niryuu/sni-each-converted huggingface dataset:
One of the most important concerns for managing public health is the prevention of infectious diseases. Although vaccines provide the most effective means for preventing infectious diseases, there are two main reasons why it is often difficult to reach a socially optimal level of vaccine coverage: (i) the emergence of operational issues (such as yield uncertainty) on the supply side, and (ii) the existence of negative network effects on the consumption side. In particular, uncertainties about production yield and vaccine imperfections often make manufacturing some vaccines a risky process and may lead the manufacturer to produce below the socially optimal level. At the same time, negative network effects provide incentives to potential consumers to free ride off the immunity of the vaccinated population. In this research, we consider how a central policy-maker can induce a socially optimal vaccine coverage through the use of incentives to both consumers and the vaccine manufacturer. We consider a monopoly market for an imperfect vaccine; we show that a fixed two-part subsidy is unable to coordinate the market, but derive a two-part menu of subsidies that leads to a socially efficient level of coverage.
Output: Operational issues and network effects in vaccine markets
An octahydroisochromene scaffold has been introduced into a known SARS 3CL protease inhibitor as a novel hydrophobic core to interact with the S2 pocket of the protease. An alkyl or aryl substituent was also introduced at the 1-position of the octahydroisochromene scaffold and expected to introduce additional interactions with the protease. Sharpless-Katsuki asymmetric epoxidation and Sharpless asymmetric dihydroxylation were employed to construct the octahydroisochromene scaffold. The introductions of the P1 site His-al and the substituent at 1-position was achieved using successive reductive amination reactions. Our initial evaluations of the diastereo-isomeric mixtures (16a-d) revealed that the octahydroisochromene moiety functions as a core hydrophobic scaffold for the S2 pocket of the protease and the substituent at the 1-position may form additional interactions with the protease. The inhibitory activities of the diastereoisomerically-pure inhibitors (3a-d) strongly suggest that a specific stereo-isomer of the octahydroisochromene scaffold, (1S, 3S) 3b, directs the P1 site imidazole, the warhead aldehyde, and substituent at the 1-position of the fused ring to their appropriate pockets in the protease.
Output: Evaluation of an octahydroisochromene scaffold used as a novel SARS 3CL protease inhibitor
Duck plague virus (DPV) is a representative pathogen transmitted among aquatic animals that causes gross lesions and immune inhibition in geese and ducks. The mechanism of organ tropism and innate immune evasion of DPV has not been completely deciphered due to a lack of cell models to study the innate immune manipulation and pathogenicity of aquatic viruses. In the present study, we isolated five types of duck primary cells [duck embryo fibroblasts (DEFs), neurons, astrocytes, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages] to identify appropriate cell models for DPV, using tropism infection and innate immunologic assays. Cells responded differently to stimulation with DNA viruses or RNA virus analogs. DPV infection exhibited broad tropism, as the recombinant virulent strain (CHv-GFP) infected DEFs, neurons, astrocytes, and monocytes/macrophages, but not the PBMCs, as the expression of EGFP was negligible. The basal levels of innate immunity molecules were highest in monocytes/macrophages and lower in DEFs and astrocytes. Conversely, the titer and genomic copy number of the attenuated virus strain was higher in DEFs and astrocytes than in neurons and monocytes/macrophages. The titer and genomic copy number of the attenuated virus strain were higher compared with the virulent strain in DEFs, neurons, and astrocytes. The innate immune response was not significantly induced by either DPV strain in DEFs, neurons, or astrocytes. The virulent strain persistently infected monocytes/macrophages, but the attenuated strain did so abortively, and this was accompanied by the phenomenon of innate immune inhibition and activation by the virulent and attenuated strains, respectively. Blockage of IFNAR signaling promoted replication of the attenuated strain. Pre-activation of IFNAR signaling inhibited infection by the virulent strain. The selection assay results indicated that induction of innate immunity plays an essential role in controlling DPV infection, and monocytes/macrophages are an Tian et al. Duck Primary Cells Infection Models important cell model for further investigations. Our study provided practical methods for isolating and culturing duck primary cells, and our results will facilitate further investigations of organ tropism, innate immune responses, latent infection, and the effectiveness of antiviral drugs for treating DPV and potentially other aerial bird pathogens.
Output: Isolation and Selection of Duck Primary Cells as Pathogenic and Innate Immunologic Cell Models for Duck Plague Virus
Background: A critical adaptation strategy for reducing heat-related health risk under climate change is to establish a heat warning system with a proper threshold that requires evaluation of heat-health relationships using empirical data. Objectives: This work presents a new approach to selecting proper health-based thresholds for a heat warning system which are different from thresholds of heat-health relationship. Methods: The proposed approach examined heat-health relationships through analyzing 15 years of health records with a modified generalized additive model (GAM), compared risk ratio increments (RRIs) of threshold candidates against a reference, assessed frequency of days above these candidates, and presented results graphically for easy communication. The candidate with the maximum RRI and proper occurring frequency is potentially the best threshold. Three heat indicators, including wet-bulb globe temperature (WBGT), temperature (T), and apparent temperature (AT), as well as three health outcomes, including all-cause mortality, heatrelated hospital admissions, and heat-related emergency visits were evaluated. Results: Risk ratios for all three health outcomes showed a consistent rising trend with increasing threshold candidates for all three heat indicators among different age and gender groups. WBGT had the most obvious increasing trend of RRIs with the three health outcomes. The maximum RRI was observed in heat-related emergency visits (242%), followed by heat-related hospital admissions (73%), and all-cause mortality (9%). The RRIs assessed for the three health outcomes pointed to the same thresholds, 33.0°C, 34.0°C, and 37.5°C for WBGT, T, and AT, respectively. The number of days above these thresholds and for warning to be issued ranged between 0 and 7 days during 2000-2014. Discussion: This study demonstrated a new approach to determining heat-warning thresholds with different heat indicators and health outcomes. The proposed approach provides a straightforward, feasible, and flexible scientific tool that assists the authorities around the world in selecting a proper threshold for a heat warning system.
