niryuu/sni-each-converted huggingface dataset:
Flu response centre Public health Helpline Emerging disease s u m m a r y Objective: To assess the operational experience and knowledge of staff who worked in the West Midlands Flu Response Centre (FRC) during the 'containment' phase of influenza A(H1N1)pdm09. using an online self-administered questionnaire. The questionnaire included sections related to the respondents' FRC experience, knowledge about influenza A(H1N1)pdm09 and the containment phase. Results: This study had a 51% (89/176) response rate. Of the respondents, 59% were female, 64% were of White ethnicity, 55% were clinicians, 46% were aged 25e44 years, and 67% had no previous call centre experience. A significant proportion (P < 0.001) of respondents believed that the FRC had made a positive contribution to the public health management of the containment phase. Nearly all respondents indicated that they were familiar with the terms 'pandemic flu' or 'influenza pandemic' (99%), understood the aim of the containment phase (90%), and knew the severity of the illness caused by the virus (97%). However, specific knowledge was lacking regarding a number of public health interventions, and overall knowledge scores for clinicians and non-clinicians were similar. Conclusion: This study is the first to report on the characteristics of FRC staff during the containment phase of influenza A(H1N1)pdm09 pandemic. Although overall, staff evaluation of the West Midlands FRC was very positive, a number of knowledge gaps were identified. This study provides valuable insights which can contribute to preparedness planning.
Output: Characteristics of flu response centre staff in the West Midlands
Heterogeneity in disease transmission is widespread and, when not accounted for, can 12 produce unpredictable outbreaks of infectious disease. Despite this, precisely how 13 different sources of variation in host traits drive heterogeneity in disease transmission is 14 poorly understood. Here we dissected the sources of variation in pathogen transmission 15 using Drosophila melanogaster and Drosophila C Virus as a host-pathogen model 16 system. We found that infected lifespan, viral growth, virus shedding, and viral load at 17 death were all significantly influenced by fly genetic background, sex and female mating 18 status. To understand how variation in each of these traits may generate heterogeneity 19 in disease transmission, we estimated individual transmission potential by integrating 20 data on virus shedding and lifespan alongside previously collected data on social 21 aggregation. We found that ~15% of between-individual heterogeneity in disease 22 transmission was explained by a significant interaction between genetic and sex-specific 23 variation. We also characterised the amount of variation in viral load, virus shedding, and 24 lifespan following infection that could be explained by genetic background and sex. 25 Amongst the determinants of individual variation in disease transmission these sources 26 of host variation play roles of varying importance, with genetic background generally 27 playing the largest role. Our results highlight the importance of characterising sources of 28 variation in multiple host traits when studying disease transmission at the individual-level. 29 30
Output: Dissecting genetic and sex-specific host heterogeneity in pathogen transmission 1 potential 2 3 4
Human coronaviruses (HCoVs) are associated with a variety of clinical presentations in children, but their role in disease remains uncertain. The objective of our prospective study was to investigate HCoVs associations with various clinical presentations in hospitalized children up to 6 years of age. Children hospitalized with acute bronchiolitis (AB), acute gastroenteritis (AGE), or febrile seizures (FS), and children admitted for elective surgical procedures (healthy controls) were included in the study. In patients with AB, AGE, and FS, a nasopharyngeal (NP) swab and blood sample were obtained upon admission and the follow-up visit 14 days later, whereas in children with AGE a stool sample was also acquired upon admission; in healthy controls a NP swab and stool sample were taken upon admission. Amplification of polymerase 1b gene was used to detect HCoVs in the specimens. HCoVs-positive specimens were also examined for the presence of several other viruses. HCoVs were most often detected in children with FS (19/192, 9 .9%, 95% CI: 6-15%), followed by children with AGE (19/218, 8.7%, 95% CI: 5.3-13.3%) and AB (20/308, 6.5%, 95% CI: 4.0-9.8%). The presence of other viruses was a common finding, most frequent in the group of children with AB (19/20, 95%, 95% CI: 75.1-99.8%), followed by FS (10/19, 52.6%, 95% CI: 28.9-75.6%) and AGE (7/19, 36.8%, 95% CI: 16.3-61.6%). In healthy control children HCoVs were detected in 3/156 (1.9%, 95% CI: 0.4-5.5%) NP swabs and 1/150 (0.7%, 95% CI: 0.02-3.3%) stool samples. It seems that an etiological role of HCoVs is most likely in children with FS, considering that they had a higher proportion of positive HCoVs results than patients with AB and those with AGE, and had the highest viral load; however, the co-detection of other viruses was 52.6%.
