN2 methylated QSOX1 coding sequence region, leading to enhanced QSOX1 translation through m5C reader Y-box binding protein 1 (YBX1).ConclusionsOur study reveals a critical function of aberrant RNA m5C modification via the NSUN2-YBX1-QSOX1 axis in mediating intrinsic resistance to gefitinib in EGFR-mutant NSCLC.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12943-023-01780-4. |
BackgroundDifferent histological growth patterns (HGP) describing the tumor-to-liver interface have been described in colorectal liver metastases and have been associated with a strong prognostic value. However, HGP of peritoneal metastases (PM) of colorectal cancer (CRC) have not yet been described. Our objective was to determine whether distinct HGP can be identified in PMCRC and to evaluate their potential prognostic value in these patients.MethodsThis retrospective study included 38 patients who underwent curative-intent surgery for PMCRC between July 2012 and March 2019, with PCI≤6, and who had not received preoperative chemotherapy. In each patient, the tumor-to-peritoneum interface was evaluated in the excised peritoneal nodules. The association between HGP and postoperative survival was analyzed by using the Kaplan–Meier method.ResultsTwo distinct HGP were identified: apushing-type (P-HGP), characterized by a fibrous rim separating the PM and peritoneum, and aninfiltrating-type (I-HGP), characterized by focal penetration of tumor cells into the surrounding peritoneal lining without a fibrous rim. Fifteen patients had dominant P-HGP, and 23 patients had dominant I-HGP. Patients with dominant P-HGP (>50% tumor-peritoneum interface) had a significantly better DFS (30 months) than those with P-HGP <50% (9 months;p= 0.029). Patients with a P-HGP dominance >60% had better OS (131 months) than those with P-HGP <60% (41 months;p= 0.044).ConclusionsThis is the first description of two distinct, reproducible HGP in PMCRC. The dominant P-HGP is associated with a favorable prognosis in patients with PMCRC, compared with I-HGP, suggesting that this parameter could ultimately represent a new prognostic biomarker. |
Medical devices provide important infrastructural support in modern healthcare systems. However, in low- and middle-income countries (LMICs), inadequate maintenance and management of devices due to a shortage of healthcare personnel (not only doctors and nurses but also other professionals including biomedical engineers [BMEs]) has resulted in inefficient and weak healthcare systems. High-income countries, including Japan, have resolved these problems by developing human resources and technologies to maintain and manage these systems. In this paper, we discuss the possibility of mitigating these problems in LMICs through human resource development and technology, based on lessons from Japan’s experience. The problem of medical device management in LMICs stems from the fact that there are few professionals, such as BMEs, in charge of the management of medical devices and that clinical engineering departments in charge of device management have not been established. Since the 1980s, Japan has introduced a licensing system for BMEs, establishing operational guidelines to clarify their responsibilities within hospitals and using technology to utilize data and reduce workloads. Nevertheless, workload problems and high costs required to introduce computerized management systems persist. Moreover, it would be difficult to implement the same measures as those adopted in Japan in LMICs where there is an overwhelming shortage of medical personnel. It may be necessary to further reduce workloads for data entry and device management; use up-to-date, inexpensive, and user-friendly technology; and train non-BME personnel to operate and maintain equipment. |
Although a low-grade vascular tumor, Kaposi sarcoma (KS) can have mucosal, and visceral involvement. Additionally, disfiguring disseminated lesions can be seen in patients with human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS). KS may cause lymphatic obstruction leading to chronic lymphedema that further contributes to progressive cutaneous hypertrophy and severe disfigurement in the form of non-filarial elephantiasis nostras verrucosa (ENV).This report highlights a case of a 33-year-old male with AIDS who presented in acute respiratory distress with bilateral lower extremity nodular lesions. We confirmed a diagnosis of KS with overlying ENV via a multi-disciplinary approach. Collaboratively, we optimized our patient and observed adequate treatment response and overall improvement in clinical status.Our report emphasizes the importance of a multi-disciplinary approach in recognizing a rare presentation of ENV. Recognition of the disease and understanding the extent of the disease are crucial in preventing irreversible disease progression and allowing for maximum response. |
AbstractSepsis is a dysregulated host response to infection that results in life-threatening organ dysfunction. Virtually every body system can be affected by this syndrome to greater or lesser extents. Gene transcription and downstream pathways are either up- or downregulated, albeit with considerable fluctuation over the course of the patient’s illness. This multi-system complexity contributes to a pathophysiology that remains to be fully elucidated. Consequentially, little progress has been made to date in developing new outcome-improving therapeutics. Endocrine alterations are well characterised in sepsis with variations in circulating blood levels and/or receptor resistance. However, little attention has been paid to an integrated view of how these hormonal changes impact upon the development of organ dysfunction and recovery. Here, we present a narrative review describing the impact of the altered endocrine system on mitochondrial dysfunction and immune suppression, two interlinked and key aspects of sepsis pathophysiology. |
Despite routine use of DNA-hypomethylating agents (HMAs) in AML/MDS therapy, their mechanisms of action are not yet unraveled. Pleiotropic effects of HMAs include global methylome and transcriptome changes. We asked whether in blasts and T-cells from AML patients HMA-induced in vivo demethylation and remethylation occur randomly or non-randomly, and whether gene demethylation is associated with gene induction. Peripheral blood AML blasts from patients receiving decitabine (20 mg/m2day 1–5) were serially isolated for methylome analyses (days 0, 8 and 15,n= 28) and methylome-plus-transcriptome analyses (days 0 and 8,n= 23), respectively. T-cells were isolated for methylome analyses (days 0 and 8;n= 16). We noted massive, non-random demethylation at day 8, which was variable between patients. In contrast, T-cells disclosed a thousand-fold lesser, random demethylation, indicating selectivity of the demethylation for the malignant blasts. The integrative analysis of DNA demethylation and transcript induction revealed 87 genes displaying a significant inverse correlation, e.g. the tumor suppressor geneIFI27, whose derepression was validated in two AML cell lines. These results support HMA-induced, non-random early in vivo demethylation events in AML blasts associated with gene induction. Larger patient cohorts are needed to determine whether a demethylation signature may be predictive for response to this treatment. |
