title: Biomarkers of lung‐related diseases: Current knowledge by proteomic approaches

text: The lung epithelial surface is one of the vital barriers or sensors in the body responding to the external atmosphere and thereby always subjecting to direct toxicological exposure, stress, stimulus, or infection. Due to its relatively higher sensitivity in response to toxicants, the use of lung epithelial cell culture and lung tissue from animal models or patients has facilitated our learning to lung physiopathology and toxicopharmacology. The recent advancement of proteomics has made it possible to investigate the cellular response at a global level. In this review, the potential applications of proteomic approach in studying lung‐related diseases and biomarker discovery will be discussed. J. Cell. Physiol. 221: 535–543, 2009. © 2009 Wiley‐Liss, Inc.


title: Addressing the Challenges and Opportunities of the Polio Endgame: Lessons for the Future

text: The Global Commission for the Certification of the Eradication of Poliomyelitis certified the eradication of type 2 poliovirus in September 2015, making type 2 poliovirus the first human pathogen to be eradicated since smallpox. The eradication of type 2 poliovirus, the absence of detection of type 3 poliovirus worldwide since November 2012, and cornering type 1 poliovirus to only a few geographic areas of 3 countries has enabled implementation of the endgame of polio eradication which calls for a phased withdrawal of oral polio vaccine beginning with the type 2 component, introduction of inactivated poliovirus vaccine, strengthening of routine immunization in countries with extensive polio resources, and initiating activities to transition polio resources, program experience, and lessons learned to other global health initiatives. This supplement focuses on efforts by global partners to successfully launch polio endgame activities to permanently secure and sustain the enormous gains of polio eradication forever.


title: Adapting STEMI care for the COVID‐19 pandemic: The case for low‐risk STEMI triage and early discharge

text: The coronavirus pandemic has resulted in the need for rapid assessment of resource utilization within our hospital systems. Specifically, the overwhelming need for intensive care unit (ICU) beds within epicenters of the pandemic has created a need for consideration as to how acute coronary syndrome cases, and specifically ST‐elevation myocardial infarction (STEMI) patients, are managed postprocedure. While most patients in the United States continue to be managed in coronary care units after primary percutaneous coronary intervention, there is a robust literature regarding the ability to triage STEMI patients safely and efficiently with low‐risk features to non‐ICU beds. We review the various risk scores for STEMI triage and the data supporting their usage. In summary, these findings support an approach to low‐risk STEMI triage that does not come at the expense of quality patient care or outcomes, where up to two‐thirds of patients with STEMI may be able to be safely managed without ICU‐level care.


title: G-quadruplex forming sequences in the genome of all known human viruses: a comprehensive guide

text: G-quadruplexes are non-canonical nucleic acid structures that control transcription, replication, and recombination in organisms. G-quadruplexes are present in eukaryotes, prokaryotes, and viruses. In the latter, mounting evidence indicates their key biological activity. Since data on viruses are scattered, we here present a comprehensive analysis of putative G-quadruplexes in the genome of all known viruses that can infect humans. We show that the presence, distribution, and location of G-quadruplexes are features characteristic of each virus class and family. Our statistical analysis proves that their presence within the viral genome is orderly arranged, as indicated by the possibility to correctly assign up to two-thirds of viruses to their exact class based on the G-quadruplex classification. For each virus we provide: i) the list of all G-quadruplexes formed by GG-, GGG- and GGGG-islands present in the genome (positive and negative strands), ii) their position in the viral genome along with the known function of that region, iii) the degree of conservation among strains of each G-quadruplex in its genome context, iv) the statistical significance of G-quadruplex formation. This information is accessible from a database (http://www.medcomp.medicina.unipd.it/main_site/doku.php?id=g4virus) to allow the easy and interactive navigation of the results. The availability of these data will greatly expedite research on G-quadruplex in viruses, with the possibility to accelerate finding therapeutic opportunities to numerous and some fearsome human diseases.


title: Point-of-care diagnostics for respiratory viral infections

text: Introduction: Successful treatment outcomes for viral respiratory tract infections presenting from primary health care to quaternary hospitals will only be achieved with rapid, sensitive and specific identification of pathogens to allow effective pathogen-specific antiviral therapy and infection control measures. Areas covered: This review aims to explore the different point-of-care tests currently available to diagnose viral respiratory tract infections, discuss the advantages and limitations of point-of-care testing, and provide insights into the future of point-of-care tests. The following databases were searched: Medline (January 1996 to 30 September 2017) and Embase (1988 to 30 September 2017), using the following keywords: ‘point of care’, ‘respiratory virus’, ‘influenza’, ‘RSV’, ‘diagnostics’, ‘nucleic acid test’ and ‘PCR’. Expert commentary: Viral respiratory tract infections cause significant morbidity and mortality worldwide, and point-of-care tests are facilitating the rapid identification of the pathogen responsible given the similarities in clinical presentation.


title: Chapter 7 Patterns of Infection Unwanted Guests—Quick Visits and Extended Stays

text: Abstract The preceding chapters describe essential aspects of viral pathogenesis, including virus–cell interactions; viral spread within a host; and intrinsic, innate, and adaptive immune responses. This chapter extends the theme and addresses diverse patterns of viral infections that are determined by both the virus and the host. Thus, virulence or susceptibility depends upon the specific virus–host combination. This is particularly true in the case of persistent infections, which involve a delicate balance between virus and host. We will focus first on virus virulence and host susceptibility, and then turn to the complex variables that govern persistent infections. Chapters 4–6, on innate, adaptive, and aberrant immunity, and Chapters 11–15, on systems biology approaches, also provide important insights into the patterns of infection.


title: Deciphering the Biosynthetic Codes for the Potent Anti‐SARS‐CoV Cyclodepsipeptide Valinomycin in Streptomyces tsusimaensis ATCC 15141

text: Valinomycin was recently reported to be the most potent agent against severe acute respiratory‐syndrome coronavirus (SARS‐CoV) in infected Vero E6 cells. Aimed at generating analogues by metabolic engineering, the valinomycin biosynthetic gene cluster has been cloned from Streptomyces tsusimaensis ATCC 15141. Targeted disruption of a nonribosomal peptide synthetase (NRPS) gene abolishes valinomycin production, which confirms its predicted nonribosomal‐peptide origin. Sequence analysis of the NRPS system reveals four distinctive modules, two of which contain unusual domain organizations that are presumably involved in the generation of biosynthetic precursors d‐α‐hydroxyisovaleric acid and l‐lactic acid. The respective adenylation domains in these two modules contain novel substrate‐specificity‐conferring codes that might specify for a class of hydroxyl acids for the biosynthesis of the depsipeptide natural products.


docid: nbuvbrly

title: Recombinant Infectious Bronchitis Viruses Expressing Chimeric Spike Glycoproteins Induce Partial Protective Immunity against Homologous Challenge despite Limited Replication In Vivo

text: Vaccination regimes against Infectious bronchitis virus (IBV), which are based on a single virus serotype, often induce insufficient levels of cross-protection against serotypes and two or more antigenically diverse vaccines are used in attempt to provide broader protection. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, are associated with poor cross-protection. Here, homologous vaccination trials with recombinant IBVs (rIBVs), based on the apathogenic strain, BeauR, were conducted to elucidate the role of S1 in protection. A single vaccination of specific-pathogen-free chickens with rIBV expressing S1 of virulent strains M41 or QX, BeauR-M41(S1) and BeauR-QX(S1), gave incomplete protection against homologous challenge, based on ciliary activity and clinical signs. There could be conformational issues with the spike if heterologous S1 and S2 are linked, suggesting a homologous S2 might be essential. To address this, a homologous vaccination-challenge trial incorporating rIBVs expressing full spike from M41, BeauR-M41(S), and S2 subunit from M41, BeauR-M41(S2) was conducted. All chimeric viruses grew to similar titers in vitro, induced virus-specific partial protective immunity, evident by cellular infiltrations, reductions in viral RNA load in the trachea and conjunctiva and higher serum anti-IBV titers. Collectively, these findings show that vaccination with rIBVs primed the birds for challenge but the viruses were cleared rapidly from the mucosal tissues in the head. Chimeric S1 and S2 viruses did not protect as effectively as BeauR-M41(S) based on ciliary activity and clinical signs. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection. IMPORTANCE Infectious bronchitis virus causes an acute, highly contagious respiratory disease, responsible for significant economic losses to the poultry industry. Amino acid differences in the surface protein, spike (S), in particular the S1 subunit, have been associated with poor cross-protection. Available vaccines give poor cross-protection and rationally designed live attenuated vaccines, based on apathogenic BeauR, could address these. Here, to determine the role of S1 in protection, a series of homologous vaccination trials with rIBVs were conducted. Single vaccinations with chimeric rIBVs induced virus-specific partial protective immunity, characterized by reduction in viral load and serum antibody titers. However, BeauR-M41(S) was the only vaccination to improve the level of protection against clinical signs and the loss of tracheal ciliary activity. Growth characteristics show that all of the rIBVs replicated in vitro to similar levels. Booster vaccinations and an rIBV with improved in vivo replication may improve the levels of protection.


title: Transcriptome analysis of PK-15 cells in innate immune response to porcine deltacoronavirus infection

text: Porcine deltacoronavirus (PDCoV) is a newly emerged swine enteropathogenic coronavirus affecting pigs of all ages and causing diarrhea problems. Research findings indicate that PDCoV has evolved strategies to escape innate immune response in host cells, but mechanism of PDCoV in innate immune modulation is not well understood. In this study, we report our findings on identifying the alterations of host cell innate immune response affected by PDCoV infection and exploring the gene expression profiles of PK-15 cells at 0, 24, and 36 h PDCoV post infection by RNA sequencing. A total of 3,762 and 560 differentially expressed genes (DEGs) were screened by comparison of uninfected PK-15 cells and infected PK-15 cells at 24 h post infection (hpi) (INF_24h versus NC), and also comparison of infected PK-15 cells between 24 and 36 hpi (INF_36h versus INF_24h), which included 156 and 23 porcine innate immune-related genes in the DEGs of INF_24h versus NC and INF_36h versus INF_24h, respectively. Gene Ontology function classification and Kyoto Encyclopedia of Genes and Genomes signaling pathway enrichment analysis were performed based on the DEGs that exhibited the same expression tendencies with most of the innate immune-associated genes among these PK-15 cell samples described above. The enrichment results indicated that extensive gene functions and signaling pathways including innate immune-associated functions and pathways were affected by PDCoV infection. Particularly, 4 of 5 innate immune signaling pathways, which were primarily affected by PDCoV, played important roles in I-IFN’s antiviral function in innate immune response. Additionally, 16 of the host cell endogenous miRNAs were predicted as potential contributors to the modulation of innate immune response affected by PDCoV. Our research findings indicated that the innate immune-associated genes and signaling pathways in PK-15 cells could be modified by the infection of PDCoV, which provides a fundamental foundation for further studies to better understand the mechanism of PDCoV infections, so as to effectively control and prevent PDCoV-induced swine diarrheal disease outbreaks.