Output: The Role of Human Coronaviruses in Children Hospitalized for Acute Bronchiolitis, Acute Gastroenteritis, and Febrile Seizures: A 2-Year Prospective Study
The main protease of coronaviruses and the 3C protease of enteroviruses share a similar active-site architecture and a unique requirement for glutamine in the P1 position of the substrate. Because of their unique specificity and essential role in viral polyprotein processing, these proteases are suitable targets for the development of antiviral drugs. In order to obtain near-equipotent, broad-spectrum antivirals against alphacoronaviruses, betacoronaviruses, and enteroviruses, we pursued a structure-based design of peptidomimetic α-ketoamides as inhibitors of main and 3C proteases. Six crystal structures of protease−inhibitor complexes were determined as part of this study. Compounds synthesized were tested against the recombinant proteases as well as in viral replicons and virus-infected cell cultures; most of them were not cell-toxic. Optimization of the P2 substituent of the αketoamides proved crucial for achieving near-equipotency against the three virus genera. The best near-equipotent inhibitors, 11u (P2 = cyclopentylmethyl) and 11r (P2 = cyclohexylmethyl), display low-micromolar EC 50 values against enteroviruses, alphacoronaviruses, and betacoronaviruses in cell cultures. In Huh7 cells, 11r exhibits three-digit picomolar activity against the Middle East Respiratory Syndrome coronavirus.
Output: α-Ketoamides as Broad-Spectrum Inhibitors of Coronavirus and Enterovirus Replication: Structure-Based Design, Synthesis, and Activity Assessment
Background: To efficiently plan appropriate public health interventions during possible epidemics, governments must take into consideration the following factors about the general population: their knowledge of epidemics, their fears of and psychological responses to them, their level of compliance with government measures and their communities' trusted sources of information. However, such surveys among the French general population are rare. A cross-sectional study was conducted in 2006 in a representative sample of 600 subjects living in the Rhône-Alpes region (south-east France) to investigate self-reported knowledge about infectious diseases and anxiety generated by epidemic risk with particular reference to avian influenza. Data on reactions to potentially new epidemics and the confidence level in various sources of information were also collected. Respondents were most knowledgeable about AIDS, followed by avian influenza. Overall, 75% of respondents had adequate knowledge of avian influenza. The percentage was even higher (88%) among inhabitants of the Ain district, where an avian influenza epidemic had previously been reported. However, 39% expressed anxiety about this disease. In total, 20% of respondents with knowledge about avian influenza stated that they had changed their behaviours during the epizooty. Epidemics were perceived as a real threat by 27% of respondents. In the event of a highly contagious outbreak, the majority of respondents said they would follow the advice given by authorities. The study population expressed a high level of confidence in physicians and scientists, but had strong reservations about politicians, deputies and the media.
Output: Perception of epidemic's related anxiety in the General French Population: a cross-sectional study in the Rhône-Alpes region
Coronaviruses are enveloped positive-stranded RNA viruses that replicate in the cytoplasm. To deliver their nucleocapsid into the host cell, they rely on the fusion of their envelope with the host cell membrane. The spike glycoprotein (S) mediates virus entry and is a primary determinant of cell tropism and pathogenesis. It is classified as a class I fusion protein, and is responsible for binding to the receptor on the host cell as well as mediating the fusion of host and viral membranes-A process driven by major conformational changes of the S protein. This review discusses coronavirus entry mechanisms focusing on the different triggers used by coronaviruses to initiate the conformational change of the S protein: receptor binding, low pH exposure and proteolytic activation. We also highlight commonalities between coronavirus S proteins and other class I viral fusion proteins, as well as distinctive features that confer distinct tropism, pathogenicity and host interspecies transmission characteristics to coronaviruses.
Output: Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein
Laboratory-acquired infections due to a wide variety of bacteria, viruses, fungi, and parasites have been described. Although the precise risk of infection after an exposure remains poorly defined, surveys of laboratory-acquired infections suggest that Brucella species, Shigella species, Salmonella species, Mycobacterium tuberculosis, and Neisseria meningitidis are the most common causes. Physicians who care for a sick laboratory worker need to consider the likelihood of an occupationally acquired infection while advising exposed laboratory workers about postexposure prophylaxis. In addition, physicians should be aware of the importance of alerting the laboratory if infection with a high-risk agent is suspected.
Output: Laboratory-Acquired Infections
This guideline was developed as part of the 2016 Policy Research Servicing Project by the Korea Centers for Disease Control and Prevention. A multidisciplinary approach was taken to formulate this guideline to provide practical information about the diagnosis and treatment of adults with acute upper respiratory tract infection, with the ultimate aim to promote the appropriate use of antibiotics. The formulation of this guideline was based on a systematic literature review and analysis of the latest research findings to facilitate evidence-based practice, and focused on key questions to help clinicians obtain solutions to clinical questions that may arise during the care of a patient. This guideline mainly covers the subjects on the assessment of antibiotic indications and appropriate selection of antibiotics for adult patients with acute pharyngotonsillitis or acute sinusitis.
