niryuu/sni-each-converted huggingface dataset:
Background. The study objective was to investigate and synthesize available evidence relating to the psychological health of Emergency Dispatch Centre (EDC) operatives, and to identify key stressors experienced by EDC operatives. Methods. Eight electronic databases (Embase, PubMed, Medline, CINAHL, PsycInfo, PsycArticles, The Psychology and Behavioural Sciences Collection, and Google Scholar) were searched. All study designs were included, and no date limits were set. Studies were included if they were published in English, and explored the psychological health of any EDC operatives, across fire, police, and emergency medical services. Studies were excluded if they related solely to other emergency workers, such as police officers or paramedics. Methodological quality of included studies was assessed using checklists adapted from the Critical Appraisal Skills Programme. A narrative synthesis was conducted, using thematic analysis. Results. A total of 16 articles were included in the review. Two overarching themes were identified during the narrative synthesis: 'Organisational and Operational Factors' and 'Interactions with Others'. Stressors identified included being exposed to traumatic calls, lacking control over high workload, and working in under-resourced and pressured environments. Lack of support from management and providing an emotionally demanding service were additional sources of stress. Peer support and social support from friends and family were helpful in managing work-related stress. Discussion. EDC operatives experience stress as a result of their work, which appears to be related to negative psychological health outcomes. Future research should explore the long-term effects of this stress, and the potential for workplace interventions to alleviate the negative impacts on psychological health. PROSPERO Registration Number. CRD42014010806. How to cite this article Golding et al. (2017), Exploring the psychological health of emergency dispatch centre operatives: a systematic review and narrative synthesis. PeerJ 5:e3735; DOI 10.7717/peerj.3735 Subjects Emergency and Critical Care, Psychiatry and Psychology . Dean AM, Rainnie A. 2009. Frontline employees' views on organizational factors that affect the delivery of service quality in call centers. Journal of Services Marketing 23(5):326-337. Deery S, Iverson R, Walsh J. 2002. Work relationships in telephone call centres: understanding emotional exhaustion and employee withdrawal. Journal of Management Studies 39(4):471-496 M. 2012. Stress amongst nurses working in a healthcare telephone-advice service: relationship with job satisfaction, intention to leave, sickness absence, and performance. Journal of Advanced Nursing 68(7):
Output: Distributed under Creative Commons CC-BY 4.0 Exploring the psychological health of emergency dispatch centre operatives: a systematic review and narrative synthesis
Inhibitors of bacterial DD-peptidases represent potential antibiotics. In the search for alternatives to β-lactams, we have investigated a series of compounds designed to generate transition state analogue structures on reaction with DD-peptidases. The compounds contain a combination of a peptidoglycan-mimetic specificity handle and a warhead capable of delivering a tetrahedral anion to the enzyme active site. The latter include a boronic acid, two alcohols, an aldehyde and a trifluoroketone. The compounds were tested against two low molecular mass class C DDpeptidases. As expected from previous observations, the boronic acid was a potent inhibitor, but, rather unexpectedly from precedent, the trifluoroketone [D-α-aminopimelyl-(1,1,1-trifluoro-3amino)butan-2-one] was also very effective. Taking into account competing hydration, the trifluoroketone was the strongest inhibitor of the Actinomadura R39 DD-peptidase, with a subnanomolar (free ketone) inhibition constant. A crystal structure of the complex between the trifluoroketone and the R39 enzyme showed that a tetrahedral adduct had indeed formed with the active site serine nucleophile. The trifluoroketone moiety, therefore, should be considered along with boronic acids and phosphonates, as a warhead that can be incorporated into new and effective DD-peptidase inhibitors and therefore, perhaps, antibiotics. The bacterial DD-peptidases are of considerable importance in medical practice since they are the targets of β-lactam antibiotics. (1) These enzymes catalyze the final transpeptidation reaction in the biosynthesis of bacterial cell walls and are essential to bacterial survival. The β-lactams, acting as mechanism-based/transition state analogue inhibitors (2-4), are precisely structured to inactivate DD-peptidases in a manner that these enzymes have been unable to escape through evolution of a hydrolytic pathway. Bacteria have, however, been able to achieve resistance to β-lactams in a number of ways unrelated to DD-peptidase active site structure, and, in particular through evolution of β-lactamases from DD-peptidases (2,4). The β-lactamases, unlike DD-peptidases, are able to catalyze rapid β-lactam hydrolysis and thus destruction of their antibiotic activity (5).
Output: Inhibition of DD-Peptidases by a Specific Trifluoroketone: Crystal Structure of a Complex with the Actinomadura R39 DD- Peptidase † NIH Public Access Author Manuscript
RNA-RNA recombination salvages viral RNAs and contributes to their genomic variability. A recombinationally-active subgenomic promoter (sgp) has been mapped in Brome mosaic bromovirus (BMV) RNA3 (Wierzchoslawski et al., 2004. J. Virol.78, 8552-8864) and mRNA-like 5′ sgRNA3a was characterized (Wierzchoslawski et al., 2006. J. Virol. 80, 12357-12366). In this paper we describe sgRNA3a-mediated recombination in both in vitro and in vivo experiments. BMV replicase-directed co-copying of (−) RNA3 with wt sgRNA3a generated RNA3 recombinants in vitro, but it failed to when 3′-truncated sgRNA3a was substituted, demonstrating a role for the 3′ polyA tail. Barley protoplast co-transfections revealed that (i) wt sgRNA3a recombines at the 3′ and the internal sites; (ii) 3′-truncated sgRNA3as recombine more upstream; and (iii) 5′-truncated sgRNA3 recombine at a low rate. In planta co-inoculations confirmed the RNA3-sgRNA3a crossovers. In summary, the non-replicating sgRNA3a recombines with replicating RNA3, most likely via primer extension and/or internal template switching.