Mechanisms by which angiotensin-receptor blockers increase ACE2 levels


title: Apolipoprotein D in Lipid Metabolism and Its Functional Implication in Atherosclerosis and Aging

text: Dyslipidemia is characterized by increased triglyceride and low-density lipoprotein (LDL) levels, and decreased high-density lipoprotein (HDL) levels. Such an atherogenic lipid profile often predisposes an at risk individual to coronary artery disease with incompletely understood mechanisms. Apolipoprotein D (apoD) is an atypical apolipoprotein. Unlike canonical apolipoproteins that are produced mainly in liver and intestine, apoD is expressed widely in mammalian tissues. ApoD does not share significant degrees of homology in amino acid sequence with other apolipoproteins. Instead, apoD is structurally similar to lipocalins, a diverse family of lipid-binding proteins that are responsible for transporting lipids and other small hydrophobic molecules for metabolism. Plasma ApoD is present mainly in HDL and to a lesser extent in low density lipoproteins (LDL) and very low-density lipoproteins (VLDL). Genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of developing metabolic syndrome. Increased apoD deposition is detectable in atherosclerotic lesions of humans with established cardiovascular disease as well as mice with premature atherosclerosis. Moreover, apoD is associated with anti-oxidation and anti-stress activities, contributing to lifespan expansion in fruit flies. Elderly subjects and patients with Alzheimer exhibit markedly elevated apoD production in the brain. Thus, apoD is emerged as a significant player in lipid metabolism and aging. Here we focus our review on recent advances toward our understanding of apoD in lipid metabolism and address whether apoD dysregulation contributes to the pathogenesis of dyslipidemia and atherosclerosis. We will also discuss the functional implication of apoD in aging.


title: Insights and Ideas Garnered from Marine Metabolites for Development of Dual-Function Acetylcholinesterase and Amyloid-β Aggregation Inhibitors

text: Due to the diversity of biological activities that can be found in aquatic ecosystems, marine metabolites have been an active area of drug discovery for the last 30 years. Marine metabolites have been found to inhibit a number of enzymes important in the treatment of human disease. Here, we focus on marine metabolites that inhibit the enzyme acetylcholinesterase, which is the cellular target for treatment of early-stage Alzheimer’s disease. Currently, development of anticholinesterase drugs with improved potency, and drugs that act as dual acetylcholinesterase and amyloid-β aggregation inhibitors, are being sought to treat Alzheimer’s disease. Seven classes of marine metabolites are reported to possess anti-cholinesterase activity. We compared these metabolites to clinically-used acetylcholinesterase inhibitors having known mechanisms of inhibition. We performed a docking simulation and compared them to published experimental data for each metabolite to determine the most likely mechanism of inhibition for each class of marine inhibitor. Our results indicate that several marine metabolites bind to regions of the acetylcholinesterase active site that are not bound by the clinically-used drugs rivastigmine, galanthamine, donepezil, or tacrine. We use the novel poses adopted for computational drug design of tighter binding anticholinesterase drugs likely to act as inhibitors of both acetylcholinesterase activity and amyloid-β aggregation inhibition.


Employee presenteeism and occupational acquisition of COVID‐19


title: Eco-epidemiological assessment of the COVID-19 epidemic in China, January–February 2020

text: Background: The outbreak of COVID-19 in China in early 2020 provides a rich data source for exploring the ecological determinants of this new infection, which may be of relevance as the pandemic develops. Objectives: Assessing the spread of the COVID-19 across China, in relation to associations between cases and ecological factors including population density, temperature, solar radiation and precipitation. Methods: Open-access COVID-19 case data include 18,069 geo-located cases in China during January and February 2020, which were mapped onto a 0.25° latitude/longitude grid together with population and weather data (temperature, solar radiation and precipitation). Of 15,539 grid cells, 559 (3.6%) contained at least one case, and these were used to construct a Poisson regression model of cell-weeks. Weather parameters were taken for the preceding week given the established 5–7 day incubation period for COVID-19. The dependent variable in the Poisson model was incident cases per cell-week and exposure was cell population, allowing for clustering of cells over weeks, to give incidence rate ratios. Results: The overall COVID-19 incidence rate in cells with confirmed cases was 0.12 per 1,000. There was a single confirmed case in 113/559 (20.2%) of cells, while two grid cells recorded over 1,000 confirmed cases. Weekly means of maximum daily temperature varied from −28.0°C to 30.1°C, minimum daily temperature from −42.4°C to 23.0°C, maximum solar radiation from 0.04 to 2.74 MJm(−2) and total precipitation from 0 to 72.6 mm. Adjusted incidence rate ratios suggested brighter, warmer and drier conditions were associated with lower incidence. Conclusion: Though not demonstrating cause and effect, there were appreciable associations between weather and COVID-19 incidence during the epidemic in China. This does not mean the pandemic will go away with summer weather but demonstrates the importance of using weather conditions in understanding and forecasting the spread of COVID-19.


title: Global academic response to COVID‐19: Cross‐sectional study

text: This study explores the response to COVID‐19 from investigators, editors, and publishers and seeks to define challenges during the early stages of the pandemic. A cross‐sectional bibliometric review of COVID‐19 literature was undertaken between 1 November 2019 and 24 March 2020, along with a comparative review of Middle East respiratory syndrome (MERS) literature. Investigator responsiveness was assessed by measuring the volume and type of research published. Editorial responsiveness was assessed by measuring the submission‐to‐acceptance time and availability of original data. Publisher‐responsiveness was assessed by measuring the acceptance‐to‐publication time and the provision of open access. Three hundred and ninety‐eight of 2,835 COVID‐19 and 55 of 1,513 MERS search results were eligible. Most COVID‐19 studies were clinical reports (n = 242; 60.8%). The submission‐to‐acceptance [median: 5 days (IQR: 3–11) versus 71.5 days (38–106); P < .001] and acceptance‐to‐publication [median: 5 days (IQR: 2–8) versus 22.5 days (4–48·5‐; P < .001] times were strikingly shorter for COVID‐19. Almost all COVID‐19 (n = 396; 99.5%) and MERS (n = 55; 100%) studies were open‐access. Data sharing was infrequent, with original data available for 104 (26.1%) COVID‐19 and 10 (18.2%) MERS studies (P = .203). The early academic response was characterized by investigators aiming to define the disease. Studies were made rapidly and openly available. Only one‐in‐four were published alongside original data, which is a key target for improvement.


title: First comprehensive computational analysis of functional consequences of TMPRSS2 SNPs in susceptibility to SARS-CoV-2 among different populations

text: Current SARS-CoV-2 pandemy mortality created the hypothesis that some populations may be more susceptible to SARS-CoV-2. TMPRSS2 encodes a transmembrane serine protease which plays a crucial role in SARS-CoV-2 cell entry. Single nucleotide polymorphisms (SNPs) in TMPRSS2 might influence SARS-CoV2 entry into the cell. This study aimed to investigate the impact of SNPs on TMPRSS2 function and structure. In silico tools such as Ensembl, Gtex, ExPASY 2, GEPIA, CCLE, KEGG and GO were engaged to characterize TMPRSS2 and its expression profile. The functional effects of SNPs were analyzed by PolyPhen-2, PROVEN, SNAP2, SIFT and HSF. Also, Phyre2, GOR IV and PSIPRED were used to predict the secondary structure of TMPRSS2. Moreover, post-translational modification (PTM) and secretory properties were analyzed through Modpredand Phobius, respectively. Finally, miRNA profiles were investigated by PolymiRTS and miRSNPs. Out of 11,184 retrieved SNPs from dbSNP, 92 showed a different frequency between Asians and other populations. Only 21 SNPs affected the function and structure of TMPRSS2 by influencing the protein folding, PTM, splicing and miRNA function. Particularly, rs12329760 may create a de novo pocket protein. rs875393 can create a donor site, silencer and broken enhancer motifs. rs12627374 affects a wide spectrum of miRNAs profile. This study highlighted the role of TMPRSS2 SNPs and epigenetic mechanisms especially non-coding RNAs in appearance of different susceptibility to SARS-CoV-2 among different populations. Also, this study could pave the way to potential therapeutic implication of TMPRSS2 in designing antiviral drugs. Communicated by Ramaswamy H. Sarma


title: Sequence-specific detection of single-stranded DNA with a gold nanoparticle-protein nanopore approach

text: Fast, cheap and easy to use nucleic acids detection methods are crucial to mitigate adverse impacts caused by various pathogens, and are essential in forensic investigations, food safety monitoring or evolution of infectious diseases. We report here a method based on the α-hemolysin (α-HL) nanopore, working in conjunction to unmodified citrate anion-coated gold nanoparticles (AuNPs), to detect nanomolar concentrations of short single-stranded DNA sequences (ssDNA). The core idea was to use charge neutral peptide nucleic acids (PNA) as hybridization probe for complementary target ssDNAs, and monitor at the single-particle level the PNA-induced aggregation propensity AuNPs during PNA–DNA duplexes formation, by recording ionic current blockades signature of AuNP–α-HL interactions. This approach offers advantages including: (1) a simple to operate platform, producing clear-cut readout signals based on distinct size differences of PNA-induced AuNPs aggregates, in relation to the presence in solution of complementary ssDNAs to the PNA fragments (2) sensitive and selective detection of target ssDNAs (3) specific ssDNA detection in the presence of interference DNA, without sample labeling or signal amplification. The powerful synergy of protein nanopore-based nanoparticle detection and specific PNA–DNA hybridization introduces a new strategy for nucleic acids biosensing with short detection time and label-free operation.