Output: New approach to identifying proper thresholds for a heat warning system using health risk increments
In recent years it has been well established that two major constituent parts of the ubiquitin proteasome system (UPS)-the proteasome holoenzymes and a number of ubiquitin ligases-play a crucial role, not only in virus replication but also in the regulation of the immunogenicity of human immunodeficiency virus type 1 (HIV-1). However, the role in HIV-1 replication of the third major component, the deubiquitinating enzymes (DUBs), has remained largely unknown. In this study, we show that the DUB-inhibitors (DIs) P22077 and PR-619, specific for the DUBs USP7 and USP47, impair Gag processing and thereby reduce the infectivity of released virions without affecting viral protease activity. Furthermore, the replication capacity of X4-and R5-tropic HIV-1 NL4-3 in human lymphatic tissue is decreased upon treatment with these inhibitors without affecting cell viability. Most strikingly, combinatory treatment with DIs and proteasome inhibitors synergistically blocks virus replication at concentrations where mono-treatment was ineffective, indicating that DIs can boost the therapeutic effect of proteasome inhibitors. In addition, P22077 and PR-619 increase the polyubiquitination of Gag and thus its entry into the UPS and the major histocompatibility complex (MHC)-I pathway. In summary, our data point towards a model in which specific inhibitors of DUBs not only interfere with virus spread but also increase the immune recognition of HIV-1 expressing cells.
Output: Inhibitors of Deubiquitinating Enzymes Block HIV-1 Replication and Augment the Presentation of Gag-Derived MHC-I Epitopes
The remarkable capacity of some viruses to adapt to new hosts and environments is highly dependent on their ability to generate de novo diversity in a short period of time. Rates of spontaneous mutation vary amply among viruses. RNA viruses mutate faster than DNA viruses, single-stranded viruses mutate faster than doublestrand virus, and genome size appears to correlate negatively with mutation rate. Viral mutation rates are modulated at different levels, including polymerase fidelity, sequence context, template secondary structure, cellular microenvironment, replication mechanisms, proofreading, and access to post-replicative repair. Additionally, massive numbers of mutations can be introduced by some virus-encoded diversity-generating elements, as well as by host-encoded cytidine/adenine deaminases. Our current knowledge of viral mutation rates indicates that viral genetic diversity is determined by multiple virus-and host-dependent processes, and that viral mutation rates can evolve in response to specific selective pressures.
Output: Mechanisms of viral mutation
Background: On the 30th September 2009, the pandemic (H1N1) 2009 influenza vaccine was made available to adults and children aged 10 years and over, in Australia. Acceptance of a novel vaccine is influenced by perceptions of risk including risk of infection, risk of death or severe illness and risk of serious vaccine side-effects. We surveyed a sample of residents from Sydney, Australia to ascertain their risk perception, attitudes towards the pandemic and willingness to accept the pandemic (H1N1) 2009 influenza vaccine. We sampled residents using a cross-sectional intercept design during the WHO Phase 6. Members of the public were approached in shopping and pedestrian malls to undertake the survey during September and October 2009. The survey measured perceived risk, seriousness of disease, recent behavioural changes, likely acceptance of the pandemic (H1N1) 2009 vaccine and issues relating to uptake and perceived safety.
Output: Why do I need it? I am not at risk! Public perceptions towards the pandemic (H1N1) 2009 vaccine
Ranavirus cross-species infections have been documented, but the viral proteins involved in the interaction with cell receptors have not yet been identified. Here, viral cell-binding proteins and their cognate cellular receptors were investigated using two ranaviruses, Andrias davidianus ranavirus (ADRV) and Rana grylio virus (RGV), and two different cell lines, Chinese giant salamander thymus cells (GSTC) and Epithelioma papulosum cyprinid (EPC) cells. The heparan sulfate (HS) analog heparin inhibited plaque formation of ADRV and RGV in the two cell lines by more than 80% at a concentration of 5 µg/mL. In addition, enzymatic removal of cell surface HS by heparinase I markedly reduced plaque formation by both viruses and competition with heparin reduced virus-cell binding. These results indicate that cell surface HS is involved in ADRV and RGV cell binding and infection. Furthermore, recombinant viral envelope proteins ADRV-58L and RGV-53R bound heparin-Sepharose beads implying the potential that cell surface HS is involved in the initial interaction between ranaviruses and susceptible host cells. To our knowledge, this is the first report identifying cell surface HS as ranavirus binding factor and furthers understanding of interactions between ranaviruses and host cells.