Output: Infection & Chemotherapy 성인 급성 상기도 감염 항생제 사용지침 권고안
The open reading frame 2 (ORF2) of three laboratory strains, the live attenuated vaccine virus, and 18 field isolates of equine arteritis virus (EAV) from Europe and North America was sequenced. The ORF2 of EAV encodes the Gs protein that is abundantly expressed in infected cells but constitutes less than 2% of the virion protein mass. Variation of ORF2 among the i'solates facilitated phylogenetic analysis that largely confirmed results of an earlier study based on sequence divergence of ORF5 of the same isolates of EAV, despite exposure of the proteins encoded by ORF2 (Gs) and ORF5 (GL) to potentially different selective pressures in vivo. The data indicate that the G s protein is highly conserved between isolates, considerably more so than the GL protein, consistent with an important role of the Gs protein in virus replication.
Output: Genetic variation laboratory in open reading flame 2 of field isolates and strains of equine arteritis virus
Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is one of the major threats to the healthcare systems in some countries, especially in the Arabian Peninsula. MERS-CoV is considered an ideal example of the One Health concept. This is due to the animals, especially dromedary camels, play important roles in the transmission and sustainability of the virus, and the virus can be transmitted through aerosols of infected patients into the environment. However, there is some debate regarding the origin of MERS-CoV either from bats or other unknown reservoirs. The dromedary camel is the only identified animal reservoir to date. These animals play important roles in sustaining the virus in certain communities and may act as an amplifier of the virus by secreting it in their body fluids, especially in nasal and rectal discharges. MERS-CoV has been detected in the nasal and rectal secretions of infected camels, and MERS-CoV of this origin has full capacity to infect human airway epithelium in both in vitro and in vivo models. Other evidence confirms the direct transmission of MERS-CoV from camels to humans, though the role of camel meat and milk products has yet to be well studied. Human-to-human transmission is well documented through contact with an active infected patient or some silently infected persons. Furthermore, there are some significant risk factors of individuals in close contact with a positive MERS-CoV patient, including sleeping in the same patient room, removing patient waste (urine, stool, and sputum), and touching respiratory secretions from the index case. Outbreaks within family clusters have been reported, whereby some blood relative patients were infected through their wives in the same house were not infected. Some predisposing genetic factors favor MERS-CoV infection in some patients, which is worth investigating in the near future. The presence of other comorbidities may be another factor. Overall, there are many unknown/confirmed aspects of the virus/human/animal network. Here, the most recent advances in this context are discussed, and the possible reasons behind the emergence and sustainability of MERS-CoV in certain regions are presented. Identification of the exact mechanism of transmission of MERS-CoV from camels to humans and searching for new reservoir/s are of high priority. This will reduce the shedding of the virus into the environment, and thus the risk of human infection can be mitigated.
Output: Middle East Respiratory Syndrome Coronavirus and the One Health concept
Ubiquitin (UB) is a protein modifier that regulates many essential cellular processes. To initiate protein modification by UB, the E1 enzyme activates the C-terminal carboxylate of UB to launch its transfer through the E1-E2-E3 cascade onto target proteins. In this study, we used phage display to profile the specificity of the two human E1 enzymes, Ube1 and Uba6, towards the Cterminal sequence of UB ending with 71 LRLRGG 76 . Phage selection revealed that while Arg72 of UB is absolutely required for E1 recognition, UB residues at positions 71, 73 and 74 can be replaced with bulky aromatic side chains, and Gly75 of UB can be changed to Ser, Asp and Asn for efficient E1 activation. We have thus found that the E1 enzymes have substantial promiscuity regarding the UB C-terminal sequence. The UB variants from phage selection can also be transferred from E1 to E2 enzymes, however, they are blocked from further transfer to the E3 enzymes. This suggests that the C-terminal sequence of UB is important for its discharge from E2 and subsequent transfer to E3. In addition, we observed that the Leu73Phe and Leu73Tyr single mutants of UB are resistant to cleavage by deubiquitinating enzymes (DUBs), although they can be assembled by the E1-E2-E3 cascade into poly-UB chains, thus indicating differences in UB Cterminal specificities between the E1 and DUBs. Consequently these UB mutants may provide stability to UB polymers attached to cellular proteins and facilitate the elucidation of the biological signals encoded in the UB chains. Ubiquitin (UB) is a 76-residue protein that is attached to cellular proteins through an isopeptide bond between the C-terminal carboxylate of UB and the ε-amino group of a Lys residue on the modified protein. 1 Protein modifications by UB are associated with a myriad of cellular functions, including regulation of protein degradation, designation of protein
Output: Specificity of the E1-E2-E3 Enzymatic Cascade for Ubiquitin C- terminal Sequences Identified by Phage Display HHS Public Access Author manuscript Supplementary Material Refer to Web version on PubMed Central for supplementary material
The location of autocrine interactions between the v-sis protein and PDGF receptors remains uncertain and controversial. To examine whether receptor-ligand interactions can occur intracellularly, we have constructed fusion proteins that anchor v-sis to specific intracellular membranes. Fusion of a cis-Golgi retention signal from a coronavirus E1 glycoprotein to v-sis protein completely abolished its transforming ability when transfected into NIH3T3 cells. Fusion proteins incorporating mutations in this retention signal were not retained within the Golgi complex but instead were transported to the cell surface, resulting in efficient transformation. All chimeric proteins were shown to dimerize properly. Derivatives of some of these constructs were also constructed bearing the cytoplasmic tail from the glycoprotein of vesicular stomatitis virus (VSV-G). These constructs allowed examination of subcellular localization by double-label immunofluorescence, using antibodies that distinguish between the extraceUular PDGF-related domain and the VSV-G cytoplasmic tail. Colocalization of sis-E1-G with Golgi markers confirmed its targeting to the early Golgi complex. The sis-E1 constructs, targeted to the early Golgi complex, exhibited no proteo-lyric processing whereas the mutant forms of sis-E1 exhibited normal proteolytic processing. Treatment with suramin, a polyanionic compound that disrupts ligand/receptor interactions at the cell surface, was able to revert the transformed phenotype induced by the mutant sis-E1 constructs described here. Our results demonstrate that autocrine interactions between the v-sis oncoprotein and PDGF receptors within the early Golgi complex do not result in functional signal transduction. Another v-sis fusion protein was constructed by attaching the transmembrane domain and COOHterminus of TGN38, a protein that localizes to the trans-Golgi network (TGN). This construct was primarily retained intracellularly, although some of the fusion protein reached the surface. Deletion of the COOH-terminal region of the TGN38 retention signal abrogated the TGN-localization, as evidenced by very prominent cell surface localization, and resulted in increased transforming activity. The behavior of the sis-TGN38 derivatives is discussed within the context of the properties of TGN38 itself, which is known to recycle from the cell surface to the TGN.