title: Chapter 2 Expanding the Concept of Public Health

text: Abstract Ancient societies recognized the needs of sanitation, food safety, workers’ health, and medical care to protect against disease and to promote well-being and civic prosperity. New energies and knowledge since the eighteenth century produced landmark discoveries such as prevention of scurvy and vaccination against smallpox. The biological germ theory and competing miasma theory each proved effective in sanitation, and immunization in control of infectious diseases. Non-communicable diseases as the leading causes of mortality have responded to innovative preventive care of health risk factors, smoking, hypertension, obesity, physical inactivity, unhealthful diets, and diabetes mellitus. Health promotion proved effective to modern public health in tackling disease origins, individual behavior, and social and economic conditions. The global burden of infectious and non-communicable diseases, aging and chronic illness faces rising costs and still inadequate prevention. The evolution of concepts of public health will have to address these new challenges of population health.


title: Understanding SARS-CoV-2-related multisystem inflammatory syndrome in children

text: A new multisystem inflammatory syndrome apparently related to infection with SARS-CoV-2 has recently been reported in older children (known as MIS-C), manifested by severe abdominal pain, cardiac dysfunction and shock. Here, I discuss the similarities and differences between MIS-C and Kawasaki disease, focusing on their epidemiology, aetiology and pathophysiological mechanisms.


title: Comparative Proteomic Analysis of Plasma from Clinical Healthy Cows and Mastitic Cows

text: Abstract The current research presents the protein changes in plasma from healthy dairy cows and clinical mastitic cows using two-dimensional gel electrophoresis (2-DE). After staining with silver nitrate and Coomassie Blue, differential expression proteins were detected by PDQuest 7.4 software, and then subjected to ion trap mass spectrometer equipped with a Surveyor HPLC System, differential spots of protein were identified. Three protein spots that originated from preparation gels were identified to be two proteins. Overall, haptoglobin precursor was up-regulated in cows infected with clinical mastitis and could be a mastitis-associated diagnostic marker, whereas SCGB 2A1 (secretoglobin, family 2A, member 1) was down-regulated protein. Plasma protein expression patterns were changed when cows were infected with mammary gland inflammation; it suggests that analysis of differential expression protein might be useful to clarify the mechanisms involved in the pathophysiology, and find new diagnostic markers of mastitis and potential protein targets for treatment.


Le nouveau Coronavirus Covid-19 : quels risques ophtalmiques ?


title: Annonce du diagnostic et accompagnement de fin de vie du COVID-19 en période de confinement au sein d’une unité gériatrique aiguë

text: Summary In late 2019, the SARS-Cov-2 coronavirus emerged from the animal world and crossed to humans. The COVID-19 epidemic broke out in China and was declared a pandemic by WHO in March 2020. In France, hospitals in three regions experienced a massive influx of people with severe forms. COVID-specific units appeared. Within the hospital, the SARS-Cov-2 diagnostic announcement and palliative support (when indicated) required a specific approach to be developed. In an acute COVID geriatric unit, how should the diagnosis of this disease be disclosed in the setting of such intense hospital activity? What are the challenges to be met in order to offer appropriate support for these elderly people suffering from this new disease? This question is even more pressing in the setting of generalised lockdown.


title: Classification of the Universe of Immune Epitope Literature: Representation and Knowledge Gaps

text: BACKGROUND: A significant fraction of the more than 18 million scientific articles currently indexed in the PubMed database are related to immune responses to various agents, including infectious microbes, autoantigens, allergens, transplants, cancer antigens and others. The Immune Epitope Database (IEDB) is an online repository that catalogs immune epitope reactivity data derived from articles listed in the National Library of Medicine PubMed database. The IEDB is maintained and continually updated by monitoring PubMed for new, potentially relevant references. METHODOLOGY: Herein we detail the classification of all epitope-specific literature in over 100 different immunological domains representing Infectious Diseases and Microbes, Autoimmunity, Allergy, Transplantation and Cancer. The relative number of references in each category reflects past and present areas of research on immune reactivities. In addition to describing the overall landscape of data distribution, this particular characterization of the epitope reference data also allows for the exploration of possible correlations with global disease morbidity and mortality data. CONCLUSIONS/SIGNIFICANCE: While in most cases diseases associated with high morbidity and mortality rates were amongst the most studied, a number of high impact diseases such as dengue, Schistosoma, HSV-2, B. pertussis and Chlamydia trachoma, were found to have very little coverage. The data analyzed in this fashion represents the first estimate of how reported immunological data corresponds to disease-related morbidity and mortality, and confirms significant discrepancies in the overall research foci versus disease burden, thus identifying important gaps to be pursued by future research. These findings may also provide a justification for redirecting a portion of research funds into some of the underfunded, critical disease areas.


title: Infection in cancer and transplantation

text: Abstract The range of opportunist pathogens in cancer and transplant patients continues to increase. New treatment modalities and forms of immunosuppression following transplantation have improved survival from the underlying disease but can lead to prolonged immunosuppression and increased risk of infection. NICE guidelines for the management of neutropenic sepsis are now available but have aroused some controversy, particularly over the recommendation for quinolone prophylaxis in high-risk patient groups. In addition to neutropenia, long-term defects in cell-mediated immunity are exposing patients to risk of chronic, viral, protozoal and fungal infection. Advances in diagnostic techniques have the potential to improve management and limit unnecessary empirical treatment, allowing a move towards a diagnosis-driven strategy. However, interpreting the clinical validity and utility of some of these assays can be difficult, particularly for low-prevalence infection where the positive predictive value of any diagnostic test is likely to be low and prompt empirical antibacterial therapy is still indicated in neutropenic patients.


title: FOXO1-regulated lncRNA LINC01197 inhibits pancreatic adenocarcinoma cell proliferation by restraining Wnt/β-catenin signaling

text: BACKGROUND: Recent studies have revealed that numerous oncogenic long non-coding RNAs (lncRNAs) play pivotal roles in pancreatic ductal adenocarcinoma (PDAC) progression, but little is known about tumor-suppressive lncRNAs in PDAC. This study was conducted to evaluate the function of tumor-suppressive LINC01197 in PDAC progression and investigate the detailed mechanisms. METHODS: LncRNA microarray was used to identify differentially expressed lncRNAs in FOXO1-overexpressing PANC1 cells. LINC01197 expression was evaluated by quantitative PCR, Northern blotting, and fluorescence in situ hybridization. The Cancer Genome Atlas database was used to analyze the prognostic role of LNC01197 in PDAC. A luciferase reporter assay was performed to confirm the interaction between LNC01197 and FOXO1. The biological function of LINC01197 was evaluated by colony formation assay in vitro and in an animal subcutaneous tumorigenesis experiment and Ki67 staining in vivo. RNA-pulldown, western blotting, RNA immunoprecipitation assay, and co-immunoprecipitation were further performed to determine the molecular mechanism of LNC01197 and β-catenin in the Wnt pathway. RESULTS: We found that a FOXO1-related lncRNA, LINC01197, was significantly decreased in PDAC malignant tissues and that its low expression predicted poor prognosis. Moreover, LINC01197 was mainly localized in the nucleus and inhibited PDAC cell proliferation both in vitro and in vivo. Mechanistically, LINC01197 was found to bind to β-catenin and inhibit Wnt/β-catenin signaling activity by disrupting β-catenin binding to TCF4 in PDAC cells. CONCLUSIONS: The novel FOXO1/LINC01197/β-catenin axis was dysregulated during PDAC progression. Our study provides insight into the mechanisms of LINC01197 in PDAC and reveal a potential target for PDAC clinical therapy and prognostic prediction.


title: Characterization of microsatellite loci in fulvous fruit bat Rousettus leschenaulti

text: Rousettus leschenaulti is an abundant species in many countries of South‐East Asia, including south China. We isolated seven microsatellite loci in R. leschenaulti from genomic DNA enriched for CA repeats with the enriched library method. A total of 56 samples from a population in the Guangxi Province of China were tested with these microsatellite markers. The polymorphism ranged from seven to 16 alleles, and the observed heterozygosity was 84–94%. It is the first time microsatellite markers were characterized from R. leschenaulti, and these markers can be an important tool for analysing population structure and genotypic diversity.


title: ADAR1 and PACT contribute to efficient translation of transcripts containing HIV-1 trans-activating response (TAR) element

text: Human immunodeficiency virus type 1 (HIV-1) has evolved various measures to counter the host cell's innate antiviral response during the course of infection. Interferon (IFN)-stimulated gene products are produced following HIV-1 infection to limit viral replication, but viral proteins and RNAs counteract their effect. One such mechanism is specifically directed against the IFN-induced Protein Kinase PKR, which is centrally important to the cellular antiviral response. In the presence of viral RNAs, PKR is activated and phosphorylates the translation initiation factor eIF2α. This shuts down the synthesis of both host and viral proteins, allowing the cell to mount an effective antiviral response. PACT (protein activator of PKR) is a cellular protein activator of PKR, primarily functioning to activate PKR in response to cellular stress. Recent studies have indicated that during HIV-1 infection, PACT's normal cellular function is compromised and that PACT is unable to activate PKR. Using various reporter systems and in vitro kinase assays, we establish in this report that interactions between PACT, ADAR1 and HIV-1-encoded Tat protein diminish the activation of PKR in response to HIV-1 infection. Our results highlight an important pathway by which HIV-1 transcripts subvert the host cell's antiviral activities to enhance their translation.


