title: Activating transcription factor 3 is crucial for antitumor activity and to strengthen the antiviral properties of Onconase

text: Onconase is a ribonuclease that presents both antitumor and antiviral properties linked to its ribonucleolytic activity and represents a new class of RNA-damaging drugs. It has reached clinical trials for the treatment of several cancers and human papilloma virus warts. Onconase targets different RNAs in the cell cytosol but Onconase-treated cells present features that are different from a simple arrest of protein synthesis. We have used microarray-derived transcriptional profiling to identify Onconase-regulated genes in two ovarian cancer cell lines (NCI/ADR-RES and OVCAR-8). RT-qPCR analyses have confirmed the microarray findings. We have identified a network of up-regulated genes implicated in different signaling pathways that may explain the cytotoxic effects exerted by Onconase. Among these genes, activating transcription factor 3 (ATF3) plays a central role in the key events triggered by Onconase in treated cancer cells that finally lead to apoptosis. This mechanism, mediated by ATF3, is cell-type independent. Up-regulation of ATF3 may also explain the antiviral properties of this ribonuclease because this factor is involved in halting viral genome replication, keeping virus latency or preventing viral oncogenesis. Finally, Onconase-regulated genes are different from those affected by nuclear-directed ribonucleases.


title: Recommendations for control and prevention of infections for pediatric orthopedics during the epidemic period of COVID-19

text: The outbreak of Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged and spread rapidly throughout the world. As of February 29, 2020, 79 389 cases of COVID-19 have been reported, and the outbreak is linked to 2838 deaths. The population is generally susceptible to the disease, and differences in incubation periods after infection exist among individuals. These two aspects of COVID-19 pose significant challenges to pediatric orthopedic diagnosis and treatment. As a dedicated center for managing pediatric cases of SARS-CoV-2 in Shanghai, our hospital has mobilized all branches and departments to undertake joint actions for scientific prevention and control, precise countermeasure and comprehensive anti-epidemic efforts. Combined with our experience, we have consulted the relevant national regulations and the latest research advances and have formulated the prevention and control measures of SARS-CoV-2 infection, including outpatient, emergency, inpatient and surgical cares, for clinical practices of pediatric orthopedics according to the physicochemical properties of SARS-CoV-2. It may serve as practical references and recommendations for managing SARS-CoV-2 infection in other pediatric specialties and in other hospitals.


title: Identification of methylated-differentially expressed genes and pathways in esophageal squamous cell carcinoma

text: Methylation, as an epigenetic modification, can affect gene expression and play a role in the occurrence and development of cancer. This research is devoted to discover methylated-differentially expressed genes (MDEGs) in esophageal squamous cell carcinoma (ESCC) and explore special associated pathways. We downloaded GSE51287 methylation profiles and GSE26886 expression profiles from GEO DataSets, and performed a comprehensive bioinformatics analysis. Totally, 19 hypermethylated, lowly expressed genes (Hyper-LGs) were identified, and involved in regulation of cell proliferation, phosphorus metabolic process and protein kinase activity. Meanwhile, 17 hypomethylated, highly expressed genes (Hypo-HGs) were participated in collagen catabolic process, metallopeptidase and cytokine activity. Pathway analysis determined that Hyper-LGs were enriched in arachidonic acid metabolism pathway, while Hypo-HGs were primarily associated with the cytokine-cytokine receptor interaction pathway. IL 6, MMP3, MMP9, SPP1 were identified as hub genes based on the PPI network that combined 7 ranked methods included in cytoHubba, and verification was performed in human tissues. Our integrated analysis identified many novel genetic lesions in ESCC and provides a crucial molecular foundation to improve our understanding of ESCC. Hub genes, including IL 6, MMP3, MMP9 and SPP1, could be considered for use as aberrant methylation-based biomarkers to facilitate the accurate diagnosis and therapy of ESCC.


title: Assessment of PaO(2)/FiO(2) for stratification of patients with moderate and severe acute respiratory distress syndrome

text: OBJECTIVES: A recent update of the definition of acute respiratory distress syndrome (ARDS) proposed an empirical classification based on ratio of arterial partial pressure of oxygen to fraction of inspired oxygen (PaO(2)/FiO(2)) at ARDS onset. Since the proposal did not mandate PaO(2)/FiO(2) calculation under standardised ventilator settings (SVS), we hypothesised that a stratification based on baseline PaO(2)/FiO(2) would not provide accurate assessment of lung injury severity. DESIGN: A prospective, multicentre, observational study. SETTING: A network of teaching hospitals. PARTICIPANTS: 478 patients with eligible criteria for moderate (100<PaO(2)/FiO(2)≤200) and severe (PaO(2)/FiO(2)≤100) ARDS and followed until hospital discharge. INTERVENTIONS: We examined physiological and ventilator parameters in association with the PaO(2)/FiO(2) at ARDS onset, after 24 h of usual care and at 24 h under a SVS. At 24 h, patients were reclassified as severe, moderate, mild (200<PaO(2)/FiO(2)≤300) ARDS and non-ARDS (PaO(2)/FiO(2)>300). PRIMARY AND SECONDARY OUTCOMES: Group severity and hospital mortality. RESULTS: At ARDS onset, 173 patients had a PaO(2)/FiO(2)≤100 but only 38.7% met criteria for severe ARDS at 24 h under SVS. When assessed under SVS, 61.3% of patients with severe ARDS were reclassified as moderate, mild and non-ARDS, while lung severity and hospital mortality changed markedly with every PaO(2)/FiO(2) category (p<0.000001). Our model of risk stratification outperformed the stratification using baseline PaO(2)/FiO(2) and non-standardised PaO(2)/FiO(2) at 24 h, when analysed by the predictive receiver operating characteristic (ROC) curve: area under the ROC curve for stratification at baseline was 0.583 (95% CI 0.525 to 0.636), 0.605 (95% CI 0.552 to 0.658) at 24 h without SVS and 0.693 (95% CI 0.645 to 0.742) at 24 h under SVS (p<0.000001). CONCLUSIONS: Our findings support the need for patient assessment under SVS at 24 h after ARDS onset to assess disease severity, and have implications for the diagnosis and management of ARDS patients. TRIAL REGISTRATION NUMBERS: NCT00435110 and NCT00736892.


title: Remdesivir: Review of pharmacology, pre‐clinical data and emerging clinical experience for COVID‐19

text: The global pandemic of novel coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has created an urgent need for effective antivirals. Remdesivir (formerly GS‐5734) is a nucleoside analogue pro‐drug currently being evaluated in COVID‐19 clinical trials. Its unique structural features allow high concentrations of the active triphosphate metabolite to be delivered intracellularly and it evades proofreading to successfully inhibit viral RNA synthesis. In pre‐clinical models, remdesivir has demonstrated potent antiviral activity against diverse human and zoonotic β‐coronaviruses, including SARS‐CoV‐2. In this article we critically review available data on remdesivir with an emphasis on biochemistry, pharmacology, pharmacokinetics and in vitro activity against coronaviruses as well as clinical experience and current progress in COVID‐19 clinical trials.


title: The (in)significance of TB and COVID-19 co-infection

text: We read with great interest the research letter by Tadolini et al. in which they have published the first cohort of 49 cases of TB and COVID-19 co-infection. However, few issues regarding the letter need to be addressed.


title: Identification of scavenger receptor B1 as the airway microfold cell receptor for Mycobacterium tuberculosis

text: Mycobacterium tuberculosis (Mtb) can enter the body through multiple routes, including via specialized transcytotic cells called microfold cells (M cell). However, the mechanistic basis for M cell entry remains undefined. Here, we show that M cell transcytosis depends on the Mtb Type VII secretion machine and its major virulence factor EsxA. We identify scavenger receptor B1 (SR-B1) as an EsxA receptor on airway M cells. SR-B1 is required for Mtb binding to and translocation across M cells in mouse and human tissue. Together, our data demonstrate a previously undescribed role for Mtb EsxA in mucosal invasion and identify SR-B1 as the airway M cell receptor for Mtb.


title: Age-related expression of SARS-CoV-2 priming protease TMPRSS2 in the developing lung

text: The emergence of the SARS-CoV-2 novel coronavirus has led to a global pandemic (COVID-19), with more than 5 million cases as of May 2020(1). Available data suggest that severe illness and death from COVID-19 are rare in the pediatric population(2). Integrating single-cell RNA sequencing of the developing mouse lung with temporally-resolved RNA-in-situ hybridization (ISH) in mouse and human lung tissue, we found expression of SARS-CoV-2 Spike protein primer TMPRSS2 was highest in ciliated cells and type I alveolar epithelial cells (AT1) and increased with aging in mice and humans. SARS-CoV-2 RNA colocalized with TMPRSS2 mRNA in lung cells from a patient who died of SARS-CoV-2. Together, these data suggest developmental regulation of TMPRSS2 may underlie the relative protection of infants and children from severe respiratory illness.


title: A novel programed frameshift expresses the POL3 gene of retrotransposon Ty3 of yeast: Frameshifting without tRNA slippage

text: Abstract Most retroviruses and retrotransposons express their pol gene as a translational fusion to the upstream gag gene, often involving translational frameshifting. We describe here an unusual translational frameshift event occurring between the GAG3 and POL3 genes of the retrotransposon Ty3 of yeast. A +1 frameshift occurs within the sequence GCG AGU U (shown as codons of GAG3), encoding alanine-valine ( GCG A GUU ). Unlike other programed translational frameshifts described, this event does not require tRNA slippage between cognate or near-cognate codons in the mRNA. Two features distal to the GCG codon stimulate frameshifting. The low availability of the tRNA specific for the “hungry” serine codon, AGU, induces a translational pause required for frameshifting. A sequence of 12 nt distal to the AGU codon (termed the Ty3. “context”) also stimulates the event.


