niryuu/sni-each-converted huggingface dataset:
Multi-attribute decision making Multi-attribute value theory a b s t r a c t Diseases that are exotic to the pig industry in Australia were prioritised using a multicriteria decision analysis framework that incorporated weights of importance for a range of criteria important to industry stakeholders. Measurements were collected for each disease for nine criteria that described potential disease impacts. A total score was calculated for each disease using a weighted sum value function that aggregated the nine disease criterion measurements and weights of importance for the criteria that were previously elicited from two groups of industry stakeholders. One stakeholder group placed most value on the impacts of disease on livestock, and one group placed more value on the zoonotic impacts of diseases. Prioritisation lists ordered by disease score were produced for both of these groups. Vesicular diseases were found to have the highest priority for the group valuing disease impacts on livestock, followed by acute forms of African and classical swine fever, then highly pathogenic porcine reproductive and respiratory syndrome. The group who valued zoonotic disease impacts prioritised rabies, followed by Japanese encephalitis, Eastern equine encephalitis and Nipah virus, interspersed with vesicular diseases. The multi-criteria framework used in this study systematically prioritised diseases using a multi-attribute theory based technique that provided transparency and repeatability in the process. Flexibility of the framework was demonstrated by aggregating the criterion weights from more than one stakeholder group with the disease measurements for the criteria. This technique allowed industry stakeholders to be active in resource allocation for their industry without the need to be disease experts. We believe it is the first prioritisation of livestock diseases using values provided by industry stakeholders. The prioritisation lists will be used by industry stakeholders to identify diseases for further risk analysis and disease spread modelling to understand biosecurity risks to this industry.
Output: Building a picture: Prioritisation of exotic diseases for the pig industry in Australia using multi-criteria decision analysis
The present study was undertaken to determine immune response and protection efficacy of a spike (S) protein fragment containing neutralizing epitopes (4F/4R) of turkey coronavirus (TCoV) by priming with DNA vaccine and boosting with the recombinant protein from the corresponding DNA vaccine gene segment. Turkeys were vaccinated by priming with either one dose (G1-750DP) or two doses (G3-750DDP) of 750 g DNA vaccine expressing 4F/4R S fragment and boosting with one dose of 200 g 4F/4R S fragment. One dose of 100 g DNA vaccine mixed with polyethyleneimine (PEI) and sodium hyaluronate (HA) followed by one dose of 750 g DNA vaccine and one dose of 200 g 4F/4R S fragment were given to the turkeys in group G2-100DPH. After infectious challenge by TCoV, clinical signs and TCoV detected by immunofluorescence antibody (IFA) assay were observed in less number of turkeys in vaccination groups than that in challenge control groups. TCoV viral RNA loads measured by quantitative real-time reverse transcription-PCR were lower in vaccinated turkeys than those in challenge control turkeys. The turkeys in G3-750DDP produced the highest level of TCoV S protein-specific antibody and virus neutralization (VN) titer. Comparing to the turkeys in G1-750DP, significantly less TCoV were detected by IFA in the turkeys in G2-100DPH receiving an extra dose of 100 g DNA mixed with PEI and HA. The results indicated that DNA-prime protein-boost DNA vaccination regimen targeting TCoV S fragment encompassing neutralizing epitopes induced humoral immune response and partially protected turkeys against infectious challenge by TCoV.
Output: A DNA prime-protein boost vaccination strategy targeting turkey coronavirus spike protein fragment containing neutralizing epitope against infectious challenge
To examine the effect of provision of information about the infection control in the specific infection disease treatment unit in a city hospital on the outpatient's intention of outpatient service use, respondents who underwent outpatient medical care at the hospital (N = 821) were asked whether or not they intended to continue the outpatient visit at the hospital if a severe acute respiratory syndrome (SARS) patient was admitted to the unit. Although 56% of respondents replied that they could continue to visit the department if a SARS patient was admitted to the unit in the hospital before they read the information, the proportion of those who intended to continue outpatient care significantly increased by 15% after they read it. The logistic regression analyses revealed that respondents who had frequently visited the outpatient department (P < 0.001), those who felt relieved by reading the information about the unit (P < 0.001), and those who did not worry about nosocomial SARS infection inside the hospital (P < 0.001) were significantly more likely to reply that they would continue outpatient visits. We estimated that admission of a SARS patient to the unit would result in a 20% decrease in the cumulative total number of outpatients in the hospital during a 180-day interval after admission of a SARS patient to the unit, and the cumulative total number of outpatients increased by 7% after they read the information. This study suggests that providing outpatients with appropriate information about SARS infection control in the hospital had a statistically significant and substantial impact on the outpatients' intention to continue outpatient visits at the hospital.
Output: Estimation of the impact of providing outpatients with information about SARS infection control on their intention of outpatient visit
Coronaviruses are widespread in the environment, infecting humans, domesticated and wild mammals, and birds. Infections cause a variety of diseases including bronchitis, gastroenteritis, hepatitis, and encephalitis, with symptoms ranging from being nearly undetectable to rapidly fatal. A combination of interacting variables determine the pattern and severity of coronavirus-induced disease, including the infecting virus strain, its transmission strategy, and the age and immune status of the infected host. Coronavirus pathogenesis is best understood by discerning how each of these variables dictates clinical outcomes. This chapter focuses on variabilities amongst the spike (S) proteins of infecting virus strains. Diversity of coronavirus surface proteins likely contributes to epidemic disease, an important and timely topic given the recent emergence of the human SARS coronavirus.