Output: Ranaviruses Bind Cells from Different Species through Interaction with Heparan Sulfate
The hemagglutinin-esterases (HEs), envelope glycoproteins of corona-, toro-and orthomyxoviruses, mediate reversible virion attachment to O-acetylated sialic acids (O-Ac-Sias). They do so through concerted action of distinct receptor-binding (''lectin'') and receptor-destroying sialate O-acetylesterase (''esterase'') domains. Most HEs target 9-O-acetylated Sias. In one lineage of murine coronaviruses, however, HE esterase substrate and lectin ligand specificity changed dramatically as these viruses evolved to use 4-O-acetylated Sias instead. Here we present the crystal structure of the lectin domain of mouse hepatitis virus (MHV) strain S HE, resolved both in its native state and in complex with a receptor analogue. The data show that the shift from 9-O-to 4-O-Ac-Sia receptor usage primarily entailed a change in ligand binding topology and, surprisingly, only modest changes in receptor-binding site architecture. Our findings illustrate the ease with which viruses can change receptor-binding specificity with potential consequences for host-, organ and/or cell tropism, and for pathogenesis.
Output: The Murine Coronavirus Hemagglutinin-esterase Receptor-binding Site: A Major Shift in Ligand Specificity through Modest Changes in Architecture
To examine the impact of providing healthcare during or after health emergencies caused by viral epidemic outbreaks on healthcare workers´(HCWs) mental health, and to assess the available evidence base regarding interventions to reduce such impact. Design: Systematic rapid review and meta-analysis. Data sources: MEDLINE, Embase, and PsycINFO, searched up to 23 March 2020. We selected observational and experimental studies examining the impact on mental health of epidemic outbreaks on HCWs. One reviewer screened titles and abstracts, and two reviewers independently reviewed full texts. We extracted study characteristics, symptoms, prevalence of mental health problems, risk factors, mental health interventions, and its impact. We assessed risk of bias for each individual study and used GRADE to ascertain the certainty of the evidence. We conducted a narrative and tabulated synthesis of the results. We pooled data using random-effects meta-analyses to estimate the prevalence of specific mental health problems. We included 61 studies (56 examining impact on mental health and five about interventions to reduce such impact). Most were conducted in Asia (59%), in the hospital setting (79%), and examined the impact of the SARS epidemic (69%). The pooled prevalence was higher for anxiety (45%, 95% CI 21 to 69%; 6 studies, 3,373 participants), followed by depression (38%, 95% CI 15 to 60%; 7 studies, 3,636 participants), acute stress disorder (31%, 95% CI 0 to 82%, 3 studies , 2,587 participants), burnout (29%, 95% CI 25 to 32%; 3 studies; 1,168 participants), and post-traumatic stress disorder (19%, 95% CI 11 to 26%, 10 studies, 3,121 participants). Based on 37 studies, we identified factors associated with the likelihood of developing those problems, including sociodemographic (younger age and female gender), social (lack of social support, social rejection or isolation, stigmatization), and occupational (working in a high risk environment (frontline staff), specific occupational roles (e.g., nurse), and lower levels of specialised training, preparedness and job experience) factors. Five studies reported interventions for frontline HCW, two of which were educational and aimed to prevent mental health problems by increasing HCWs´ resilience. These interventions increased confidence in support and training, pandemic self-efficacy, and interpersonal problems solving (very low certainty). One multifaceted intervention implemented training and organisational changes) targeted at hospital nurses during the SARS epidemic, reporting improvements in . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not peer-reviewed) The copyright holder for this preprint .
Output: IMPACT OF VIRAL EPIDEMIC OUTBREAKS ON MENTAL HEALTH OF HEALTHCARE WORKERS: A RAPID SYSTEMATIC REVIEW
A major focus of systems biology is to characterize interactions between cellular components, in order to develop an accurate picture of the intricate networks within biological systems. Over the past decade, protein microarrays have greatly contributed to advances in proteomics and are becoming an important platform for systems biology. Protein microarrays are highly flexible, ranging from large-scale proteome microarrays to smaller customizable microarrays, making the technology amenable for detection of a broad spectrum of biochemical properties of proteins. In this article, we will focus on the numerous studies that have utilized protein microarrays to reconstruct biological networks including protein-DNA interactions, posttranslational protein modifications (PTMs), lectin-glycan recognition, pathogen-host interactions and hierarchical signaling cascades. The diversity in applications allows for integration of interaction data from numerous molecular classes and cellular states, providing insight into the structure of complex biological systems. We will also discuss emerging applications and future directions of protein microarray technology in the global frontier.
Output: Interactome Mapping: Using Protein Microarray Technology to Reconstruct Diverse Protein Networks
An optical sensor for berberine, the basic ingredient of the widely used traditional Chinese medicine Coptis Chinensis, based on its intrinsic fluorescence enhanced by butylated-␤-cyclodextrin (HDB-␤-CD) immobilized in plasticized poly(vinyl chloride) (PVC) membrane has been developed. The drastic enhancement of fluorescence intensity of berberine was attributed to the formation of an inclusion complex between HDB-␤-CD and berberine, which has been utilized as the basis of the fabrication of a berberine-sensitive fluorescence sensor. The proposed sensor was quite distinct from those fluorescent sensors for berberine reported so far which relied upon quenching the fluorescence of the sensing reagent immobilized on membrane by berberine. The response mechanism of optode membrane was discussed in detail from the view of molecular dynamics and the optimum steric configuration of the inclusion complex was presented by molecular dynamics simulation. The analytical performance characteristics of the proposed berberine-sensitive sensor were investigated. The sensor can be applied to the quantification of berberine with a linear range covering from 4.0 × 10 −7 to 2.0 × 10 −5 mol l −1 with a detection limit of 8.0 × 10 −8 mol l −1 . The sensor exhibits excellent reproducibility, reversibility and selectivity. The recommended method was successfully used for the determination of berberine in pharmaceutical preparations.