title: Single and multiple respiratory virus infections and severity of respiratory disease: A systematic review

text: Abstract Introduction There are suggestions that virus co-infections may influence the clinical outcome of respiratory virus illness. We performed a systematic review of the literature to summarise the evidence. Methods MEDLINE, EMBASE, Ovid and WEB of Science databases, major organisation websites and reference lists of published studies were searched. The quality of studies was assessed using the STROBE tool (von Elm et al., 1) Individual study data was analyzed using odds ratios and 95% confidence intervals as a measure of association between exposure (co-infection), patient outcome and results summarised using forest plots and tables Results Nineteen (19) studies from all over the world were identified and included in the review. Most of the studies 73.7% (14/19) recruited children ≤6 years old. Evidence on the role of co-infection in increasing disease severity was inconclusive. In five out of eight studies, co-infection significantly increased risk of admission to general ward (OR: 2.4, 95% CI: 1.3 - 4.4, p = 0.005; OR: 2.4, 95% CI: 1.1 - 7.7, P = 0.04; OR: 3.1, 95% CI: 2.0 - 5.1, p = <0.001; OR: 2.4, 95% CI: 1.7-3.4, p = <0.0001 and OR: 2.3, 95% CI: 1.1 - 5.1, p = 0.34), one found it did not (OR: 0.59, 95% CI: 0.4 - 0.9, p = 0.02) and the other 2 had insignificant results. Similarly on risk of admission to ICU, some studies found that co-infection significantly increased risk of admission to ICU (OR: 2.9, 95% CI: 1.4 - 5.9, p = 0.004 and OR: 3.0, 95% CI: 1.7 - 5.6, p = <0.0001), whereas others did not (OR: 0.18, 95% CI: 0.05 - 0.75, p = 0.02 and OR: 0.3, 95% CI: 0.2 - 0.6, p = <0.0001). There was no evidence for or against respiratory virus co-infections and risk of bronchiolitis or pneumonia. Conclusion The influence of co-infections on severe viral respiratory disease is still unclear. The observed conflict in outcomes could be because they were conducted in different seasons and covered different years and periods. It could also be due to bias towards the null, especially in studies where only crude analysis was conducted. Future studies should employ stratified analysis.


title: Coronavirus pandemic versus temperature in the context of Indian subcontinent: a preliminary statistical analysis

text: The novel coronavirus (COVID-19) has unleashed havoc across different countries and was declared a pandemic by the World Health Organization. Since certain evidences indicate a direct relationship of various viruses with the weather (temperature in particular), the same is being speculated about COVID-19; however, it is still under investigation as the pandemic is advancing the world over. In this study, we tried to analyze the spread of COVID-19 in the Indian subcontinent with respect to the local temperature regimes from March 9, 2020, to May 27, 2020. To establish the relation between COVID-19 and temperature in India, three different ecogeographical regions having significant temperature differences were taken into consideration for the analysis. We observed that except Maharashtra, Rajasthan and Kashmir showed a significantly positive correlation between the number of COVID-19 cases and the temperature during the period of study. The evidences based on the results presented in this research lead us to believe that the increasing temperature is beneficial to the COVID-19 spread, and the cases are going to rise further with the increasing temperature over India. We, therefore, conclude that the existing data, though limited, suggest that the spread of COVID-19 in India is not explained by the variation of temperature alone and is most likely driven by a host of other factors related to epidemiology, socioeconomics and other climatic factors. Based on the results, it is suggested that temperature should not be considered as a yardstick for planning intervention strategies for controlling the COVID-19 pandemic.


title: Personal sampler for monitoring of viable viruses; modelling of outdoor sampling conditions

text: Abstract A new personal bioaerosol sampler has recently been developed and verified to be very efficient for monitoring of viable airborne bacteria, fungi and viruses. The device is capable of providing high recovery rates even for microorganisms which are rather sensitive to physical and biological stresses. However, some mathematical procedure is required for realistic calculation of an actual concentration of viable bioaerosols in the air taking into account a rate of inactivation of targeted microorganisms, sampling parameters, and results of microbial analysis of collecting liquid from the sampler. In this paper, we develop such procedure along with the model of aerosol propagation for outdoor conditions. Combining these procedures allows one to determine the optimal sampling locations for the best possible coverage of the area to be monitored. A hypothetical episode concerned with terrorists’ attack during music concert in the central square of Novosibirsk, Russia was considered to evaluate possible coverage of the area by sampling equipment to detect bioaerosols at various locations within the square. It was found that, for chosen bioaerosol generation parameters and weather conditions, the new personal sampler would be capable to reliably detect pathogens at all locations occupied by crowd, even at distances of up to 600m from the source.


title: Development of a real-time reverse transcription loop-mediated isothermal amplification method for the rapid detection of porcine epidemic diarrhea virus

text: BACKGROUND: Porcine epidemic diarrhea (PED) is an acute and highly contagious enteric disease characterized by severe enteritis, vomiting and watery diarrhea in swine. Recently, the outbreak of the epidemic disease has been a serious problem in swine industry. The objective of this study is to develop a rapid, sensitive, and real-time reverse transcription loop-mediated isothermal amplification (RT-LAMP) method for the detection of porcine epidemic diarrhea virus (PEDV) in less equipped laboratories. RESULTS: The optimal reaction condition of the current real-time RT-LAMP for PEDV was 62 °C for 45 min. It was capable of detecting PEDV from clinical samples and differentiating PEDV from several related porcine viruses, while it did not require additional expensive equipment. The minimum detection limit of the real-time RT-LAMP assay was 0.07PFU per reaction for PEDV RNA, making this assay approximately 100-fold more sensitive than that of one-step RT-PCR. By screening a panel of clinical specimens, the results showed that this method presented a similar sensitivity with real-time RT-PCR and was somewhat sensitive than one-step RT-PCR in detection of clinical samples. CONCLUSIONS: In this study, we have developed a new real-time RT-LAMP method, which is rapid, sensitive and efficient to detect PEDV.This method holds great promises not only in laboratory detection and discrimination of PEDV but also in large scale field and clinical studies.


title: A review on current status of antiviral siRNA

text: Viral diseases like influenza, AIDS, hepatitis, and Ebola cause severe epidemics worldwide. Along with their resistant strains, new pathogenic viruses continue to be discovered so creating an ongoing need for new antiviral treatments. RNA interference is a cellular gene‐silencing phenomenon in which sequence‐specific degradation of target mRNA is achieved by means of complementary short interfering RNA (siRNA) molecules. Short interfering RNA technology affords a potential tractable strategy to combat viral pathogenesis because siRNAs are specific, easy to design, and can be directed against multiple strains of a virus by targeting their conserved gene regions. In this review, we briefly summarize the current status of siRNA therapy for representative examples from different virus families. In addition, other aspects like their design, delivery, medical significance, bioinformatics resources, and limitations are also discussed.


title: Nucleocapsid proteins: roles beyond viral RNA packaging

text: Viral nucleocapsid proteins (NCs) enwrap the RNA genomes of viruses to form NC–RNA complexes, which act as a template and are essential for viral replication and transcription. Beyond packaging viral RNA, NCs also play important roles in virus replication, transcription, assembly, and budding by interacting with viral and host cellular proteins. Additionally, NCs can inhibit interferon signaling response and function in cell stress response, such as inducing apoptosis. Finally, NCs can be the target of vaccines, benefiting from their conserved gene sequences. Here, we summarize important findings regarding the additional functions of NCs as much more than structural RNA‐binding proteins, with specific emphasis on (1) their association with the viral life cycle, (2) their association with host cells, and (3) as ideal candidates for vaccine development. WIREs RNA 2016, 7:213–226. doi: 10.1002/wrna.1326 1.. RNA Interactions with Proteins and Other Molecules > RNA–Protein Complexes; 2.. RNA Interactions with Proteins and Other Molecules > Protein–RNA Interactions: Functional Implications; 3.. Translation > Translation Regulation.


title: A multiplex real-time PCR panel assay for simultaneous detection and differentiation of 12 common swine viruses

text: Abstract Mixed infection with different pathogens is common in swine production systems especially under intensive production conditions. Quick and accurate detection and differentiation of different pathogens are necessary for epidemiological surveillance, disease management and import and export controls. In this study, we developed and validated a panel of multiplex real-time PCR/RT-PCR assays composed of four subpanels, each detects three common swine pathogens. The panel detects 12 viruses or viral serotypes, namely, VSV-IN, VSV-NJ, SVDV, CSFV, ASFV, FMDV, PCV2, PPV, PRV, PRRSV-NA, PRRSV-EU and SIV. Correlation coefficients (R2) and PCR amplification efficiencies of all singular and triplex real-time PCR reactions are within the acceptable range. Comparison between singular and triplex real-time PCR assays of each subpanel indicates that there is no significant interference on assay sensitivities caused by multiplexing. Specificity tests on 226 target clinical samples or 4 viral strains and 91 non-target clinical samples revealed that the real-time PCR panel is 100% specific, and there is no cross amplification observed. The limit of detection of each triplex real-time PCR is less than 10 copies per reaction for DNA, and less than 16 copies per reaction for RNA viruses. The newly developed multiplex real-time PCR panel also detected different combinations of co-infections as confirmed by other means of detections.


title: Procyanidins and butanol extract of Cinnamomi Cortex inhibit SARS-CoV infection

text: Abstract We found that the butanol fraction of Cinnamomi Cortex (CC/Fr.2) showed moderate inhibitory activity in wild-type severe acute respiratory syndrome coronavirus (wtSARS-CoV) and HIV/SARS-CoV S pseudovirus infections. The inhibition on pseudovirus was also seen in cells pretreated with the CC and CC/Fr.2 (IC50S, 283.4±16.3 and 149.5±13.5μg/ml, respectively), however the highest activities on wtSARS-CoV were observed when the viruses were treated by the extracts before challenging (IC50S, 43.1±2.8 and 7.8±0.3μg/ml; SIs, 8.4 and 23.1, respectively). Among the compounds fractionated from CC, procyanidin A2 and procyanidin B1 showed moderate anti-wtSARS-CoV activity (IC50S, 29.9±3.3 and 41.3±3.4μM; SIs, 37.35 and 15.69, respectively). We also sought to determine whether they could interfere with the clathrin-dependent endocytosis pathway using transferrin receptor (TfR) as an indicator. CC/Fr.2 inhibited the internalization of TfR but the procyanidins did not. Taken together, CC/Fr.2 contains unknown substances, that could inhibit the infection, probably by interfering with endocytosis, and it also contains procyanidins that did not inhibit the internalization but inhibited the infection. Therefore, CC extracts contain anti-virus activities that act through distinct mechanisms according to differences in the compounds or mixtures.