Chromosomal rearrangements of the humanKMT2A/MLLgene are associated withde novoas well as therapy-induced infant, pediatric, and adult acute leukemias. Here, we present the data obtained from 3401 acute leukemia patients that have been analyzed between 2003 and 2022. Genomic breakpoints within theKMT2Agene and the involved translocation partner genes (TPGs) andKMT2A-partial tandem duplications (PTDs) were determined. Including the published data from the literature, a total of 107 in-frameKMT2Agene fusions have been identified so far. Further 16 rearrangements were out-of-frame fusions, 18 patients had no partner gene fused to 5’-KMT2A, two patients had a 5’-KMT2Adeletion, and oneETV6::RUNX1patient had anKMT2Ainsertion at the breakpoint. The seven most frequent TPGs and PTDs account for more than 90% of all recombinations of theKMT2A, 37 occur recurrently and 63 were identified so far only once. This study provides a comprehensive analysis of theKMT2Arecombinome in acute leukemia patients. Besides the scientific gain of information, genomic breakpoint sequences of these patients were used to monitor minimal residual disease (MRD). Thus, this work may be directly translated from the bench to the bedside of patients and meet the clinical needs to improve patient survival. |
Hepatocellular carcinoma (HCC) is a malignancy with one of the worst prognoses. Long noncoding RNAs (lncRNAs) may be important in cancer development and may serve as new biomarkers for the diagnosis and treatment of various tumors, according to mounting research. The purpose of this study was to investigate the expression of INKA2-AS1 and clinical importance in HCC patients. The TCGA database was used to obtain the human tumor samples, while the TCGA and GTEx databases were used to gather the human normal samples. We screened differentially expressed genes (DEGs) between HCC and nontumor tissues. Investigations were made into the statistical significance and clinical significance of INKA2-AS1 expression. A single-sample gene set enrichment analysis (ssGSEA) was used to examine potential relationships between immune cell infiltration and INKA2-AS1 expression. In this investigation, we found that HCC specimens had considerably greater levels of INKA2-AS1 expression than nontumor specimens. When utilizing the TCGA datasets and the GTEx database, high INKA2-AS1 expression showed an AUC value for HCC of 0.817 (95% confidence interval: 0.779 to 0.855). Pan-cancer assays revealed that numerous tumor types had dysregulated levels of INKA2-AS1. Gender, histologic grade, and pathologic stage were all substantially correlated with high INKA2-AS1 expression. A survival study indicated that HCC patients with high INKA2-AS1 expression have shorter OS, DSS, and PFI than those with low INKA2-AS1 expression. Multivariate analysis indicated that INKA2-AS1 expression was an independent prognostic factor for OS of patients with HCC. According to immune analysis, the expression of INKA2-AS1 was favorably correlated with T helper cells, Th2 cells, macrophages, TFH, and NK CD56bright cells and negatively correlated with Th17 cells, pDC, cytotoxic cells, DC, Treg, Tgd, and Tcm. The results of this study collectively suggest that INKA2-AS1 has the potential to be a novel biomarker for predicting the prognosis of HCC patients as well as a significant immune response regulator in HCC. |
AbstractBackgroundGalectin‐9 and myeloid‐derived suppressor cells (MDSCs) have an important role in tumors, but their clinical values in chronic lymphocytic leukemia (CLL) have not been fully elucidated. This study aimed to analyze the prognosis values of Galectin‐9 and MDSCs in CLL.MethodsThe concentrations of Galectin‐9, argininase‐1, and inducible nitric oxide synthase in serum were detected by enzyme‐linked immune sorbent assay. The expression of Tim‐3 protein in peripheral blood mononuclear cell was detected by Western blot. Flow cytometry was used to analyze the percentages of Tim‐3 on T‐cells (CD3+T, CD4+T, and CD8+T cells) and MDSCs.ResultsOur results showed that Galectin‐9 and MDSCs significantly increased in CLL patients and were closely related to the disease progression. Patient's receiver operating characteristic, progression‐free survival, and Cox regression analysis showed that Galectin9 and MDSCs were poor prognostic factors of CLL.ConclusionGalectin‐9 and MDSCs were associated with clinical progression and could be important prognostic indicators for CLL. |
BackgroundIschemic stroke with active cancer is thought to have a unique mechanism compared to conventional stroke etiologies. There is no gold standard guideline for secondary prevention in patients with cancer-related stroke, hence, adequate type of antithrombotic agent for treatment is controversial.MethodsSubjects who were enrolled in National Health Insurance System Customized Research data during the period between 2010 and 2015 were observed until 2019. Subject diagnosed with ischemic stroke within six months before and 12 months after a cancer diagnosis was defined as cancer-related stroke patient. To solve immeasurable time bias, the drug exposure evaluation was divided into daily units, and each person-day was classified as four groups: antiplatelet, anticoagulant, both types, and unexposed to antithrombotic drugs. To investigate bleeding risk and mortality, Cox proportional hazards regression model with time-dependent covariates were used.ResultsTwo thousand two hundred eighty-five subjects with cancer-related stroke were followed and analyzed. A group with anticoagulation showed high estimated hazard ratios (HRs) of all bleeding events compared to a group with antiplatelet (major bleeding HR, 1.35; 95% confidence interval [CI], 1.20–1.52;p< 0.001). And the result was also similar in the combination group (major bleeding HR, 1.54; 95% CI, 1.13–2.09;p= 0.006). The combination group also showed increased mortality HR compared to antiplatelet group (HR, 1.72; 95% CI, 1.47–2.00;p< 0.001).ConclusionsBleeding risk increased in the anticoagulant-exposed group compared to antiplatelet-exposed group in cancer-related stroke patients. Thus, this result should be considered when selecting a secondary prevention drug.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12883-023-03208-4. |
AbstractAssessing plant diversity during community succession based on plant trait and phylogenetic features within a community (alpha scale) and among communities (beta scale) could improve our understanding of community succession mechanism. However, whether changes of community functional diversity at alpha and beta scale are structured by different traits and whether integrating plant traits and phylogeny can enhance the ability in detecting diversity pattern have not been studied in detail. Thirty plots representing different successional stages were established on the Loess Plateau of China and 15 functional traits were measured for all coexisting species. We first analyzed the functional alpha and beta diversity along succession by decomposing species trait into alpha and beta components and then integrated key traits with phylogenetic information to explore their roles in shaping species turnover during community succession. We found that functional alpha diversity increased along successional stages and was structured by morphological traits, while beta diversity decreased during succession and was more structured by stoichiometry traits. Phylogenetic alpha diversity showed congruent pattern with functional alpha diversity because of phylogenetic conservation of trait alpha components (variation within community), while beta diversity showed incongruent pattern due to phylogenetic randomness of trait beta components (variation among communities). Furthermore, only integrating relatively conserved traits (plant height and seed mass) and phylogenetic information can raise the detecting ability in assessing diversity change. Overall, our results reveal the increasing niche differentiation within community and functional convergence among communities with succession process, indicating the importance of matching traits with scale in studying community functional diversity and the asymmetry of traits and phylogeny in reflecting species ecological differences under long‐term selection pressures. |