Output: Optical sensor for berberine utilizing its intrinsic fluorescence enhanced by the formation of inclusion complex with butylated-␤-cyclodextrin
Transgenic plant-derived vaccines comprise a new type of bioreactor that combines plant genetic engineering technology with an organism's immunological response. This combination can be considered as a bioreactor that is produced by introducing foreign genes into plants that elicit special immunogenicity when introduced into animals or human beings. In comparison with traditional vaccines, plant vaccines have some significant advantages, such as low cost, greater safety, and greater effectiveness. In a number of recent studies, antigen-specific proteins have been successfully expressed in various plant tissues and have even been tested in animals and human beings. Therefore, edible vaccines of transgenic plants have a bright future. This review begins with a discussion of the immune mechanism and expression systems for transgenic plant vaccines. Then, current advances in different transgenic plant vaccines will be analyzed, including vaccines against pathogenic viruses, bacteria, and eukaryotic parasites. In view of the low expression levels for antigens in plants, high-level expression strategies of foreign protein in transgenic plants are recommended. Finally, the existing safety problems in transgenic plant vaccines were put forward will be discussed along with a number of appropriate solutions that will hopefully lead to future clinical application of edible plant vaccines.
Output: MINI-REVIEW Recent advances and safety issues of transgenic plant-derived vaccines
Background: During the early phases of the 2009 pandemic, subjects with influenza-like illness only had laboratory testing specific for the new A(H1N1)pdm09 virus. Findings: Between 25 th May and 7 th June 2009, during the pandemic CONTAIN phase, A(H1N1)pdm09 virus was detected using nucleic acid tests in only 56 of 1466 (3.8%) samples meeting the clinical case definition required for A(H1N1)pdm09 testing. Two hundred and fifty-five randomly selected A(H1N1)pdm09 virus-negative samples were tested for other respiratory viruses using a real-time multiplex PCR assay. Of the 255 samples tested, 113 (44.3%) had other respiratory viruses detected: rhinoviruses 63.7%, seasonal influenza A 17.6%, respiratory syncytial virus 7.9%, human metapneumovirus 5.3%, parainfluenzaviruses 4.4%, influenza B virus 4.4%, and enteroviruses 0.8%. Viral co-infections were present in 4.3% of samples. Conclusions: In the very early stages of a new pandemic, limiting testing to only the novel virus will miss other clinically important co-circulating respiratory pathogens.
Output: Pandemic clinical case definitions are non- specific: multiple respiratory viruses circulating in the early phases of the 2009 influenza pandemic in New South Wales, Australia
Recent results have provided increasing evidence for the existence of an intermediate membrane compartment between the rough endoplasmic reticulum and the Golgi complex which seems to function in protein sorting and the regulation of membrane traffic in the early part of the exocytic pathway . Localization of resident marker proteins has shown that this compartment consists of both peripheral and central elements . The aim of the present review is to combine the data on the pre-Golgi compartment with previous ideas of membrane traffic at the ER-Golgi interface . We propose a model which describes how mobile, endosome-like elements of the pre-Golgi compartment function in the generation of the compositional andfunctional boundary between the widely distributed ER and the more central4 located Golgi stacks .
Output: Pathways of protein sorting and membrane traffic between the rough endoplasmic reticulum and the Golgi complex jaakko Saraste *t and Esa Kuismanent
Zika virus (ZIKV) is transmitted by Aedes mosquitoes and exhibits genetic variation with African and Asian lineages. ZIKV Natal RGN strain, an Asian-lineage virus, has been identified in brain tissues from fetal autopsy cases with microcephaly and is suggested to be a neurotropic variant. However, ZIKV Natal RGN strain has not been isolated; its biological features are not yet illustrated. This study rescued and characterized recombinant, single-round infectious particles (SRIPs) of the ZIKV Natal RGN strain using reverse genetic and synthetic biology techniques. The DNA-launched replicon of ZIKV Natal RGN was constructed and contains the EGFP reporter, lacks prM-E genes, and replicates under CMV promoter control. The peak in the ZIKV Natal RGN SRIP titer reached 6.25 × 10 6 TCID50/mL in the supernatant of prM-E-expressing packaging cells 72 h post-transfection with a ZIKV Natal RGN replicon. The infectivity of ZIKV Natal RGN SRIPs has been demonstrated to correlate with the green florescence intensity of the EGFP reporter, the SRIP-induced cytopathic effect, and ZIKV's non-structural protein expression. Moreover, ZIKV Natal RGN SRIPs effectively self-replicated in rhabdomyosarcoma/muscle, glioblastoma/astrocytoma, and retinal pigmented epithelial cells, displaying unique cell susceptibility with differential attachment activity. Therefore, the recombinant ZIKV Natal RGN strain was rescued as SRIPs that could be used to elucidate the biological features of a neurotropic strain regarding cell tropism and pathogenic components, apply for antiviral agent screening, and develop vaccine candidates.