Output: Recombination of 5′ subgenomic RNA3a with genomic RNA3 of Brome mosaic bromovirus in vitro and in vivo
Coronavirus (CoV) envelope (E) protein ion channel activity was determined in channels formed in planar lipid bilayers by peptides representing either the transmembrane domain of severe acute respiratory syndrome CoV (SARS-CoV) E protein, or the full-length E protein. Both of them formed a voltage independent ion conductive pore with symmetric ion transport properties. Mutations N15A and V25F located in the transmembrane domain prevented the ion conductivity. E protein derived channels showed no cation preference in non-charged lipid membranes, whereas they behaved as pores with mild cation selectivity in negatively-charged lipid membranes. The ion conductance was also controlled by the lipid composition of the membrane. Lipid charge also regulated the selectivity of a HCoV-229E E protein derived peptide. These results suggested that the lipids are functionally involved in E protein ion channel activity, forming a protein-lipid pore, a novel concept for CoV E protein ion channel entity.
Output: Coronavirus E protein forms ion channels with functionally and structurally-involved membrane lipids
One of the main tasks in biological sequence analysis is biological sequence comparison. Numerous efficient methods have been developed for sequence comparison. Traditional sequence comparison is based on sequence alignment. In this report, we propose a novel alignment-free method based on the relative Lempel-Ziv complexity to compare biological sequences. The vertebrate transferring genomes and the spike protein sequences are prepared and tested to evaluate the validity of the method. We use this method to build phylogenetic tree of two groups of the sequences. The result demonstrates that our method is powerful and efficient.
Output: A relative Lempel-Ziv complexity: Application to comparing biological sequences
This article employs a state-of-the-art panel threshold model by allowing for regime intercepts, in order to shed new light on the asymmetric/ nonlinear effects of local and global sentiments on expected industry stock returns among 11 Asian countries during the period from 1996 to 2010. Empirical evidence demonstrates that once the regime intercept is included, the asymmetric effects of global sentiment on oil & gas, financials, and health care industry returns become less under optimism, as compared with under pessimism. More critically, the positive (negative) impact of global sentiment above (under) the threshold turns significant, indicating that global optimism leads industry returns to be overvalued, while pessimism leads them to be undervalued. For local market sentiment, our results support that higher local sentiment enhances the returns of basic materials, telecommunications, and utilities industries. The empirical results confirm that the nexus of industry returns and investor sentiments is subject to change between different sentimental intervals.
Output: Asymmetric effects of investor sentiment on industry stock returns: Panel data evidence
We performed experiments to determine the effect of PKR activation on respiratory syncytial virus (RSV) replication. We first determined that RSV infection activates PKR which induces the phosphorylation of eIF2α, resulting in the formation of host stress granules. We used RNA interference to decrease endogenous PKR levels. RSV replication was not altered in cells deficient for PKR expression. However, RSV-mediated stress granule formation was significantly reduced in PKR-knockdown cells. As an alternative method to block PKR activation, we used treatment with the kinase inhibitor 2-aminopurine (2-AP). We observed that 2-AP treatment significantly reduced viral replication. We also treated PKR-knockdown cells with 2-AP and inoculated with RSV. Under these conditions, 2-AP treatment diminished viral replication in the absence of PKR expression. These results suggest that PKR activation has a minimal effect on RSV replication and that the antiviral effect of 2-AP during RSV infection likely occurs via a PKR-independent mechanism.
Output: Activation of protein kinase R is required for induction of stress granules by respiratory syncytial virus but dispensable for viral replication
Background: Adverse events are associated with significant morbidity, mortality and cost in hospitalized patients. Measuring adverse events is necessary for quality improvement, but current detection methods are inaccurate, untimely and expensive. The advent of electronic health records and the development of automated methods for encoding and classifying electronic narrative data, such as natural language processing, offer an opportunity to identify potentially better methods. The objective of this study is to determine the accuracy of using automated methods for detecting three highly prevalent adverse events: a) hospital-acquired pneumonia, b) catheter-associated bloodstream infections, and c) in-hospital falls. Methods/design: This validation study will be conducted at two large Canadian academic health centres: the McGill University Health Centre (MUHC) and The Ottawa Hospital (TOH). The study population consists of all medical, surgical and intensive care unit patients admitted to these centres between 2008 and 2014. An automated detection algorithm will be developed and validated for each of the three adverse events using electronic data extracted from multiple clinical databases. A random sample of MUHC patients will be used to develop the automated detection algorithms (cohort 1, development set). The accuracy of these algorithms will be assessed using chart review as the reference standard. Then, receiver operating characteristic curves will be used to identify optimal cut points for each of the data sources. Multivariate logistic regression and the areas under curve (AUC) will be used to identify the optimal combination of data sources that maximize the accuracy of adverse event detection. The most accurate algorithms will then be validated on a second random sample of MUHC patients (cohort 1, validation set), and accuracy will be measured using chart review as the reference standard. The most accurate algorithms validated at the MUHC will then be applied to TOH data (cohort 2), and their accuracy will be assessed using a reference standard assessment of the medical chart. Discussion: There is a need for more accurate, timely and efficient measures of adverse events in acute care hospitals. This is a critical requirement for evaluating the effectiveness of preventive interventions and for tracking progress in patient safety through time.