title: Particularités épidémiologiques et prévention des infections nosocomiales virales

text: Résumé Objectifs Décrire les caractéristiques épidémiologiques des infections nosocomiales virales (INV) et les principes de leur prévention. Épidémiologie De nombreux facteurs concourent à une sous-évaluation des INV : l’intrication des infections communautaires et nosocomiales pour les viroses saisonnières, la durée d’incubation entraînant une manifestation après la sortie du patient, les difficultés diagnostiques. Les populations les plus à risques d’INV sont les enfants, les personnes âgées et tous les immunodéprimés. Chez ces derniers, le risque de formes cliniques graves et/ou chroniques est important. Le réservoir principal des virus responsables d’INV est constitué des sujets infectés, symptomatiques ou non. Les porteurs asymptomatiques, notamment le personnel de soins, représentent un risque élevé de transmission. Les principales voies de transmission sont les voies digestive, respiratoire, cutanéomuqueuse et l’exposition au sang et produits biologiques. Une revue des principaux virus impliqués en fonction des modes de transmission est présentée. Prévention Les mesures préventives des INV sont capitales. Au premier plan, figure l’application rigoureuse des précautions standard d’hygiène et, dans certaines situations, des précautions d’isolement septique. En cas d’épidémie de grande ampleur, le regroupement des patients infectés pourra être instauré. La prévention spécifique repose principalement sur la vaccination, la chimioprophylaxie (varicelle-zona, herpès, grippe, accident d’exposition au sang) et la sélection clinique et biologique des donneurs de sang, d’organes, de tissus et de cellules. Summary Objectives To describe epidemiological features of viral nosocomial infections (VNI) and their prevention principles. Epidemiology Many factors lead to underestimate VNI: difficulty to distinguish between community-acquired and nosocomial infections for seasonal viral diseases, incubation time leading to symptoms after patient discharge, difficulty for diagnosis. Population at high risks of VNI are the children, the elderly and the immunocompromized patients. The risk of severe diseases is high in this last population. The main reservoir of virus is infected symptomatic or asymptomatic individuals. Asymptomatic carriers, especially health care workers, are a major source of transmission. Main routes of transmission are the fecal–oral route, the respiratory route, cutaneous or mucous contact and blood and body fluids exposure. A review of the main virus involved in VNI is presented. Prevention Preventive measures, such as strict adherence to standard precautions and, in some instances, to isolation procedures, are critical to control VNI. In a major outbreak situation, it may be necessary to consider cohort isolation. Specific control measures rely on immunization, antiviral drug prophylaxis (varicella–zooster, herpes, influenza, exposure to blood) and clinical and biological screening of organ, blood, tissue and cell donors.


title: Establishment of a nanoparticle-assisted RT-PCR assay to distinguish field strains and attenuated strains of porcine epidemic diarrhea virus

text: Porcine epidemic diarrhea virus (PEDV) can cause serious disease and even death in neonatal piglets, resulting in serious damage to the swine industry worldwide. Open reading frame 3 (ORF3) is the only accessory gene in the PEDV genome. Previous studies have indicated that PEDV vaccine strains have a partial deletion in ORF3. In this study, a nanoparticle-assisted polymerase chain reaction (nanoparticle-assisted RT-PCR) assay targeting the ORF3 of PEDV was developed to distinguish PEDV field strains from attenuated strains by using a specific pair of primers. The PCR products of field strains and attenuated strains were 264 bp and 215 bp in length, respectively. The sensitivity and specificity of this assay were also assessed. The nanoparticle-assisted RT-PCR assay was 10-100 times more sensitive than the conventional RT-PCR assay, with no cross-reactions when amplifying porcine pseudorabies virus (PRV), porcine circovirus type 2 (PCV2), classical swine fever virus (CSFV), porcine parvovirus (PPV), porcine reproductive and respiratory syndrome virus (PRRSV), porcine rotavirus (RV), and porcine transmissible gastroenteritis virus (TGEV). The nanoparticle-assisted RT-PCR assay we describe here can be used to distinguish field strains from vaccine strains of PEDV, and it shows promise for reducing economic loss due to PEDV infection.


title: Vimentin Modulates Infectious Internalization of Human Papillomavirus 16 Pseudovirions

text: Human papillomavirus (HPV) infection is the most common viral infection of the reproductive tract, with virtually all cases of cervical cancer being attributable to infection by oncogenic HPVs. However, the exact mechanism and receptors used by HPV to infect epithelial cells are controversial. The current entry model suggests that HPV initially attaches to heparan sulfate proteoglycans (HSPGs) at the cell surface, followed by conformational changes, cleavage by furin convertase, and subsequent transfer of the virus to an as-yet-unidentified high-affinity receptor. In line with this model, we established an in vitro infection system using the HSPG-deficient cell line pgsD677 together with HPV16 pseudovirions (HPV16-PsVs). While pgsD677 cells were nonpermissive for untreated HPV16-PsVs, furin cleavage of the particles led to a substantial increase in infection. Biochemical pulldown assays followed by mass spectrometry analysis showed that furin-precleaved HPV16-PsVs specifically interacted with surface-expressed vimentin on pgsD677 cells. We further demonstrated that both furin-precleaved and uncleaved HPV16-PsVs colocalized with surface-expressed vimentin on pgsD677, HeLa, HaCaT, and NIKS cells, while binding of incoming viral particles to soluble vimentin protein before infection led to a substantial decrease in viral uptake. Interestingly, decreasing cell surface vimentin by small interfering RNA (siRNA) knockdown in HeLa and NIKS cells significantly increased HPV16-PsV infectious internalization, while overexpression of vimentin had the opposite effect. The identification of vimentin as an HPV restriction factor enhances our understanding of the initial steps of HPV-host interaction and may lay the basis for the design of novel antiviral drugs preventing HPV internalization into epithelial cells. IMPORTANCE Despite HPV being a highly prevalent sexually transmitted virus causing significant disease burden worldwide, particularly cancer of the cervix, cell surface events preceding oncogenic HPV internalization are poorly understood. We herein describe the identification of surface-expressed vimentin as a novel molecule not previously implicated in the infectious internalization of HPV16. Contrary to our expectations, vimentin was found to act not as a receptor but rather as a restriction factor dampening the initial steps of HPV16 infection. These results importantly contribute to our current understanding of the molecular events during the infectious internalization of HPV16 and open a new direction in the development of alternative drugs to prevent HPV infection.


title: Structural host-microbiota interaction networks

text: Hundreds of different species colonize multicellular organisms making them “metaorganisms”. A growing body of data supports the role of microbiota in health and in disease. Grasping the principles of host-microbiota interactions (HMIs) at the molecular level is important since it may provide insights into the mechanisms of infections. The crosstalk between the host and the microbiota may help resolve puzzling questions such as how a microorganism can contribute to both health and disease. Integrated superorganism networks that consider host and microbiota as a whole–may uncover their code, clarifying perhaps the most fundamental question: how they modulate immune surveillance. Within this framework, structural HMI networks can uniquely identify potential microbial effectors that target distinct host nodes or interfere with endogenous host interactions, as well as how mutations on either host or microbial proteins affect the interaction. Furthermore, structural HMIs can help identify master host cell regulator nodes and modules whose tweaking by the microbes promote aberrant activity. Collectively, these data can delineate pathogenic mechanisms and thereby help maximize beneficial therapeutics. To date, challenges in experimental techniques limit large-scale characterization of HMIs. Here we highlight an area in its infancy which we believe will increasingly engage the computational community: predicting interactions across kingdoms, and mapping these on the host cellular networks to figure out how commensal and pathogenic microbiota modulate the host signaling and broadly cross-species consequences.


title: Risk factors for 2019 novel coronavirus disease (COVID-19) patients progressing to critical illness: a systematic review and meta-analysis

text: Importance: With the rising number of COVID-19 cases, global health resources are strained by the pandemic. No proven effective therapies or vaccines for this virus are currently available. In order to maximize the use of limited medical resources, distinguishing between mild and severe patients as early as possible has become pivotal. Objective: To systematically review evidence for the risk factors of COVID-19 patients progressing to critical illness. Evidence Review: We conducted a comprehensive search for primary literature in both Chinese and English electronic bibliographic databases. The American agency for health research and quality tool was used for quality assessment. A meta-analysis was undertaken using STATA version 15.0. Results: Twenty articles (4062 patients) were eligible for this systematic review and meta-analysis. First and foremost, we observed that elderly male patients with a high body mass index, high breathing rate and a combination of underlying diseases (such as hypertension, diabetes, cardiovascular disease, and chronic obstructive pulmonary disease) were more likely to develop severe COVID-19 infections. Second, compared with non-severe patients, severe patients had more serious symptoms such as fever and dyspnea. Besides, abnormal laboratory tests were more prevalent in severe patients than in mild cases, such as elevated levels of white blood cell counts, liver enzymes, lactate dehydrogenase, creatine kinase, C-reactive protein and procalcitonin, as well as decreased levels of lymphocytes and albumin. Interpretation: This is the first systematic review exploring the risk factors for severe illness in COVID-19 patients. Our study may be helpful for clinical decision-making and optimizing resource allocation.


title: The effects of natural disasters on international tourism: A global analysis

text: Tourism is shaped by a wide range of factors and forces, including exogenous ones that have no direct link with the tourism sector. Natural disasters and unexpected events are prime examples of such determining factors, as they have profound effects on individuals and society, and as a result have the potential to affect tourism flows considerably. Several theoretical arguments exist why natural disasters and unexpected events could influence tourist destination choices. However, empirical research to confirm the nature and extent of impacts of disasters on tourism is lacking. To address this gap, this paper incorporates a dataset on natural and man-made disaster events into a model of international tourism flows to evaluate the effect of different types of disasters on international arrivals at the national level. Findings provide evidence that the occurrence of different types of event change tourist flows to varying degrees. Although in some cases a positive effect is estimated, in general the impacts are negative, resulting in reduced tourist arrivals following an event. Understanding the relationship between disaster events and tourism is helpful for destination managers who make critical decisions in relation to recovery, reconstruction and marketing.


title: Characteristics, risk factors and outcomes among the first consecutive 1096 patients diagnosed with COVID-19 in Kuwait

text: BACKGROUND: In Kuwait, prior to the first case of COVID-19 being reported in the country, mass screening of incoming travelers from countries with known outbreaks was performed and resulted in the first identified cases in the country. All COVID-19 cases at the time and subsequently after, were transferred to a single center, Jaber Al-Ahmad Al-Sabah Hospital, where the patients received standardized investigations and treatments. The objective of this study was to characterize the demographics, clinical manifestations, and outcomes in this unique patient population. METHODS: This retrospective cohort study was conducted between 24th February 2020 and 20th April 2020. All consecutive patients in the entire State of Kuwait diagnosed with COVID-19 according to WHO guidelines and admitted to Jaber Al-Ahmad Al-Sabah Hospital were included. Patients received standardized investigations and treatments. Multivariable analysis was used to determine the associations between risk factors and outcomes (admission to intensive care and/or mortality). FINDINGS: Of 1096 patients, the median age was 41 years and 81% of patients were male. Most patients were asymptomatic on admission (46.3%), of whom 35 later developed symptoms, and 59.7% had no signs of infection. Only 3.6% of patients required an ICU admission and 1.7% were dead at the study's cutoff date. On multivariable analysis, the risk factors found to be significantly associated with admission to intensive care were age above 50 years old, a qSOFA score above 0, smoking, elevated CRP and elevated procalcitonin levels. Asthma, smoking and elevated procalcitonin levels correlated significantly with mortality in our cohort.