AbstractThe second polar body (PB2) transfer in assisted reproductive technology is regarded as the most promising mitochondrial replacement scheme for preventing the mitochondrial disease inheritance owing to its less mitochondrial carryover and stronger operability. However, the mitochondrial carryover was still detectable in the reconstructed oocyte in conventional second polar body transfer scheme. Moreover, the delayed operating time would increase the second polar body DNA damage. In this study, we established a spindle‐protrusion‐retained second polar body separation technique, which allowed us to perform earlier second polar body transfer to avoid DNA damage accumulation. We could also locate the fusion site after the transfer through the spindle protrusion. Then, we further eliminated the mitochondrial carryover in the reconstructed oocytes through a physically based residue removal method. The results showed that our scheme could produce a nearly normal proportion of normal‐karyotype blastocysts with further reduced mitochondrial carryover, both in mice and humans. Additionally, we also obtained mouse embryonic stem cells and healthy live‐born mice with almost undetectable mitochondrial carryover. These findings indicate that our improvement in the second polar body transfer is conducive to the development and further mitochondria carryover elimination of reconstructed embryos, which provides a valuable choice for future clinical applications of mitochondrial replacement. |
Introduction:The evaluation of hospital performance often receives great attention. Hospitals refer to patient ratings to undertake quality-improvement activities. However, little is known about the factors that contribute the most to these patient ratings. This study aimed to investigate the association of relevant factors, such as doctors’ and nurses’ performance, with patients’ ratings of hospitals, using the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPSⓇ) questionnaire.Methods:A cross-sectional study was conducted among patients who were hospitalized in Japan, from January 2020 to September 2021. Patients’ hospital rating scale scores between 0 and 10 were collected and dichotomized. A score of 8 or higher was defined as a high rating. A multivariate logistic regression analysis was conducted to investigate the association between patients’ ratings of the hospital and other items in the HCAHPSⓇquestionnaire.Results:The frequency of patients’ high and poor hospital ratings were 207 (69%) and 93 (31%), respectively, of 300 respondents. A significant association was observed for the patient’s age (adjusted odds ratio (AOR): 1.02; 95% confidence interval (CI): 1.00-1.04), doctor’s communication (AOR: 10.47; 95% CI: 3.17-34.58), and discharge planning (AOR: 3.53; 95% CI: 1.96-6.36) with a positive patient rating of the hospital.Conclusions:An emphasis on doctor communication and discharge planning is essential in improving patients’ ratings of hospitals. Further research is needed to determine the factors that contribute the most to patients’ ratings of hospitals. |
BackgroundTo evaluate the clinical efficacy of percutaneous biliary drainage (PBD) combined with125I seed strand brachytherapy (ISSB) for the treatment of hilar cholangiocarcinoma (HCCA).MethodsThe clinical data of 64 patients with HCCA (median age 62.5, male 29, female 35) treated in our department from April 2017 to April 2021 were retrospectively analyzed. Thirty-four patients in the experimental group (EG) were treated with PBD combined with ISSB, while 30 patients in the control group (CG) were treated with PBD alone. The primary study endpoints were technical success, clinical success and the 2-month local tumor control (LTC) rate. Secondary endpoints were early/late complications, median progression-free survival (mPFS) and overall survival (mOS).ResultsThe technical and clinical success in the EG and CG showed no significant differences (100 vs. 100%, 94.1 vs. 93.3%,P> 0.05). Both early and late complications showed no significant differences between the two groups (P> 0.05). The 2-month LTC rates were significantly better in the EG versus the CG (94.1% vs. 26.7%, 157.7 ± 115.3 vs. 478.1 ± 235.3 U/ml), respectively (P< 0.05). The mPFS and mOS were 4.3 (95% CI 3.9–4.7) months and 2.8 (95% CI 2.5–3.1) months and 13.5 (95% CI 10.7–16.3) months and 8.8 (95% CI 7.8–9.8) months, respectively, with significant differences (P< 0.05).ConclusionPBD combined with ISSB is a safe and effective treatment for HCCA that can inhibit local tumors and prolong PFS and OS. |
PurposeTo evaluate the feasibility and clarify the appropriate indications for extubation immediately after single-stage laryngotracheal reconstruction (SS-LTR) in pediatric subglottic stenosis (SGS).MethodsA retrospective study was performed from July 2017 to July 2022. All patients underwent SS-LTR with anterior costal cartilage graft. Information such as demographics, comorbidities, history of intubation or tracheostomy, Classification and grading of airway stenosis, the operation-specific decannulation rate and overall decannulation rate were analyzed.ResultsTwenty-two patients with simple SGS were identified. The median age at SS-LTR was 19 months (IQR = 18.5 months). Fourteen patients (63.6%) were intubated prior to the presentation of symptoms. Fourteen patients (63.6%) required preoperative tracheostomy to maintain a secure airway. Eight patients (36.4%) had congenital SGS, 10 patients (45.5%) had acquired SGS, and 4 patients (18.2%) had mixed SGS. Three patients had Grade II stenosis. Nineteen patients had Grade III stenosis. Comorbidities were found in 10 patients (45.5%). Major comorbidities were pneumonia. Congenital airway anomalies were found in 6 patients (27.3%). After anesthesia, all 22 patients were successfully extubated and returned to the general ward. Twenty patients had a satisfactory airway after SS-LTR. Two patients required reintubation or tracheostomy after operation. Operation-specific decannulation rate was 90.9%. The overall decannulation rate is 100%.ConclusionSS-LTR with anterior costal cartilage graft is an effective method to treat simple SGS ranging from Grades I to III in children. Extubation immediately after surgery is safe and feasible. |