Output: 4 Diversity of Coronavirus Spikes: Relationship to Pathogen Entry and Dissemination
Influenza viruses replicate within the nucleus of the host cell. This uncommon RNA virus trait provides influenza with the advantage of access to the nuclear machinery during replication. However, it also increases the complexity of the intracellular trafficking that is required for the viral components to establish a productive infection. The segmentation of the influenza genome makes these additional trafficking requirements especially challenging, as each viral RNA (vRNA) gene segment must navigate the network of cellular membrane barriers during the processes of entry and assembly. To accomplish this goal, influenza A viruses (IAVs) utilize a combination of viral and cellular mechanisms to coordinate the transport of their proteins and the eight vRNA gene segments in and out of the cell. The aim of this review is to present the current mechanistic understanding for how IAVs facilitate cell entry, replication, virion assembly, and intercellular movement, in an effort to highlight some of the unanswered questions regarding the coordination of the IAV infection process.
Output: influenza A virus Cell entry, Replication, virion Assembly and Movement
Factors affecting a residential unit's price are always of interest to homebuyers and building developers, especially in a city like Hong Kong which is known for expensive housing. Literature review indicates that the governing factors can be categorized into architectural and environmental attributes. Among different methods commonly used for pricing, the hedonic price approach is viewed as the most suitable. However, the successful use of this method requires that homebuyers know and choose the attributes. Whilst choosing architectural attributes are not a problem for homebuyers, the same does not apply to environmental attributes. Previous studies by the authors have proposed some simple indicators for quantifying the environmental attributes. Based upon the developed performance indicators and the transaction records of two representative housing estates (Royal Ascot ¼ RA and City One Shatin ¼ COS), details of the properties, including transaction prices, architectural particulars and environmental characteristics were numerically transformed for the hedonic price analysis. The analysis results revealed that the willingness to pay (percentage of house price in parenthesis) for architectural and environmental attributes was HK$302.3/ft 2 (5.8%) and HK$886.8/ft 2 (28.2%), respectively, for RA and HK$1672.7/ ft 2 (31.9%) and HK$111.5/ft 2 (3.5%) for COS. It was found that elasticity of substitution (ES) of environmental attributes contributed 3.4e13.3% of the property price, compared to 0.6e5.5% for architectural attributes.
Output: Development of price models for architectural and environmental quality for residential developments in Hong Kong
Ribosomes are specialized entities that participate in regulation of gene expression through their rRNAs carrying ribozyme activity. Ribosome biogenesis is overactivated in p53-inactivated cancer cells, although involvement of p53 on ribosome quality is unknown. Here, we show that p53 represses expression of the rRNA methyl-transferase fibrillarin (FBL) by binding directly to FBL. High levels of FBL are accompanied by modifications of the rRNA methylation pattern, impairment of translational fidelity, and an increase of internal ribosome entry site (IRES)-dependent translation initiation of key cancer genes. FBL overexpression contributes to tumorigenesis and is associated with poor survival in patients with breast cancer. Thus, p53 acts as a safeguard of protein synthesis by regulating FBL and the subsequent quality and intrinsic activity of ribosomes.
Output: Article p53 Acts as a Safeguard of Translational Control by Regulating Fibrillarin and rRNA Methylation in Cancer
Background: Respiratory Syncytial Virus (RSV) infection is usually restricted to the respiratory epithelium. Few studies have documented the presence of RSV in the systemic circulation, however there is no consistent information whether virus detection in the blood correlates with disease severity. Methods: Balb/c mice were inoculated with live RSV, heat-inactivated RSV or medium. A subset of RSV-infected mice was treated with anti-RSV antibody 72 h post-inoculation. RSV RNA loads were measured by PCR in peripheral blood from day 1-21 post-inoculation and were correlated with upper and lower respiratory tract viral loads, the systemic cytokine response, lung inflammation and pulmonary function. Immunohistochemical staining was used to define the localization of RSV antigens in the respiratory tract and peripheral blood. Results: RSV RNA loads were detected in peripheral blood from day 1 to 14 post-inoculation, peaked on day 5 and significantly correlated with nasal and lung RSV loads, airway obstruction, and blood CCL2 and CXCL1 expression. Treatment with anti-RSV antibody reduced blood RSV RNA loads and improved airway obstruction. Immunostaining identified RSV antigens in alveolar macrophages and peripheral blood monocytes. Conclusions: RSV RNA was detected in peripheral blood upon infection with live RSV, followed a time-course parallel to viral loads assessed in the respiratory tract and was significantly correlated with RSV-induced airway disease.