title: AVCpred: an integrated web server for prediction and design of antiviral compounds

text: Viral infections constantly jeopardize the global public health due to lack of effective antiviral therapeutics. Therefore, there is an imperative need to speed up the drug discovery process to identify novel and efficient drug candidates. In this study, we have developed quantitative structure–activity relationship (QSAR)‐based models for predicting antiviral compounds (AVCs) against deadly viruses like human immunodeficiency virus (HIV), hepatitis C virus (HCV), hepatitis B virus (HBV), human herpesvirus (HHV) and 26 others using publicly available experimental data from the ChEMBL bioactivity database. Support vector machine (SVM) models achieved a maximum Pearson correlation coefficient of 0.72, 0.74, 0.66, 0.68, and 0.71 in regression mode and a maximum Matthew's correlation coefficient 0.91, 0.93, 0.70, 0.89, and 0.71, respectively, in classification mode during 10‐fold cross‐validation. Furthermore, similar performance was observed on the independent validation sets. We have integrated these models in the AVCpred web server, freely available at http://crdd.osdd.net/servers/avcpred. In addition, the datasets are provided in a searchable format. We hope this web server will assist researchers in the identification of potential antiviral agents. It would also save time and cost by prioritizing new drugs against viruses before their synthesis and experimental testing.


title: Burden of influenza, healthcare seeking behaviour and hygiene measures during the A(H1N1)2009 pandemic in France: a population based study

text: BACKGROUND: Influenza surveillance systems do not allow the identification of the true burden of illness caused by influenza in the community because they are restricted to consulting cases. A study was conducted to estimate the incidence and the burden of self-defined influenza, and to describe healthcare seeking behavior for self-defined influenza during the A(H1N1)2009 pandemic in the French population. METHODS: We conducted a random-based retrospective cross-sectional telephone survey between May 2009 and April 2010 among a random sample of the French population. RESULTS: For the 10 076 people included, 107 episodes of self-defined influenza were reported. The annual incidence of self-defined influenza was estimated at 13 942 cases per 100 000 inhabitants (CI95% 10 947 – 16 961), 62.1% (CI95% 50.5 – 72.5) of cases consulted a physician and 11.3% (CI95% 5.5 - 21.7) used a face mask. Following recommendations, 37.5% (CI95% 35.5 – 39.5) of people in the survey reported washing their hands more often during the pandemic season, and there was a positive association with being vaccinated against A(H1N1)2009 influenza, being a women, being a child (< 15 years) or living in a big city (≥ 100 000 inhabitants). CONCLUSIONS: Self-defined influenza causes a significant burden of illness in the French population and is a frequent cause for consultation. These results allow a more accurate interpretation of influenza surveillance data and an opportunity to adapt future health education messages.


title: 10 Impacts of virus-mediated manipulation of host Dynein

text: Abstract In general viruses' modus operandi to propagate is achieved by the co-opting host cell components, membranes, proteins, and machineries to their advantage. This is true for virtually every aspect of a virus' replication cycle from virus entry to the budding or release of progeny virus particles. In this chapter, we will discuss new information on the impacts of virus-mediated manipulation of Dynein motor complexes and associated machineries and factors. We will highlight how these host cell components impact on pathogenicity and immune responses, as many of the virus-mediated hijacked components also play pivotal roles in immune responses to pathogen insult. There are several comprehensive reviews that define virus–Dynein interactions including the first edition of this book that describes how viruses manipulate the host cell machineries their advantage. An updated table is included to summarize these virus–host interactions. Notably, barriers to intracellular translocation represent major hurdles to viral components during de novo infection and during active replication and the generation of progeny virus particles. Clearly, the subversion of host cell molecular motor protein activities takes advantage of constitutive and regulated membrane trafficking events and will target virus components to intracytoplasmic locales and membrane assembly. Broadening our understanding of the interplay between viruses, Dynein and the cytoskeleton will likely inform on new types of therapies. Continual enhancement of the breadth of new information on how viruses manipulate host cell biology will inevitably aid in the identification of new targets that can be poisoned to block old, new, and emerging viruses alike in their tracks.


title: Better Epitope Discovery, Precision Immune Engineering, and Accelerated Vaccine Design Using Immunoinformatics Tools

text: Computational vaccinology includes epitope mapping, antigen selection, and immunogen design using computational tools. Tools that facilitate the in silico prediction of immune response to biothreats, emerging infectious diseases, and cancers can accelerate the design of novel and next generation vaccines and their delivery to the clinic. Over the past 20 years, vaccinologists, bioinformatics experts, and advanced programmers based in Providence, Rhode Island, USA have advanced the development of an integrated toolkit for vaccine design called iVAX, that is secure and user-accessible by internet. This integrated set of immunoinformatic tools comprises algorithms for scoring and triaging candidate antigens, selecting immunogenic and conserved T cell epitopes, re-engineering or eliminating regulatory T cell epitopes, and re-designing antigens to induce immunogenicity and protection against disease for humans and livestock. Commercial and academic applications of iVAX have included identifying immunogenic T cell epitopes in the development of a T-cell based human multi-epitope Q fever vaccine, designing novel influenza vaccines, identifying cross-conserved T cell epitopes for a malaria vaccine, and analyzing immune responses in clinical vaccine studies. Animal vaccine applications to date have included viral infections of pigs such as swine influenza A, PCV2, and African Swine Fever. “Rapid-Fire” applications for biodefense have included a demonstration project for Lassa Fever and Q fever. As recent infectious disease outbreaks underscore the significance of vaccine-driven preparedness, the integrated set of tools available on the iVAX toolkit stand ready to help vaccine developers deliver genome-derived, epitope-driven vaccines.


title: A four year seasonal survey of the relationship between outdoor climate and epidemiology of viral respiratory tract infections in a temperate climate

text: Abstract Background The relation between weather conditions, viral transmission and seasonal activity of respiratory viruses is not fully understood. Objectives To investigate the impact of outdoor weather in a temperate climate setting on the seasonal epidemiology of viruses causing respiratory tract infections, particularly influenza A (IFA). Study design In total, 20,062 clinical nasopharyngeal swab samples referred for detection of respiratory pathogens using a multiplex PCR panel, between October 2010 and July 2013, were included. Results of PCR detection were compared with local meteorological data for the same period. Results Low temperature and vapor pressure (VP) were associated with weekly incidence of IFA, respiratory syncytial virus, metapneumovirus, bocavirus and adenovirus but no association with relative humidity was found. The incidence of human rhinovirus and enterovirus was independent of temperature. During seasonal IFA outbreaks, the weekly drop of average temperature (compared with the week before) was strongly associated with the IFA incidence recorded the following week. Conclusion A sudden drop in outdoor temperature might activate the annual influenza epidemic in a temperate climate by facilitating aerosol spread in dry air. These conditions also seem to affect the incidence of other respiratory pathogens but not human rhino- or enterovirus, suggesting that routes of infection other than aerosol may be relevant for these agents.


Letter to the editor regarding “corona-steps for tracheotomy in codid-19 patients: a staff-safe method for airway management”


title: Human iPSC-Derived Cardiomyocytes are Susceptible to SARS-CoV-2 Infection

text: Coronavirus disease 2019 (COVID-19) is a viral pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is predominantly defined by respiratory symptoms, but cardiac complications including arrhythmias, heart failure, and viral myocarditis are also prevalent. Although the systemic ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well-understood. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model system to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and immunofluorescence demonstrated that SARS-CoV-2 can enter and replicate within hiPSC-CMs, localizing at perinuclear locations within the cytoplasm. Viral cytopathic effect induced hiPSC-CM apoptosis and cessation of beating after 72 hours of infection. These studies show that SARS-CoV-2 can infect hiPSC-CMs in vitro, establishing a model for elucidating the mechanisms of infection and potentially a cardiac-specific antiviral drug screening platform.


title: GUESS WHO'S COMING TO DINNER: COVID-19 IN A COVID-FREE UNIT

text: OBJECTIVES: To assess the impact of the pandemic on surgical activity and the occurrence and features of Covid-19 in a Covid-free urologic unit in a regional hospital in Northern Italy. METHODS: Our Department is the only urologic service in the Trento Province, near Lombardy, the epicenter of Covid-19 in our Country. We reviewed the surgical and ward activities during the 4 weeks following the national lockdown (March 9-April 5, 2020). The following outcomes were investigated: surgical load, rate of admissions and bed occupation, and the rate and characteristics of unrecognized Covid-positive patients. Data were compared with that of the same period of 2019 (March 11-April 7). RESULTS AND CONCLUSIONS: 63%, 70%, 64%, and 71%, decline in surgery, endoscopy, bed occupation, and admission, respectively, occurred during the 4 weeks after the lockdown, as compared to 2019. Urgent procedures also declined by 32%. Three (8%) of 39 admissions regarded unrecognized Covid-19 overlapping or misinterpreted with urgent urologic conditions such as fever-associated urinary stones or hematuria. In spite of a significant reduction of activity, a non-negligible portion of admissions to our Covid-free unit regarded unrecognized Covid-19. In order to preserve its integrity, we propose an enhanced triage prior to the admission to a Covid-free unit including not only routine questions on fever and respiratory symptoms but also non-respiratory symptoms, history of exposure, and a survey about the social and geographic origin of the patient.


title: Virus Transfer from Personal Protective Equipment to Healthcare Employees’ Skin and Clothing

text: We evaluated a personal protective equipment removal protocol designed to minimize wearer contamination with pathogens. Following this protocol often resulted in virus transfer to hands and clothing. An altered protocol or other measures are needed to prevent healthcare worker contamination.


title: Nitric oxide-generating compound GSNO suppresses porcine circovirus type 2 infection in vitro and in vivo

text: BACKGROUND: Nitric oxide (NO), an important signaling molecule with biological functions, has antimicrobial activity against a variety of pathogens including viruses. To our knowledge, little information is available about the regulatory effect of NO on porcine circovirus type 2 (PCV2) infection. This study was conducted to investigate the antiviral activity of NO generated from S-nitrosoglutathione (GSNO), during PCV2 infection of PK-15 cells and BALB/c mice. RESULTS: GSNO released considerable NO in the culture medium of PK-15 cells, and NO was scavenged by its scavenger hemoglobin (Hb) in a dose-dependent manner. NO strongly inhibited PCV2 replication in PK-15 cells, and the antiviral effect was reversed by Hb. An in vivo assay indicated that GSNO treatment reduced the progression of PCV2 infection in mice, evident as reductions in the percentages of PCV2-positive sera and tissue samples and in the viral DNA copies in serum samples. GSNO also improved the growth performance and immune organs (spleens and thymuses) of the PCV2-infected mice to some degree. CONCLUSIONS: Our data demonstrate that the NO-generating compound GSNO suppresses PCV2 infection in PK-15 cells and BALB/c mice, indicating that NO and its donor, GSNO, have potential value as antiviral drugs against PCV2 infection.