Output: The Rescue and Characterization of Recombinant, Microcephaly-Associated Zika Viruses as Single-Round Infectious Particles
Classical swine fever (CSF) is a highly contagious viral disease of pigs which causes major economic losses worldwide. No specific drug is currently available for the effective treatment of CSFV infection; however, RNA interference (RNAi) has been applied successfully to inhibit the replication of human and other animal viruses. In this study, three effective siRNAs targeting NS3 of CSFV were selected. siNS3-2 targeting NS3 gene was chosen for further experimentation, while siN1 and siN2 targeting N pro gene, and siNS5B targeting NS5B gene describe previously. Single, double and quadruple anti-CSFV siRNA expression plasmids, with loxp sites at each end of the selectable marker genes, were constructed and analyzed using the same promoters or four different promoters, targeting N pro , NS3 and NS5B genes of CSFV. Results indicate that single or multiple siRNA expression plasmids can efficiently inhibit CSFV replication and that inhibition was markedly stronger when multiple siRNAs were expressed targeting different genes of CSFV. Since RNAi applied to anti-CSFV research, this study provides anti-CSFV methods by single and multiple siRNA expression which can target most viral isolates of different subtypes and prevent viral escape. It also provides a basis for development of CSFV-resistant transgenic pigs.
Output: In vitro inhibition of CSFV replication by multiple siRNA expression
Surveillance European bat lyssavirus Rabies Zoonoses Conservation A B S T R A C T Worldwide, there are more than 1100 species of the Order Chiroptera, 45 of which are present in Europe, and 16 in the UK. Bats are reservoirs of, or can be infected by, several viral diseases, including rabies virus strains (in the Lyssavirus genus). Within this genus are bat variants that have been recorded in Europe; European bat lyssavirus 1 (EBLV-1), European bat lyssavirus 2 (EBLV-2) and, four currently unclassified isolates. Since 1977, 783 cases of EBLVs (by isolation of viral RNA) have been recorded in Europe. EBLV-1 or EBLV-2 has been identified in 12 bat species, with over 95% of EBLV-1 infections identified in Eptesicus serotinus. EBLV-2 is associated with Myotis species (Myotis daubentonii and Myotis dasycneme). A programme of passive surveillance in the United Kingdom between 1987 and 2004 tested 4871 bats for lyssaviruses. Of these, four M. daubentonii (3.57% of submitted M. daubentonii) were positive for EBLV-2. Potential bias in the passive surveillance includes possible overrepresentation of synanthropic species and regional biases caused by varying bat submission numbers from different parts of the UK. In 2003, active surveillance in the UK began, and has detected an antibody prevalence level of 1-5% of EBLV-2 in M. daubentonii (n = 350), and one bat with antibodies to EBLV-1 in E. serotinus (n = 52). No cases of live lyssavirus infection or lyssavirus viral RNA have been detected through active surveillance. Further research and monitoring regarding prevalence, transmission, pathogenesis and immunity is required to ensure that integrated bat conservation continues throughout Europe, whilst enabling informed policy decision regarding both human and wildlife health issues.
Output: European bat lyssaviruses: Distribution, prevalence and implications for conservation
Human respiratory syncytial virus (HRSV) is a major cause of pediatric infection and also causes disease in the elderly and those with underlying respiratory problems. There is no vaccine for HRSV and anti-viral therapeutics are not broadly applicable. To investigate the effect of HRSV biology in children, nasopharyngeal aspirates were taken from children with different viral loads and a combined high throughput RNAseq and label free quantitative proteomics approach was used to characterize the nucleic acid and proteins in these samples. HRSV proteins were identified in the nasopharyngeal aspirates from infected children, and their abundance correlated with viral load (Ct value), confirming HRSV infection. Analysis of the HRSV genome indicated that the children were infected with sub-group A virus and that minor variants in nucleotide frequency occurred in discrete clusters along the HRSV genome, and within a patient clustered distinctly within the glycoprotein gene. Data from the samples were binned into four groups; no-HRSV infection (control), high viral load (Ct < 20), medium viral load (Ct = 20-25), and low viral load (Ct > 25). Cellular proteins associated with the anti-viral response (e.g., ISG15) were identified in the nasopharyngeal aspirates and their abundance was correlated with viral load. These combined approaches have not been used before to study HRSV biology in vivo and can be readily applied to the study the variation of virus host interactions. Table S1 : ANOVA Comparison of abundance. Author Contributions: Conceptualization, W.A. and J.A.H.; methodology, W.A., D.A.M., N.Y.R., and S.A.; software, W.A. and D.A.M.; formal analysis, W.A., G.P., N.Y.R., and S.A.; resources, E.C.-G.; data curation, S.A.; writing-original draft preparation, W.A. and J.A.H.; writing-review and editing, all authors.; supervision, J.A.H. and O.T.; project administration, W.A. and J.A.H.; funding acquisition, W.A. and J.A.H.