title: Modulation of the immune response by Middle East respiratory syndrome coronavirus

text: Coronavirus (CoV) infections are commonly associated with respiratory and enteric disease in humans and animals. In 2012, a new human disease called Middle East respiratory syndrome (MERS) emerged in the Middle East. MERS was caused by a virus that was originally called human coronavirus‐Erasmus Medical Center/2012 but was later renamed as Middle East respiratory syndrome coronavirus (MERS‐CoV). MERS‐CoV causes high fever, cough, acute respiratory tract infection, and multiorgan dysfunction that may eventually lead to the death of the infected individuals. The exact origin of MERS‐CoV remains unknown, but the transmission pattern and evidence from virological studies suggest that dromedary camels are the major reservoir host, from which human infections may sporadically occur through the zoonotic transmission. Human to human transmission also occurs in healthcare facilities and communities. Recent studies on Middle Eastern respiratory continue to highlight the need for further understanding the virus‐host interactions that govern disease severity and infection outcome. In this review, we have highlighted the major mechanisms of immune evasion strategies of MERS‐CoV. We have demonstrated that M, 4a, 4b proteins and Plppro of MERS‐CoV inhibit the type I interferon (IFN) and nuclear factor‐κB signaling pathways and therefore facilitate innate immune evasion. In addition, nonstructural protein 4a (NSP4a), NSP4b, and NSP15 inhibit double‐stranded RNA sensors. Therefore, the mentioned proteins limit early induction of IFN and cause rapid apoptosis of macrophages. MERS‐CoV strongly inhibits the activation of T cells with downregulation of antigen presentation. In addition, uncontrolled secretion of interferon ɣ‐induced protein 10 and monocyte chemoattractant protein‐1 can suppress proliferation of human myeloid progenitor cells.


title: Metagenomic analysis reveals clinical SARS-CoV-2 infection and bacterial or viral superinfection and colonization

text: BACKGROUND: More than two months separated the initial description of SARS-CoV-2 and discovery of its widespread dissemination in the United States. Despite this lengthy interval, implementation of specific quantitative reverse transcription (qRT)-PCR-based SARS-CoV-2 tests in the US has been slow, and testing is still not widely available. Metagenomic sequencing offers the promise of unbiased detection of emerging pathogens, without requiring prior knowledge of the identity of the responsible agent or its genomic sequence. METHODS: To evaluate metagenomic approaches in the context of the current SARS-CoV-2 epidemic, laboratory-confirmed positive and negative samples from Seattle, Washington were evaluated by metagenomic sequencing, with comparison to a 2019 reference genomic database created before the emergence of SARS-CoV-2. RESULTS: Within 36 hours our results showed clear identification of a novel human Betacoronavirus, closely related to known Betacoronaviruses of bats, in laboratory-proven cases of SARS-CoV-2. A subset of samples also showed superinfection or colonization with human parainfluenza virus 3 or Moraxella species, highlighting the need to test directly for SARS-CoV-2 as opposed to ruling out an infection using a viral respiratory panel. Samples negative for SARS-CoV-2 by RT-PCR were also negative by metagenomic analysis, and positive for Rhinovirus A and C. Unlike targeted SARS-CoV-2 qRT-PCR testing, metagenomic analysis of these SARS-CoV-2 negative samples identified candidate etiological agents for the patients’ respiratory symptoms. CONCLUSION: Taken together, these results demonstrate the value of metagenomic analysis in the monitoring and response to this and future viral pandemics.


Ethical Guidelines and Moral Distress During the COVID-19 Pandemic: The Trainees’ Perspective


title: Insertional protein engineering for analytical molecular sensing

text: The quantitative detection of low analyte concentrations in complex samples is becoming an urgent need in biomedical, food and environmental fields. Biosensors, being hybrid devices composed by a biological receptor and a signal transducer, represent valuable alternatives to non biological analytical instruments because of the high specificity of the biomolecular recognition. The vast range of existing protein ligands enable those macromolecules to be used as efficient receptors to cover a diversity of applications. In addition, appropriate protein engineering approaches enable further improvement of the receptor functioning such as enhancing affinity or specificity in the ligand binding. Recently, several protein-only sensors are being developed, in which either both the receptor and signal transducer are parts of the same protein, or that use the whole cell where the protein is produced as transducer. In both cases, as no further chemical coupling is required, the production process is very convenient. However, protein platforms, being rather rigid, restrict the proper signal transduction that necessarily occurs through ligand-induced conformational changes. In this context, insertional protein engineering offers the possibility to develop new devices, efficiently responding to ligand interaction by dramatic conformational changes, in which the specificity and magnitude of the sensing response can be adjusted up to a convenient level for specific analyte species. In this report we will discuss the major engineering approaches taken for the designing of such instruments as well as the relevant examples of resulting protein-only biosensors.


Approche québécoise de Santé publique face à la pandémie de COVID-19


docid: aupjlpfm

title: The ability of single genes vs full genomes to resolve time and space in outbreak analysis

text: BACKGROUND: Inexpensive pathogen genome sequencing has had a transformative effect on the field of phylodynamics, where ever increasing volumes of data have promised real-time insight into outbreaks of infectious disease. As well as the sheer volume of pathogen isolates being sequenced, the sequencing of whole pathogen genomes, rather than select loci, has allowed phylogenetic analyses to be carried out at finer time scales, often approaching serial intervals for infections caused by rapidly evolving RNA viruses. Despite its utility, whole genome sequencing of pathogens has not been adopted universally and targeted sequencing of loci is common in some pathogen-specific fields. RESULTS: In this study we highlighted the utility of sequencing whole genomes of pathogens by re-analysing a well-characterised collection of Ebola virus sequences in the form of complete viral genomes (≈19 kb long) or the rapidly evolving glycoprotein (GP, ≈2 kb long) gene. We have quantified changes in phylogenetic, temporal, and spatial inference resolution as a result of this reduction in data and compared these to theoretical expectations. CONCLUSIONS: We propose a simple intuitive metric for quantifying temporal resolution, i.e. the time scale over which sequence data might be informative of various processes as a quick back-of-the-envelope calculation of statistical power available to molecular clock analyses.


title: In reply to the letter to the editor "Tele(oral)medicine: A new approach during the COVID‐19 crisis"

text: We would like tocongratulate Villa et al fora recent published letter to the editor(Villa et al; 2020), emphasizing the use of tele(oral)medicine as an effective diagnostic tool(Estai et al, 2018),which could be usefulin the current time of crisis.The COVID‐19 pandemic, and the social isolation measures mandatedby health authorities haveled toa reassessing of the professional practicesin our Dental College.


title: Genetic characterization of a new astrovirus detected in dogs suffering from diarrhoea

text: Abstract Astroviruses have been described in several animals species frequently associated with diarrhoea, especially in young animals. In dogs, astrovirus-like particles have been observed sporadically and very little is known about their epidemiology and characteristics. In this paper, we describe the detection of astrovirus-like particles in symptomatic puppies. Furthermore, for the first time in this species, the presumptive identification made by electron microscopy was confirmed by genetic analysis of the viral RNA conducted directly on the clinical specimens. Genetic sequences of ORF2 (2443 nt), encoding for the capsid protein, and partial sequence of ORF1b (346 nt), encoding for the viral polymerase, identified the viruses as member of the family Astroviridae. The phylogenetic analysis clearly clustered canine astroviruses in the genus Mamastrovirus. Relative closest similarities were revealed with a cluster comprising human, porcine and feline astroviruses, based on the ORF2 sequences available. Based on the species definition for astroviruses and on the data obtained in this study, we suggest a new species of astrovirus – canine astrovirus, CaAstV – to be included in the genus Mamastrovirus.


title: Clinical review: Influenza pandemic – physicians and their obligations

text: An influenza pandemic threatens to be the most lethal public health crisis to confront the world. Physicians will have critical roles in diagnosis, containment and treatment of influenza, and their commitment to treat despite increased personal risks is essential for a successful public health response. The obligations of the medical profession stem from the unique skills of its practitioners, who are able to provide more effective aid than the general public in a medical emergency. The free choice of profession and the societal contract from which doctors derive substantial benefits affirm this commitment. In hospitals, the duty will fall upon specialties that are most qualified to deal with an influenza pandemic, such as critical care, pulmonology, anesthesiology and emergency medicine. It is unrealistic to expect that this obligation to treat should be burdened with unlimited risks. Instead, risks should be minimized and justified against the effectiveness of interventions. Institutional and public cooperation in logistics, remuneration and psychological/legal support may help remove the barriers to the ability to treat. By stepping forward in duty during such a pandemic, physicians will be able to reaffirm the ethical center of the profession and lead the rest of the healthcare team in overcoming the medical crisis.


docid: pcctrxvf

title: Viral etiologies of influenza‐like illness and severe acute respiratory infections in Thailand

text: BACKGROUND: Information on the burden, characteristics and seasonality of non‐influenza respiratory viruses is limited in tropical countries. OBJECTIVES: Describe the epidemiology of selected non‐influenza respiratory viruses in Thailand between June 2010 and May 2014 using a sentinel surveillance platform established for influenza. METHODS: Patients with influenza‐like illness (ILI; history of fever or documented temperature ≥38°C, cough, not requiring hospitalization) or severe acute respiratory infection (SARI; history of fever or documented temperature ≥38°C, cough, onset <10 days, requiring hospitalization) were enrolled from 10 sites. Throat swabs were tested for influenza viruses, respiratory syncytial virus (RSV), metapneumovirus (MPV), parainfluenza viruses (PIV) 1‐3, and adenoviruses by polymerase chain reaction (PCR) or real‐time reverse transcriptase‐PCR. RESULTS: We screened 15 369 persons with acute respiratory infections and enrolled 8106 cases of ILI (5069 cases <15 years old) and 1754 cases of SARI (1404 cases <15 years old). Among ILI cases <15 years old, influenza viruses (1173, 23%), RSV (447, 9%), and adenoviruses (430, 8%) were the most frequently identified respiratory viruses tested, while for SARI cases <15 years old, RSV (196, 14%) influenza (157, 11%) and adenoviruses (90, 6%) were the most common. The RSV season significantly overlapped the larger influenza season from July to November in Thailand. CONCLUSIONS: The global expansion of influenza sentinel surveillance provides an opportunity to gather information on the characteristics of cases positive for non‐influenza respiratory viruses, particularly seasonality, although adjustments to case definitions may be required.