Output: Respiratory Syncytial Virus (RSV) RNA loads in peripheral blood correlates with disease severity in mice
Endoribonuclease-prepared siRNA (esiRNA) is an alternative tool to chemical synthetic siRNA for gene silencing. Since esiRNAs are directed against long target sequences, the genetic variations in the target sequences will have little influence on their effectiveness. The ability of esiRNAs to inhibit hepatitis B virus (HBV) gene expression and replication was tested. EsiRNAs targeting the coding region of HBV surface antigen (HBsAg) and the nucleocapsid (HBcAg) inhibited specifically the expression of HBsAg and HBcAg when cotransfected with the respective expression plasmids. Both esiRNAs reduced the HBV transcripts and replication intermediates in transient transfected cells and cells with HBV genomes integrated stably. Compared with synthetic siRNA, esiRNA targeting HBsAg was less effective than the selected synthetic siRNA in terms of the inhibition of HBV gene expression and replication. However, while the ability of synthetic siRNAs for specific gene silencing was impaired strongly by the nucleotide substitutions within the target sequences. The efficiency of gene silencing by esiRNAs was not influenced by sequence variation. The transfection of esiRNA did not induce interferon-stimulated genes (ISGs) like STAT1 and ISG15, indicating the absence of off-target effects. In general, esiRNAs strongly inhibited HBV gene expression and replication and may have an advantage against HBV strains which are variable genetically.
Output: Inhibition of hepatitis B virus gene expression and replication by endoribonuclease-prepared siRNA
The abdominal region is the large part of the body extending from the diaphragm to the pelvis. It includes the abdominal and pelvic cavities, bound by bone and muscle. The peritoneum is the largest and most complexly arranged serous membrane in the body. It forms the lining of the peritoneal cavity, which extends in abdominal cavity and contains the gastrointestinal tract; major abdominal organs, such as the liver, spleen, pancreas, urinary bladder, ovaries, and uterus; and many nerves, vessels, and lymph nodes. The peritoneum extends caudally in the pelvic cavity in males and females (as vaginal tunic and vaginal process, respectively). It is a serous membrane, divided into the parietal peritoneum, which covers the inner surface of the abdominal wall (the abdominal fascia) and the pelvic and scrotal cavities; the visceral peritoneum, which covers the abdominal, pelvic, and scrotal organs; and the connecting peritoneum, which extends between organs or between an organ and the parietal peritoneum, forming peritoneal folders that are divided into mesenteries, omenta, and ligaments. The purpose of the peritoneum is to provide a frictionless surface over which the viscera can move. It also serves as a site of fluid transport. A capillary film of serous fluid separates the parietal and visceral layers of the peritoneum from one another and lubricates the peritoneal surfaces. The retroperitoneal region extends dorsal to the peritoneal and pelvic cavities from the diaphragm to the pelvic inlet. It is bordered dorsally by the vertebrae and paraspinal muscles and laterally by the muscular abdominal and pelvic walls. The kidneys, ureters, and adrenal glands are considered to be retroperitoneal organs. The descending aorta, caudal vena cava, lumbar lymph nodes, cisterna chili, lymphatics, fat, and much of the abdominal wall musculature are also are also located in the
Output: The Peritoneal Cavity, Retroperitoneum, and Abdominal Wall
A loop-mediated isothermal amplification (LAMP) assay was developed for the detection of herpes simplex virus 1 (HSV-1). The specificity of the assay was tested using DNA extracted from HSV-1-infected rabbit corneal epithelium cultures, HSV-2 grown on Vero cell line, cytomegalovirus (CMV) (AD-169), varicella zoster virus (VZV) (Oka-vaccine), adenovirus, Aspergillus flavus and Staphylococcus aureus. The specificity of LAMP was confirmed by bidirectional sequencing of the amplicons. The sensitivity of the LAMP assay was tested using different concentrations of HSV-1 DNA. To evaluate the application of the LAMP assay in clinical diagnosis, we tested vitreous samples from 20 patients with suspected viral retinitis using LAMP and real-time PCR for HSV-1. The LAMP primers amplified only HSV-1 DNA; no LAMP products were detected with the DNAs of HSV-2, CMV, VZV, adenovirus A. flavus and S. aureus. The sequences of the positive HSV-1 LAMP products perfectly (99-100%) matched the HSV-1 sequences deposited in the GenBank database. LAMP is as sensitive as real-time PCR, with the lowest detection limit being 10 copies/lL of HSV-1 DNA. Of the 20 patients with suspected viral retinitis, four tested positive for HSV-1 using real-time PCR and LAMP. A 100% concordance was observed across the two methods. The LAMP assay is a rapid, highly specific and sensitive method for the diagnosis of retinitis caused by HSV-1.
Output: Loop-mediated isothermal amplification assay for the diagnosis of retinitis caused by herpes simplex virus-1
We have investigated the interactions between cationic NN16 and BDBR0011 carbosilane dendrimers with red blood cells or their cell membranes. The carbosilane dendrimers used possess 16 cationic functional groups. Both the dendrimers are made of water-stable carbon-silicon bonds, but NN16 possesses some oxygen-silicon bonds that are unstable in water. The nucleic acid used in the experiments was targeted against GAG-1 gene from the human immunodeficiency virus, HIV-1. By binding to the outer leaflet of the membrane, carbosilane dendrimers decreased the fluidity of the hydrophilic part of the membrane but increased the fluidity of the hydrophobic interior. They induced hemolysis, but did not change the morphology of the cells. Increasing concentrations of dendrimers induced erythrocyte aggregation. Binding of short interfering ribonucleic acid (siRNA) to a dendrimer molecule decreased the availability of cationic groups and diminished their cytotoxicity. siRNA-dendrimer complexes changed neither the fluidity of biological membranes nor caused cell hemolysis. Addition of dendriplexes to red blood cell suspension induced echinocyte formation.