BackgroundPolycystic ovary syndrome (PCOS) is underdiagnosed, but factors associated with women’s report of diagnosis are not well-understood, particularly social determinants of health. Therefore, in a population-based cohort, we compared the characteristics of women with self-reported PCOS vs. women who have unrecognized PCOS vs. women without PCOS.MethodsWe performed a secondary data analysis of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, a population-based, prospective cohort of Black and White women. Participants were women (n = 2028) who responded to the question, “Did a doctor or nurse ever tell you that you had polycystic ovarian syndrome or polycystic ovarian disease?” at the year 15 examination. Women who answered “yes” were defined as having self-reported PCOS. Women who answered “no or not sure” were defined as having unrecognized PCOS if they also had irregular menses and hyperandrogenemia between 20 and 30 years of age. Exposures of interest included social determinants of health, symptoms including irregular menses and hirsutism, and comorbid conditions.ResultsForty-three (2.1%) of women had self-reported PCOS, 135 (6.7%) had unrecognized PCOS, and 1850 (91%) women were without PCOS. In logistic regression models adjusting for age, race, and center, women with self-reported PCOS were more likely to have obesity (OR 1.83, 95% CI 1.22, 2.75) and diabetes (OR 2.37, 95% CI 1.05, 5.33) compared to women without PCOS. Women with unrecognized PCOS were more likely to have hypertension (OR 1.68, 95% CI 1.03, 2.74) and food insecurity (OR 1.94, 95% CI 1.25, 3.01) compared to women without PCOS.ConclusionsUnrecognized PCOS is common. Self-report of PCOS is not associated with access to healthcare. Women who report PCOS are more often obese and comorbidities may contribute to recognition of PCOS.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12905-023-02394-0. |
BackgroundOral health has a direct impact on health-related quality of life (HRQoL). Hence, general health and oral health cannot be separated. Pediatricians play a pivotal role in providing primary care for infants and are the first to interact with them since birth. Therefore, the aim of this study was to evaluate the knowledge, perceptions, and behavior of Syrian pediatricians regarding children’s oral health.MethodsThis was a cross-sectional study. The questionnaire consisted of six main sections and required answers regarding demographic characteristics, knowledge, behavior, perceptions, and training received in oral health. The association between categorical variables was tested with Pearson’s chi-square tests and Fishers exact tests using SPSS ver. 23.ResultsThe response rate was 43.12% (229/531). Most of the participants (64.02%) got a poor level of knowledge and no significant association was found between knowledge level and years of experience (p= 0.270). The majority of the participants (99.13%) perceived that diet, bacteria, and sugar exposure time are the etiological factors of dental caries. The overwhelming majority of the participants (98.25%) acknowledged the need for further oral health training during residency.ConclusionsMost pediatricians reported a poor level of knowledge. It is recommended to update the postgraduate and residency curriculum to equip pediatricians with adequate knowledge regarding children’s oral health. |
Background:Rheumatoid arthritis (RA) joint inflammation severely affects joint function and quality of life in patients and leads to joint deformities and limb disability. The non-steroidal anti-inflammatory drugs used in the treatment of RA do not fully control the progression of joint inflammation and bone destruction and have notable adverse reactions. Traditional Chinese medicine formula JuanBiQiangGu Granules (JBQG) are commonly used for the treatment of RA inflammation and delay of bone destruction, but has not been evaluated through high-quality clinical studies. There is a pressing need for well-designed, randomized, parallel, controlled clinical studies to evaluate the exact effect of JBQG on RA joint inflammation and improvement of patient quality of life.Methods:This is a randomized, parallel, controlled clinical study in which 144 patients with rheumatoid arthritis who met the inclusion criteria were randomly assigned to 2 groups in a 1:1 ratio. The JBQG group received methotrexate 7.5 mg qw and JBQG granules 8 mg tid, while the MTX group received methotrexate 7.5 mg qw. The endpoint was 12 weeks after treatment. Relevant indices at baseline, 4 weeks, 8 weeks, and 12 weeks after treatment were observed and recorded, and DAS28-ESR, HAQ-DI, and Sharp scores were recorded for each patient. Blood samples were collected to test for CRP, ESR, TNF-α, IL-1β, IL-6, IL-17, and INF-γ, and adverse reactions and liver and kidney function (AST, ALT, Cr, BUN) were recorded for safety assessment. After 12 weeks of treatment, the effect of JBQG granules on disease activity, improvement in bone damage, and patient quality of life scores and safety in RA patients were evaluated.Results:A total of 144 subjects completed treatment (71 in the JBQG group and 73 in the MTX group) and were included in the analysis. At baseline, there were no significant differences between the groups in terms of the observed indicators (p> 0.05). After treatment, 76.06% of patients in the JBQG group had DAS28-ESR levels below or equal to Low, including 45.07% in Remission and 5.63% in High, compared to 53.1% in the MTX group below or equal to Low, 12.33% in Remission, and 17.81% in High. CRP was significantly reduced (8.54 ± 5.87 vs. 11.86 ± 7.92,p< 0.05,p= 0.005), ESR was significantly reduced (15.1 ± 6.11 vs. 21.96 ± 9.19,p< 0.0001), TNF-α was significantly reduced (1.44 ± 0.83 vs. 1.85 ± 1.07,p< 0.05,p= 0.011), IL-17 was significantly reduced (0.53 ± 0.33 vs. 0.71 ± 0.38,p< 0.05,p= 0.004), and INF-γ was significantly reduced (3.2 ± 1.51 vs. 3.89 ± 1.77,p< 0.05,p= 0.014). The median (IQR) OPG in the JBQG group was 2.54 (2.21–3.01), significantly higher than in the MTX group 2.06 (1.81–2.32),p< 0.0001), and the median (IQR)β-CTX in the JBQG group was 0.4 (0.32–0.43), significantly lower than in the MTX group 0.55 (0.47–0.67),p< 0.0001). The median (IQR) VSA scores were 2 (1–3), a decrease from 3 (2–4) in the MTX group (p< 0.0001). The median (IQR) Sharp scores were 1 (1–2), a decrease from 2 (1–2) in the MTX group, but the difference was not statistically significant (p> 0.05,p= 0.28). The median (IQR) HAQ-DI scores were 11 (8–16), significantly lower than in the MTX group 26 (16–30) (p< 0.0001). The median (IQR) AST in the JBQG group was 16 (12–20), with a significant difference compared to the MTX group 19 (13–25) (p< 0.01,p= 0.004); the median (IQR) ALT in the JBQG group was 14 (10–18), with a significant difference compared to the MTX group 16 (11–22.5) (p< 0.05,p= 0.015). There were no statistically significant differences in Cr or BUN (p> 0.05).Conclusion:JuanBiQiangGu Granules can be used to treat patients with rheumatoid arthritis, alleviate joint inflammation, reduce the incidence of adverse reactions to methotrexate, and has good safety.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/index.html; identifier: ChiCTR2100046373. |