Output: Accuracy of using automated methods for detecting adverse events from electronic health record data: a research protocol
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Current therapies confer partial benefits either by incompletely improving airflow limitation or by reducing acute exacerbations, hence new therapies are desirable. In the absence of robust early predictors of clinical efficacy, the potential success of novel therapeutic agents in COPD will not entirely be known until the drugs enter relatively large and costly clinical trials. New predictive models in humans, and new study designs are being sought to allow for confirmation of pharmacodynamic and potentially clinically meaningful effects in early development. This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD.
Output: Challenge models to assess new therapies in chronic obstructive pulmonary disease
Background: Platelets are associated with HIV in the blood of infected individuals and might modulate viral dissemination, particularly if the virus is directly transmitted into the bloodstream. The C-type lectin DC-SIGN and the novel HIV attachment factor CLEC-2 are expressed by platelets and facilitate HIV transmission from platelets to T-cells. Here, we studied the molecular mechanisms behind CLEC-2-mediated HIV-1 transmission. Binding studies with soluble proteins indicated that CLEC-2, in contrast to DC-SIGN, does not recognize the viral envelope protein, but a cellular factor expressed on kidney-derived 293T cells. Subsequent analyses revealed that the cellular mucin-like membranous glycoprotein podoplanin, a CLEC-2 ligand, was expressed on 293T cells and incorporated into virions released from these cells. Knock-down of podoplanin in 293T cells by shRNA showed that virion incorporation of podoplanin was required for efficient CLEC-2-dependent HIV-1 interactions with cell lines and platelets. Flow cytometry revealed no evidence for podoplanin expression on viable T-cells and peripheral blood mononuclear cells (PBMC). Podoplanin was also not detected on HIV-1 infected T-cells. However, apoptotic bystander cells in HIV-1 infected cultures reacted with anti-podoplanin antibodies, and similar results were obtained upon induction of apoptosis in a cell line and in PBMCs suggesting an unexpected link between apoptosis and podoplanin expression. Despite the absence of detectable podoplanin expression, HIV-1 produced in PBMC was transmitted to Tcells in a CLEC-2-dependent manner, indicating that T-cells might express an as yet unidentified CLEC-2 ligand. Conclusions: Virion incorporation of podoplanin mediates CLEC-2 interactions of HIV-1 derived from 293T cells, while incorporation of a different cellular factor seems to be responsible for CLEC-2-dependent capture of PBMC-derived viruses. Furthermore, evidence was obtained that podoplanin expression is connected to apoptosis, a finding that deserves further investigation.
Output: Open Access RESEARCH Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2
Background: Taiwan experienced one of the most serious outbreaks of severe acute respiratory syndrome (SARS) during the 2003 epidemic. Public health nurses faced unprecedented challenges in implementing an extensive quarantine policy to prevent disease spread. Their professional confidence, however, was shattered during the SARS crisis. This paper assesses factors related to public health nurses' confidence in managing community SARS control programs. Methods: In May 2003, we sent structured questionnaires to all 361 health centers in Taiwan and asked the public health nurses responsible for epidemic control to complete. A total of 312 completed surveys were returned for a response rate of 86.4%. Descriptive methods and logistic regression were used to analyze the data. Results: Most public health nurses (71.9%) expressed a general lack of confidence in handling the SARS epidemic. Confidence was significantly associated with perceived epidemic severity (OR, 0.58; 95% CI: 0.35-0.99), daily epidemic updates (OR, 2.26; 95% CI: 1.28-3.98), and number of cases in the community (OR, 2.21; 95% CI: 1.13-4.31). Conclusion: Nurses' individual risk perception and prompt update of epidemic information significantly affect levels of professional confidence, a key factor influencing quarantine implementation success. Strategies to promote productive interagency collaboration and advocate participatory policy making involving health workers at all levels are needed to control effectively infectious disease outbreaks. (Am J Infect Control 2006;34:176-81.) 