Output: High Resolution Analysis of Respiratory Syncytial Virus Infection In Vivo
The massive abundance of studies relating to tropical medicine and health has increased strikingly over the last few decades. In the field of tropical medicine and health, a well-conducted systematic review and meta-analysis (SR/MA) is considered a feasible solution for keeping clinicians abreast of current evidence-based medicine. Understanding of SR/MA steps is of paramount importance for its conduction. It is not easy to be done as there are obstacles that could face the researcher. To solve those hindrances, this methodology study aimed to provide a step-by-step approach mainly for beginners and junior researchers, in the field of tropical medicine and other health care fields, on how to properly conduct a SR/MA, in which all the steps here depicts our experience and expertise combined with the already well-known and accepted international guidance. We suggest that all steps of SR/MA should be done independently by 2-3 reviewers' discussion, to ensure data quality and accuracy. Conclusion: SR/MA steps include the development of research question, forming criteria, search strategy, searching databases, protocol registration, title, abstract, full-text screening, manual searching, extracting data, quality assessment, data checking, statistical analysis, double data checking, and manuscript writing.
Output: A step by step guide for conducting a systematic review and meta-analysis with simulation data
Background: Pre-weaning diarrhea (PWD) in mink, also known as "sticky kits", is a frequently occurring syndrome in suckling mink kits on commercial mink farms. Outbreaks of PWD result in weakened kits, increased mortality and reduced growth and welfare as well as considerable economic losses for the farmers. The syndrome is regarded as multifactorial with a complex etiology, and studies have focused on associations with environment, management and dam characteristics. The present study was conducted from May to June 2015 and included 70 dams with mink litters with and without PWD. The aims were to examine associations between PWD and mastitis (bacterial infection and histological signs of inflammation or other lesions in the mammary gland), and to examine associations between PWD and other dam-related characteristics (age, litter size, body mass index, and weight and number of active mammary glands of the dam). Results: Using multivariable mixed logistic regression analyses with farm id as a random intercept, we found that the odds for PWD in the litter were significantly higher in 1 year old dams versus > 1 year old (OR = 13.3, CI 2.0-90.2, P = 0.01), higher if litter size observed after birth was > 5 kits versus ≤ 5 kits (OR = 16.5, CI 2.2-123.7, P = 0.01), higher if the number of active mammary glands per kit was ≤ 1.5 versus > 1.5 glands per kit (OR = 6.5, CI 1.2-36.0), P = 0.03), and higher in farms with high prevalence of PWD versus low prevalence (OR = 16.8, CI 2.9-97.6, P = 0.002). There were no significant associations between PWD and bacterial infection, histological signs of inflammation or other lesions of the mammary gland, body mass index or weight of mammary gland per kit. Conclusion: Pre-weaning diarrhea had a statistically significant association with age of the dam, litter size and the number of active mammary glands per kit. However, PWD was not associated with mastitis, body mass index and weight of mammary gland tissue per kit.
Output: Dam characteristics associated with pre-weaning diarrhea in mink (Neovison vison)
This article investigates an epidemic spreading among several locations through a transportation system, with a hub connecting these locations. Public transportation is not only a bridge through which infections travel from one location to another but also a place where infections occur since individuals are typically in close proximity to each other due to the limited space in these systems. A mathematical model is constructed to study the spread of an infectious disease through such systems. A variant of the next generation method is proposed and used to provide upper and lower bounds of the basic reproduction number for the model. Our investigation indicates that increasing transportation efficiency, and improving sanitation and ventilation of the public transportation system decrease the chance of an outbreak occurring. Moreover, discouraging unnecessary travel during an epidemic also decreases the chance of an outbreak. However, reducing travel by infectives while allowing susceptibles to travel may not be enough to avoid an outbreak.
Output: Spatial spread of an epidemic through public transportation systems with a hub
Since emerging in 2012, Middle East Respiratory Syndrome Coronavirus (MERS-CoV) has been a global public health threat with a high fatality rate and worldwide distribution. There are no approved vaccines or therapies for MERS until now. Passive immunotherapy with neutralizing monoclonal antibodies (mAbs) is an effective prophylactic and therapeutic reagent against emerging viruses. In this article, we review current advances in neutralizing mAbs against MERS-CoV. The receptor-binding domain (RBD) in the spike protein of MERS-CoV is a major target, and mouse, camel, or human-derived neutralizing mAbs targeting RBD have been developed. A major problem with neutralizing mAb therapy is mutant escape under selective pressure, which can be solved by combination of neutralizing mAbs targeting different epitopes. Neutralizing mAbs are currently under preclinical evaluation, and they are promising candidate therapeutic agents against MERS-CoV infection.
Output: viruses Neutralizing Monoclonal Antibodies as Promising Therapeutics against Middle East Respiratory Syndrome Coronavirus Infection
A nucleotide variability in the sequence of the gene encoding for the transmembrane protein M of canine coronavirus (CCV) is described. A total of 177 faecal samples from pups with enteritis were analysed by a PCR and n-PCR specific for CCV. Four samples, collected from a dog presenting a long-duration shedding of CCV, and a sample from another diarrhoeic dog, were found positive by PCR but negative by n-PCR. Sequence analysis of the samples revealed silent nucleotide substitutions in the binding site of the internal primer used for the n-PCR. Moreover, the nucleotide substitutions occurring over the whole fragment of the five samples analysed were similar.