Purpose:To determine the anatomic and visual outcomes of pars plana vitrectomy for uncomplicated, primary macula-off rhegmatogenous retinal detachment (RRD) with and without internal limiting membrane (ILM) peeling.Methods:This retrospective chart review comprised 129 patients with uncomplicated, primary macula-off RRD presenting between January 1, 2016, and May 31, 2021. Thirty-six patients (27.9%) had ILM peeling and 93 (72.0%) did not. The primary outcome was the rate of recurrent RRD. Secondary outcomes included preoperative and postoperative best-corrected visual acuity (BCVA), epiretinal membrane (ERM) formation, and macular thickness.Results:No significant difference was found in the risk for recurrent RRD between patients who had ILM peeling and those who did not (2.8% [1/36] and 5.4% [5/93], respectively) (P= 1.00). The final postoperative BCVA was better in eyes that did not have ILM peeling (P<.001). No ERM occurred in the group with ILM peeling, whereas ERM occurred in 27 patients (29.0%) who did not have ILM peeling. The temporal macular retina was thinner in eyes in which ILM peeling was performed.Conclusions:The risk for recurrent RRD was not statistically lower in eyes having ILM peeling of the macula in uncomplicated, primary macula-off RRD. Despite a reduction in postoperative ERM formation, eyes having macular ILM peeling had worse postoperative VA. |
AbstractSmall non-coding RNAs (sRNAs) are key regulators of post-transcriptional gene expression in bacteria. Despite the identification of hundreds of bacterial sRNAs, their roles on bacterial physiology and virulence remain largely unknown, as is the case of bacteria of theBurkholderia cepaciacomplex (Bcc). Bcc is a group of opportunistic pathogens with relatively large genomes that can cause lethal lung infections amongst cystic fibrosis (CF) patients. To characterise sRNAs expressed by Bcc bacteria when infecting a host, the nematodeCaenorhabditis eleganswas used as an infection model by the epidemic CF strainB. cenocepaciaJ2315. A total of 108 new and 31 previously described sRNAs with a predicted Rho independent terminator were identified, most of them located on chromosome 1. RIT11b, a sRNA downregulated underC. elegansinfection conditions, was shown to directly affectB. cenocepaciavirulence, biofilm formation, and swimming motility. RIT11b overexpression reduced the expression of the direct targetsdusAandpyrC, involved in biofilm formation, epithelial cell adherence, and chronic infections in other organisms. The in vitro direct interaction of RIT11b with thedusAandpyrCmessengers was demonstrated by electrophoretic mobility shift assays. To the best of our knowledge this is the first report on the functional characterization of a sRNA directly involved inB. cenocepaciavirulence.Key points• 139 sRNAs expressed by B. cenocepacia during C. elegans infection were identified• The sRNA RIT11b affects B. cenocepacia virulence, biofilm formation, and motility• RIT11b directly binds to and regulates dusA and pyrC mRNAsSupplementary InformationThe online version contains supplementary material available at 10.1007/s00253-023-12530-3. |
BackgroundProlonged exposure to HIV and anti-retroviral therapy (ART) has been linked with endothelial cell activation which subsequently predisposes people living with HIV (PLWH) to cardiovascular diseases. Serum biomarkers of endothelial cell activation such as E-Selectin and endothelial cell-specific molecule-1 (ESM-1) could aid in early detection of PLWH at a risk of cardiovascular diseases. However, there is a paucity of data on these biomarkers like E-selectin and endothelial cell-specific molecule-1 (ESM-1) among PLWH on long term ART (≥ 10 years) in Uganda. The aim of this study is to determine the serum levels of these biomarkers in this population.MethodsThis was a cross-sectional study where we randomly sampled 73 stored serum samples of PLWH who were enrolled in the Infectious Diseases Institute (IDI) ART long term (ALT cohort). We measured serum levels of E-selectin and ESM-1 by ELISA. Data was summarized using median and interquartile range. Inferential statistics were performed to determine predictors of elevated levels of E-selectin.ResultsOf the 73 samples analyzed, 38 (52.1%) were from female participants. The mean age was 54 ± 9.0 years. Twenty participants (27.4%) had a history of smoking while 52 (71.2%) had a history of alcohol intake. Twenty-five (34.3%) of the participants were overweight whereas 4 (5.6%) were obese. Fifty-four (74%) had an undetectable viral load (≤ 0 copies/ml) and the mean duration of ART at the time of sampling (2014/2015) was 10.4 ± 0.4 years. While serum levels of ESM-1 were not detectable in any of our samples, the median E-selectin levels was 147.6 μm/L ranging from 8.44 μm/L and 1,979.36 μm/L. Sixty-seven participants (91.8%) had elevated levels of E-selectin (> 39 μm/L). CD4 count > 500 cells/µl compared to lower counts was a predictor of elevated levels of E-Selectin (adjusted Odd Ratio 12.5, 95% CI (1.03 — 149.95, p < 0.05).ConclusionsThe majority (91.8%) of PLWH on long term ART had elevated levels of E-selectin. Having high CD4 count (> 500 cells/µl) was predictive of elevated levels of E-Selectin. Future work should longitudinally assess the trend of levels of E-selectin and ESM-1 while assessing for cardiovascular diseases endpoint.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12981-023-00519-x. |
IntroductionModern consciousness research has developed diagnostic tests to improve the diagnostic accuracy of different states of consciousness via electroencephalography (EEG)-based mental motor imagery (MI), which is still challenging and lacks a consensus on how to best analyse MI EEG-data. An optimally designed and analyzed paradigm must detect command-following in all healthy individuals, before it can be applied in patients, e.g., for the diagnosis of disorders of consciousness (DOC).MethodsWe investigated the effects of two important steps in the raw signal preprocessing on predicting participant performance (F1) and machine-learning classifier performance (area-under-curve, AUC) in eight healthy individuals, that are based solely on MI using high-density EEG (HD-EEG): artifact correction (manual correction with vs. without Independent Component Analysis [ICA]), region of interest (ROI; motor area vs. whole brain), and machine-learning algorithm (support-vector machine [SVM] vs. k-nearest neighbor [KNN]).ResultsResults revealed no significant effects of artifact correction and ROI on predicting participant performance (F1) and classifier performance (AUC) scores (allps > 0.05) in the SVM classification model. In the KNN model, ROI had a significant influence on the classifier performance [F(1,8.939)= 7.585,p= 0.023]. There was no evidence for artifact correction and ROI selection changing the prediction of participants performance and classifier performance in EEG-based mental MI if using SVM-based classification (71–100% correct classifications across different signal preprocessing methods). The variance in the prediction of participant performance was significantly higher when the experiment started with a resting-state compared to a mental MI task block [X2(1)= 5.849,p= 0.016].DiscussionOverall, we could show that classification is stable across different modes of EEG signal preprocessing when using SVM models. Exploratory analysis gave a hint toward potential effects of the sequence of task execution on the prediction of participant performance, which should be taken into account in future studies. |