Output: Confidence in controlling a SARS outbreak: Experiences of public health nurses in managing home quarantine measures in Taiwan
Background. Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic in central and northeastern China. This article describes the first identified patient with SFTS and a retrospective study on SFTS in Japan. Methods. Virologic and pathologic examinations were performed on the patient's samples. Laboratory diagnosis of SFTS was made by isolation/genome amplification and/or the detection of anti-SFTSV immunoglobulin G antibody in sera. Physicians were alerted to the initial diagnosis and asked whether they had previously treated patients with symptoms similar to those of SFTS. Results. A female patient who died in 2012 received a diagnosis of SFTS. Ten additional patients with SFTS were then retrospectively identified. All patients were aged ≥50 years and lived in western Japan. Six cases were fatal. The ratio of males to females was 8:3. SFTSV was isolated from 8 patients. Phylogenetic analyses indicated that all of the Japanese SFTSV isolates formed a genotype independent to those from China. Most patients showed symptoms due to hemorrhage, possibly because of disseminated intravascular coagulation and/or hemophagocytosis. Conclusions. SFTS has been endemic to Japan, and SFTSV has been circulating naturally within the country.
Output: The First Identification and Retrospective Study of Severe Fever With Thrombocytopenia Syndrome in Japan
Zika virus (ZIKV) infection can cause severe congenital diseases, such as microcephaly, ocular defects and arthrogryposis in fetuses, and Guillain-Barré syndrome in adults. Efficacious therapeutic treatments for infected patients, as well as prophylactic treatments to prevent new infections are needed for combating ZIKV infection. Here, we report that ZIKV-specific human polyclonal antibodies (SAB-155), elicited in transchromosomal bovine (TcB), provide significant protection from infection by ZIKV in STAT2 knockout (KO) golden Syrian hamsters both prophylactically and therapeutically. These antibodies also prevent testicular lesions in this hamster model. Our data indicate that antibody-mediated immunotherapy is effective in treating ZIKV infection. Because suitable quantities of highly potent human polyclonal antibodies can be quickly produced from the TcB system against ZIKV and have demonstrated therapeutic efficacy in a small animal model, they have the potential as an effective countermeasure against ZIKV infection.
Output: Human Polyclonal Antibodies Produced from Transchromosomal Bovine Provides Prophylactic and Therapeutic Protections Against Zika Virus Infection in STAT2 KO Syrian Hamsters
We describe the first genome isolation of Middle East respiratory syndrome coronavirus (MERS-CoV) in Kenya. This fatal zoonotic pathogen was first described in the Kingdom of Saudi Arabia in 2012. Epidemiological and molecular evidence revealed zoonotic transmission from camels to humans and between humans. Currently, MERS-CoV is classified by the WHO as having high pandemic potential requiring greater surveillance. Previous studies of MERS-CoV in Kenya mainly focused on site-specific and archived camel and human serum samples for antibodies. We conducted active nationwide cross-sectional surveillance of camels and humans in Kenya, targeting both nasal swabs and plasma samples from 1,163 camels and 486 humans collected from January 2016 to June 2018. A total of 792 camel plasma samples were positive by ELISA. Seroprevalence increased with age, and the highest prevalence was observed in adult camels (82.37%, 95% confidence interval (CI) 79.50-84.91). More female camels were significantly seropositive (74.28%, 95% CI 71.14-77.19) than male camels (P \ 0.001) (53.74%, 95% CI 48.48-58.90). Only 11 camel nasal swabs were positive for MERS-CoV by reverse transcription-quantitative PCR. Phylogenetic analysis of whole genome sequences showed that Kenyan MERS-CoV clustered within sub-clade C2, which is associated with the African clade, but did not contain signature deletions of orf4b in African viruses. None of the human plasma screened contained neutralizing antibodies against MERS-CoV. This study confirms the geographically widespread occurrence of MERS-CoV in Kenyan camels. Further one-health surveillance approaches in camels, wildlife, and human populations are needed.
Output: Genetic Evidence of Middle East Respiratory Syndrome Coronavirus (MERS-Cov) and Widespread Seroprevalence among Camels in Kenya
Consisting of nearly 60 functional genes, porcine interferon (IFN)-complex represents an evolutionary surge of IFN evolution in domestic ungulate species. To compare with humans and mice, each of these species contains about 20 IFN functional genes, which are better characterized using the conventional IFN-α/β subtypes as examples. Porcine IFN-complex thus represents an optimal model for studying IFN evolution that resulted from increasing viral pressure during domestication and industrialization. We hypothesize and justify that porcine IFN-complex may extend its functionality in antiviral and immunomodulatory activity due to its superior molecular diversity. Furthermore, these unconventional IFNs could even confer some functional and signaling novelty beyond that of the well-studied IFN-α/β subtypes. Investigations into porcine IFN-complex will further our understanding of IFN biology and promote IFN-based therapeutic designs to confront swine viral diseases.
Output: viruses Porcine Interferon Complex and Co-Evolution with Increasing Viral Pressure after Domestication
A reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay was developed and optimized to detect bovine viral diarrhea viral (BVDV) RNA. The RT-LAMP assay is highly sensitive and able to detect 4.67 × 10 0 copies of BVDV RNA. Additionally, the RT-LAMP method is capable of detecting both genotypes of BVDV. No cross-reaction with other bovine viruses was observed. The ability of RT-LAMP to detect BVDV RNA from bovine fecal swabs was also evaluated. Of the 88 fecal swabs, 38 were found to be positive by RT-LAMP assay, whereas 39 were positive by real-time RT-PCR. Taken together, the BVDV specific RT-LAMP method is highly specific and sensitive and can be used as a rapid and direct diagnostic assay for testing clinical samples.
