niryuu/sni-each-converted huggingface dataset:
Data from EV-D68-infected patients demonstrate that pathological changes in the lower respiratory tract are principally characterized by severe respiratory illness in children and acute flaccid myelitis. However, lack of a suitable animal model for EV-D68 infection has limited the study on the pathogenesis of this critical pathogen, and the development of a vaccine. Ferrets have been widely used to evaluate respiratory virus infections. In the current study, we used EV-D68-infected ferrets as a potential animal to identify impersonal indices, involving clinical features and histopathological changes in the upper and lower respiratory tract (URT and LRT). The research results demonstrate that the EV-D68 virus leads to minimal clinical symptoms in ferrets. According to the viral load detection in the feces, nasal, and respiratory tracts, the infection and shedding of EV-D68 in the ferret model was confirmed, and these results were supported by the EV-D68 VP1 immunofluorescence confocal imaging with α2,6-linked sialic acid (SA) in lung tissues. Furthermore, we detected the inflammatory cytokine/chemokine expression level, which implied high expression levels of interleukin (IL)-1a, IL-8, IL-5, IL-12, IL-13, and IL-17a in the lungs. These data indicate that systemic observation of responses following infection with EV-D68 in ferrets could be used as a model for EV-D68 infection and pathogenesis.
Output: Nasal Infection of Enterovirus D68 Leading to Lower Respiratory Tract Pathogenesis in Ferrets (Mustela putorius furo)
Sialic acid linked to glycoproteins and gangliosides is used by many viruses as a receptor for cell entry. These viruses include important human and animal pathogens, such as influenza, parainfluenza, mumps, corona, noro, rota, and DNA tumor viruses. Attachment to sialic acid is mediated by receptor binding proteins that are constituents of viral envelopes or exposed at the surface of nonenveloped viruses. Some of these viruses are also equipped with a neuraminidase or a sialyl-O-acetyl-esterase. These receptor-destroying enzymes promote virus release from infected cells and neutralize sialic acid-containing soluble proteins interfering with cell surface binding of the virus. Variations in the receptor specificity are important determinants for host range, tissue tropism, pathogenicity, and transmissibility of these viruses.
Output: Sialic Acid Receptors of Viruses
Bats have been shown to serve as natural reservoirs for numerous emerging viruses including severe acute respiratory syndrome coronavirus (SARS-CoV). In the present study, we report the discovery of bat CoV genes in Indonesian Moluccan naked-backed fruit bats (Dobsonia moluccensis). A partial RNA-dependent RNA polymerase gene sequence was detected in feces and tissues samples from the fruit bats, and the region between the RdRp and helicase genes could also be amplified from fecal samples. Phylogenetic analysis suggested that these bat CoVs are related to members of the genus Betacoronavirus.
Output: Detection of coronavirus genomes in Moluccan naked-backed fruit bats in Indonesia
We employed the staggered extension process (StEP) to shuffle the S1 genes from four infectious bronchitis virus (IBV) strains representing four unique serotypes. Upon creating a shuffled S1 gene library, we randomly selected 25 clones and analyzed them by DNA sequencing. In total, eleven clones contained novel S1 gene recombinants. Based on sequence data, each recombinant was unique and contained a fulllength open reading frame. The average number of crossovers per recombinant was 5 and the average number of point mutations was 1.3, leading mostly to non-synonymous amino acid changes. No recombinant contained sequences from all four parental genes and no recombinant contained any sequence from the distantly related Delaware 072 strain. Our data suggests that recombination between distantly related IBV strains within the S1 gene probably does not readily occur. This finding is extremely important in light of the common industry vaccination practice of mixing different live-attenuated IBV strains.