BackgroundConsumption of ultra-processed foods (UPFs) has been linked to risk of chronic diseases, with scant evidence in relation to multiple sclerosis (MS).MethodsWe tested associations between UPF consumption and likelihood of a first clinical diagnosis of central nervous system demyelination (FCD) (267 cases, 508 controls), a common precursor to MS. We used data from the 2003–2006 Ausimmune Study and logistic regression with full propensity score matching for age, sex, region of residence, education, smoking history, body mass index, physical activity, history of infectious mononucleosis, dietary misreporting, and total energy intake.ResultsHigher UPF consumption was statistically significantly associated with an increased likelihood of FCD (adjusted odds ratio = 1.08; 95% confidence interval = 1.0,1.15;p= 0.039), representing an 8% increase in likelihood of FCD per one energy-adjusted serving/day of UPFs.ConclusionHigher intakes of UPF were associated with increased likelihood of FCD in this Australian cohort. Nutrition education and awareness of healthy eating patterns may benefit those at high risk of FCD. |
Introduction:To date, the appropriate epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) for patients aged ≥75 years with advancedEGFRmutation-positive, nonsmall cell lung cancer remain unknown.Methods:This study included a total of 89 patients aged ≥75 years who were diagnosed withEGFRmutation-positive, nonsmall cell lung cancer and treated with EGFR-TKIs at the Tokyo Metropolitan Geriatric Hospital and Nihon University ITABASHI Hospital from 2009 to 2020. The patients were classified into five groups based on their treatment: gefitinib (n = 23), erlotinib (n = 4), afatinib (n = 3), first-line osimertinib (n = 23), and TKI to TKI (n = 36). The efficacy and safety of each EGFR-TKI were analyzed.Results:No significant differences in the overall survival and progression-free survival were observed among the groups. However, a significantly higher incidence of drug-induced interstitial lung disease (ILD) was detected with osimertinib than with the first-generation EGFR-TKIs (p = 0.008).Conclusions:In older patients withEGFRmutation-positive lung cancer, the incidence of drug-induced ILD was significantly increased during osimertinib treatment. This outcome should be noted when treating older patients with osimertinib who may not always want to live longer but want to live better. |
BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with atrial fibrillation (AF). Insulin resistance (IR) is the main cause of the high prevalence of AF in NAFLD patients. The triglyceride-glucose index (TyG) is a novel IR-related indicator implicated in the incidence and severity of NAFLD. However, the role of TyG in determining the risk for AF in patients with NAFLD remains unclear.MethodsA retrospective study was conducted on 912 patients diagnosed with NAFLD via ultrasonography. These patients were divided into two groups: (1) NAFLD+ AF and (2) NAFLD+ non-AF. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to assess the correlation between the TyG index and the high risk for AF. A receiver operating characteristic (ROC) curve was constructed to evaluate the predictive value for the TyG index for AF. Restricted cubic splines (RCS) were used to test the linear correlation between TyG and the risk for AF.ResultsA total of 204 patients with AF and 708 patients without AF were included in this study. The LASSO logistic regression analysis showed that TyG was an independent risk factor for AF (odds ratio [OR] = 4.84, 95% confidence interval [CI] 2.98–7.88, P < 0.001). The RCS showed that the risk for AF increased linearly with TyG over the entire TyG range; this risk was also evident when the patients were analyzed based on sex (P for nonlinear > 0.05). In addition, the correlation between TyG and AF was a consistent finding in subgroup analysis. Furthermore, ROC curve analysis showed that TyG levels combined with traditional risk factors improved the predictive value for atrial fibrillation.ConclusionThe TyG index is useful in assessing the risk for atrial fibrillation in patients with NAFLD. Patients with NAFLD and increased TyG indices have higher risks for atrial fibrillation. Therefore, TyG indices should be assessed when managing patients with NAFLD.Supplementary InformationThe online version contains supplementary material available at 10.1186/s13098-023-01012-1. |
Hepatocellular carcinoma (HCC) is a typical inflammation-driven cancer and ranks sixth in the incidence rate worldwide. The role of adenylate uridylate- (AU-) rich element genes (AREGs) in HCC remains unclear. HCC-related datasets were acquired from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. Differentially expressed AREGs (DE-AREGs) between HCC samples and healthy controls were identified. The univariate Cox and LASSO analyses were performed to determine the prognostic genes. Furthermore, a signature and corresponding nomogram were configured for the clinical prediction of HCC. The potential signature-related biological significance was explored using functional and pathway enrichment analysis. Additionally, immune infiltration analysis was also performed. Finally, the expression of prognostic genes was verified using real-time quantitative polymerase chain reaction (RT-qPCR). A total of 189 DE-AREGs between normal and HCC samples were identified, wherein CENPA, TXNRD1, RABIF, UGT2B15, and SERPINE1 were selected to generate an AREG-related signature. Moreover, the prognostic accuracy of the AREG-related signature was also confirmed. Functional analysis indicated that the high-risk score was related to various functions and pathways. Inflammation and immune-related analyses indicated that the difference of T cell and B cell receptor abundance, microvascular endothelial cells (MVE), lymphatic endothelial cells (lye), pericytes, stromal cells, and the six immune checkpoints was statistically significant between the different risk groups. Similarly, RT-qPCR outcomes of these signature genes were also significant. In conclusion, an inflammation-associated signature based on five DE-AREGs was constructed, which could act as a prognostic indicator of patients with HCC. |
Adsorption hysteresis is a phenomenon related to phase transitions that can impact applications such as gas storage and separations in porous materials. Computational approaches can greatly facilitate the understanding of phase transitions and phase equilibria in porous materials. In this work, adsorption isotherms for methane, ethane, propane, and n-hexane were calculated from atomistic grand canonical Monte Carlo (GCMC) simulations in a metal-organic framework having both micropores and mesopores to better understand hysteresis and phase equilibria between connected pores of different size and the external bulk fluid. At low temperatures, the calculated isotherms exhibit sharp steps accompanied by hysteresis. As a complementary simulation method, canonical (NVT) ensemble simulations with Widom test particle insertions are demonstrated to provide additional information about these systems. The NVT+Widom simulations provide the full van der Waals loop associated with the sharp steps and hysteresis, including the locations of the spinodal points and points within the metastable and unstable regions that are inaccessible to GCMC simulations. The simulations provide molecular-level insight into pore filling and equilibria between high- and low-density states within individual pores. The effect of framework flexibility on adsorption hysteresis is also investigated for methane in IRMOF-1. |