Output: A reverse transcription loop-mediated isothermal amplification method for rapid detection of bovine viral diarrhea virus
Background-Healthcare-associated transmission of respiratory viruses is a concerning patient safety issue. Design-Surveillance for influenza virus among a cohort of healthcare workers (HCWs) was conducted in a tertiary care children's hospital from November 2009 until April 2010, using biweekly nasal swab collection. If a subject reported respiratory symptoms, an additional specimen was collected. Specimens from ill HCWs and a randomly selected sample from asymptomatic subjects were tested for additional respiratory viruses by multiplex PCR. Results-From 170 enrolled subjects, 1404 nasal swabs were collected. Influenza circulated at very low levels during the surveillance period and 74.2% of subjects received influenza vaccination. Influenza was not detected in any specimen. Multiplex respiratory virus PCR analysis of all 119 samples from symptomatic subjects and 200 specimens from asymptomatic subjects yielded a total of 42 positive specimens; 7 (16.7%) in asymptomatic subjects. Viral shedding was associated with report of any symptom (OR 13.06, p<0.0001,) and younger age (OR 0.96, p=0.023, 95% CI 0.92-0.99) when controlled for gender and occupation of physician or nurse. After the surveillance period, 46% of subjects reported working while ill with an influenza-like illness during the previous influenza season.
Output: Respiratory Virus Shedding in a Cohort of On-Duty Healthcare Workers Undergoing Prospective Surveillance
Over the last decade, it has become clear that the role of angiotensin II extends far beyond recognized renal and cardiovascular effects. The presence of an autologous renin-angiotensin system has been demonstrated in almost all tissues of the body. It is now known that angiotensin II acts both independently and in synergy with TGF-beta to induce fibrosis via the angiotensin type 1 receptor (AT 1 ) in a multitude of tissues outside of the cardiovascular and renal systems, including pulmonary fibrosis, intra-abdominal fibrosis, and systemic sclerosis. Interestingly, recent studies have described a paradoxically regenerative effect of the angiotensin system via stimulation of the angiotensin type 2 receptor (AT 2 ). Activation of AT 2 has been shown to ameliorate fibrosis in animal models of skeletal muscle, gastrointestinal, and neurologic diseases. Clinical reports suggest a beneficial role for modulation of angiotensin II signaling in cutaneous scarring. This article reviews current knowledge on the role that angiotensin II plays in tissue fibrosis, as well as current and potential therapies targeting this system.
Output: Modulation of angiotensin II signaling in the prevention of fibrosis
Minus-one ribosomal frameshifting is a translational recoding mechanism widely utilized by many RNA viruses to generate accurate ratios of structural and catalytic proteins. An RNA pseudoknot structure located in the overlapping region of the gag and pro genes of Simian Retrovirus type 1 (SRV-1) stimulates frameshifting. However, the experimental characterization of SRV-1 pseudoknot (un)folding dynamics and the effect of the base triple formation is lacking. Here, we report the results of our singlemolecule nanomanipulation using optical tweezers and theoretical simulation by steered molecular dynamics. Our results directly reveal that the energetic coupling between loop 2 and stem 1 via minorgroove base triple formation enhances the mechanical stability. The terminal base pair in stem 1 (directly in contact with a translating ribosome at the slippery site) also affects the mechanical stability of the pseudoknot. The −1 frameshifting efficiency is positively correlated with the cooperative onestep unfolding force and inversely correlated with the one-step mechanical unfolding rate at zero force. A significantly improved correlation was observed between −1 frameshifting efficiency and unfolding rate at forces of 15-35 pN, consistent with the fact that the ribosome is a force-generating molecular motor with helicase activity. No correlation was observed between thermal stability and −1 frameshifting efficiency. Recent advances in the discovery and understanding of complex RNA structures, dynamics, and functions have dramatically changed our view of RNA's role in biology. RNA has been found to play increasingly important and diverse regulatory and catalytic roles in many biological processes ranging from replication, transcription, splicing, to translation 1 . In this study, we focus on understanding how the translation reading frame can be regulated by cis-acting mRNA structures. The translation process is highly regulated and remarkably accurate. Normally, the reading frame needs to be maintained at a constant frame (0 frame) because shifting of the reading frame results in the generation of completely different protein products. Minus-one ribosomal frameshifting is a translational regulatory mechanism programmed by cis-acting mRNA structures and widely utilized by viruses and cells 2-13 . During − 1 ribosomal frameshifting, a ribosome is positioned at a certain sequence of mRNA called slippery sequence, and has a certain probability to move one nucleotide backward, before continuing translation in the new reading frame (− 1 frame) 11, 14, 15 . Minus-one frameshifting is important for (i) maintaining a fixed ratio of certain gene products through the translation of a fusion protein by bypassing the original 0 frame stop codon, and (ii) regulating the half-lives of mRNAs by employing mRNA degradation pathways through premature translation termination at a − 1 frame stop codon 11, 13 .