title: The sialic acid binding activity of the S protein facilitates infection by porcine transmissible gastroenteritis coronavirus

text: BACKGROUND: Transmissible gastroenteritis virus (TGEV) has a sialic acid binding activity that is believed to be important for enteropathogenicity, but that has so far appeared to be dispensable for infection of cultured cells. The aims of this study were to determine the effect of sialic acid binding for the infection of cultured cells under unfavorable conditions, and comparison of TGEV strains and mutants, as well as the avian coronavirus IBV concerning their dependence on the sialic acid binding activity. METHODS: The infectivity of different viruses was analyzed by a plaque assay after adsorption times of 5, 20, and 60 min. Prior to infection, cultured cells were either treated with neuraminidase to deplete sialic acids from the cell surface, or mock-treated. In a second approach, pre-treatment of the virus with porcine intestinal mucin was performed, followed by the plaque assay after a 5 min adsorption time. A student's t-test was used to verify the significance of the results. RESULTS: Desialylation of cells only had a minor effect on the infection by TGEV strain Purdue 46 when an adsorption period of 60 min was allowed for initiation of infection. However, when the adsorption time was reduced to 5 min the infectivity on desialylated cells decreased by more than 60%. A TGEV PUR46 mutant (HAD3) deficient in sialic acid binding showed a 77% lower titer than the parental virus after a 5 min adsorption time. After an adsorption time of 60 min the titer of HAD3 was 58% lower than that of TGEV PUR46. Another TGEV strain, TGEV Miller, and IBV Beaudette showed a reduction in infectivity after neuraminidase treatment of the cultured cells irrespective of the virion adsorption time. CONCLUSIONS: Our results suggest that the sialic acid binding activity facilitates the infection by TGEV under unfavorable environmental conditions. The dependence on the sialic acid binding activity for an efficient infection differs in the analyzed TGEV strains.


title: Models of epidemics: when contact repetition and clustering should be included

text: BACKGROUND: The spread of infectious disease is determined by biological factors, e.g. the duration of the infectious period, and social factors, e.g. the arrangement of potentially contagious contacts. Repetitiveness and clustering of contacts are known to be relevant factors influencing the transmission of droplet or contact transmitted diseases. However, we do not yet completely know under what conditions repetitiveness and clustering should be included for realistically modelling disease spread. METHODS: We compare two different types of individual-based models: One assumes random mixing without repetition of contacts, whereas the other assumes that the same contacts repeat day-by-day. The latter exists in two variants, with and without clustering. We systematically test and compare how the total size of an outbreak differs between these model types depending on the key parameters transmission probability, number of contacts per day, duration of the infectious period, different levels of clustering and varying proportions of repetitive contacts. RESULTS: The simulation runs under different parameter constellations provide the following results: The difference between both model types is highest for low numbers of contacts per day and low transmission probabilities. The number of contacts and the transmission probability have a higher influence on this difference than the duration of the infectious period. Even when only minor parts of the daily contacts are repetitive and clustered can there be relevant differences compared to a purely random mixing model. CONCLUSION: We show that random mixing models provide acceptable estimates of the total outbreak size if the number of contacts per day is high or if the per-contact transmission probability is high, as seen in typical childhood diseases such as measles. In the case of very short infectious periods, for instance, as in Norovirus, models assuming repeating contacts will also behave similarly as random mixing models. If the number of daily contacts or the transmission probability is low, as assumed for MRSA or Ebola, particular consideration should be given to the actual structure of potentially contagious contacts when designing the model.


title: The Ethanol Extract from Lonicera japonica Thunb. Regresses Nonalcoholic Steatohepatitis in a Methionine- and Choline-Deficient Diet-Fed Animal Model

text: Nonalcoholic steatohepatitis (NASH) is characterized as fat accumulation in the hepatic tissue associated with various degrees of inflammation and progressive fibrosis. The potent anti-inflammatory and ethnopharmacological properties of Lonicera japonica Thunb. (Caprifoliaceae) make it an excellent source of novel medicinal targets for the treatment of NASH. The aim of the study was to investigate the effects of L. japonica ethanol extract (LJEE) on NASH in mice. C57BL/6J mice were fed with methionine-choline-deficient diet (MCDD) for eight weeks to promote the development of NASH. After development of the model, the mice were administered LJEE once daily via oral gavage at doses of 100, 200, or 300 mg/kg for another four weeks. Simultaneous treatments with LJEE (300 mg/kg/day) resulted in pronounced improvements in liver steatosis, ballooning degeneration, and inflammation. LJEE prevented MCDD-induced plasma level increases in aspartate aminotransferase and alanine aminotransferase. LJEE significantly reduced hepatic malondialdehyde level and ameliorated hepatic inflammation and fibrosis in MCDD-fed mice, which were associated with down-regulation of cytochrome P450 2E1 suppression of multiple proinflammatory and profibrotic genes. LJEE can prevent hepatic steatosis by reducing hepatic peroxisome acyl-CoA:diacylglycerol acyltransferase 2 expression, as well as by inducing proliferator-activated receptor α expression. In addition, the LJEE treatments caused significant reduction in the phosphorylated form of Jun N-terminal kinase along with an increase in the phosphorylated level of extra cellular signal-regulated kinase 1/2. Our study demonstrated the protective role of LJEE in ameliorating nutritional steatohepatitis.


title: Integration of small world networks with multi-agent systems for simulating epidemic spatiotemporal transmission

text: This study proposes an integrated model based on small world network (SWN) and multi-agent system (MAS) for simulating epidemic spatiotemporal transmission. In this model, MAS represents the process of spatiotemporal interactions among individuals, and SWN describes the social relation network among agents. The model is composed of agent attribute definitions, agent movement rules, neighborhoods, construction of social relation network among agents and state transition rules. The construction of social relation network and agent state transition rules is essential for implementing the proposed model. The decay effects of infection “memory”, distance and social relation between agents are introduced into the model, which are unavailable in traditional models. The proposed model is used to simulate the transmission process of flu in Guangzhou City based on the swarm software platform. The integration model has better performance than the traditional SEIR model and the pure MAS based epidemic model. This model has been applied to the simulation of the transmission of epidemics in real geographical environment. The simulation can provide useful information for the understanding, prediction and control of the transmission of epidemics.


title: Neurogliogenesis in the mature olfactory system: A possible protective role against infection and toxic dust

text: Abstract The outpost position of the olfactory bulb (OB) between the direct inputs from sensory neurons of the nasal epithelium and other parts of the brain suggests its highest vulnerability among all brain structures to penetration of exogenous agents. A number of neurotropic viruses have been found to invade the brain through the OB. There is growing evidence that microscopic particles of toxic dusts can propagate from the nasal epithelium to the OB and further into the brain. These harmful agents impair cellular elements of the brain. Apparently, cells in the OB are the most affected, as they are the first to encounter viral infections and toxic particles. It is well known that neuronal and glial progenitors are continuously generated from neuronal stem cells in the subventricular zone of the adult brain and then migrate predominantly into the OB. Therefore, it is feasible to suggest that substitution of injured or dead cells in the OB by new-born neurons, differentiating from progenitors, plays a role in protecting the OB neuronal microcircuits from destruction. Furthermore, some cytokines and chemokines released in response to infection and/or intoxication can modulate different stages of neurogenesis (proliferation, migration, and differentiation). We hypothesize that continuous neurogenesis in the olfactory system throughout adulthood evolved as a protective mechanism to prevent impairment of the most ancient but vitally important sensory system. In addition, differentiation of a substantial portion of progenitors to glial cells, including macrophages and microglia, may create an additional barrier to exogenous agents on their way deep to the brain.


title: Pancreatic Myeloid Sarcoma

text: Myeloid sarcoma is an isolated extramedullary tumor mass consisting of immature myeloid cells. It is characterized by highly variable outcomes and usually disrupts the normal architecture of the normal tissue in which it originates. It may occur de novo or be associated with other hematological malignancies. Clinical presentation of myeloid sarcomas can be highly variable based on the tumor site, size, and extent of tissue involvement. The diagnosis of myeloid sarcoma is challenging and requires a high index of suspicion. Tissue sampling followed by the use of auxiliary studies is essential for diagnosis. Moreover, bone marrow sampling is necessary to exclude morrow involvement. Currently, the recommended therapeutic regimens for myeloid sarcoma are similar to those for acute myeloid leukemia. Much work remains to be accomplished as myeloid sarcomas, if initially missed or misdiagnosed, have poor overall survival rates. Furthermore, prognostic factors for this malignancy remain poorly understood.


title: Comparative Functional Analysis of 12 Mammalian IFN-λ4 Orthologs

text: IFN-λ4 is a novel type-III interferon with strong clinical significance in humans. Only a subset of individuals—up to 10% of Asians, 50% of Europeans, and 90% of Africans—carry the ΔG allele of a genetic variant rs368234815-TT/ΔG and are genetically able to produce IFN-λ4 protein. Carriers of the ΔG allele have impaired ability to clear infection with hepatitis C virus (HCV). IFN-λ4 is also predicted to exist and be functionally important in several nonhuman mammals. In this study, we present the first comparative analysis of 12 mammalian IFN-λ4 orthologs in a human hepatic cell line, HepG2, which supports signaling of the human IFN-λ4. We show that despite differences in protein sequences, functional properties of the recombinant human and nonhuman IFN-λ4 proteins are comparable—they are all expressed as predominantly cytoplasmic proteins that are biologically active for induction of interferon signaling. We show that several IFN-λ4 orthologs can be detected by Western blotting, flow cytometry, and confocal imaging using a monoclonal antibody developed for the human IFN-λ4. Studies of IFN-λ4 in animals should help improve our understanding of the biology of this novel clinically important interferon in normal and disease conditions.