Output: Variation of the sequence in the gene encoding for transmembrane protein M of canine coronavirus (CCV)
Severe acute respiratory syndrome coronavirus (SARS-CoV) 7a is an accessory protein with no known homologues. In this study, we report the interaction of a SARS-CoV 7a and small glutamine-rich tetratricopeptide repeat-containing protein (SGT). SARS-CoV 7a and human SGT interaction was identified using a two-hybrid system screen and confirmed with interaction screens in cell culture and cellular co-localization studies. The SGT domain of interaction was mapped by deletion mutant analysis and results indicated that tetratricopeptide repeat 2 (aa 125-158) was essential for interaction. We also showed that 7a interacted with SARS-CoV structural proteins M (membrane) and E (envelope), which have been shown to be essential for virus-like particle formation. Taken together, our results coupled with data from studies of the interaction between SGT and HIV-1 vpu indicated that SGT could be involved in the life-cycle, possibly assembly of SARS-CoV.
Output: Severe acute respiratory syndrome coronavirus protein 7a interacts with hSGT q
Infectious bovine keratoconjunctivitis (IBK), also known as pinkeye, is one of the most common eye diseases in cattle. Several pathogens have been associated with IBK cases, however, Moraxella bovis, Moraxella bovoculi, Mycoplasma bovis, Mycoplasma bovoculi and bovine herpesvirus type 1 (BHV-1) are most frequently observed. A multiplex real-time PCR assay using two reactions was developed for the detection and differentiation of these five pathogens. Detection sensitivities of the multiplex assays were compared to singleplex reactions testing for the same targets. Correlation coefficients (R 2 ) of > 0.99, and PCR efficiencies between 92 and 106% were demonstrated in all singleplex and multiplex real-time PCR reactions. The limits of detection (LOD) of multiplex assays for Moraxella bovis, Moraxella bovoculi, Mycoplasma bovis, Mycoplasma bovoculi and BHV-1 were 19, 23, 25, 24 and 26 copies per reaction, respectively. No cross amplification was observed for specificity testing of 179 IBK positive clinical samples and 55 non-target clinical samples. Percentage of clinical samples positive for Mycoplasma bovoculi, Moraxella bovoculi, Moraxella bovis, BHV-1 and Mycoplasma bovis were 88.8% (159/179), 75.9% (136/179), 60.3% (108/179), 11.7% (21/179) and 10.0% (18/179), respectively. Moraxella bovis, Moraxella bovoculi and Mycoplasma bovoculi were more prevalent than Mycoplasma bovis and BHV-1 in IBK samples collected from animals in this study population. Our data indicates that the multiplex real-time PCR panel assay is highly sensitive and highly specific for the detection and differentiation of the five major pathogens associated with bovine pinkeye. Fig. 3. The prevalence of the five pathogens in IBK samples. Panel A: Prevalence of the five pathogens from the 179 bovine ocular swab samples that were subjected to multiplex real-time PCR testing. Panel B: Co-infections among the three most prevalent IBK pathogens in the 179 positive clinical samples: 95 (53.0%) samples were positive for both Moraxella bovis and Moraxella bovoculi; 100 (55.8%) samples were positive for both Moraxella bovis and Mycoplasma bovoculi; 129 (72.0%) samples were positive for both Moraxella bovoculi and Mycoplasma bovoculi and 93 (51.9%) samples were positive for Moraxella bovis, Moraxella bovoculi and Mycoplasma bovoculi. W. Zheng, et al. 
Output: A multiplex real-time PCR assay for the detection and differentiation of five bovine pinkeye pathogens
Background: Cats are susceptible to feline panleukopenia virus (FPV) and canine parvovirus (CPV) variants 2a, 2b and 2c. Detection of FPV and CPV variants in apparently healthy cats and their persistence in white blood cells (WBC) and other tissues when neutralising antibodies are simultaneously present, suggest that parvovirus may persist long-term in the tissues of cats post-infection without causing clinical signs. The aim of this study was to screen a population of 54 cats from Sardinia (Italy) for the presence of both FPV and CPV DNA within buffy coat samples using polymerase chain reaction (PCR). The DNA viral load, genetic diversity, phylogeny and antibody titres against parvoviruses were investigated in the positive cats. Results: Carnivore protoparvovirus 1 DNA was detected in nine cats (16.7%). Viral DNA was reassembled to FPV in four cats and to CPV (CPV-2b and 2c) in four cats; one subject showed an unusually high genetic complexity with mixed infection involving FPV and CPV-2c. Antibodies against parvovirus were detected in all subjects which tested positive to DNA parvoviruses. Conclusions: The identification of FPV and CPV DNA in the WBC of asymptomatic cats, despite the presence of specific antibodies against parvoviruses, and the high genetic heterogeneity detected in one sample, confirmed the relevant epidemiological role of cats in parvovirus infection.