Output: Mechanical unfolding kinetics of the SRV-1 gag-pro mRNA pseudoknot: possible implications for −1 ribosomal frameshifting stimulation OPEN
Newcastle disease is considered the number one disease constraint to poultry production in low and middle-income countries, however poultry that is raised in resource-poor areas often experience multiple environmental challenges. Heat stress has a negative impact on production, and immune response to pathogens can be negatively modulated by heat stress. Candidate genes and regions chosen for this study were based on previously reported associations with response to immune stimulants, pathogens, or heat, including: TLR3, TLR7, MX, MHC-B (major histocompatibility complex, gene complex), IFI27L2, SLC5A1, HSPB1, HSPA2, HSPA8, IFRD1, IL18R1, IL1R1, AP2A2, and TOLLIP. Chickens of a commercial egg-laying line were infected with a lentogenic strain of NDV (Newcastle disease virus); half the birds were maintained at thermoneutral temperature and the other half were exposed to high ambient temperature before the NDV challenge and throughout the remainder of the study. Phenotypic responses to heat, to NDV, or to heat + NDV were measured. Selected SNPs (single nucleotide polymorphisms) within 14 target genes or regions were genotyped; and genotype effects on phenotypic responses to NDV or heat + NDV were tested in each individual treatment group and the combined groups. Seventeen significant haplotype effects, among seven genes and seven phenotypes, were detected for response to NDV or heat or NDV + heat. These findings identify specific genetic variants that are associated with response to heat and/or NDV which may be useful in the genetic improvement of chickens to perform favorably when faced with pathogens and heat stress.
Output: Association of Candidate Genes with Response to Heat and Newcastle Disease Virus
Urbanization is intensifying worldwide, with two-thirds of the human population expected to reside in cities within 30 years. The role of cities in human infectious disease is well established, but less is known about how urban landscapes influence wildlife-pathogen interactions. Here, we draw on recent advances in wildlife epidemiology to consider how environmental changes linked with urbanization can alter the biology of hosts, pathogens and vectors. Although urbanization reduces the abundance of many wildlife parasites, transmission can, in some cases, increase among urbanadapted hosts, with effects on rarer wildlife or those living beyond city limits. Continued rapid urbanization, together with risks posed by multi-host pathogens for humans and vulnerable wildlife populations, emphasize the need for future research on wildlife diseases in urban landscapes.
Output: Urbanization and the ecology of wildlife diseases
DNA aptamers specifically recognizing microbial cells and viruses have a range of analytical and therapeutic applications. This article describes recent advances in the development of aptamers targeting specific pathogens (e.g., live bacteria, whole viral particles, and virally-infected mammalian cells). Specific aptamers against pathogens have been used as affinity reagents to develop sandwich assays, to label and to image cells, to bind with cells for flow-cytometry analysis, and to act as probes for development of whole-cell biosensors. Future applications of aptamers to pathogens will benefit from recent advances in improved selection and new aptamers containing modified nucleotides, particularly slow off-rate modified aptamers (SOMAmers).
Output: Selection and analytical applications of aptamers binding microbial pathogens
word count: 91 Manuscript word count: 713 J o u r n a l P r e -p r o o f 2 Abstract The well-being of the health care workforce is the cornerstone of every well-functioning health system. As a result of the pandemic, medical healthcare providers are under an enormous amount of workload pressure along with increased total health expenditures. The overwhelming burden of COVID-19 illness could lead to caregiver burnout. Direct-to-consumer telemedicine can enable patients to connect with their healthcare provider at a distance. This virtual platform could be used by smartphones or webcam-enabled computers and allows physicians to effectively screen patients with early signs of COVID-19 before they reach to hospital.
Output: Journal Pre-proof COVID-19 and Telemedicine: Immediate action required for maintaining healthcare providers well-being COVID-19 and Telemedicine: Immediate action required for maintaining healthcare providers well-being
Herpesviruses constitute a family of large DNA viruses widely spread in vertebrates and causing a variety of different diseases. They possess dsDNA genomes ranging from 120 to 240 kbp encoding between 70 to 170 open reading frames. We previously reported the protein interaction networks of two herpesviruses, varicella-zoster virus (VZV) and Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we systematically tested three additional herpesvirus species, herpes simplex virus 1 (HSV-1), murine cytomegalovirus and Epstein-Barr virus, for protein interactions in order to be able to perform a comparative analysis of all three herpesvirus subfamilies. We identified 735 interactions by genome-wide yeasttwo-hybrid screens (Y2H), and, together with the interactomes of VZV and KSHV, included a total of 1,007 intraviral protein interactions in the analysis. Whereas a large number of interactions have not been reported previously, we were able to identify a core set of highly conserved protein interactions, like the interaction between HSV-1 UL33 with the nuclear egress proteins UL31/UL34. Interactions were conserved between orthologous proteins despite generally low sequence similarity, suggesting that function may be more conserved than sequence. By combining interactomes of different species we were able to systematically address the low coverage of the Y2H system and to extract biologically relevant interactions which were not evident from single species.