Output: The v-sis Oncoprotein Loses Transforming Activity When Targeted to the Early Golgi Complex
Drug repurposing offers an expedited and economical route to develop new clinical therapeutics in comparison to traditional drug development. Growthbased high-throughput screening is concomitant with drug repurposing and enables rapid identification of new therapeutic uses for investigated drugs; however, this traditional method is not compatible with microorganisms with abnormal growth patterns such as Staphylococcus aureus small-colony variants (SCV). SCV subpopulations are auxotrophic for key compounds in biosynthetic pathways, which result in low growth rate. SCV formation is also associated with reduced antibiotic susceptibility, and the SCV's ability to revert to the normal cell growth state is thought to contribute to recurrence of S. aureus infections. Thus, there is a critical need to identify antimicrobial agents that are potent against SCV in order to effectively treat chronic infections. Accordingly, here we describe adapting an adenylate kinase (AK)-based cell death reporter assay to identify members of a Food and Drug Administration (FDA)approved drug library that display bactericidal activity against S. aureus SCV. Four library members, daunorubicin, ketoconazole, rifapentine, and sitafloxacin, exhibited potent SCV bactericidal activity against a stable S. aureus SCV. Further investigation showed that sitafloxacin was potent against methicillin-susceptible and -resistant S. aureus, as well as S. aureus within an established biofilm. Taken together, these results demonstrate the ability to use the AK assay to screen small-molecule libraries for SCV bactericidal agents and highlight the therapeutic potential of sitafloxacin to be repurposed to treat chronic S. aureus infections associated with SCV and/or biofilm growth states. IMPORTANCE Conventional antibiotics fail to successfully treat chronic osteomyelitis, endocarditis, and device-related and airway infections. These recurring infections are associated with the emergence of SCV, which are recalcitrant to conventional antibiotics. Studies have investigated antibiotic therapies to treat SCV-related infections but have had little success, emphasizing the need to identify novel antimicrobial drugs. However, drug discovery is a costly and time-consuming process. An alternative strategy is drug repurposing, which could identify FDA-approved and wellcharacterized drugs that could have off-label utility in treating SCV. In this study, we adapted a high-throughput AK-based assay to identify 4 FDA-approved drugs, daunorubicin, ketoconazole, rifapentine, and sitafloxacin, which display antimicrobial activity against S. aureus SCV, suggesting an avenue for drug repurposing in order to effectively treat SCV-related infections. Additionally, this screening paradigm can Citation Trombetta RP, Dunman PM, Schwarz EM, Kates SL, Awad HA. 2018. A highthroughput screening approach to repurpose FDA-approved drugs for bactericidal applications against Staphylococcus aureus small-colony variants. mSphere 3:e00422-18.
Output: A High-Throughput Screening Approach To Repurpose FDA-Approved Drugs for Bactericidal Applications against Staphylococcus aureus Small-Colony Variants
Existing and emerging infectious diseases are among the most pressing global threats to biodiversity, food safety and human health. The complex interplay between host, pathogen and environment creates a challenge for conserving species, communities and ecosystem functions, while mediating the many known ecological and socio-economic negative effects of disease. Despite the clear ecological and evolutionary contexts of host-pathogen dynamics, approaches to managing wildlife disease remain predominantly reactionary, focusing on surveillance and some attempts at eradication. A few exceptional studies have heeded recent calls for better integration of ecological concepts in the study and management of wildlife disease; however, evolutionary concepts remain underused. Applied evolution consists of four principles: evolutionary history, genetic and phenotypic variation, selection and eco-evolutionary dynamics. In this article, we first update a classical framework for understanding wildlife disease to integrate better these principles. Within this framework, we explore the evolutionary implications of environment-disease interactions. Subsequently, we synthesize areas where applied evolution can be employed in wildlife disease management. Finally, we discuss some future directions and challenges. Here, we underscore that despite some evolutionary principles currently playing an important role in our understanding of disease in wild animals, considerable opportunities remain for fostering the practice of evolutionarily enlightened wildlife disease management.