title: Infection-control knowledge, attitude, practice, and risk perception of occupational exposure to Zika virus among nursing students in Korea: A cross-sectional survey

text: Abstract Background As the number of patients with Zika virus infection increases worldwide, nursing students who conduct clinical practice in hospitals tend to at risk of Zika virus infection. Therefore, this study was conducted to identify nursing students’ knowledge, attitudes, practices, and risk perceptions of infection prevention related to occupational exposure to Zika virus infection, and to identify correlations among the related variables. Methods This cross-sectional study included 249 nursing students from 3 nursing colleges located in 3 Korean cities, with experience in hospital clinical practice. A questionnaire to assess the knowledge, attitudes, practices, and risk perceptions of Zika virus infection was developed through a literature review and was subjected to pilot testing and validation. Results The level of infection-control knowledge for Zika virus was 54.5 of 100 points, and that of practice was 4.5 of 5 points. The infection-prevention attitude score was 4.4 of 5 points, and the risk-perception score was 2.3 of 5 points. Significant differences emerged in infection-prevention attitude toward Zika virus based on Zika virus vaccination intention. Additionally, practice and risk-perception scores differed significantly based on gender and Zika virus vaccination intention. Knowledge significantly correlated with attitude and attitude toward preventive behavior. Conclusion Improvement in infection-control knowledge for Zika virus can help improve nurses’ related attitudes, which in turn could promote effective practice. Considering the characteristics of nursing students, it is necessary to develop and apply an effective and viable education program related to the prevention of Zika virus infection.


title: A non-linear model of information sharing practices in academic communities

text: Abstract A new model of information sharing practices in academic communities is based on Latour's circulatory system of scientific facts, and some elements of Foster's non-linear model of information-seeking behavior. The main proposition of this model is that information-sharing practices and context simultaneously shape each other. The proposed model supports Foster's conceptualization of information practices as non-linear processes, but its emphasis on the interdependence between context and information practices provides a more effective means to capture complex negotiations involved in information-sharing practices. The proposition is that the major reason for nonlinearity in information practices is a continuous shifting of actors' interests, pressures, and concerns. Capturing these dynamic relations becomes possible through this model. The model also offers a way to generate a number of research questions and hypotheses, and as such it could be a useful tool for empirical studies on information sharing in academic communities.


Infectious disease surveillance in China


title: Expression of Immunogenic Glycoprotein S Polypeptides from Transmissible Gastroenteritis Coronavirus in Transgenic Plants

text: Abstract The use of transgenic plants as vaccine production systems was described recently. We report on the immunological response elicited by two recombinant versions of the glycoprotein S from the swine-transmissible gastroenteritis coronavirus (TGEV) expressed in transgenic plants. Arabidoposis plants were genetically transformed with cDNAs constructs encoding either the N-terminal domain (amino acid residues 1–750) or the full-length glycoprotein S of TGEV, responsible for the neutralizing antibody induction against the virus, under the control of the cauliflower mosaic virus 35S (CaMV 35S) promoter. Genomic DNA and mRNA analyses of leaf extracts from transformed plants demonstrated the incorporation of the foreign cDNA into the arabidopsis genome, as well as their transcription. Expression of recombinant polypeptides were observed in most transgenic plants by ELISA using specific antibodies. Mice immunized with leaf extracts from transgenic plants developed antibodies that reacted specifically with TGEV in ELISA, immunoprecipitated the virus-induced protein, and neutralized the virus infectivity. From these results, we conclude that transgenic plants expressing glycoprotein S polypeptides may possibly be used as a source of recombinant antigen for vaccine production.


title: Estimating the generation interval for coronavirus disease (COVID-19) based on symptom onset data, March 2020

text: BACKGROUND: Estimating key infectious disease parameters from the coronavirus disease (COVID-19) outbreak is essential for modelling studies and guiding intervention strategies. AIM: We estimate the generation interval, serial interval, proportion of pre-symptomatic transmission and effective reproduction number of COVID-19. We illustrate that reproduction numbers calculated based on serial interval estimates can be biased. METHODS: We used outbreak data from clusters in Singapore and Tianjin, China to estimate the generation interval from symptom onset data while acknowledging uncertainty about the incubation period distribution and the underlying transmission network. From those estimates, we obtained the serial interval, proportions of pre-symptomatic transmission and reproduction numbers. RESULTS: The mean generation interval was 5.20 days (95% credible interval (CrI): 3.78–6.78) for Singapore and 3.95 days (95% CrI: 3.01–4.91) for Tianjin. The proportion of pre-symptomatic transmission was 48% (95% CrI: 32–67) for Singapore and 62% (95% CrI: 50–76) for Tianjin. Reproduction number estimates based on the generation interval distribution were slightly higher than those based on the serial interval distribution. Sensitivity analyses showed that estimating these quantities from outbreak data requires detailed contact tracing information. CONCLUSION: High estimates of the proportion of pre-symptomatic transmission imply that case finding and contact tracing need to be supplemented by physical distancing measures in order to control the COVID-19 outbreak. Notably, quarantine and other containment measures were already in place at the time of data collection, which may inflate the proportion of infections from pre-symptomatic individuals.


title: Membrane ectopeptidases targeted by human coronaviruses

text: Six coronaviruses, including the recently identified Middle East respiratory syndrome coronavirus, are known to target the human respiratory tract causing mild to severe disease. Their interaction with receptors expressed on cells located in the respiratory tract is an essential first step in the infection. Thus far three membrane ectopeptidases, dipeptidyl peptidase 4 (DPP4), angiotensin-converting enzyme 2 (ACE2) and aminopeptidase N (APN), have been identified as entry receptors for four human-infecting coronaviruses. Although the catalytic activity of the ACE2, APN, and DPP4 peptidases is not required for virus entry, co-expression of other host proteases allows efficient viral entry. In addition, evolutionary conservation of these receptors may permit interspecies transmissions. Because of the physiological function of these peptidase systems, pathogenic host responses may be potentially amplified and cause acute respiratory distress.


title: Transcriptome profiling of whitefly guts in response to Tomato yellow leaf curl virus infection

text: BACKGROUND: Plant viruses in agricultural crops are of great concern worldwide, and over 75% of them are transmitted from infected to healthy plants by insect vectors. Tomato yellow leaf curl virus (TYLCV) is a begomovirus, which is the largest and most economically important group of plant viruses, transmitted by the whitefly Bemisia tabaci. The circulation of TYLCV in the insect involves complex insect-virus interactions, whereas the molecular mechanisms of these interactions remain ambiguous. The insect gut as a barrier for viral entry and dissemination is thought to regulate the vector specificity. However, due to its tiny size, information for the responses of whitefly gut to virus infection is limited. METHODS: We investigated the transcriptional response of the gut of B. tabaci Middle East-Asia Minor 1 species to TYLCV infection using Illumina sequencing. RESULTS: A total of 5207 differentially expressed genes (DEGs) between viruliferous and non-viruliferous whitefly guts were identified. Enrichment analyses showed that cargo receptor and ATP-binding cassette (ABC) transporters were enriched in DEGs, and might help the virus to cross gut barrier. TYLCV could perturb cell cycle and DNA repair as a possible result of its replication in the whitefly. Our data also demonstrated that TYLCV can activate whitefly defense responses, such as antimicrobial peptides. Meanwhile, a number of genes involved in intracellular signaling were activated by TYLCV infection. CONCLUSIONS: Our results reveal the complex insect-virus relationship in whitefly gut and provide substantial molecular information for the role of insect midguts in virus transmission. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12985-018-0926-6) contains supplementary material, which is available to authorized users.


title: Different rates of (non-)synonymous mutations in astrovirus genes; correlation with gene function

text: BACKGROUND: Complete genome sequences of the Astroviridae include human, non-human mammalian and avian species. A consensus topology of astroviruses has been derived from nucleotide substitutions in the full-length genomes and from non-synonymous nucleotide substitutions in each of the three ORFs. Analyses of synonymous substitutions displayed a loss of tree structure, suggesting either saturation of the substitution model or a deviant pattern of synonymous substitutions in certain virus species. RESULTS: We analyzed the complete Astroviridae family for the inference of adaptive molecular evolution at sites and in branches. High rates of synonymous mutations are observed among the non-human virus species. Deviant patterns of synonymous substitutions are found in the capsid structural genes. Purifying selection is a dominant force among all astrovirus genes and only few codon sites showed values for the dN/dS ratio that may indicate site-specific molecular adaptation during virus evolution. One of these sites is the glycine residue of a RGD motif in ORF2 of human astrovirus serotype 1. RGD or similar integrin recognition motifs are present in nearly all astrovirus species. CONCLUSION: Phylogenetic analysis directed by maximum likelihood approximation allows the inclusion of significantly more evolutionary history and thereby, improves the estimation of dN and dS. Sites with enhanced values for dN/dS are prominent at domains in charge of environmental communication (f.i. VP27 and domain 4 in ORF1a) more than at domains dedicated to intrinsic virus functions (f.i. VP34 and ORF1b (the virus polymerase)). Integrin recognition may play a key role in astrovirus to target cell attachment.


title: Zika fever and congenital Zika syndrome: An unexpected emerging arboviral disease

text: Summary Unlike its mosquito-borne relatives, such as dengue, West Nile, and Japanese encephalitis viruses, which can cause severe human diseases, Zika virus (ZIKV) has emerged from obscurity by its association with a suspected “congenital Zika syndrome”, while causing asymptomatic or mild exanthematous febrile infections which are dengue- or rubella-like in infected individuals. Despite having been discovered in Uganda for almost 60 years, <20 human cases were reported before 2007. The massive epidemics in the Pacific islands associated with the ZIKV Asian lineage in 2007 and 2013 were followed by explosive outbreaks in Latin America in 2015. Although increased mosquito breeding associated with the El Niño effect superimposed on global warming is suspected, genetic changes in its RNA virus genome may have led to better adaptation to mosquitoes, other animal reservoirs, and human. We reviewed the epidemiology, clinical manifestation, virology, pathogenesis, laboratory diagnosis, management, and prevention of this emerging infection. Laboratory diagnosis can be confounded by cross-reactivity with other circulating flaviviruses. Besides mosquito bite and transplacental transmission, the risk of other potential routes of transmission by transfusion, transplantation, sexual activity, breastfeeding, respiratory droplet, and animal bite is discussed. Epidemic control requires adequate clearance of mosquito breeding grounds, personal protection against mosquito bite, and hopefully a safe and effective vaccine.