Output: Interaction of cationic carbosilane dendrimers and their complexes with siRNA with erythrocytes and red blood cell ghosts
We have developed a novel tuberculosis (TB) vaccine; a combination of the DNA vaccines expressing mycobacterial heat shock protein 65 (HSP65) and interleukin 12 (IL-12) delivered by the hemagglutinating virus of Japan (HVJ)envelope and -liposome (HSP65+IL-12/HVJ). This vaccine provided remarkable protective efficacy in mouse model compared to the BCG. This vaccine also provided therapeutic efficacy against multi-drug resistant TB (MDR-TB) and extremely drug resistant TB (XDR-TB) in murine models. Furthermore, we extended our studies to a cynomolgus monkey model, which is currently the best animal model of human tuberculosis. This novel vaccine provided a higher level of the protective efficacy than BCG based upon the assessment of mortality. The BCG prime and HSP65+IL-12/HVJ vaccine (boost) by the prime-boost method showed a synergistic prophylactic effect in the monkey. Furthermore, this vaccine exerted therapeutic efficacy (100% survival) and augmentation of immune responses in the TB-infected monkeys.HVJ-Envelope/HSP65 DNA+IL-12 DNA vaccine increased the body weight of TB-infected monkeys, improved the ESR, and augmented the immuneresponses (proliferation of PBL and IL-2 production). The enhancement of IL-2 production from monkeys treated with this vaccine was correlated with the therapeutic efficacy of the vaccine. These data indicate that our novel DNA vaccine might be useful against Mycobacterium tuberculosis including XDR-TB and MDR-TB for human therapeutic clinical trials.
Output: 4th Vaccine and ISV Annual Global Congress A Novel Therapeutic and Prophylactic Vaccine against Tuberculosis Using the Cynomolgus Monkey Model and Mouse Model Open access under CC BY-NC-ND license
Background: Infection control professionals (ICP) who have experienced disaster response have not been assessed in terms of the lessons they have learned, gaps they perceive in disaster preparedness, and their perceived priorities for future emergency response training. Methods: Focus groups were conducted at the APIC 2006 Conference to evaluate ICPs' perceived needs related to disaster planning topics, products they feel are needed for education and reference materials, and lessons learned from past disasters. Results: ICPs' role in disaster preparedness and response is essential, even in noninfectious disease emergencies. Infection control issues in shelters, such as overcrowding, foodborne illness, lack of restroom facilities, inadequate environmental cleaning procedures and products, difficulty assessing disease outbreaks in shelters, inability to isolate potentially contagious patients, and too few hand hygiene supplies can contribute to secondary disease transmission. Other important topics on which ICPs need to be trained include surge capacity, employee health and safety, incident command system, educating responders and the public on disaster preparedness, addressing changing standards/recommendations, and partnering with public health. ICPs need quick reference materials, such as checklists, templates, tool kits, and algorithms to better equip them for disaster response. Conclusion: Infection control must continue to partner with public health and other responding agencies to address gaps in disaster planning. (Am J Infect Control 2007;35:374-81.) 
Output: Disaster preparedness lessons learned and future directions for education: Results from focus groups conducted at the 2006 APIC Conference
Viroporins are viral proteins with ion channel (IC) activity that play an important role in several processes, including virus replication and pathogenesis. While many coronaviruses (CoVs) encode two viroporins, severe acute respiratory syndrome CoV (SARS-CoV) encodes three: proteins 3a, E, and 8a. Additionally, proteins 3a and E have a PDZ-binding motif (PBM), which can potentially bind over 400 cellular proteins which contain a PDZ domain, making them potentially important for the control of cell function. In the present work, a comparative study of the functional motifs included within the SARS-CoV viroporins was performed, mostly focusing on the roles of the IC and PBM of E and 3a proteins. Our results showed that the full-length E and 3a proteins were required for maximal SARS-CoV replication and virulence, whereas viroporin 8a had only a minor impact on these activities. A virus missing both the E and 3a proteins was not viable, whereas the presence of either protein with a functional PBM restored virus viability. E protein IC activity and the presence of its PBM were necessary for virulence in mice. In contrast, the presence or absence of the homologous motifs in protein 3a did not influence virus pathogenicity. Therefore, dominance of the IC and PBM of protein E over those of protein 3a was demonstrated in the induction of pathogenesis in mice. Aguilella VM, Sola I, Enjuanes L. 2018. Role of severe acute respiratory syndrome coronavirus viroporins E, 3a, and 8a in replication and pathogenesis. mBio 9:e02325-17. https://doi .
Output: Role of Severe Acute Respiratory Syndrome Coronavirus Viroporins E, 3a, and 8a in Replication and Pathogenesis
Smallpox was declared eradicated in 1980. However recently, the need of agents effective against poxvirus infection has emerged again. In this paper, we report an original finding that two redox-modulating agents, the ethacrynic and ␣-lipoic acids (EA, LA), inhibit growth of vaccinia virus (VACV) in vitro. The effect of EA and LA was compared with those of ␤-mercaptoethanol, DTT and ascorbic acid, but these agents increased VACV growth in HeLa G cells. The inhibitory effects of EA and LA on the growth of VACV were further confirmed in several cell lines of different embryonic origin, in epithelial cells, fibroblasts, macrophages and T-lymphocytes. Finally, we have analyzed the mechanism of action of the two agents. They both decreased expression of VACV late genes, as demonstrated by western blot analysis and activity of luciferase expressed under control of different VACV promoters. In contrast, they did not inhibit virus entry into the cell, expression of VACV early genes or VACV DNA synthesis. The results suggest new directions in development of drugs effective against poxvirus infection.