Output: Applying evolutionary concepts to wildlife disease ecology and management
Methods for investigating human pain have been developed over the last 100 years. Typically, researchers focus on people with clinical pain, or on healthy participants undergoing laboratory-controlled paininduction techniques focussed mostly on exogenously generated skin nociception. Less commonly investigated are acute pain experiences that emerge naturally. Six common painful complaints were identified: headache, muscular pain, visceral pain, menstrual pain, dental pain, and pain associated with upper respiratory tract infection. Methods used to recruit participants with the natural occurrence of each pain complaint were identified, and features of their use reviewed. Also reviewed were experimental analogues designed to mimic these pains, with the exception of menstrual pain. Headache and menstrual pain appear to be most effectively researched in their naturally occurring form, whereas muscle and dental pain may be more easily induced. Upper respiratory tract infection and abdominal pain provide further challenges for researchers. Summary guidance is offered, and directions for methods development outlined. Ó
Output: Comprehensive review Methods for studying naturally occurring human pain and their analogues
Emergencies in theriogenology practice go beyond just saving the life of the patient, but also preserving its reproductive abilities. Camelid emergency medicine is a relatively new field. This paper discusses the most common reproductive emergencies, their diagnosis, treatment, and prognosis in male and female camelids. The conclusions drawn are based primarily on clinical observations by the authors over the last 25 years. Special consideration is given to peculiarities of the species, particularly in the choice of obstetrical manipulations and therapies. #
Output: Reproductive emergencies in camelids
In this work, we use a within-host viral dynamic model to describe the SARS-CoV-2 kinetics in host. Chest radiograph score data are used to estimate the parameters of that model. Our result shows that the basic reproductive number of SARS-CoV-2 in host growth is around 3.79. Using the same method we also estimate the basic reproductive number of MERS virus is 8.16 which is higher than SARS-CoV-2. The PRCC method is used to analyze the sensitivities of model parameters and the drug effects on virus growth are also implemented to analyze the model.
Output: The within-host viral kinetics of SARS-CoV-2
This article reviews and highlights the current development of DNA-based bioanalytical microsystems for point-of-care diagnostics and on-site monitoring of food and water. Recent progresses in the miniaturization of various biological processing steps for the sample preparation, DNA amplification (polymerase chain reaction), and product detection are delineated in detail. Product detection approaches utilizing "portable" detection signals and electrochemistry-based methods are emphasized in this work. The strategies and challenges for the integration of individual processing module on the same chip are discussed.
Output: DNA-based bioanalytical microsystems for handheld device applications
The generation and use of avian antibodies is of increasing interest in a wide variety of applications within the life sciences. Due to their phylogenetic distance, mechanisms of immune diversification and the way in which they deposit IgY immunoglobulin in the egg yolk, chickens provide a number of advantages compared to mammals as hosts for immunization. These advantages include: the one-step purification of antibodies from egg yolk in large amounts facilitates having a virtually continuous supply; the epitope spectrum of avian antibodies potentially grants access to novel specificities; the broad absence of cross-reactivity with mammalian epitopes avoids assay interference and improves the performance of immunological techniques. The polyclonal nature of IgY antibodies has limited their use since avian hybridoma techniques are not well established. Recombinant IgY, however, can be generated from mammalian monoclonal antibodies which makes it possible to further exploit the advantageous properties of the IgY scaffold. Moreover, cloning and selecting the immune repertoire from avian organisms is highly efficient, yielding antigen-specific antibody fragments. The recombinant approach is well suited to circumvent any limitations of polyclonal antibodies. This review presents comprehensive information on the generation, purification, modification and applications of polyclonal and monoclonal IgY antibodies.
Output: Avian IgY antibodies and their recombinant equivalents in research, diagnostics and therapy
Avian infectious bronchitis virus (IBV) encodes 15 nonstructural proteins (nsps) which play crucial roles in RNA transcription and genome replication. One of them, nsp3, contains an ADRP (adenosine diphosphate-ribose-1 0 -phosphatase) domain which was revealed in recent studies to have ADP-ribose-1 0 -monophosphatase (Appr-1 0 -pase) activity. Appr-1 0 -pase catalyzes the conversion of ADPribose-1 0 -monophosphate (Appr-1 0 -p) to ADP-ribose in the tRNA-splicing pathway. The gene segment encoding the IBV nsp3 ADRP domain has been cloned and expressed in Escherichia coli. The protein has been crystallized and the crystals diffracted to 1.8 Å resolution. They belonged to space group P1, with unit-cell parameters a = 41.1, b = 43.2, c = 48.9 Å , = 78.0, = 80.0, = 73.6 . Each asymmetric unit contains two molecules.