Output: Evolutionarily Conserved Herpesviral Protein Interaction Networks
Background: One strategy available to public health officials during a pandemic is physician recommendations for isolation of infected individuals. This study was undertaken during the height of the Australian pandemic (H1N1) 2009 outbreak to measure self-reported willingness to comply with physician recommendations to stay home for seven days, and to compare responses for the current strain of pandemic influenza, avian influenza, seasonal influenza, and the common cold. Methods: Data were collected as part of the Queensland Social Survey (QSS) 2009, which consisted of a standardized introduction, 37 demographic questions, and research questions incorporated through a cost-sharing arrangement. Four questions related to respondents' anticipated compliance with a physician's advice to stay home if they had a common cold, seasonal influenza, pandemic (H1N1) 2009 influenza or avian influenza were incorporated into QSS 2009, with responses recorded using a balanced Likert scale ranging from "very unlikely" to "very likely." Discordance between responses for different diseases was analysed using McNemar's test. Associations between demographic variables and anticipated compliance were analysed using Pearson's chi-square or chisquare for linear-by-linear association, and confirmed using multivariate logistic regression; p < 0.05 was used to establish statistical significance. Results: Self-reported anticipated compliance increased from 59.9% for the common cold to 71.3% for seasonal influenza (p < .001), and to 95.0% for pandemic (H1N1) 2009 influenza and 94.7% for avian influenza (p < 0.001 for both versus seasonal influenza). Anticipated compliance did not differ for pandemic (H1N1) 2009 and avian influenza (p = 0.815). Age and sex were both associated with anticipated compliance in the setting of seasonal influenza and the common cold. Notably, 27.1% of health and community service workers would not comply with physician advice to stay home for seasonal influenza. Conclusions: Ninety-five percent of people report they would comply with a physicians' advice to stay home for seven days if they are diagnosed with pandemic (H1N1) 2009 or avian influenza, but only 71% can be expected to comply in the setting of seasonal influenza and fewer still can be expected to comply if they are diagnosed with a common cold. Sub-populations that might be worthwhile targets for public health messages aimed at increasing the rate of self-imposed isolation for seasonal influenza include males, younger people, and healthcare workers.
Output: Self-reported anticipated compliance with physician advice to stay home during pandemic (H1N1) 2009: Results from the 2009 Queensland Social Survey
Although the impact of pathogens on the evolution of the mammalian immune system is still under debate, proteins, which both regulate immune responses and serve as cellular receptors for pathogens should be at the forefront of pathogen-driven host evolution. The CEA (carcinoembryonic antigen) gene family codes for such proteins and indeed shows tremendous species-specific variation between human and rodents. Since little is known about the CEA gene family in other lineages of placental mammals, we expected to gain new insights into the evolution of the rapidly diverging CEA family by analyzing the CEA family of the dog. Here we describe the complete CEA gene family in the dog. We found that the gene coding for the ITIM-bearing immunoregulatory molecule CEACAM1 gave rise to a recent expansion of the canine CEA gene family by gene duplication, similar to that previously found in humans and mice. However, while the murine and human CEACAMs (carcinoembryonic antigen-related cell adhesion molecules) are predominantly secreted and GPI-anchored, respectively, in the dog, most of the CEACAMs represent ITAM-bearing transmembrane proteins. One of these proteins, CEACAM28, exhibits nearly complete sequence identity with the ligand-binding N domain of CEACAM1, but antagonizing signaling motifs in the cytoplasmic tail. Comparison of nonsynonymous and synonymous substitutions indicates that the CEACAM28 N domain is under the strongest purifying selection of all canine CEACAM1-related CEACAMs. In addition, CEACAM28 shows a similar expression pattern in resting immune cells and tissues as CEACAM1. However, upon activation CEACAM28 mRNA and CEACAM1 mRNA are differentially regulated. Conclusion: Thus, CEACAM1 and CEACAM28 are the first paired immune receptors identified within the CEA gene family, which are expressed on T cells and are most likely involved in the fine-tuning of T cell responses. The direction of gene conversion accompanied by purifying selection and expression in immune cells suggests the possibility that CEACAM28 evolved in response to selective pressure imposed by species-specific pathogens.
Output: Species-specific evolution of immune receptor tyrosine based activation motif-containing CEACAM1-related immune receptors in the dog
This article presents a systematic framework of 12 essentials, or basic elements, of science-based policy. The 12 essentials are grouped into three categories, or areas, as follows: 1) knowledge generation, which includes credible design, accurate data, sound analysis, and comprehensive synthesis; 2) knowledge exchange, which includes relevant content, appropriate translation, timely dissemination, and modulated release; and 3) knowledge uptake, which includes accessible information, readable message, motivated user, and rewarding outcome.