Output: Ethacrynic and ␣-lipoic acids inhibit vaccinia virus late gene expression
Tables S4.1 and S4.2 show the goodness-of-fit results (burn-in 1,000,000 iterations, 1,000,000 iterations per graph, 1000 graphs) for the multilevel exponential random graph model (ERGM) for the relationships network. Results were generated using MPNet [1] [2] [3] . Table S4 .1 shows the results for just the bipartite network. Column 1 lists the various statistics that are evaluated. Column 2 shows the value of the statistic for the empirical network ("Sample"). Columns 3 and 4 show the mean ("Mean") and sample standard deviation ("Std. Dev."), respectively, of the statistic over simulated networks. Column 5 shows the "t-ratio", defined as (observed value-mean value)/standard deviation. For each parameter, using standard methodology, the model is a good fit for the empirical network if the "t-ratio" has absolute value less than 0.1 for parameters explicitly in the model (shown in boldface) and less than 2 otherwise.
Output: S4 Appendix: Multilevel ERGM Goodness of Fit
Overuse of emergency rooms (ER) is a public health problem. To investigate this issue, a cross-sectional survey was conducted at the ERs of King Abdul-Aziz Hospital, King Fahd Hospital, and Al-Thaghor Hospital in November 2013 with the aims of estimating emergency service utilization for non-urgent cases, identifying the predictors of ER utilization for non-urgent cases, and measuring patients' knowledge of primary healthcare centers (PHCCs). Patients were interviewed using a structured questionnaire and the data were analyzed using the Statistical Package for the Social Sciences. We recruited 300 patients; males comprised 50.7% of the sample. A higher proportion of patients with non-urgent cases visited the ER three to four times a year (P=0.001). A higher proportion of patients without emergencies had not attempted to visit an outpatient clinic before the ER (P=0.003). Most patients without emergencies thought the ER was the first place to consult in case of illness. Most patients who visited the ER were single, < 15 years, and had lower incomes. Patients requested ER services for primary care-treatable conditions because of limited services and resources as well as limited working hours at PHCCs. Most patients (90.0%) were knowledgeable about PHCCs, with those of lower education being more knowledgeable. Patients reported long ER waiting times (≥ 3 hours), no organization (85.9%), and lack of medical staff. Overall, overuse of ER services is high at the Ministry of Health hospitals in Jeddah. The risk factors for ER overuse are age < 15 years, singlehood, and low incomes. Policy makers and health providers have a challenging task to control ER overuse. We recommend developing strategies to implement policies aimed at reducing non-urgent ER use as well as making healthcare services more available to the population.
Output: Utilization of the Emergency Department and Predicting Factors Associated With Its Use at the Saudi Ministry of Health General Hospitals
Background: Respiratory protection effi ciency of facemasks is critically important in the battle against communicable respiratory infections such as infl uenza and severe acute respiratory syndrome (SARS). We studied the spatial distributions of simulated virus-laden respiratory droplets when human subjects wore facemasks and were exposed to regulatory viral droplets by conducting in vivo experiments in facemask use. Methods: Transmission pathway of aerosols of Fluorescein-KCl solution through facemasks and protective effi ciency of facemasks were examined by using normal surgical facemasks and two facemasks with exhaust valves (Facemask A) and exhaust holes (Facemask B) covered with the same surgical fi lters situated at the back of the facemasks. Fluorescein-KCl solution was sprayed onto the faces of participants wearing the facemasks and performing intermittent exercises on a treadmill in a climatic chamber. Results: Experimental results showed that when droplets spread onto a person face-to-face over short distances, 92.3% to 99.5% of droplets were blocked by the front surface of the facemask, whereas only 0.5% to 7.7% of droplets reached the back of the facemask. Both facemasks A and B had near or over 99% protection effi ciency, compared with that of 95.5% to 97% of surgical facemasks. Using the same fi lters as normal surgical masks, facemasks A and B provided more effective respiratory protection against communicable respiratory infections such as infl uenza and SARS by the location of the breathing pathway to the back of the facemasks. Conclusions: Separating the breathing pathway from the virus-contaminated area in facemasks can provide more effective protection against communicable respiratory infections such as infl uenza and SARS.
Output: Transmission of communicable respiratory infections and facemasks
Ontario nurses were employed as the front-line workers when SARS descended upon Toronto in March 2003. Once the crisis had subsided, many nurses remarked that SARS had forever altered their chosen profession; employment, which they once viewed as relatively safe, had been transformed into potentially life-threatening. This discussion provides descriptions of these expressions through nurses who experienced the crisis and chose to go on the public record. Secondly, it compares the subjective perceptions of those nurses to those held by nurses who worked through historical epidemics of unknown or contested epidemiology. The historical literature on nursing in yellow fever, cholera and influenza epidemics has been employed to offer insight. The goal is to determine whether the SARS outbreak was a unique experience for nurses or whether similar experiences were shared by nurses in the past? In summary, the reactions of nurses when confronted with the possibility of contracting a deadly disease remain altogether human, not dissimilar in past or present. Nurses' responses to SARS can be usefully studied within a larger historical vision of crisis nursing, and information or impressions from earlier crises are potentially of interest to the nursing profession.