All biological processes use or produce heat. Traditional microcalorimeters have been utilized to study the metabolic heat output of living organisms and heat production of exothermic chemical processes. Current advances in microfabrication have made possible the miniaturization of commercial microcalorimeters, resulting in a few studies on the metabolic activity of cells at the microscale in microfluidic chips. Here we present a new, versatile, and robust microcalorimetric differential design based on the integration of heat flux sensors on top of microfluidic channels. We show the design, modeling, calibration, and experimental verification of this system by utilizingEscherichia coligrowth and the exothermic base catalyzed hydrolysis of methyl paraben as use cases. The system consists of a Polydimethylsiloxane based flow-through microfluidic chip with two 46 µl chambers and two integrated heat flux sensors. The differential compensation of thermal power measurements allows for the measurement of bacterial growth with a limit of detection of 1707 W/m3, corresponding to 0.021OD (2 ∙ 107bacteria). We also extracted the thermal power of a singleEscherichia coliof between 1.3 and 4.5 pW, comparable to values measured by industrial microcalorimeters. Our system opens the possibility for expanding already existing microfluidic systems, such as drug testing lab-on-chip platforms, with measurements of metabolic changes of cell populations in form of heat output, without modifying the analyte and minimal interference with the microfluidic channel itself. |
BackgroundThis study aimed to apply near-infrared spectroscopy (NIRS) to monitor cerebral oxygen saturation (SrO2) level in neonates before and after the change of mechanical ventilation mode, and thus, the effects of the change of mechanical ventilator mode on SrO2level in neonates were assessed.MethodsThis trial was designed as an observational study .A total of 70 neonates who were admitted to the Department of Neonatology of Beijing Luhe Hospital Affiliated to Capital Medical University (Beijing, China) between September 2019 and October 2021 and required respiratory support were included. The variations of SrO2 level before and after the change of mechanical ventilation mode, including changing from Synchronized intermittent mandatory ventilation (SIMV) to noninvasive ventilation (NIV, group 1), and from NIV to oxygen inhalation (group 2), were monitored by Enginmed EGOS-600 A. The changes of SrO2level at 30 min before and 1 h after the change of ventilation mode were compared between the two groups.ResultsThe SrO2level in the group 1 30 min before, as well as 10 min, 30 min, and 1 h after the change of ventilation mode was 62.54 ± 3.36%, 65.43 ± 3.98%, 64.38 ± 4.23%, and 64.63 ± 3.71%, respectively. The SrO2level at all the points after the change of ventilation mode increased compared with 30 min before the change (P < 0.05). The SrO2level in the group 2 at each time point was 62.67 ± 4.69%, 64.61 ± 5.00%, 64.04 ± 4.48%, and 64.55 ± 4.32%, respectively. Compared with 30 min before ventilator weaning, the SrO2level at all the points after ventilator weaning increased (P < 0.05). Peak inspiratory pressure (PIP) excluding Nasal Continuous Positive Airway Pressure (NCPAP)) in group 1 was lower than that before extubation, and the difference was statistically significant (P = 0) (Table 7).ConclusionsSrO2level showed an increasing trend after the change of ventilation mode, and the increase of SrO2level at 10 min after the change of ventilation mode was the most prominent. From SIMV to NIV, increased SrO2 levels may be associated with decreased PIP. |
PurposeConvolutional neural networks (CNNs) are increasingly being developed for automated fracture detection in orthopaedic trauma surgery. Studies to date, however, are limited to providing classification based on the entire image—and only produce heatmaps for approximate fracture localization instead of delineating exact fracture morphology. Therefore, we aimed to answer (1) what is the performance of a CNN that detects, classifies, localizes, and segments an ankle fracture, and (2) would this be externally valid?MethodsThe training set included 326 isolated fibula fractures and 423 non-fracture radiographs. The Detectron2 implementation of the Mask R-CNN was trained with labelled and annotated radiographs. The internal validation (or ‘test set’) and external validation sets consisted of 300 and 334 radiographs, respectively. Consensus agreement between three experienced fellowship-trained trauma surgeons was defined as the ground truth label. Diagnostic accuracy and area under the receiver operator characteristic curve (AUC) were used to assess classification performance. The Intersection over Union (IoU) was used to quantify accuracy of the segmentation predictions by the CNN, where a value of 0.5 is generally considered an adequate segmentation.ResultsThe final CNN was able to classify fibula fractures according to four classes (Danis-Weber A, B, C and No Fracture) with AUC values ranging from 0.93 to 0.99. Diagnostic accuracy was 89% on the test set with average sensitivity of 89% and specificity of 96%. External validity was 89–90% accurate on a set of radiographs from a different hospital. Accuracies/AUCs observed were 100/0.99 for the ‘No Fracture’ class, 92/0.99 for ‘Weber B’, 88/0.93 for ‘Weber C’, and 76/0.97 for ‘Weber A’. For the fracture bounding box prediction by the CNN, a mean IoU of 0.65 (SD ± 0.16) was observed. The fracture segmentation predictions by the CNN resulted in a mean IoU of 0.47 (SD ± 0.17).ConclusionsThis study presents a look into the ‘black box’ of CNNs and represents the first automated delineation (segmentation) of fracture lines on (ankle) radiographs. The AUC values presented in this paper indicate good discriminatory capability of the CNN and substantiate further study of CNNs in detecting and classifying ankle fractures.Level of evidenceII, Diagnostic imaging study. |
IntroductionThe Semantic Web community provides a common Resource Description Framework (RDF) that allows representation of resources such that they can be linked. To maximize the potential of linked data - machine-actionable interlinked resources on the Web - a certain level of quality of RDF resources should be established, particularly in the biomedical domain in which concepts are complex and high-quality biomedical ontologies are in high demand. However, it is unclear which quality metrics for RDF resources exist that can be automated, which is required given the multitude of RDF resources. Therefore, we aim to determine these metrics and demonstrate an automated approach to assess such metrics of RDF resources.MethodsAn initial set of metrics are identified through literature, standards, and existing tooling. Of these, metrics are selected that fulfil these criteria: (1) objective; (2) automatable; and (3) foundational. Selected metrics are represented in RDF and semantically aligned to existing standards. These metrics are then implemented in an open-source tool. To demonstrate the tool, eight commonly used RDF resources were assessed, including data models in the healthcare domain (HL7 RIM, HL7 FHIR, CDISC CDASH), ontologies (DCT, SIO, FOAF, ORDO), and a metadata profile (GRDDL).ResultsSix objective metrics are identified in 3 categories:Resolvability(1),Parsability(1), andConsistency(4), and represented in RDF. The tool demonstrates that these metrics can be automated, and application in the healthcare domain shows non-resolvable URIs (ranging from 0.3% to 97%) among all eight resources and undefined URIs in HL7 RIM, and FHIR. In the tested resources no errors were found forparsabilityand the other threeconsistencymetrics for correct usage of classes and properties.ConclusionWe extracted six objective and automatable metrics from literature, as the foundational quality requirements of RDF resources to maximize the potential of linked data. Automated tooling to assess resources has shown to be effective to identify quality issues that must be avoided. This approach can be expanded to incorporate more automatable metrics so as to reflect additional quality dimensions with the assessment tool implementing more metrics.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12911-023-02182-8. |