title: An Overview of Severe Acute Respiratory Syndrome–Coronavirus (SARS-CoV) 3CL Protease Inhibitors: Peptidomimetics and Small Molecule Chemotherapy

text: [Image: see text] Severe acute respiratory syndrome (SARS) is caused by a newly emerged coronavirus that infected more than 8000 individuals and resulted in more than 800 (10–15%) fatalities in 2003. The causative agent of SARS has been identified as a novel human coronavirus (SARS-CoV), and its viral protease, SARS-CoV 3CL(pro), has been shown to be essential for replication and has hence been recognized as a potent drug target for SARS infection. Currently, there is no effective treatment for this epidemic despite the intensive research that has been undertaken since 2003 (over 3500 publications). This perspective focuses on the status of various efficacious anti-SARS-CoV 3CL(pro) chemotherapies discovered during the last 12 years (2003–2015) from all sources, including laboratory synthetic methods, natural products, and virtual screening. We describe here mainly peptidomimetic and small molecule inhibitors of SARS-CoV 3CL(pro). Attempts have been made to provide a complete description of the structural features and binding modes of these inhibitors under many conditions.


title: Impact of COVID-19 on gastrointestinal endoscopy practice in India: a cross-sectional study

text: Background and study aims Gastrointestinal endoscopy, being an aerosol-generating procedure, has the potential to transmit Severe Acute Respiratory Distress Syndrome Corona Virus-2 (SARS-CoV-2) during the current pandemic. Adequate knowledge is the key to prevention. A survey, perhaps the first, was conducted among Indian endoscopists to assess the impact of Coronavirus Disease (COVID)-19 on gastroinestinal endoscopy practice in the country. Methods From April 24 to 28, 2020, an electronic survey (using Google Form) was conducted with 23 questions (single or multiple answers) on: (1) endoscopy practice before the pandemic; (2) knowledge about COVID-19; and (3) its impact on endoscopy practice. Results Responses were received from 375 of 1205 (31.1 %) endoscopists. Most (35.7 %) were young (31–40 years), practicing in corporate multi-speciality hospitals (44.6 %) or independent practice set-up (17.7 %) in metropolitan cities (55.6 %) and urban areas (42.3 %). In most units (75.4 %), fewer than 10 % of procedures performed are endoscopies, as compared to before the pandemic. A reduction in volume of endoscopy related to restriction of the routine procedures by the latest guideline was reported by 86.9 % of respondents. Most are using N95 masks (74.7 %) and/or complete personal protective equipment (PPE, 49.2 %) during endoscopic procedures . Only 18.3 % of respondents had access to negative pressure rooms either within (5.4 %) or outside (12.9 %) the usual endoscopy suite. Conclusion Endoscopy units in India are performing fewer than 10 % of their usual volumes due to current restrictions. Resources to follow current international guidelines, including use of negative pressure rooms and PPE, are limited. Alternate measures are needed to keep up the services.


title: Worse progression of COVID‐19 in men: Is Testosterone a key factor?

text: BACKGROUND: The novel Severe Acute Respiratory Syndrome Coronavirus (SARS‐CoV‐2) disease 2019 (COVID‐19) seems to have a worse clinical course among infected men compared to women, thus, highlighting concerns about gender predisposition to serious prognosis. Therefore, androgens, particularly testosterone (T), could be suspected as playing a critical role in driving this excess of risk. However, gonadal function in critically ill men is actually unknown, mainly because serum T concentration is not routinely measured in clinical practice, even more in this clinical context. OBJECTIVE: To overview on possible mechanisms by which serum T levels could affect the progression of COVID‐19 in men. METHODS: Authors searched PubMed/Medline, Web of Science, EMBASE, Cochrane Library, Google, and Institutional websites for medical subheading terms and free text words referred to “SARS‐CoV‐2”, “COVID‐19”, “testosterone”, “male hypogonadism”, “gender” “immune system”, “obesity”, “thrombosis” until May 19(th) 2020. RESULTS: T, co‐regulating the expression of angiotensin‐converting enzyme 2 and transmembrane protease serine 2 in host cells, may facilitate SARS‐CoV‐2 internalization. Instead, low serum T levels may predispose to endothelial dysfunction, thrombosis and defective immune response, leading to both impaired viral clearance and systemic inflammation. Obesity, one of the leading causes of severe prognosis in infected patients, is strictly associated with functional hypogonadism, and may consistently strengthen the aforementioned alterations, ultimately predisposing to serious respiratory and systemic consequences. DISCUSSION AND CONCLUSION: T in comparison to estrogen may predispose men to a widespread COVID‐19 infection. Low serum levels of T, which should be supposed to characterize the hormonal milieu in seriously ill individuals, may predispose men, especially aged men, to poor prognosis or death. Further studies are needed to confirm these pathophysiological assumptions and to promptly identify adequate therapeutic strategies.


We Can’t Just Wash Our Hands: a Primary Care Physician’s Thoughts on COVID-19 and Her Community


docid: apytopay

title: Ethnoveterinary knowledge of farmers in bilingual regions of Switzerland – is there potential to extend veterinary options to reduce antimicrobial use?

text: ETHNOPHARMACOLOGICAL RELEVANCE: In the pre-antibiotic era, a broad spectrum of medicinal plants was used to treat livestock. This knowledge was neglected in European veterinary medicine for decades but kept alive by farmers. Emergence of multidrug resistant bacterial strains requires a severely restricted use of antibiotics in veterinary medicine. We conducted a survey on the ethnoveterinary knowledge of farmers in the bilingual (French and German speaking) Western region of Switzerland, namely the cantons of Fribourg, Neuchâtel and Jura, and in the French speaking part of the canton of Bern. AIM OF THE STUDY: To find out whether differences exist in plants used by farmers in French speaking and bilingual regions of Switzerland as compared to our earlier studies conducted in Switzerland. Additional focus was on plants that are used in diseases which commonly are treated with antimicrobials, on plants used in skin afflictions, and on plants used in animal species such as horses, for which the range of veterinary medicinal products is limited. MATERIAL AND METHODS: We conducted in 2015 semistructured interviews with 62 dialog partners, mainly cattle keeping farmers but also 18 horse keeping farmers. Of these, 41 were native French (FNS) and 21 native German speakers (GNS). Detailed information about homemade herbal remedies (plant species, plant part, manufacturing process) and the corresponding use reports (target animal species, category of use, route of administration, dosage, source of knowledge, frequency of use, last time of use and farmers satisfaction) were collected. RESULTS: A total of 345 homemade remedies were reported, of which 240 contained only one plant species (Homemade Single Species Herbal Remedy Reports; HSHR). A total of 289 use reports (UR) were mentioned for the 240 HSHR, and they comprised 77 plant species belonging to 41 botanical families. Of these, 35 plant species were solely reported from FNS, 20 from GNS, and 22 from both. Taking into account earlier ethnoveterinary studies conducted in Switzerland only 10 (FNS) and 6 (GNS) plant species connected with 7% of FNS and GNS UR respectively were “unique” to the respective language group. The majority of the UR (219) was for treatment of cattle, while 38 UR were intended to treat horses. The most UR were for treatment of gastrointestinal and skin diseases. The most frequently mentioned plants were Linum usitatissimum L., Coffea L., Matricaria chamomilla L., Camellia sinensis (L.) Kuntze, and Quercus robur L. for gastrointestinal diseases, and Calendula officinalis L., Hypericum perforatum L. and Sanicula europaea L. for skin afflictions. CONCLUSION: No clear differences were found between the medicinal plants used by French native speakers and German native speakers. Several of the reported plants seem to be justified to widen the spectrum of veterinary therapeutic options in gastrointestinal and dermatological disorders in cattle and horses, and to reduce, at least to a certain degree, the need for antibiotic treatments. Our findings may help to strengthen the role of medicinal plants in veterinary research and practice, and to consider them as a further measure in official strategies for lowering the use of antibiotics.


title: Surge after the surge: Anticipating the increased volume and needs of patients with head and neck cancer after the peak in COVID‐19

text: The novel coronavirus disease 2019 (COVID‐19) pandemic continues to have extensive effects on public health as it spreads rapidly across the globe. Patients with head and neck cancer are a particularly susceptible population to these effects, and we expect there to be a potential surge in patients presenting with head and neck cancers after the surge in COVID‐19. Furthermore, the impact of social distancing measures could result in a shift toward more advanced disease at presentation. With appropriate anticipation, multidisciplinary head and cancer teams could potentially minimize the impact of this surge and plan for strategies to provide optimal care for patients with head and neck cancer.


title: SARS-CoV-2 infection induces EMT-like molecular changes, including ZEB1-mediated repression of the viral receptor ACE2, in lung cancer models

text: COVID-19 is an infectious disease caused by SARS-CoV-2, which enters host cells via the cell surface proteins ACE2 and TMPRSS2. Using normal and malignant models and tissues from the aerodigestive and respiratory tracts, we investigated the expression and regulation of ACE2 and TMPRSS2. We find that ACE2 expression is restricted to a select population of highly epithelial cells and is repressed by ZEB1, in concert with ZEB1’s established role in promoting epithelial to mesenchymal transition (EMT). Notably, infection of lung cancer cells with SARS-CoV-2 induces metabolic and transcriptional changes consistent with EMT, including upregulation of ZEB1 and AXL, thereby downregulating ACE2 post-infection. This suggests a novel model of SARS-CoV-2 pathogenesis in which infected cells shift toward an increasingly mesenchymal state and lose ACE2 expression, along with its acute respiratory distress syndrome-protective effect, in a ZEB1-dependent manner. AXL-inhibition and ZEB1-reduction, as with bemcentinib, offers a potential strategy to reverse this effect.


title: Chapter 16 Antiviral Evaluation of Herbal Drugs

text: Abstract The viral infection and resistance to the existing antiviral drugs are alarming, which is a serious public health concern. Medicinal plants are valuable resources for treatment of viral infections and can be used for the management of infections like herpes simplex virus (HSV), human immunodeficiency virus (HIV), influenza, etc. The antiviral screening of plant extracts should be highly selective, specific, and sensitive for bioactivity guided isolation of the active compounds from the plant extracts. The antiviral screening system should be validated for accuracy, reproducibility, simplicity, and cost effectiveness. This chapter highlights on various aspects for screening and evaluation of antiviral natural components including factors affecting antiviral in vivo studies, host cells, organisms, and culture media followed by different virus-specific assays for antiviral screening of natural products.