title: RNA decay during gammaherpesvirus infection reduces RNA polymerase II occupancy of host promoters but spares viral promoters

text: In mammalian cells, widespread acceleration of cytoplasmic mRNA degradation is linked to impaired RNA polymerase II (Pol II) transcription. This mRNA decay-induced transcriptional repression occurs during infection with gammaherpesviruses including Kaposi’s sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV68), which encode an mRNA endonuclease that initiates widespread RNA decay. Here, we show that MHV68-induced mRNA decay leads to a genome-wide reduction of Pol II occupancy at mammalian promoters. This reduced Pol II occupancy is accompanied by down-regulation of multiple Pol II subunits and TFIIB in the nucleus of infected cells, as revealed by mass spectrometry-based global measurements of protein abundance. Viral genes, despite the fact that they require Pol II for transcription, escape transcriptional repression. Protection is not governed by viral promoter sequences; instead, location on the viral genome is both necessary and sufficient to escape the transcriptional repression effects of mRNA decay. We propose a model in which the ability to escape from transcriptional repression is linked to the localization of viral DNA within replication compartments, providing a means for these viruses to counteract decay-induced transcript loss.


title: Clinical severity of rhinovirus/enterovirus compared to other respiratory viruses in children

text: BACKGROUND: Human rhinovirus/enterovirus (HRV/ENT) infections are commonly identified in children with acute respiratory infections (ARIs), but data on their clinical severity remain limited. OBJECTIVES: We compared the clinical severity of HRV/ENT to respiratory syncytial virus (RSV), influenza A/B (FLU), and other common respiratory viruses in children. PATIENTS/METHODS: Retrospective study of children with ARIs and confirmed single positive viral infections on mid‐turbinate swabs by molecular assays. Outcome measures included hospital admission and, for inpatients, a composite endpoint consisting of intensive care admission, hospitalization >5 days, oxygen requirements or death. RESULTS: A total of 116 HRV/ENT, 102 RSV, 99 FLU, and 64 other common respiratory viruses were identified. Children with single HRV/ENT infections presented with significantly higher rates of underlying immunosuppressive conditions compared to those with RSV (37·9% versus 13·6%; P < 0·001), FLU (37·9% versus 22%; P = 0·018) or any other single viral infection (37·9% versus 22·5%; P = 0·024). In multivariable analysis adjusted for underlying conditions and age, children with HRV/ENT infections had increased odds of hospitalization compared to children with RSV infections (OR 2·6; 95% CI 1·4, 4·8; P < 0·003) or FLU infections (OR 3·0; 95% CI 1·6, 5·8; <0·001) and increased odds of severe clinical disease among inpatients (OR 3·0; 95% CI 1·6,5·6; P = 0·001) when compared to those with FLU infections. CONCLUSIONS: Children with HRV/ENT had a more severe clinical course than those with RSV and FLUA/B infections and often had significant comorbidities. These findings emphasize the importance of considering HRV/ENT infection in children presenting with severe acute respiratory tract infections.


title: Nidovirus RNA polymerases: Complex enzymes handling exceptional RNA genomes

text: Abstract Coronaviruses and arteriviruses are distantly related human and animal pathogens that belong to the order Nidovirales. Nidoviruses are characterized by their polycistronic plus-stranded RNA genome, the production of subgenomic mRNAs and the conservation of a specific array of replicase domains, including key RNA-synthesizing enzymes. Coronaviruses (26–34 kilobases) have the largest known RNA genomes and their replication presumably requires a processive RNA-dependent RNA polymerase (RdRp) and enzymatic functions that suppress the consequences of the typically high error rate of viral RdRps. The arteriviruses have significantly smaller genomes and form an intriguing package with the coronaviruses to analyse viral RdRp evolution and function. The RdRp domain of nidoviruses resides in a cleavage product of the replicase polyprotein named non-structural protein (nsp) 12 in coronaviruses and nsp9 in arteriviruses. In all nidoviruses, the C-terminal RdRp domain is linked to a conserved N-terminal domain, which has been coined NiRAN (nidovirus RdRp-associated nucleotidyl transferase). Although no structural information is available, the functional characterization of the nidovirus RdRp and the larger enzyme complex of which it is part, has progressed significantly over the past decade. In coronaviruses several smaller, non-enzymatic nsps were characterized that direct RdRp function, while a 3′-to-5′ exoribonuclease activity in nsp14 was implicated in fidelity. In arteriviruses, the nsp1 subunit was found to maintain the balance between genome replication and subgenomic mRNA production. Understanding RdRp behaviour and interactions during RNA synthesis and subsequent processing will be key to rationalising the evolutionary success of nidoviruses and the development of antiviral strategies.


title: THE INTRACELLULAR CARGO RECEPTOR ERGIC-53 IS REQUIRED FOR THE PRODUCTION OF INFECTIOUS ARENAVIRUS, CORONAVIRUS, AND FILOVIRUS PARTICLES

text: Arenaviruses and hantaviruses cause severe and often fatal diseases in humans. Little is known regarding host proteins required for their propagation. We identified human proteins that interact with the glycoproteins (GPs) of a prototypic arenavirus and hantavirus and show that the lectin ERGIC-53 - a cargo receptor required for cellular glycoprotein trafficking within the early exocytic pathway - associates with arenavirus, hantavirus, coronavirus, orthomyxovirus, and filovirus GPs. ERGIC-53 binds to arenavirus GPs through a lectin-independent mechanism, traffics to arenavirus budding sites, and is incorporated into arenavirus particles. ERGIC-53 is required for arenavirus, coronavirus, and filovirus propagation; in its absence, GP-containing virus particles form, but are noninfectious due, in part, to their inability to attach to host cells. Thus, we have identified a class of pathogen-derived ERGIC-53 ligands, a lectin-independent basis for their association with ERGIC-53, and a role for ERGIC-53 in the propagation of several highly pathogenic RNA virus families.


COVID-19, Medicare-for-All, and the Uncertain Future of Emergency Medicine


title: Pulmonary Metagenomic Sequencing Suggests Missed Infections in Immunocompromised Children

text: Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant morbidity and mortality. To develop a highly sensitive metagenomic next generation sequencing (mNGS) assay capable of evaluating the pulmonary microbiome and identifying diverse pathogens in the lungs of immunocompromised children. We collected 41 lower respiratory specimens from 34 immunocompromised children undergoing evaluation for pulmonary disease at 3 children’s hospitals from 2014-2016. Samples underwent mechanical homogenization, paired RNA/DNA extraction, and metagenomic sequencing. Sequencing reads were aligned to the NCBI nucleotide reference database to determine taxonomic identities. Statistical outliers were determined based on abundance within each sample and relative to other samples in the cohort. We identified a rich cross-domain pulmonary microbiome containing bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Samples with bacterial outliers had significantly depressed alpha-diversity (median 0.58, IQR 0.33-0.62 vs. median 0.94, IQR 0.93-0.95, p<0.001). Potential pathogens were detected in half of samples previously negative by clinical diagnostics, demonstrating increased sensitivity for missed pulmonary pathogens (p<0.001). An optimized mNGS assay for pulmonary microbes demonstrates significant inoculation of the lower airways of immunocompromised children with diverse bacteria, fungi, and viruses. Potential pathogens can be identified based on absolute and relative abundance. Ongoing investigation is needed to determine the pathogenic significance of outlier microbes in the lungs of immunocompromised children with pulmonary disease.


title: Plant molecular farming: systems and products

text: Plant molecular farming is a new and promising industry involving plant biotechnology. In this review, we describe several diverse plant systems that have been developed to produce commercially useful proteins for pharmaceutical and industrial uses. The advantages and disadvantages of each system are discussed. The first plant-derived molecular farming products have reached the marketplace and other products are poised to join them during the next few years. We explain the rationale for using plants as biofactories. We also describe the products currently on the market, and those that appear likely to join them in the near future. Lastly, we discuss the issue of public acceptance of molecular farming products.


title: Functionality testing of stem cell grafts to predict infectious complications after allogeneic hematopoietic stem cell transplantation

text: BACKGROUND AND OBJECTIVES: Allogeneic hematopoietic stem cell transplantation (HSCT) is a routine clinical procedure performed to treat patients with haematological malignancies, primary immune deficiencies or metabolic disorders. Infections during lymphopenia after allogeneic HSCT are associated with high mortality and morbidity. Typical infectious agents are Epstein–Barr virus, cytomegalovirus, herpes simplex virus, varicella‐zoster virus and fungi. The study aim was to evaluate whether measurement of the responses of antigen‐specific T‐cells, recognizing infectious pathogens would correlate to protective functions in the stem cell recipient post‐transplant. MATERIALS AND METHODS: Twenty‐one grafts were analysed by flow cytometry and cells were stimulated in vitro with relevant infectious antigens, followed by evaluation of T‐cell proliferation and cytokine production. Results were compared to the recipients’ clinical records 1‐year post‐transplantation. RESULTS: We show that an extensive repertoire of transferred antigen‐specific T‐cells from allogeneic donor grafts against infectious agents, involved in post‐transplant infections, are linked to an absence of infectious complications for the recipient up‐to 1‐year post‐transplant. The protective effect was associated with antigen‐specific T‐cell proliferation and IL‐1β secretion. CONCLUSION: Our results suggest that assaying T‐cell function before HSCT could determine individual risks for infectious complications and thus aid in clinical decision‐making regarding prophylactic and pre‐emptive anti‐infective therapy.


title: From Easing Lockdowns to Scaling-Up Community-Based COVID-19 Screening, Testing, and Contact Tracing in Africa – Shared Approaches, Innovations, and Challenges to Minimize Morbidity and Mortality

text: The arrival of COVID-19 to the African continent resulted in a range of locally relevant lockdown measures, which curtailed the spread of SARS-CoV-2 but caused economic hardship for large sections of the population. African countries now face difficult choices regarding easing of lockdowns and sustaining effective public health control measures and surveillance. Control of the COVID-19 pandemic will require efficient community screening, testing, contact tracing, and behavioral change interventions, adequate resources, and a well-supported, community-based team of trained, protected personnel. We discuss COVID-19 screening-testing-contact tracing approaches used in selected African countries and the need for shared, affordable, innovative methods to overcome challenges and minimize mortality rates. This crisis presents a unique opportunity to align COVID-19 services with those already in place for HIV, TB, Malaria, and other non-communicable diseases (NCDs) through mobilization of Africa's inter-professional healthcare workforce to contain the pandemic. By addressing the challenges, the detrimental effect of the COVID-19 pandemic on African citizens can be minimized.