AbstractBackground and AimDiet is a major contributor to irritable bowel syndrome (IBS) and is also a powerful tool for treatment of IBS. This study compared two diets and explored the effectiveness of the diets when combined with a probiotic for treatment of IBS‐D patients.MethodsPhase I, patients were randomized into groups; control, cold/spicy/fried restricted diet (CSF res diet), IgG positive restricted diet (IgG res diet), and a combination both diets (CSF + IgG res diet). Phase II, patients were randomized into IgG res diet + placebo and IgG res diet + probiotic. Both interventions were 12 weeks in duration. Symptom Severity Scale (IBS‐D‐SSS) and IgG titer were assessed at the beginning and the end of the study.ResultsTotals of 214 and 167 patients completed the two parts of the study, respectively. After intervention, IBS‐D‐SSS and TIgG grade were significantly improved compared to baseline, with results similar to the control group. In general, there were decreases in IBS‐D‐SSS and TIgG grade that were significantly different among the groups. There were exceptions; no differences were observed for IBS‐D‐SSS between the IgG res diet and CSF + IgG res diet, or TIgG grade between the CSF res diet, IgG res diet, and CSF + IgG res diet. However, the CSF res diet and IgG res diet had a synergistic effect that decreased IBS‐D‐SSS and TIgG titer, with a greater contribution by the IgG res diet. Therefore, we evaluated the IgG res diet with either placebo or probiotic and found that IBS‐D‐SSS and TIgG grade decreased from baseline. There was a significant decrease in IBS‐D‐SSS with the probiotic but TIgG grade was not significantly different between the IgG diet + placebo and IgG diet + probiotic diet.ConclusionsBoth the CSF res diet and IgG res diet improved IBS symptoms and demonstrated synergy, although the IgG res diet had a greater contribution. Further, when intolerant foods cannot be eliminated from a diet, avoiding uncooked, cold, spicy, fried, and alcoholic foods is a superior choice. The IgG res diet combined with Bifidobacteria was the best dietary choice and may function though a non‐IgG pathway. |
Introduction: To maintain high vaccination rates, vaccination interventions should be targeted according to interests such as parents' knowledge, attitudes, beliefs, and vaccine hesitancy.Methods: This research was conducted between June 2020 and April 2021 using a questionnaire about optional vaccines (OVs) in Turkey.Results: A total of 241 physicians participated and 14 physicians were excluded due to insufficient data. Finally, a total of 227 physicians, including 115 pediatricians and 112 family physicians, were included in the study. The mean age of pediatricians and family physicians was 33.42 ± 8.25 years and 35.46 ± 11.09 years, respectively. There was no significant difference between pediatricians and family physicians in terms of age and gender (p > 0.05). Nearly half of all physicians (49%) stated that they do not have sufficient knowledge about OVs. Pediatricians (64%) stated that they have sufficient knowledge at a higher rate than family physicians (37%) (p = 0.000). Physicians who declared having sufficient knowledge informed families about OVs more frequently than those with insufficient knowledge (p = 0.000). Pediatricians provide information about OVs more frequently than family physicians (p = 0.001). Rotavirus and meningococcal vaccines were the most frequently recommended vaccines.Conclusions: Rotavirus and meningococcal B were the most recommended OVs. About half of the physicians participating in the study stated that they did not have sufficient knowledge about OVs. Physicians with sufficient knowledge of OVs recommend OVs more frequently. |
BackgroundSCs and STs, historically marginalized communities in India, have been subjected to social and economic discrimination for centuries. Despite affirmative action policies, these communities face systemic discrimination and exclusion in various aspects of their lives. Poor health conditions among SC and ST women are caused by insufficient consumption of nutritious food, leading to undernutrition and related health issues. To address gaps in the literature regarding the nutritional status of these women, this study aims to compare the BMI of SC and ST women in West Bengal and investigate the factors affecting their BMI. The study's findings can inform targeted interventions to improve the nutritional status of SC and ST women in West Bengal and reduce disparities in their health outcomes.Materials and methodsThis study analyzed data from the National Family Health Survey (NFHS-5) to examine the distribution of underweight and non-underweight SC and ST women in West Bengal. The sample included 5,961 non-pregnant reproductive-aged SC women and 1,496 non-pregnant reproductive-aged ST women. A binary logistic regression model was used to determine how background characteristics affect the nutritional status (BMI) of respondents, while a multivariate decomposition analysis was conducted to identify the covariates contributing to the nutritional status difference between SC and ST women. QGIS 2.18.25 software was utilized to map the spatial distribution of underweight and non-underweight SC and ST reproductive-aged women.ResultsThis study examines the nutritional status and differential background characteristics among SC and ST women in West Bengal, India. Results show that undernutrition affects the ST population more than the SC population, with age, marital status, religion, place of residence, educational status, and wealth quintile being significant factors affecting nutritional status. Food and dietary habits also impact nutritional status, with milk or curd, pulses or beans, dark green leafy vegetables, eggs, and fish being associated with lower rates of underweight. Binary logistic regression analysis reveals significant associations between socio-demographic factors and underweight status among SC and ST women. Socio-demographic factors were found to be the major contributors to the gap between SC and ST women, followed by food and dietary factors. The study highlights the need for targeted interventions to improve the nutritional status of marginalized communities like SC and ST women in West Bengal.ConclusionThe study highlights a significant population suffering from underweight in West Bengal, with socio-economic factors and dietary habits significantly contributing to the nutritional gap between SC and ST reproductive-aged women. Policy implications suggest targeted interventions to improve access to education and employment opportunities and promote a healthy and balanced diet to reduce the gap. Future studies could explore vulnerability risks of these domains. |
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