Output: Structural Biology and Crystallization Communications Purification, crystallization and preliminary crystallographic analysis of avian infectious bronchitis virus nsp3 ADRP domain
Monoclonal antibodies (MAbs) against two major structural proteins of the cell-adapted Mebus strain of bovine coronavirus (BCV-L9) were produced and characterized. Seven MAbs reacted with the peplomeric glycoprotein, gplOO/S, while three MAbs reacted with the nucleoprotein p53/N in Western blot analysis of BCV polypeptides. MAbs to gplOO/S reacted with discontinuous epitopes of gplOO/S in Westerns under mild but not under standard denaturing conditions. In contrast, MAbs to p53/N reacted in both types of Westerns, and those epitopes were thus continuous. MAbs to p53/N failed to neutralize BCV infectivity, while 4 MAbs to gplOO/S neutralized BCV effectively. Cross reactivity of MAbs to gplOO/S specified by five virulent wild-type strains and two high passage, cell-culture-adapted strains in mildly denaturing Westerns and neutralization assays indicated that two epitopes were conserved in all seven strains, while two epitopes of the avirulent strains were not detected in the wild-type strains. Non-neutralizing MAbs of gplOO/S reacted with all seven strains in Westerns with the exception of one MAb that was specific for the highly cell-adapted strain BCV-L9.
Output: Comparison of Bovine Coronavirus (BCV) Antigens: Monoclonal Antibodies to the Spike Glycoprotein Distinguish between Vaccine and Wild-Type Strains
Purpose: Despite their controversial role, corticosteroids (CS) are frequently administered to patients with H1N1 virus infection with severe respiratory failure secondary to viral pneumonia. We hypothesized that invasive pulmonary aspergillosis (IPA) is a frequent complication in critically ill patients with H1N1 virus infection and that CS may contribute to this complication. Methods: We retrospectively selected all adult patients with confirmed H1N1 virus infection admitted to the intensive care unit (ICU) of two tertiary care hospitals from September 2009 to March 2011. Differences in baseline factors, risk factors, and outcome parameters were studied between patients with and without IPA. Results: Of 40 critically ill patients with confirmed H1N1, 9 (23 %) developed IPA 3 days after ICU admission. Five patients had proven and four had probable IPA. Significantly more IPA patients received CS within 7 days before ICU admission (78 versus 23 %, p = 0.002). IPA patients also received significantly higher doses of CS before ICU admission [hydrocortisone equivalent 800 (360-2,635) versus 0 (0-0) mg, p = 0.005]. On multivariate analysis, use of CS before ICU admission was independently associated with IPA [odds ratio (OR) 14.4 (2.0-101.6), p = 0.007]. Conclusions: IPA was diagnosed in 23 % of critically ill patients with H1N1 virus infection after a median of 3 days after ICU admission. Our data suggest that use of CS 7 days before ICU admission is an independent risk factor for fungal superinfection. These findings may have consequences for clinical practice as they point out the need for increased awareness of IPA, especially in those critically ill H1N1 patients already receiving CS.
Output: Invasive pulmonary aspergillosis is a frequent complication of critically ill H1N1 patients: a retrospective study
a b s t r a c t Nucleocapsid (N) protein of porcine reproductive and respiratory syndrome virus (PRRSV) plays a central role in virus replication. In this study, serial N-and C-terminal truncations of N protein were performed in the context of type 2 PRRSV infectious cDNA clone, and our results revealed that a stretch of inter-genotypic variable N terminal residues aa 5-13 ( 5 NGKQQKKK 13 K) and the last four inter-genotypic variable aa residues ( 120 SPS 123 A) at the C terminus of N protein were dispensable for type 2 PRRSV infectivity. All the recovered deletion mutant viruses had spontaneous mutations in the N coding region, including substitution, deletion and insertion. We re-engineered the additional internal deletion with or without the original C-terminal deletion back into wild-type APRRS and found that the internal domain spanning the inter-genotypic variable residues 39-42 ( 39 KGP 42 G) and conserved residues 48-52 ( 48 KNPE 52 K), respectively, were dispensable for type 2 PRRSV viability. These results demonstrated that N protein contains non-essential regions for virus viability in cell culture. Such dispensable regions could be utilized as insertion site for foreign tag expression and the rescued viruses could be the candidates for marker vaccine.
Output: Identification of non-essential regions in nucleocapsid protein of porcine reproductive and respiratory syndrome virus for replication in cell culture
The concurrent use of N95 filtering facepiece respirators with powered air-purifying respirators during aerosol-generating medical procedures in patients with severe respiratory pathogens has been promoted as offering additional protection against infectious agents. The purpose of this article is to examine the impact of this additional respiratory equipment upon protection and personal performance. The presumed additive protective effect of an N95 filtering facepiece respirator used concurrently with a powered air-purifying respirator has not been subjected to rigorous scientific investigation. The burden imposed by additional respiratory protective equipment should not be discounted, and the potentially minor contribution to protection may be offset by the negative impact on personal performance. Novel uses of protective equipment occasionally are spawned during crisis situations, but their generalized applicability to healthcare workers should ultimately be evidence-based. (Am J Infect Control 2008;36:135-41.) 