title: Detection of HIV cDNA Point Mutations with Rolling-Circle Amplification Arrays

text: In this paper we describe an isothermal rolling-circle amplification (RCA) protocol to detect gene point mutations on chips. The method is based on an allele-specific oligonucleotide circularization mediated by a special DNA ligase. The probe is circularized when perfect complementary sequences between the probe oligonucleotide and HIV cDNA gene. Mismatches around the ligation site can prevent probe circularization. The circularized probe (C-probe) can be amplified by rolling circle amplification to generate multimeric singlestranded DNA (ssDNA) under isothermal conditions. There are four sequence regions to bind respectively with fluorescent probe, RCA primer, solid probe and HIV cDNA template in the C-probe which we designed. These ssDNA products are hybridized with fluorescent probes and solid probes which are immobilized on a glass slide composing a regular microarray pattern. The fluorescence signals can be monitored by a scanner in the presence of HIV cDNA templates, whereas the probes cannot be circularized and signal of fluorescence cannot be found. The RCA array has capability of high-throughput detection of the point mutation and the single-nucleotide polymorphism (SNP). The development of C-probe-based technologies offers a promising prospect for situ detection, microarray, molecular diagnosis, single nucleotide polymorphism, and whole genome amplification.


title: Wildlife Trade and Human Health in Lao PDR: An Assessment of the Zoonotic Disease Risk in Markets

text: Although the majority of emerging infectious diseases can be linked to wildlife sources, most pathogen spillover events to people could likely be avoided if transmission was better understood and practices adjusted to mitigate risk. Wildlife trade can facilitate zoonotic disease transmission and represents a threat to human health and economies in Asia, highlighted by the 2003 SARS coronavirus outbreak, where a Chinese wildlife market facilitated pathogen transmission. Additionally, wildlife trade poses a serious threat to biodiversity. Therefore, the combined impacts of Asian wildlife trade, sometimes termed bush meat trade, on public health and biodiversity need assessing. From 2010 to 2013, observational data were collected in Lao PDR from markets selling wildlife, including information on volume, form, species and price of wildlife; market biosafety and visitor origin. The potential for traded wildlife to host zoonotic diseases that pose a serious threat to human health was then evaluated at seven markets identified as having high volumes of trade. At the seven markets, during 21 observational surveys, 1,937 alive or fresh dead mammals (approximately 1,009 kg) were observed for sale, including mammals from 12 taxonomic families previously documented to be capable of hosting 36 zoonotic pathogens. In these seven markets, the combination of high wildlife volumes, high risk taxa for zoonoses and poor biosafety increases the potential for pathogen presence and transmission. To examine the potential conservation impact of trade in markets, we assessed the status of 33,752 animals observed during 375 visits to 93 markets, under the Lao PDR Wildlife and Aquatic Law. We observed 6,452 animals listed by Lao PDR as near extinct or threatened with extinction. The combined risks of wildlife trade in Lao PDR to human health and biodiversity highlight the need for a multi-sector approach to effectively protect public health, economic interests and biodiversity.


title: Cannabis et neurodéveloppement

text: Résumé Le développement cérébral est un phénomène complexe, qui s’étend de la vie fœtale à l’adolescence, pendant laquelle la maturation cérébrale suit une série d’événements ordonnés incluant des périodes critiques de plasticité. Le cerveau est particulièrement sensible à l’environnement pendant ces remaniements. Le système endocannabinoïde participe directement et indirectement à ces processus de plasticité et de maturation. Le delta-9-tetrahydrocanabinol, principal composant psychoactif du cannabis, diffuse dans le placenta, le lait maternel et le cerveau. Il interagit avec le système endocannabinoïde, notamment par l’activation des récepteurs aux cannabinoïdes 1 CB1R, ce qui peut entraîner des altérations du neurodéveloppement et du fonctionnement des circuits neuronaux. Par conséquent, l’exposition au cannabis in utero, en période périnatale ainsi qu’à l’adolescence est susceptible d’entraîner des perturbations de la maturation cérébrale dont les conséquences, sur le plan cognitif, psychotique et addictif, persistent bien au-delà de la période d’exposition. Plusieurs facteurs modulent le risque de telles complications mais les études réalisées sur des modèles animaux ainsi que chez l’homme ont montré qu’une exposition durant les phases critiques, en particulier durant la phase de développement périnatal et à l’adolescence, constitue en soi un facteur de risque. Les données actuelles incitent à diffuser une information objective aux jeunes, pour prévenir et limiter les consommations précoces. Summary Brain development is a complex phenomenon, stretching from fetal life to adolescence, during which brain maturation proceeds through a series of ordered events including critical periods of plasticity. The brain is particularly sensitive to the environment during these changes. The endocannabinoid system participates directly and indirectly in these plasticity and maturation processes. The main psychoactive component of cannabis, the delta-9-tetrahydrocanabinol, can cross the placental barrier, is present in breastmilk and diffuses in the brain. It interacts with the endocannabinoid signaling, especially through the activation of cannabinoid receptors 1 CB1R, which can lead to abnormal neurodevelopmental processes and neuronal circuits functions. Therefore, exposure to cannabis in utero, in perinatal phase, as well as during the adolescence disrupts the brain maturation and can cause disturbances on the cognitive, psychotic and addictive levels that persist far beyond the period of exposure. Several factors modulate the risk of such complications, but studies performed in animal models as well as in human cohorts have shown that exposure during both the critical perinatal and adolescence phases is a risk factor per se. Current knowledge encourages the dissemination of objective information to young people, to prevent and limit early exposure and its consequences.


title: Hepatitis C virus exploits cyclophilin A to evade PKR

text: Counteracting innate immunity is essential for successful viral replication. Host cyclophilins (Cyps) have been implicated in viral evasion of host antiviral responses, although the mechanisms are still unclear. Here, we show that hepatitis C virus (HCV) co-opts the host protein CypA to aid evasion of antiviral responses dependent on the effector protein kinase R (PKR). Pharmacological inhibition of CypA rescues PKR from antagonism by HCV NS5A, leading to activation of an interferon regulatory factor-1 (IRF1)-driven cell intrinsic antiviral program that inhibits viral replication. These findings further the understanding of the complexity of Cyp-virus interactions, provide mechanistic insight into the remarkably broad antiviral spectrum of Cyp inhibitors, and uncover novel aspects of PKR activity and regulation. Collectively, our study identifies a novel antiviral mechanism that harnesses cellular antiviral immunity to suppress viral replication.


title: Prone positioning to improve oxygenation and relieve respiratory symptoms in awake, spontaneously breathing non-intubated patients with COVID-19 pneumonia

text: Emergency departments are facing an unprecedented challenge in dealing with patients who have coronavirus disease 2019 (COVID-19). The massive number of cases evolving to respiratory failure are leading to a rapid depletion of medical resources such as respiratory support equipment, which is more critical in low- and middle-income countries. In this context, any therapeutic and oxygenation support strategy that conserves medical resources should be welcomed. Prone positioning is a well-known ventilatory support strategy to improve oxygenation levels. Self-proning can be used in the management of selected patients with COVID-19 pneumonia. Here, we describe our experience with two COVID-19-positive patients who were admitted with respiratory failure. The patients were successfully managed with self-proning and noninvasive oxygenation without the need for intubation.


title: HUSBANDRY OF DAIRY ANIMALS | Buffalo: Asia

text: Domestic buffaloes (Bubalus bubalis) of swamp type (for draught) and river type (for milk) dominate the tropical Asia with slightly more than 169.4 million. They breed throughout the year and produce two calves every 3 years and are fed mainly on straw, crop residues, and mineral supplements. Assisted reproductive technologies such as artificial insemination and embryo transfer have also been introduced and implemented in buffalo production with less success due to difficulty in detecting estrus. Providing good feed and feeding remain a challenge in buffalo husbandry due to limited feed resources. With improved management and proper breeding, the milk production from buffaloes has increased from 1500 to 5000 l per lactation. The river type buffalo currently produces about 73.2 million tonnes of milk annually.


title: LUCS: a high-resolution nucleic acid sequencing tool for accurate long-read analysis of individual DNA molecules

text: Nucleic acid sequence analyses are fundamental to all aspects of biological research, spanning aging, mitochondrial DNA (mtDNA) and cancer, as well as microbial and viral evolution. Over the past several years, significant improvements in DNA sequencing, including consensus sequence analysis, have proven invaluable for high-throughput studies. However, all current DNA sequencing platforms have limited utility for studies of complex mixtures or of individual long molecules, the latter of which is crucial to understanding evolution and consequences of single nucleotide variants and their combinations. Here we report a new technology termed LUCS (Long-molecule UMI-driven Consensus Sequencing), in which reads from third-generation sequencing are aggregated by unique molecular identifiers (UMIs) specific for each individual DNA molecule. This enables in-silico reconstruction of highly accurate consensus reads of each DNA molecule independent of other molecules in the sample. Additionally, use of two UMIs enables detection of artificial recombinants (chimeras). As proof of concept, we show that application of LUCS to assessment of mitochondrial genomes in complex mixtures from single cells was associated with an error rate of 1X10(-4) errors/nucleotide. Thus, LUCS represents a major step forward in DNA sequencing that offers high-throughput capacity and high-accuracy reads in studies of long DNA templates and nucleotide variants in heterogenous samples.


title: Meta-analysis of several epidemic characteristics of COVID-19

text: As the COVID-19 pandemic has strongly disrupted people’s daily work and life, a great amount of scientific research has been conducted to understand the key characteristics of this new epidemic. In this manuscript, we focus on four crucial epidemic metrics with regard to the COVID-19, namely the basic reproduction number, the incubation period, the serial interval and the epidemic doubling time. We collect relevant studies based on the COVID-19 data in China and conduct a meta-analysis to obtain pooled estimates on the four metrics. From the summary results, we conclude that the COVID-19 has stronger transmissibility than SARS, implying that stringent public health strategies are necessary.