Output: Godzilla in the corridor: The Ontario SARS crisis in historical perspective
Cryo-EM single-particle analysis has proven powerful in determining the structures of rigid macromolecules. However, many protein complexes are flexible and can change conformation and composition as a result of functionally-associated dynamics. Such dynamics are poorly captured by current analysis methods. Here, we present cryoDRGN, an algorithm that for the first time 42 eukaryotic ribosome, the assembling bacterial ribosome, and the pre-catalytic spliceosome 43 complex. In these machines, we discover new conformational states and observe dynamic 44 molecular motions. CryoDRGN is distributed as an open-source tool 22 that can be easily integrated 45 in existing pipelines and is freely available at cryodrgn.
Output: Title: CryoDRGN: Reconstruction of heterogeneous structures from cryo-electron micrographs using neural networks CryoDRGN reveals dynamic continuous motions in the pre-catalytic spliceosome
Direct-acting antivirals are effective tools to control viral infections. SARS-CoV-2 is a coronavirus associated with the epidemiological outbreak in late 2019. Previous reports showed that HIV-1 protease inhibitors could block SARS-CoV main protease. Based on that and using an in silico approach, we evaluated SARS-CoV-2 main protease as a target for HIV-1 protease inhibitors to reveal the structural features related to their antiviral effect. Our results showed that several HIV inhibitors such as lopinavir, ritonavir, and saquinavir produce strong interaction with the active site of SARS-CoV-2 main protease. Furthermore, broad library protease inhibitors obtained from PubChem and ZINC (www.zinc.docking.org) were evaluated. Our analysis revealed 20 compounds that could be clustered into three groups based on their chemical features. Then, these structures could serve as leading compounds to develop a series of derivatives optimizing their activity against SARS-CoV-2 and other coronaviruses. Altogether, the results presented in this work contribute to gain a deep understanding of the molecular pharmacology of SARS-CoV-2 treatment and validate the use of protease inhibitors against SARS-CoV-2.
Output: UNREVEALING SEQUENCE AND STRUCTURAL FEATURES OF NOVEL CORONAVIRUS USING IN SILICO APPROACHES: THE MAIN PROTEASE AS MOLECULAR TARGET
Context: The 2-1-1 helpline is a social services innovation that has spread rapidly throughout the U.S. Policy diffusion theory suggests that policymakers seek to reduce uncertainty by anticipating the effects of a proposed innovation through tools such as cost-benefıt analyses. Few policy diffusion studies have examined use of information, such as cost-benefıt analyses, in the diffusion process. The purpose of this study is to examine how cost-benefıt analyses were used during the rapid diffusion of 2-1-1 across states. The paper also describes components of 2-1-1 cost-benefıt analyses. Evidence acquisition: In 2011, cost-benefıt analyses of 2-1-1 and substantive citations of them were identifıed through scholarly key word searches using Academic Search Premier and Web of Science, general Internet searches using Google search terms, and communications with academicians and 2-1-1 practitioners through personal contact and e-mail discussion groups. To be included in this study, documents had to be related to 2-1-1 helplines, present information about their costs and benefıts, and be formal documents. The documents were catalogued and analyzed for costbenefıt analyses or references to analyses, and stated purpose. Evidence synthesis: Of the 19 documents that met eligibility inclusion criteria, nine were original cost-benefıt analyses and ten referenced analyses conducted for other jurisdictions. The diffusion of2-1-1 helplinesin the U.S.hasbeen influenced by interjurisdictionalexchange of cost-benefıt analyses, in both the creation of original analyses and/or the referencing of previous work. (Am J Prev Med 2012;43(6S5):S497-S505) Am J Prev Med 2012;43(6S5):S497-S505 S497 S498 Shank / Am J Prev Med 2012;43(6S5):S497-S505 www.ajpmonline.org S502 Shank / Am J Prev Med 2012;43(6S5):S497-S505 www.ajpmonline.org
Output: A Review of the Role of Cost-Benefit Analyses in 2-1-1 Diffusion
Screening for thousands of viruses and other pathogenic microorganisms, including bacteria, fungi, and parasites, in human tumor tissues will provide a better understanding of the contributory role of the microbiome in the predisposition for, causes of, and therapeutic responses to the associated cancer. Metagenomic assays designed to perform these tasks will have to include rapid and economical processing of large numbers of samples, supported by straightforward data analysis pipeline and flexible sample preparation options for multiple input tissue types from individual patients, mammals, or environmental samples. To meet these requirements, the PathoChip platform was developed by targeting viral, prokaryotic, and eukaryotic genomes with multiple DNA probes in a microarray format that can be combined with a variety of upstream sample preparation protocols and downstream data analysis. PathoChip screening of DNA plus RNA from formalin-fixed, paraffin-embedded tumor tissues demonstrated the utility of this platform, and the detection of oncogenic viruses was validated using independent PCR and deep sequencing methods. These studies demonstrate the use of the PathoChip technology combined with PCR and deep sequencing as a valuable strategy for detecting the presence of pathogens in human cancers and other diseases. Citation Baldwin DA, Feldman M, Alwine JC, Robertson ES. 2014. Metagenomic assay for identification of microbial pathogens in tumor tissues. mBio 5(5):e01714-14.