Output: Evaluation of the rationale for concurrent use of N95 filtering facepiece respirators with loose-fitting powered air-purifying respirators during aerosol-generating medical procedures
The origin of viruses remains mysterious because of their diverse and patchy molecular and functional makeup. Although numerous hypotheses have attempted to explain viral origins, none is backed by substantive data. We take full advantage of the wealth of available protein structural and functional data to explore the evolution of the proteomic makeup of thousands of cells and viruses. Despite the extremely reduced nature of viral proteomes, we established an ancient origin of the "viral supergroup" and the existence of widespread episodes of horizontal transfer of genetic information. Viruses harboring different replicon types and infecting distantly related hosts shared many metabolic and informational protein structural domains of ancient origin that were also widespread in cellular proteomes. Phylogenomic analysis uncovered a universal tree of life and revealed that modern viruses reduced from multiple ancient cells that harbored segmented RNA genomes and coexisted with the ancestors of modern cells. The model for the origin and evolution of viruses and cells is backed by strong genomic and structural evidence and can be reconciled with existing models of viral evolution if one considers viruses to have originated from ancient cells and not from modern counterparts.
Output: A phylogenomic data-driven exploration of viral origins and evolution
Web-based social media is increasingly being used across different settings in the health care industry. The increased frequency in the use of the Internet via computer or mobile devices provides an opportunity for social media to be the medium through which people can be provided with valuable health information quickly and directly. While traditional methods of detection relied predominately on hierarchical or bureaucratic lines of communication, these often failed to yield timely and accurate epidemiological intelligence. New web-based platforms promise increased opportunities for a more timely and accurate spreading of information and analysis. This article aims to provide an overview and discussion of the availability of timely and accurate information. It is especially useful for the rapid identification of an outbreak of an infectious disease that is necessary to promptly and effectively develop public health responses. These web-based platforms include search queries, data mining of web and social media, process and analysis of blogs containing epidemic key words, text mining, and geographical information system data analyses. These new sources of analysis and information are intended to complement traditional sources of epidemic intelligence. Despite the attractiveness of these new approaches, further study is needed to determine the accuracy of blogger statements, as increases in public participation may not necessarily mean the information provided is more accurate. The shift in human interaction and media consumption to online communication has changed the way people seek information. The increased frequency in the use of the Internet via computer or mobile devices provides an opportunity for social media to be the means of providing people with valuable health information directly and quickly. The development of web-based social media analytics has given public health officers and physicians an earlier insight into the emergence and spread of infectious diseases. Availability of timely and accurate information is especially useful for the rapid identification of an outbreak of an infectious disease necessary to promptly and effectively develop public health responses.
Output: Mining social media and web searches for disease detection
Tuberculosis (TB) is the leading global infectious cause of death. Understanding TB transmission is critical to creating policies and monitoring the disease with the end goal of TB elimination. To our knowledge, there has been no systematic review of key transmission parameters for TB. We carried out a systematic review of the published literature to identify studies estimating either of the two key TB transmission parameters: the serial interval (SI) and the reproductive number. We identified five publications that estimated the SI and 56 publications that estimated the reproductive number. The SI estimates from four studies were: 0.57, 1.42, 1.44 and 1.65 years; the fifth paper presented age-specific estimates ranging from 20 to 30 years (for infants <1 year old) to <5 years (for adults). The reproductive number estimates ranged from 0.24 in the Netherlands (during 1933-2007) to 4.3 in China in 2012. We found a limited number of publications and many high TB burden settings were not represented. Certain features of TB dynamics, such as slow transmission, complicated parameter estimation, require novel methods. Additional efforts to estimate these parameters for TB are needed so that we can monitor and evaluate interventions designed to achieve TB elimination. https://www.cambridge.org/core/terms. https://doi.
Output: Epidemiology and Infection Quantifying TB transmission: a systematic review of reproduction number and serial interval estimates for tuberculosis
Background. Precision public health is a state-of-the-art concept in public health research and its application in health care. Application of information technology in field of epidemiology paves the way to its transformation to digital epidemiology. A geospatial epidemiological model was simulated to estimate the spread of Ebola virus disease after a hypothetical outbreak in India. Methods. It was a simulation study based on SEIR (Susceptible-Exposed-Infectious-Recovered) compartmental model. Simulation was done in Spatiotemporal Epidemiological Modeler (STEM). Epidemiological profile of Ebola virus, that transmitted throughout the Sierra Leon in 2014-2016, was fitted into the SEIR deterministic compartment model designed for India.