title: Personal Protective Equipment for Healthcare Workers during the COVID-19 Pandemic

text: The coronavirus disease (COVID-19) pandemic has posed a challenge for healthcare systems, and healthcare workers (HCWs) are at high risk of exposure. Protecting HCWs is of paramount importance to maintain continuous patient care and keep healthcare systems functioning. Used alongside administrative and engineering control measures, personal protective equipment (PPE) is the last line of defense and the core component of protection. Current data suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is mainly transmitted through respiratory droplets and close contact. Airborne transmission may occur during aerosol-generating procedures. However, the modes of transmission still remain uncertain, especially regarding the possibility of airborne transmission when aerosol-generating procedures are not performed. Thus, there are some inconsistencies in the respiratory protective equipment recommended by international and national organizations. In Korea, there have been several modifications to PPE recommendations offering options in choosing PPE for respiratory and body protection, which confuses HCWs; they are often unsure what to wear and when to wear it. The choice of PPE is based on the risk of exposure and possible modes of transmission. The level of protection provided by PPE differs based on standards and test methods. Thus, understanding them is the key in selecting the proper PPE. This article reviews evidence on the mode of SARS-CoV-2 transmission, compares the current PPE recommendations of the World Health Organization with those in Korea, and discusses standard requirements and the proper selection of PPE.


title: Assembly and budding of influenza virus

text: Abstract Influenza viruses are causative agents of an acute febrile respiratory disease called influenza (commonly known as “flu”) and belong to the Orthomyxoviridae family. These viruses possess segmented, negative stranded RNA genomes (vRNA) and are enveloped, usually spherical and bud from the plasma membrane (more specifically, the apical plasma membrane of polarized epithelial cells). Complete virus particles, therefore, are not found inside infected cells. Virus particles consist of three major subviral components, namely the viral envelope, matrix protein (M1), and core (viral ribonucleocapsid [vRNP]). The viral envelope surrounding the vRNP consists of a lipid bilayer containing spikes composed of viral glycoproteins (HA, NA, and M2) on the outer side and M1 on the inner side. Viral lipids, derived from the host plasma membrane, are selectively enriched in cholesterol and glycosphingolipids. M1 forms the bridge between the viral envelope and the core. The viral core consists of helical vRNP containing vRNA (minus strand) and NP along with minor amounts of NEP and polymerase complex (PA, PB1, and PB2). For viral morphogenesis to occur, all three viral components, namely the viral envelope (containing lipids and transmembrane proteins), M1, and the vRNP must be brought to the assembly site, i.e. the apical plasma membrane in polarized epithelial cells. Finally, buds must be formed at the assembly site and virus particles released with the closure of buds. Transmembrane viral proteins are transported to the assembly site on the plasma membrane via the exocytic pathway. Both HA and NA possess apical sorting signals and use lipid rafts for cell surface transport and apical sorting. These lipid rafts are enriched in cholesterol, glycosphingolipids and are relatively resistant to neutral detergent extraction at low temperature. M1 is synthesized on free cytosolic polyribosomes. vRNPs are made inside the host nucleus and are exported into the cytoplasm through the nuclear pore with the help of M1 and NEP. How M1 and vRNPs are directed to the assembly site on the plasma membrane remains unclear. The likely possibilities are that they use a piggy-back mechanism on viral glycoproteins or cytoskeletal elements. Alternatively, they may possess apical determinants or diffuse to the assembly site, or a combination of these pathways. Interactions of M1 with M1, M1 with vRNP, and M1 with HA and NA facilitate concentration of viral components and exclusion of host proteins from the budding site. M1 interacts with the cytoplasmic tail (CT) and transmembrane domain (TMD) of glycoproteins, and thereby functions as a bridge between the viral envelope and vRNP. Lipid rafts function as microdomains for concentrating viral glycoproteins and may serve as a platform for virus budding. Virus bud formation requires membrane bending at the budding site. A combination of factors including concentration of and interaction among viral components, increased viscosity and asymmetry of the lipid bilayer of the lipid raft as well as pulling and pushing forces of viral and host components are likely to cause outward curvature of the plasma membrane at the assembly site leading to bud formation. Eventually, virus release requires completion of the bud due to fusion of the apposing membranes, leading to the closure of the bud, separation of the virus particle from the host plasma membrane and release of the virus particle into the extracellular environment. Among the viral components, M1 contains an L domain motif and plays a critical role in budding. Bud completion requires not only viral components but also host components. However, how host components facilitate bud completion remains unclear. In addition to bud completion, influenza virus requires NA to release virus particles from sialic acid residues on the cell surface and spread from cell to cell. Elucidation of both viral and host factors involved in viral morphogenesis and budding may lead to the development of drugs interfering with the steps of viral morphogenesis and in disease progression.


title: Harvesting Patterns from Textual Web Sources with Tolerance Rough Sets

text: Construction of knowledge repositories from web corpora by harvesting linguistic patterns is of benefit for many natural language-processing applications that rely on question-answering schemes. These methods require minimal or no human intervention and can recursively learn new relational facts-instances in a fully automated and scalable manner. This paper explores the performance of tolerance rough set-based learner with respect to two important issues: scalability and its effect on concept drift, by (1) designing a new version of the semi-supervised tolerance rough set-based pattern learner (TPL 2.0), (2) adapting a tolerance form of rough set methodology to categorize linguistic patterns, and (3) extracting categorical information from a large noisy dataset of crawled web pages. This work demonstrates that the TPL 2.0 learner is promising in terms of precision@30 metric when compared with three benchmark algorithms: Tolerant Pattern Learner 1.0, Fuzzy-Rough Set Pattern Learner, and Coupled Bayesian Sets-based learner.


title: Asymmetric nexus between temperature and COVID-19 in the top ten affected provinces of China: A current application of quantile-on-quantile approach

text: Abstract The present study examines the asymmetrical effect of temperature on COVID-19 (Coronavirus Disease) from 22 January 2020 to 31 March 2020 in the 10 most affected provinces in China. This study used the Sim & Zhou' quantile-on-quantile (QQ) approach to analyze how the temperature quantities affect the different quantiles of COVID-19. Daily COVID-19 and, temperature data collected from the official websites of the Chinese National Health Commission and Weather Underground Company (WUC) respectively. Empirical results have shown that the relationship between temperature and COVID-19 is mostly positive for Hubei, Hunan, and Anhui, while mostly negative for Zhejiang and Shandong provinces. The remaining five provinces Guangdong, Henan, Jiangxi, Jiangsu, and Heilongjiang are showing the mixed trends. These differences among the provinces can be explained by the differences in the number of COVID-19 cases, temperature, and the province's overall hospital facilitations. The study concludes that maintaining a safe and comfortable atmosphere for patients while COVID-19 is being treated may be rational.


title: Virological and molecular characterization of a mammalian orthoreovirus type 3 strain isolated from a dog in Italy

text: Abstract A mammalian orthoreovirus (MRV) strain was isolated from a pup with fatal diarrhea, which had a concurrent infection by canine parvovirus type 2. The reovirus isolate showed an atypical hemagglutination pattern and a retarded electrophoretic mobility of the S1 segment, which is characteristic of MRV type 3 (MRV-3). Assignment of the isolated virus to MRV-3 was confirmed by type-specific RT-PCR assays, targeting the S1 gene, and by subsequent sequence analysis of the PCR product. By phylogeny based on the S1 gene of several MRVs, the isolate fell into lineage E, along with the murine strain T3C9/61 and the bovine strains T3C18/61 and T3C31/59. Conversely, L1 sequences were found to segregate regardless of the viral type. A total of 110 fecal samples, 56 nasal and 31 ocular swabs from dogs with diarrhea or nasal/ocular discharge were tested by a nested-PCR assay specific for reoviruses, and no sample was found to contain MRV RNA, a finding that is apparently in contrast with the seroprevalence (25.77%) observed in dogs.


Cogito ergo sum


title: Chapter 3 Bacteria, Viruses, and the Microbiome

text: Abstract Bacterial and viral illnesses have been a constant threat to well-being. Because of their ability to mutate, continuous surveillance is necessary to prevent diseases. Even with this, the possibility of viral spread from animal to human, and then between humans, is a worrisome prospect. Many bacteria have also been encouraged to mutate so that they have become resistant to standard antiobiotic treatments, including those that were considered the last bastion of defense. Aside from these foreign particles, microbiota comprising bacteria, viruses, fungi, archaea, and protists occupy much of the human body. Typically, beneficial and potentially harmful microbes live harmoniously, but under a variety of conditions (e.g., antibiotic treatment, stressors, and toxicant exposure), dysbiosis or frank loss of bacteria occurs. These microbiota variations may affect immune functioning, thus increasing vulnerability to a range of physical illnesses, and by virtue of brain changes imparted may promote psychological disorders.


title: Pneumonies communautaires graves de l'adulte

text: Résumé Les pneumonies aiguës communautaires sont des causes fréquentes d'hospitalisation et de mortalité. La reconnaissance immédiate des formes sévères sur des critères simples, cliniques, radiologiques et biologiques, est une étape importante pour une prise en charge rapide en réanimation afin de contrôler les défaillances d'organes. Les prélèvements appropriés microbiologiques précèdent l'antibiothérapie qui doit être instituée très rapidement après le diagnostic de pneumonie. Malgré les techniques d'identification, la moitié seulement des pneumonies sont documentées. Cette antibiothérapie, initialement probabiliste, intègre les germes pathogènes les plus souvent responsables, extra- et intracellulaires ; elle doit toujours être active sur le pneumocoque, bactérie la plus fréquente. L'association d'une β-lactamine et d'un macrolide ou d'une fluoroquinolone répond le mieux à cet objectif. Les fluoroquinolones actives sur le pneumocoque se sont substituées aux précédentes dans les plus récentes recommandations. Dans le cas exceptionnel des patients ayant des facteurs de risque particuliers, le traitement probabiliste doit prendre en compte Pseudomonas aeruginosa. La gravité d'une partie des pneumonies communautaires justifie le recours à des traitements adjuvants. L'antibiothérapie doit être réévaluée dans les 72 heures dans le but d'apprécier son efficacité, de l'adapter éventuellement et de la simplifier. La poursuite des antibiotiques à large spectre expose le patient à des effets indésirables et contribue aux résistances bactériennes. Pour les pneumonies dues au pneumocoque, les fluoroquinolones actives sur le pneumocoque pourront constituer une alternative en cas d'évolution importante des résistances du pneumocoque aux β-lactamines. La mortalité persistante des pneumonies reste sévère. Ceci doit stimuler l'amélioration de la prise en charge initiale et faire rechercher de nouvelles thérapeutiques. Abstract Community-acquired pneumonias are major causes of hospitalization and death. Immediate assessment of severity, based on accurate clinical criteria, is an important step for rapid intensive care management and control of organ failures. Appropriate microbiological sampling should be performed prior to the antimicrobial therapy that should be initiated promptly after the diagnostic. Despite identification techniques, only 50% of community-acquired pneumonia cases are documented. Antibiotherapy is initially empirical. The goal is to provide optimal therapy for the most commonly identified causes of lethal pneumonia: extracellular and intracellular pathogens. A therapeutic regimen with a β-lactam combined with a macrolide or a fluoroquinolone is recommended. This combination should be always active against pneumococci. Despite increased pneumococcal penicillin resistance, the recent recommendations are not modified. Respiratory fluoroquinolones may be an alternative in case of major increase of pneumococcal resistance to β-lactams. In some special populations, with regard to underlying structural disease of the lung and other risk factors, Pseudomonas aeruginosa must be taken into account. The severity of some community-acquired pneumonias necessitates the use of adjunctive treatments. Reassessment should be undertaken 72 hours after initiation of therapy in order to evaluate the response to treatment, to simplify or to readapt the empirical treatment. Unjustified continuation of wide spectrum antibiotics leads to adverse events and widespread of bacterial resistance. The poor outcome of severe pneumonias justifies research on initial process of care and new therapeutics.