Output: Metagenomic Assay for Identification of Microbial Pathogens in Tumor Tissues
The objective of this study was to explore the use and perceptions of a local Severe Acute Respiratory Syndrome (SARS) Extranet and its potential to support future information and communication applications. The SARS Extranet was a single, managed electronic and limited access system to manage local, provincial and other SARS control information. Methods: During July, 2003, a web-based and paper-based survey was conducted with 53 SARS Steering Committee members in Hamilton. It assessed the use and perceptions of the Extranet that had been built to support the committee during the SARS outbreak. Before distribution, the survey was user-tested based on a think-aloud protocol, and revisions were made. Quantitative and qualitative questions were asked related to frequency of use of the Extranet, perceived overall usefulness of the resource, rationale for use, potential barriers, strengths and limitations, and potential future uses of the Extranet. The response rate was 69.4% (n = 34). Of all respondents, 30 (88.2%) reported that they had visited the site, and rated it highly overall (mean = 4.0; 1 = low to 5 = high). However, the site was rated 3.4 compared with other communications strategies used during the outbreak. Almost half of all respondents (44.1%) visited the site at least once every few days. The two most common reasons the 30 respondents visited the Extranet were to access SARS Steering Committee minutes (63.3%) and to access Hamilton medical advisories (53.3%). The most commonly cited potential future uses for the Extranet were the sending of private emails to public health experts (63.3%), and surveillance (63.3%). No one encountered personal barriers in his or her use of the site, but several mentioned that time and duplication of email information were challenges. Despite higher rankings of various communication strategies during the SARS outbreak, such as email, meetings, teleconferences, and other web sites, users generally perceived a local Extranet as a useful support for the dissemination of local information during public health emergencies.
Output: BMC Medical Informatics and Decision Making A Severe Acute Respiratory Syndrome extranet: supporting local communication and information dissemination
The spike (S) protein of porcine transmissible gastroenteritis virus (TGEV) is located within the viral envelope and is the only structural protein that possesses epitopes capable of inducing virus-neutralizing antibodies. Among the four N-terminal antigenic sites A, B, C, and D, site A and to a lesser extent site D (S-AD) induce key neutralizing antibodies. Recently, we expressed S-AD (rS-AD) in recombinant form. In the current study, we used the rS-AD as an immobilized target to identify peptides from a phage-display library with application for diagnosis. Among the 9 phages selected that specifically bound to rS-AD, the phage bearing the peptide TLNMHLFPFHTG bound with the highest affinity and was subsequently used to develop a phage-based ELISA for TGEV. When compared with conventional antibody-based ELISA, phagemediated ELISA was more sensitive; however, it did not perform better than semi-quantitative RT-PCR, though phage-mediated ELISA was quicker and easier to set up.
Output: Phage display for identifying peptides that bind the spike protein of transmissible gastroenteritis virus and possess diagnostic potential
Pelargonium sidoides is a medical herb and respective extracts are used very frequently for the treatment of respiratory tract infections. However, the effects of Pelargonium sidoides and a special extract prepared from its roots (EPs 7630) on human immune cells are not fully understood. Here we demonstrate that EPs 7630 induced a rapid and dosedependent production of TNF-α, IL-6, and IL-10 by human blood immune cells. This EPs 7630-induced cytokine profile was more pro-inflammatory in comparison with the profile induced by viral or bacterial infection-mimicking agents. The search for EPs 7630 target cells revealed that T-cells did not respond to EPs 7630 stimulation by production of TNF-α, IL-6, or IL-10. Furthermore, pretreatment of T-cells with EPs 7630 did not modulate their TNF-α, IL-6, and IL-10 secretion during subsequent activation. In contrast to lymphocytes, monocytes showed clear intracellular TNF-α staining after EPs 7630 treatment. Accordingly, EPs 7630 predominantly provoked activation of MAP kinases and inhibition of p38 strongly reduced the monocyte TNF-α production. The pretreatment of blood immune cells with EPs 7630 lowered their secretion of TNF-α and IL-10 and caused an IL-6 dominant response during second stimulation with viral or bacterial infection-mimicking agents. In summary, we demonstrate that EPs 7630 activates human monocytes, induces MAP kinase-dependent pro-inflammatory cytokines in these cells, and specifically modulates their production capacity of mediators known to lead to an increase of acute phase protein production in the liver, neutrophil generation in the bone marrow, and the generation of adaptive Th17 and Th22 cells.