Output: A Simulation Study on Hypothetical Ebola Virus Transmission in India Using Spatiotemporal Epidemiological Modeler (STEM): A Way towards Precision Public Health
Background: Avian leukosis virus (ALV) is a major infectious disease that impacts the poultry industry worldwide. Despite intensive efforts, no effective vaccine has been developed against ALV because of mutations that lead to resistant forms. Therefore, there is a dire need to develop antiviral agents for the treatment of ALV infections and RNA interference (RNAi) is considered an effective antiviral strategy. Results: In this study, the avian leukosis virus subgroup J (ALV-J) proviral genome, including the gag genes, were treated as targets for RNAi. Four pairs of miRNA sequences were designed and synthesized that targeted different regions of the gag gene. The screened target (i.e., the gag genes) was shown to effectively suppress the replication of ALV-J by 19.0-77.3%. To avoid the generation of escape variants during virus infection, expression vectors of multi-target miRNAs were constructed using the multi-target serial strategy (against different regions of the gag, pol, and env genes). Multi-target miRNAs were shown to play a synergistic role in the inhibition of ALV-J replication, with an inhibition efficiency of viral replication ranging from 85.0-91.2%. Conclusion: The strategy of multi-target miRNAs might be an effective method for inhibiting ALV replication and the acquisition of resistant mutations.
Output: Enhanced inhibition of Avian leukosis virus subgroup J replication by multi-target miRNAs
Background: Foodborne norovirus outbreak data in Japan from [2005][2006], involving virological surveillance of all symptomatic and asymptomatic individuals, were reanalyzed to estimate the asymptomatic ratio of norovirus infection along with the risk of infection and the probability of virus shedding. Methods: Employing a statistical model that is considered to capture the data-generating process of the outbreak and virus surveillance, maximum likelihood estimation of the asymptomatic ratio was implemented. Results: Assuming that all norovirus outbreaks (n = 55) were the result of random sampling from an identical distribution and ignoring genogroup and genotype specificities, the asymptomatic ratio was estimated at 32.1% (95% confidence interval [CI], 27.7-36.7). Although not significant, separate estimation of the asymptomatic ratio of the GII.4 genotype appeared to be greater than other genotypes and was estimated at 40.7% (95% CI, 32.8-49.0). Conclusion: The present study offered the first explicit empirical estimates of the asymptomatic ratio of norovirus infection in natural infection settings. The estimate of about 30% was consistent with those derived from volunteer challenge studies. Practical difficulty in controlling GII.4 outbreaks was supported by the data, considering that a large estimate of the asymptomatic ratio was obtained for the GII.4 genotype.
Output: Estimating the Asymptomatic Ratio of Norovirus Infection During Foodborne Outbreaks With Laboratory Testing in Japan
The Psychiatric-Medical Comorbidity section will focus on the prevalence and impact of psychiatric disorders in patients with chronic medical illness as well as the prevalence and impact of medical disorders in patients with chronic psychiatric illness. Objective: Severe acute respiratory syndrome (SARS) was the first massive infectious disease outbreak of the 21st century. However, it is unlikely that this outbreak will be the last. This study aimed to evaluate the long-term psychiatric morbidities in survivors of SARS. Method: This is a cohort study designed to investigate psychiatric complications among SARS survivors treated in the United Christian Hospital 30 months after the SARS outbreak. Psychiatric morbidities were assessed by the Structured Clinical Interview for DSM-IV, the Impact of Events Scale-Revised and the Hospital Anxiety and Depression Scale. Functional outcomes were assessed by the Medical Outcomes Study 36-Item Short-Form Health Survey. Results: Ninety subjects were recruited, yielding a response rate of 96.8%. Post-SARS cumulative incidence of DSM-IV psychiatric disorders was 58.9%. Current prevalence for any psychiatric disorder at 30 months post-SARS was 33.3%. One-fourth of the patients had post-traumatic stress disorder (PTSD), and 15.6% had depressive disorders. Conclusion: The outbreak of SARS can be regarded as a mental health catastrophe. PTSD was the most prevalent long-term psychiatric condition, followed by depressive disorders. Our results highlight the need to enhance preparedness and competence of health care professionals in detecting and managing the psychological sequelae of future comparable infectious disease outbreaks.
Output: Psychiatric-Medical Comorbidity Long-term psychiatric morbidities among SARS survivors
Cell culture Buffalo green monkey (BGM) kidney cells, HeLa R19 cells, and rhabdomyosarcoma RD cells were grown at 37°C, 5% CO 2 in DMEM Ready Mix (PAA) containing 10% fetal bovine serum or in DMEM (Lonza) supplemented with 10% fetal bovine serum. Vero, HeLa H and BGM cells used in the multicycle antiviral assays were grown in MEM supplemented with 10% FCS (Integro), 2 mM Lglutamine and 20 mM HEPES. HAP1 cells (Carette et al., 2011) (provided by Thijn Brummelkamp, NKI, Amsterdam, The Netherlands) were grown in IMDM supplemented with 10% fetal bovine serum.
Output: SUPPLEMENTAL INFORMATION TO: Itraconazole inhibits enterovirus replication by targeting the oxysterol-binding protein (OSBP)