Output: Twelve Essentials of Science-based Policy • Centers for Disease Control and Prevention 7
Journal Pre-proof 1 such as ventilators in limited supply, preparations should be made ahead of time on how to allocate these finite resources. More information about COVID-19 can be found in [2], [3], and [7] . The best course of action to "flatten the curve" is to follow WHO guidelines. The best way to keep hospitals under capacity is social distancing: limiting or cancelling large gatherings, only travelling when necessary, and keeping a distance from others all help to prevent the spread. The presented heuristic is based on the exponential growth of the data collected Journal Pre-proof J o u r n a l P r e -p r o o f 4 WWK, MAM, WP, AW-D, PFZ, DS, TA, AHZ, MD, AND JM by WHO situation reports for days 31 to 57. As pointed out in [4] the predictability could be improved by pairwise comparisons based on abductive reasoning [5]. Abduction is frequently used in diagnostic expert systems. The abductive reasoning (or inference) process was used for this study. It is a type of logical inference which starts with a set of observations and then searches for Journal Pre-proof J o u r n a l P r e -p r o o f 1,000,000 COVID-19 CASES X Journal Pre-proof J o u r n a l P r e -p r o o f
Output: Journal Pre-proof 1000,000 cases of COVID-19 outside of China: The date predicted by a simple heuristic 1,000,000 CASES OF COVID-19 OUTSIDE OF CHINA: THE DATE PREDICTED BY A SIMPLE HEURISTIC
To express the 3 0 -region (1152 bp) of the cag7 gene of Helicobacter pylori 51 strain, encoding the C-terminal 383 amino acid (ct383 aa) region of Cag7 protein that is known to cover the needle region of T4SS, in a live delivery vehicle Lactococcus lactis, the cag7-ct383 gene was amplified by PCR. DNA sequence analysis revealed that the amino acid sequence of Cag7-ct383 of H. pylori 51 shared 98.4% and 97.4% identity with H. pylori 26695 and J99, respectively. Intramuscular injection of the GST-Cag7-ct383 fusion protein into a rat could raise the anti-Cag7 antibody, indicating the immunogenicity of the Cag7-ct383 protein. When the cag7-ct383 gene was cloned in Escherichia coli-L. lactis shuttle vector (pMG36e) and transformed into L. lactis, the transformant could produce the Cag7-ct383 protein, as evidenced by Western blot analysis. The Cag7-ct383 protein level in the L. lactis transformant reached a maximum at the early stationary phase without extracellular secretion. The oral administration of the L. lactis transformant into mice generated anti-Cag7 antibody in serum in five of five mice. These results suggest that L. lactis transformant expressing Cag7-ct383 protein may be applicable as an oral vaccine to induce mucosal and systemic immunity to H. pylori.
Output: Oral administration of Lactococcus lactis expressing Helicobacter pylori Cag7-ct383 protein induces systemic anti-Cag7 immune response in mice
Handwashing is the most fundamental way to prevent the spread of infectious diseases. Correct handwashing can prevent 50 to 70% of water-infections and foodborne-infections. We report the results of a fact-finding study on general handwashing attitude and practice in the Republic of Korea by analyzing habits and awareness among adults and students (grades 4 to 12) based on the 2006 to 2014 National Handwashing Surveys and observational surveys. The awareness survey was performed by telephone interviews with adults and students in 16 municipalities and provinces sampled by quota for region, sex and age. The observational survey was performed in subway, railway, and other public restrooms in seven municipalities selected through systematic sampling. Adults and students washed their hands with soap/sanitizer an average of 6.6 and 5.2 times daily, respectively, in 2014, an increase and decrease compared to 2006 (4.8) and 2013 (6.8). Their average daily handwashing frequency in 2014, 9.8 and 8.3, was higher than in 2006 (7.6), but lower than in 2013 (10.3).The percentage of participants handwashing with soap after using the restroom (29.5%) has been increasing since 2009, but remain slower than in other countries (42% to 49%). The percentages of participants handwashing with water in 2014, 2013, and 2011 were 57.5%, 72.6%, and 71.4%, respectively. Handwashing with soap is an important national public health issue, and national projects promoting it should be given high priority. Research support is necessary to provide scientific evidence of the importance of handwashing with soap and to develop and implement evidence-based policies.
Output: Open Access Handwashing with soap and national handwashing projects in Korea: focus on the National Handwashing Survey, 2006-2014
All coronaviruses (CoVs), including the causative agent of severe acute respiratory syndrome (SARS), encode a nucleocapsid (N) protein that harbors two independent RNA binding domains of known structure, but poorly characterized RNA binding properties. We show here that the Nterminal domain (NTD) of N protein from mouse hepatitis virus (MHV), a virus most closely related to SARS-CoV, employs aromatic amino acidnucleobase stacking interactions with a triple adenosine motif to mediate high-affinity binding to single-stranded RNAs containing the transcriptional regulatory sequence (TRS) or its complement (cTRS). Stoichiometric NTD fully unwinds a TRS-cTRS duplex that mimics a transiently formed transcription intermediate in viral subgenomic RNA synthesis. Mutation of the solvent-exposed Y127, positioned on the β-platform surface of our 1.75 Å structure, binds the TRS far less tightly and is severely crippled in its RNA unwinding activity. In contrast, the C-terminal domain (CTD) exhibits no RNA unwinding activity. Viruses harboring Y127A N mutation are strongly selected against and Y127A N does not support an accessory function in MHV replication. We propose that the helix melting activity of the coronavirus N protein NTD plays a critical accessory role in subgenomic RNA synthesis and other processes requiring RNA remodeling.
Output: Coronavirus N Protein N-Terminal Domain (NTD) Specifically Binds the Transcriptional Regulatory Sequence (TRS) and Melts TRS-cTRS RNA Duplexes