Output: The Pelargonium sidoides Extract EPs 7630 Drives the Innate Immune Defense by Activating Selected MAP Kinase Pathways in Human Monocytes
There is a dearth of information on the seroprevalence of bovine norovirus (BoNoV) and nebovirus in cattle of the US. In this retrospective study, serum IgG antibodies to two bovine enteric caliciviruses, GIII.2 Bo-NoV (Bo/CV186-OH/00/US) and genetically and antigenically distinct nebovirus (Bo/NB/80/US), were evaluated in feedlot and veal calves from different regions of the US during 1999-2001. Three groups of 6-to 7-month-old feedlot calves from New Mexico (NM) (n=103), Arkansas (AR) (n=100) and Ohio (OH) (n=140) and a group of 7-to 10-day-old Ohio veal calves (n=47) were studied. Serum samples were collected pre-arrival or at arrival to the farms for the NM, AR and OH calves and 35 days after arrival for all groups for monitoring seroconversion rates during the period. Virus-like particles of Bo/CV186-OH/00/US and Bo/NB/80/US were expressed using the baculovirus expression system and were used in ELISA to measure antibodies. A high seroprevalence of 94-100 % and 78-100 % was observed for antibodies to GIII.2 BoNoV and nebovirus, respectively, in the feedlot calves tested. In the Ohio veal farm, an antibody seroprevalence of 94-100 % and 40-66 % was found for GIII.2 BoNoV and nebovirus, respectively. Increased seropositive rates of 38-85 % for GIII.2 BoNoV and 26-83 % for nebovirus were observed at 35 days after arrival and commingling on farms for all groups. Infection of calves with either GIII.2 BoNoV or nebovirus, or both viruses, appeared to be common in the regions studied in the US during 1999-2001. These two viruses likely remain endemic because no commercial vaccines are available. C. Thomas and K. Jung contributed equally to this work.
Output: Retrospective serosurveillance of bovine norovirus (GIII.2) and nebovirus in cattle from selected feedlots and a veal calf farm in 1999 to 2001 in the United States
Human T-cell Immunoglobulin and Mucin-domain containing proteins (TIM1, 3, and 4) specifically bind phosphatidylserine (PS). TIM1 has been proposed to serve as a cellular receptor for hepatitis A virus and Ebola virus and as an entry factor for dengue virus. Here we show that TIM1 promotes infection of retroviruses and virus-like particles (VLPs) pseudotyped with a range of viral entry proteins, in particular those from the filovirus, flavivirus, New World arenavirus and alphavirus families. TIM1 also robustly enhanced the infection of replication-competent viruses from the same families, including dengue, Tacaribe, Sindbis and Ross River viruses. All interactions between TIM1 and pseudoviruses or VLPs were PS-mediated, as demonstrated with liposome blocking and TIM1 mutagenesis experiments. In addition, other PS-binding proteins, such as Axl and TIM4, promoted infection similarly to TIM1. Finally, the blocking of PS receptors on macrophages inhibited the entry of Ebola VLPs, suggesting that PS receptors can contribute to infection in physiologically relevant cells. Notably, infection mediated by the entry proteins of Lassa fever virus, influenza A virus and SARS coronavirus was largely unaffected by TIM1 expression. Taken together our data show that TIM1 and related PS-binding proteins promote infection of diverse families of enveloped viruses, and may therefore be useful targets for broad-spectrum antiviral therapies.
Output: TIM-family Proteins Promote Infection of Multiple Enveloped Viruses through Virion-associated Phosphatidylserine
Microbes have made a phenomenal contribution to the health and well-being of people throughout the world. In addition to producing many primary metabolites, such as amino acids, vitamins and nucleotides, they are capable of making secondary metabolites, which constitute half of the pharmaceuticals on the market today and provide agriculture with many essential products. This review centers on these beneficial secondary metabolites, the discovery of which goes back 80 years to the time when penicillin was discovered by Alexander Fleming.
Output: Microbial drug discovery: 80 years of progress
Background: Influenza-like illness (ILI) may be caused by a variety of pathogens. Clinical observations are of little help to recognise myxovirus infection and implement appropriate prevention measures. The limited use of molecular tools underestimates the role of other common pathogens. Objectives: During the early weeks of the 2009-2010 flu pandemic, a clinical and virological survey was conducted in adult and paediatric patients with ILI referred to two French University hospitals in Paris and Tours. Aims were to investigate the different pathogens involved in ILI and describe the associated symptoms. Methods: H1N1v pandemic influenza diagnosis was performed with real time RT-PCR assay. Other viral aetiologies were investigated by the molecular multiplex assay RespiFinder19H. Clinical data were collected prospectively by physicians using a standard questionnaire. Results: From week 35 to 44, endonasal swabs were collected in 413 patients. Overall, 68 samples (16.5%) were positive for H1N1v. In 13 of them, other respiratory pathogens were also detected. Among H1N1v negative samples, 213 (61.9%) were positive for various respiratory agents, 190 in single infections and 23 in mixed infections. The most prevalent viruses in H1N1v negative single infections were rhinovirus (62.6%), followed by parainfluenza viruses (24.2%) and adenovirus (5.3%). 70.6% of H1N1v cases were identified in patients under 40 years and none after 65 years. There was no difference between clinical symptoms observed in patients infected with H1N1v or with other pathogens. Our results highlight the high frequency of non-influenza viruses involved in ILI during the pre-epidemic period of a flu alert and the lack of specific clinical signs associated with influenza infections. Rapid diagnostic screening of a large panel of respiratory pathogens may be critical to define and survey the epidemic situation and to provide critical information for patient management.
Output: High Burden of Non-Influenza Viruses in Influenza-Like Illness in the Early Weeks of H1N1v Epidemic in France