title: A new comprehensive method for detection of livestock-related pathogenic viruses using a target enrichment system

text: Abstract We tested usefulness of a target enrichment system SureSelect, a comprehensive viral nucleic acid detection method, for rapid identification of viral pathogens in feces samples of cattle, pigs and goats. This system enriches nucleic acids of target viruses in clinical/field samples by using a library of biotinylated RNAs with sequences complementary to the target viruses. The enriched nucleic acids are amplified by PCR and subjected to next generation sequencing to identify the target viruses. In many samples, SureSelect target enrichment method increased efficiencies for detection of the viruses listed in the biotinylated RNA library. Furthermore, this method enabled us to determine nearly full-length genome sequence of porcine parainfluenza virus 1 and greatly increased Breadth, a value indicating the ratio of the mapping consensus length in the reference genome, in pig samples. Our data showed usefulness of SureSelect target enrichment system for comprehensive analysis of genomic information of various viruses in field samples.


title: Malaria in China: a longitudinal population-based surveillance study

text: This study aims to ascertain the long-term epidemic trends of malaria and evaluates the probability of achieving the eradication goal by 2020 in China. Data on malaria incidence and deaths were extracted from the China Information System for Disease Control and Prevention. The epidemic trends by sex, age and spatial distribution and predictions of malaria were estimated by using Joinpoint and Poisson regressions. From 1950 to 2016, 227 668 374 malaria cases were reported in China, with an annualised average incidence of 337.02 (336.98–337.07, 95% confidence interval (CI)) per 100 000 population. The incidence decreased with an average annual per cent change (AAPC) of −11.4% (−16.6 to −6.0). There were 36 085 malaria deaths, with an annualised average mortality of 0.534 (0.529–0.540) per 1 000 000 population. The mortality decreased with an AAPC of −8.7% (−13.7 to −3.4). The predicted number of malaria cases and deaths for 2020 is 2 562 and 10, respectively, and zero for indigenous cases. The disease burden of malaria dramatically decreased in China. Though, the goal of malaria elimination is realistic by 2020 in China, routine clinical and entomological surveillance should be continually conducted, especially for the cross-border areas and imported malaria cases.


title: Data–model fusion to better understand emerging pathogens and improve infectious disease forecasting

text: Ecologists worldwide are challenged to contribute solutions to urgent and pressing environmental problems by forecasting how populations, communities, and ecosystems will respond to global change. Rising to this challenge requires organizing ecological information derived from diverse sources and formally assimilating data with models of ecological processes. The study of infectious disease has depended on strategies for integrating patterns of observed disease incidence with mechanistic process models since John Snow first mapped cholera cases around a London water pump in 1854. Still, zoonotic and vector‐borne diseases increasingly affect human populations, and methods used to successfully characterize directly transmitted diseases are often insufficient. We use four case studies to demonstrate that advances in disease forecasting require better understanding of zoonotic host and vector populations, as well of the dynamics that facilitate pathogen amplification and disease spillover into humans. In each case study, this goal is complicated by limited data, spatiotemporal variability in pathogen transmission and impact, and often, insufficient biological understanding. We present a conceptual framework for data–model fusion in infectious disease research that addresses these fundamental challenges using a hierarchical state‐space structure to (1) integrate multiple data sources and spatial scales to inform latent parameters, (2) partition uncertainty in process and observation models, and (3) explicitly build upon existing ecological and epidemiological understanding. Given the constraints inherent in the study of infectious disease and the urgent need for progress, fusion of data and expertise via this type of conceptual framework should prove an indispensable tool.


title: Biocides and Novel Antimicrobial Agents for the Mitigation of Coronaviruses

text: In December, 2019, a highly infectious and rapidly spreading new pneumonia of unknown cause was reported to the Chinese WHO Country Office. A cluster of these cases had appeared in Wuhan, a city in the Hubei Province of China. These infections were found to be caused by a new coronavirus which was given the name “2019 novel coronavirus” (2019-nCoV). It was later renamed “severe acute respiratory syndrome coronavirus 2,” or SARS-CoV-2 by the International Committee on Taxonomy of Viruses on February 11, 2020. It was named SARS-CoV-2 due to its close genetic similarity to the coronavirus which caused the SARS outbreak in 2002 (SARS-CoV-1). The aim of this review is to provide information, primarily to the food industry, regarding a range of biocides effective in eliminating or reducing the presence of coronaviruses from fomites, skin, oral/nasal mucosa, air, and food contact surfaces. As several EPA approved sanitizers against SARS-CoV-2 are commonly used by food processors, these compounds are primarily discussed as much of the industry already has them on site and is familiar with their application and use. Specifically, we focused on the effects of alcohols, povidone iodine, quaternary ammonium compounds, hydrogen peroxide, sodium hypochlorite (NaOCl), peroxyacetic acid (PAA), chlorine dioxide, ozone, ultraviolet light, metals, and plant-based antimicrobials. This review highlights the differences in the resistance or susceptibility of different strains of coronaviruses, or similar viruses, to these antimicrobial agents.


title: Patient counseling through the pelvicalyceal-shaped labyrinth: in search of an easy understanding of the upcoming stone removal: a pilot study

text: OBJECTIVE: To investigate the impact of a mobile application (app) displaying a visualization of the internal anatomy of the pelvicalyceal system (PCS) and of kidney stones on patient understanding of their affected kidney anatomy and their upcoming percutaneous nephrolithotripsy (PCNL). MATERIALS AND METHODS: One-hundred patients who required PCNL were included in this study, and all patients were non-randomly distributed into two groups: counselled using only 3D-reconstructed computed tomography (CT) images (group 1) or using only the “InsKid” app (group 2). Patient data were obtained from CT scans as Digital Imaging and Communications in Medicine (DICOM) format and converted into stereolithography (STL) format. All patients completed the questionnaire after counselling, and the results were compared between groups. RESULTS: Patients from group 2 better understood the anatomy of their affected kidney by 53%; awareness regarding their stone location was better by 32%; the steps of planned surgery, as well as possible complications, were more transparent for patients using the app by 24% and 56%, respectively. The number of patients who were dissatisfied with the mobile counselling dropped by 70%. The average duration of consultation with the 3D reconstruction of CT images was 10.9 ± 0.6 min, while counselling using our program reliably led to a reduction in this duration (7.3 ± 0.5 min). CONCLUSION: The InsKid app is a freely available, easy-to-use educational software that improves patient counselling without considerable financial expense or long waiting periods for use.


title: Lactate dehydrogenase-elevating virus (LDV): subgenomic mRNAs, mRNA leader and comparison of 3'-terminal sequences of two LDV isolates

text: Abstract The 3'-terminal 1314 nucleotides of the genome of one isolate of lactate dehydrogenase-elevating virus, LDV-P, has been derived by sequence analyses of cDNAs from several genomic libraries and compared to that of another LDV isolate, LDV-C (Godeny et al. (1990) Virol. 177, 768–771). The 3'-non-coding segment of 80 nucleotides of the two LDV genomes is identical, whereas marked, but varying nucleotide and amino acid divergence is apparent in the three upstream overlapping open reading frames (ORF). The third ORF from the 3'-end exhibits only 82% nucleotide and 90% amino acid identity, whereas the 3'-terminal ORF, which encodes the nucleocapsid protein, exhibits approximately 99% amino acid identity. The second 3'-terminal ORF encodes an 18.8 kDa protein which lacks N-glycosylation sites but possesses 2 or 3 potential transmembrane helices in the N-terminal half of the molecule. A similar membrane organization is observed for the corresponding protein of equine arteritis virus and the M protein of mouse hepatitis virus. The sequence analyses combined with Northern hybridization analyses of RNA from LDV-infected macrophages and spleens of LDV-infected mice indicate that the three ORFs encoded by the 3'-terminal end of the LDV genome are expressed via the three smallest mRNAs (mRNAs 6–8) of the seven subgenomic mRNAs of LDV (mRNAs 2–8), which range in size from about 0.8 to 3.6 kb. All mRNAs have been shown to carry poly(A)-tracts and a common leader sequence. The seven mRNAs were produced in infected macrophage cultures concomitantly with genomic LDV RNA. Maximum LDV RNA synthesis was observed between 6 and 8 h post-infection. The same seven subgenomic mRNAs were detected in macrophages infected with three different isolates of LDV, but different relative amounts of some of the mRNAs were produced. The relative proportions of molecules of mRNAs 1–8 present in 6 h LDV-P-infected macrophages were about 13, 5, 5, 8, 6, 11, 11 and 27% of the total, respectively.


title: Year in review 2005: Critical Care – Respirology: mechanical ventilation, infection, monitoring, and education

text: We summarize all original research in the field of respiratory intensive care medicine published in 2005 in Critical Care. Twenty-seven articles were grouped into the following categories and subcategories to facilitate rapid overview: mechanical ventilation (physiology, spontaneous breathing during mechanical ventilation, high frequency oscillatory ventilation, side effects of mechanical ventilation, sedation, and prone positioning); infection (pneumonia and sepsis); monitoring (ventilatory monitoring, pulmonary artery catheter and pulse oxymeter); and education (training and health outcome).