Output: Molecular analysis of carnivore Protoparvovirus detected in white blood cells of naturally infected cats
Viral infections of the central nervous system (CNS) necessitate rapid, yet tightly controlled responses to contain viral spread while limiting tissue damage. All CNS resident cell types are equipped with pattern recognition receptors (PRRs) to respond to viruses. The resulting activation of IFN-α/β, proinflammatory cytokines and chemokines is dependent on the virus replication strategy, tropism and PRR distribution. Although IFN-α/β induced antiviral mediators are essential to restrict initial viral spread, adaptive immunity promoted by chemokines, cytokines and metalloproteinases is equally critical in lowering viral burden. Recognition of viral antigen presented by MHC molecules is critical for T cell retention and function. Non lytic clearance mechanisms mediated by IFN-γ and antibodies prevail in providing protection. Targeted intervention can be achieved by PRR stimulation, chemokine-receptor blockade and immune modulation of T cell function. However, due to the extensive positive and negative feedback signaling cascades linking innate and adaptive immune responses, enhanced anti-viral functions will have to be counterbalanced to avoid pathology.
Output: Neuroimmunology of central nervous system viral infections: the cells, molecules and mechanisms involved
During viral and bacterial infections, the innate immune system recognizes various types of pathogen-associated molecular patterns (PAMPs), such as nucleic acids, via a series of membrane-bound or cytosolic pattern-recognition receptors. These include Toll-like receptors (TLRs), RIG-I-like receptors (RLRs), AIM2-like receptors (ALRs), and cytosolic DNA sensors. The binding of PAMPs to these receptors triggers the production of type I interferon (IFN) and inflammatory cytokines. Type I IFN induces the expression of interferon stimulated genes (ISGs), which protect surrounding cells from infection. Some ISGs are nucleic acids-binding proteins that bind viral nucleic acids and suppress their replication. As nucleic acids are essential components that store and transmit genetic information in every species, infectious pathogens have developed systems to escape from the host nucleic acid recognition system. Host cells also have their own nucleic acids that are frequently released to the extracellular milieu or the cytoplasm during cell death or stress responses, which, if able to bind pattern-recognition receptors, would induce autoimmunity and inflammation. Therefore, host cells have acquired mechanisms to protect themselves from contact with their own nucleic acids. In this review, we describe recent research progress into the nucleic acid recognition mechanism and the molecular bases of discrimination between self and non-self-nucleic acids.
Output: Discrimination Between Self and Non-Self-Nucleic Acids by the Innate Immune System
on behalf of the Microbes, Allergy, and Asthma Committee Nashville, Tenn; Chicago, Ill; Charlottesville, Va; Manchester, United Kingdom; and Athens, Greece Children who begin wheezing during early childhood are frequently seen by health care providers in primary care, in hospitals, and in emergency departments, and by allergists and pulmonologists. When a young child, such as the 2 yearold patient presented here, is evaluated for wheezing, a frequent challenge for clinicians is to determine whether the symptoms represent transient, viral-induced wheezing or whether sufficient risk factors are present to suspect that the child may experience recurrent wheezing and develop asthma. Most factors that influence prognosis are not mutually exclusive, are interrelated (ie, cofactors), and often represent gene-environment interactions. Many of these risk factors have been, and continue to be, investigated in prospective studies to decipher their relative importance with the goal of developing new therapies and interventions in the future. The etiologies of wheezing in young children, diagnostic methods, treatment, prognostic factors, and potential targets for prevention of the development of asthma are discussed. Ó
Output: Wheezing Exacerbations in Early Childhood: Evaluation, Treatment, and Recent Advances Relevant to the Genesis of Asthma
To determine the factors that predict in-hospital mortality among patients who require hospitalization for the treatment of community-acquired pneumonia (CAP). Study design: Prospective observational study of all patients who were admitted to six hospitals in Edmonton, AL, Canada, with a diagnosis of CAP from November 15, 2000, to November 14, 2002. Pneumonia was defined as two or more respiratory symptoms and signs and an opacity on a chest radiograph as interpreted by the attending physician. Results: A total of 3,043 patients were enrolled in the study, 246 of whom died (8.1%). On multivariate analysis, increasing pneumonia severity score, increasing age, site of care, consultation with a respirologist or infectious diseases physician, and functional status at the time of admission were all independently predictive of mortality. Increasing pneumonia severity risk score, increasing age, site of hospitalization, functional status, and consultation with an infectious diseases physician or a respirologist were independently associated with both early (< 5 days) and late (> 5 days) mortality. In contrast, partial or complete use of the pneumonia pathway was associated with decreased early mortality, but had no effect on late mortality. A low lymphocyte count and a high serum potassium level were associated with early but not with late mortality. The type of antibiotic therapy had an effect on late but not on early mortality. Conclusions: Functional status at the time of hospital admission is a powerful predictor of mortality and should be incorporated into any scores or models that are used to predict mortality. While there are some common predictors of early and late in-hospital mortality, early mortality is not affected by the timing or type of antibiotic therapy, whereas late mortality is influenced by the type of antibiotic therapy. Hyperkalemia and lymphopenia are associated with early mortality. Abbreviations: CAP ϭ community-acquired pneumonia; CI ϭ confidence interval; FSA ϭ forward sortation area; HRCT ϭ high-resolution CT; OR ϭ odds ratio C ommunity-acquired pneumonia (CAP) is a common illness with an incidence rate of approximately 11.6/1,000 adults per year, 1 of which approx-
Output: Factors Influencing In-hospital Mortality in Community-Acquired Pneumonia* A Prospective Study of Patients Not Initially Admitted to the ICU