title: Travel, Migration and Emerging Infectious Diseases

text: Emerging infectious diseases (EID) threaten public health and are sustained by increasing global commerce, travel and disruption of ecological systems. Travelers could play a role in importing EIDs and could be a sentinel of major epidemics. In connection with the extension of poverty, urbanization, extensive livestock rearing and globalization, we could be exposed to a third epidemiological transition characterized by zoonotic diseases and infections with multidrug-resistant bacteria. The risk appears low for emerging infectious diseases, or very low for high-risk emerging infectious diseases, but higher for multidrug-resistant enterobacteriaceae carriage with possibly limited consequences. The role played by migrants is weaker than imagined. Immigrants don’t play the role of sentinel epidemic so far. They could play a role in importing multidrug-resistant enterobacteriaceae, but it is poorly evaluated.


title: Calreticulin as a hydrophilic chimeric molecular adjuvant enhances IgG responses to the spike protein of severe acute respiratory syndrome coronavirus

text: Fragment 450–650 of the spike (S) protein (S450–650) of severe acute respiratory syndrome‐associated coronavirus (SARS‐CoV) contains epitopes capable of being recognized by convalescent sera of SARS patients. Vaccination of mice with recombinant S450–650 (rS450–650) can induce Abs against SARS‐CoV, although the titer is relatively low. In the present study, a fusion protein linking a fragment (residues 39–272) of murine calreticulin (CRT) to S450–650 in a prokaryotic expression system was created. Compared with target antigen alone, the recombinant fusion product (rS450–650‐CRT) has much improved hydrophilicity and immunogenicity. The S450–650‐specific IgG Abs of BALB/c mice subcutaneously immunized with rS450–650‐CRT were in substantially higher titer (approximately fivefold more). Furthermore, the fusion protein, but not rS450–650 alone, was able to elicit S450–650‐specific IgG responses in T cell deficient nude mice. Given that rCRT/39–272 can drive the maturation of bone‐marrow‐derived dendritic cells, directly activate macrophages and B cells, and also elicit helper T cell responses in vivo, we propose that fragment 39–272 of CRT is an effective molecular adjuvant capable of enhancing target Ag‐specific humoral responses in both a T cell‐dependent and independent manner. Fusion protein rS450–650‐CRT is a potential candidate vaccine against SARS‐CoV infection.


title: Transmission Electron Microscopy Studies of Cellular Responses to Entry of Virions: One Kind of Natural Nanobiomaterial

text: Virions are one kind of nanoscale pathogen and are able to infect living cells of animals, plants, and bacteria. The infection is an intrinsic property of the virions, and the biological process provides a good model for studying how these nanoparticles enter into cells. During the infection, the viruses employ different strategies to which the cells have developed respective responses. For this paper, we chose Bombyx mori cypovirus 1 (BmCPV-1) interactions with midgut cells from silkworm, and severe acute respiratory syndrome (SARS) associated coronavirus interactions with Vero E6 cells, as examples to demonstrate the response of eukaryotic cells to two different types of virus from our previous studies. The bacteriophage-bacteria interactions are also introduced to elucidate how the bacteriophage conquers the barrier of cell walls in the prokaryotic cells to transport genome into the host.


title: Representative Contact Diaries for Modeling the Spread of Infectious Diseases in Taiwan

text: Recent studies of infectious diseases have attempted to construct more realistic parameters of interpersonal contact patterns from diary-approach surveys. To ensure that such diary-based contact patterns provide accurate baseline data for policy implementation in densely populated Taiwan, we collected contact diaries from a national sample, using 3-stage systematic probability sampling and rigorous in-person interviews. A representative sample of 1,943 contact diaries recorded a total of 24,265 wide-range, face-to-face interpersonal contacts during a 24-hour period. Nearly 70% of the contacts occurred outside of respondents' households. The most active age group was schoolchildren (ages 5–14), who averaged around 16–18 daily contacts, about 2–3 times as many as the least active age groups. We show how such parameters of contact patterns help modify a sophisticated national simulation system that has been used for years to model the spread of pandemic diseases in Taiwan. Based on such actual and representative data that enable researchers to infer findings to the whole population, our analyses aim to facilitate implementing more appropriate and effective strategies for controlling an emerging or pandemic disease infection.


On the way to low-dose medicines


title: Has COVID-19 Changed Crime? Crime Rates in the United States during the Pandemic

text: In response to the COVID-19 pandemic, state-level governments across the United States issued mandatory stay-at-home orders around the end of March 2020. Though intended to stop the spread of the COVID-19 virus, the lockdowns have had sweeping impacts on life in ways which were not originally planned. This study’s purpose is to investigate the extent to which governmental responses to COVID-19 have impacted crime rates in the U.S. Compared to the pre-pandemic year of 2019, crime – as measured by calls for service to law enforcement – has decreased markedly. However, there are multiple indications that the crime drop is being driven by decreases in minor offenses which are typically committed in peer groups. At the same time, serious crimes which are generally not committed with co-offenders (namely homicide and intimate partner violence) have either remained constant or increased. As such, the crime drop appears to be hiding a very disturbing trend where homicides remain unchanged and intimate partner batteries are increasing. Since many offenders would presumably be committing less serious crimes in a non-pandemic world, we raise attention to the possibility that mandatory lockdown orders may have taken minor offenders and placed them into situations where there is rampant opportunity for intimate partner violence, serious batteries, and homicides. While crime in the U.S. appears to be down overall, this good news should not blind us to a troubling co-occurring reality – a reality that paints a dim picture of unintended consequences to public health and criminal justice finances as a result of COVID-19 lockdowns.


title: Proteolytic cleavage of the SARS-CoV-2 spike protein and the role of the novel S1/S2 site

text: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19) has rapidly spread to the entire world within a few months. The origin of SARS-CoV-2 has been related to the lineage B Betacoronavirus SARS-CoV and SARS-related coronaviruses found in bats. Early characterizations of the SARS-CoV-2 genome revealed the existence of a distinct 4 amino acid insert within the spike (S) protein (underlined, SPRRAR↓S), at the S1/S2 site located at the interface between the S1 receptor binding subunit and the S2 fusion subunit. Notably, this insert appears to be a distinguishing feature among SARS-related sequences and introduces a potential cleavage site for the protease furin. Here, we investigate the potential role of this novel S1/S2 cleavage site and present direct biochemical evidence for proteolytic processing by a variety of proteases. We discuss these findings in the context of the origin of SARS-CoV-2, viral stability and transmission.


title: Seroprevalence, cross antigenicity and circulation sphere of bat-borne hantaviruses revealed by serological and antigenic analyses

text: Bats are newly identified reservoirs of hantaviruses (HVs) among which very divergent HVs have been discovered in recent years. However, their significance for public health remains unclear since their seroprevalence as well as antigenic relationship with human-infecting HVs have not been investigated. In the present study archived tissues of 1,419 bats of 22 species from 6 families collected in 5 south and southwest provinces in China were screened by pan-HV RT-PCR following viral metagenomic analysis. As a result nine HVs have been identified in two bat species in two provinces and phylogenetically classified into two species, Laibin virus (LAIV, ICTV approved species, 1 strain) and Xuan son virus (XSV, proposed species, 8 strains). Additionally, 709 serum samples of these bats were also analyzed by ELISA to investigate the seroprevalence and cross-reactivity between different HVs using expressed recombinant nucleocapsid proteins (rNPs) of LAIV, XSV and Seoul virus (SEOV). The cross-reactivity of some bat sera were further confirmed by western blot (WB) using three rNPs followed by fluorescent antibody virus neutralization test (FAVNT) against live SEOV. Results showed that the total HV seropositive rate of bat sera was 18.5% (131/709) with many cross reacting with two or all three rNPs and several able to neutralize SEOV. WB analysis using the three rNPs and their specific hyperimmune sera demonstrated cross-reactivity between XSV/SEOV and LAIV/XSV, but not LAIV/SEOV, indicating that XSV is antigenically closer to human-infecting HVs. In addition a study of the distribution of the viruses identified an area covering the region between Chinese Guangxi and North Vietnam, in which XSV and LAIV circulate within different bat colonies with a high seroprevalence. A circulation sphere of bat-borne HVs has therefore been proposed.


title: COVID-19: General anesthesia precautions

text: [Figure: see text]


title: Exploiting the Legacy of the Arbovirus Hunters

text: In recent years, it has become evident that a generational gap has developed in the community of arbovirus research. This apparent gap is due to the dis-investment of training for the next generation of arbovirologists, which threatens to derail the rich history of virus discovery, field epidemiology, and understanding of the richness of diversity that surrounds us. On the other hand, new technologies have resulted in an explosion of virus discovery that is constantly redefining the virosphere and the evolutionary relationships between viruses. This paradox presents new challenges that may have immediate and disastrous consequences for public health when yet to be discovered arboviruses emerge. In this review we endeavor to bridge this gap by providing a historical context for the work being conducted today and provide continuity between the generations. To this end, we will provide a narrative of the thrill of scientific discovery and excitement and the challenges lying ahead.


How Do Viruses Avoid Inhibition by Endogenous Cellular MicroRNAs?


title: The SARS Coronavirus 3a Protein Causes Endoplasmic Reticulum Stress and Induces Ligand-Independent Downregulation of the Type 1 Interferon Receptor

text: The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is reported to cause apoptosis of infected cells and several of its proteins including the 3a accessory protein, are pro-apoptotic. Since the 3a protein localizes to the endoplasmic reticulum (ER)-Golgi compartment, its role in causing ER stress was investigated in transiently transfected cells. Cells expressing the 3a proteins showed ER stress based on activation of genes for the ER chaperones GRP78 and GRP94. Since ER stress can cause differential modulation of the unfolded protein response (UPR), which includes the inositol-requiring enzyme 1 (IRE-1), activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK) pathways, these were individually tested in 3a-expressing cells. Only the PERK pathway was found to be activated in 3a-expressing cells based on (1) increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2α) and inhibitory effects of a dominant-negative form of eIF2α on GRP78 promoter activity, (2) increased translation of activating transcription factor 4 (ATF4) mRNA, and (3) ATF4-dependent activation of the C/EBP homologous protein (CHOP) gene promoter. Activation of PERK affects innate immunity by suppression of type 1 interferon (IFN) signaling. The 3a protein was found to induce serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and to increase IFNAR1 ubiquitination. Confocal microscopic analysis showed increased translocation of IFNAR1 into the lysosomal compartment and flow cytometry showed reduced levels of IFNAR1 in 3a-expressing cells. These results provide further mechanistic details of the pro-apoptotic effects of the SARS-CoV 3a protein, and suggest a potential role for it in attenuating interferon responses and innate immunity.