Output: Using DNA Shuffling to Create Novel Infectious Bronchitis Virus S1 Genes: Implications for S1 Gene Recombination
Background: The amount of information available about millions of different subjects is growing every day. This has led to the birth of new search tools specialized in different domains, because classical information retrieval models have trouble dealing with the special characteristics of some of these domains. Evidence-based Medicine is a case of a complex domain where classical information retrieval models can help search engines retrieve documents by considering the presence or absence of terms, but these must be complemented with other specific strategies which allow retrieving and ranking documents including the best current evidence and methodological quality. Objective: The goal is to present a ranking algorithm able to select the best documents for clinicians considering aspects related to the relevance and the quality of said documents. Methods: In order to assess the effectiveness of this proposal, an experimental methodology has been followed by using Medline as a data set and the Cochrane Library as a gold standard. Results: Applying the evaluation methodology proposed, and after submitting 40 queries on the platform developed, the MAP (Mean Average Precision) obtained was 20.26%. Conclusions: Successful results have been achieved with the experiments, improving on other studies, but under different and even more complex circumstances. with real users [ 5 , 6 ]; nevertheless, there are studies that question whether technology applied to clinical information retrieval is useful and cast doubt on the ability of scientists to search appropriately [7] . Hence, it is necessary to develop algorithms to improve the quality of search results, especially as finding the best studies may suppose a better treatment for patients [8] . An example may be the algorithm proposed in [9] which models quality criteria through fuzzy prototypes in order to filter Personal Health Records (PHRs). This is only one example of documents in Medicine, but there are many other types of documents (review articles, original studies, case reports, etc.) that are important, especially in Evidence-based Medicine (EBM). According to [10] , EBM is "the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients." Therefore, EBM consists of integrating the best research evidence with clinical expertise and patient values. It is based on two main principles, the application of the best available evidence from the scientific method to medical decision making [11] and the assessment of the quality of evidence of the advantages and disadvantages of treatments [12] .
Output: A relevance and quality-based ranking algorithm applied to evidence-base d me dicine
Over the past decade, the number of countries reporting falsified (fake, spurious/falsely labeled/counterfeit) medicines and the types and quantities of fraudulent drugs being distributed have increased greatly. The obstacles in combating falsified pharmaceuticals include 1) lack of consensus on definitions, 2) paucity of reliable and scalable technology to detect fakes before they reach patients, 3) poor global and national leadership and accountability systems for combating this scourge, and 4) deficient manufacturing and regulatory challenges, especially in China and India where fake products often originate. The major needs to improve the quality of the world's medicines fall into three main areas: 1) research to develop and compare accurate and affordable tools to identify high-quality drugs at all levels of distribution; 2) an international convention and national legislation to facilitate production and utilization of high-quality drugs and protect all countries from the criminal and the negligent who make, distribute, and sell life-threatening products; and 3) a highly qualified, well-supported international science and public health organization that will establish standards, drug-quality surveillance, and training programs like the U.S. Food and Drug Administration. Such leadership would give authoritative guidance for countries in cooperation with national medical regulatory agencies, pharmaceutical companies, and international agencies, all of which have an urgent interest and investment in ensuring that patients throughout the world have access to good quality medicines. The organization would also advocate strongly for including targets for achieving good quality medicines in the United Nations Millennium Development Goals and Sustainable Development Goals.
Output: Responding to the Pandemic of Falsified Medicines
A Cucumber green mottle mosaic virus (CGMMV) was used to present a truncated dengue virus type 2 envelope (E) protein binding region from amino acids 379 to 423 (EB4). The EB4 gene was inserted at the terminal end of the CGMMV coat protein (CP) open reading frame (ORF). Read-through sequences of TMV or CGMMV, CAA-UAG-CAA-UUA, or AAA-UAG-CAA-UUA were, respectively, inserted in between the CP and the EB4 genes. The chimeric clones, pRT, pRG, and pCG+FSRTRE, were transcribed into full-length capped recombinant CGMMV transcripts. Only constructs with the wild-type CGMMV read-through sequence yielded infectious viruses following infection of host plant, muskmelon (Cucumis melo) leaves. The ratio of modified to unmodified CP for the read-through expression clone developed was also found to be approximately 1:1, higher than what has been previously reported. It was also observed that infectivity was not affected by differences in pI between the chimera and its wild counterpart. Analysis of recombinant viruses after 21-days-postinculation (dpi) revealed that deletions occurred resulting in partial reversions of the viral population to near wild type and suggesting that this would be the limiting harvest period for obtaining true to type recombinants with this construct.
Output: Virus-Specific Read-Through Codon Preference Affects Infectivity of Chimeric Cucumber Green Mottle Mosaic Viruses Displaying a Dengue Virus Epitope
19 Objectives: Development and validation of a single-step and accurate reverse transcriptase loop-20 mediated isothermal amplification technique (RT-LAMP) for rapid identification of SARS COV-2 21 relative to commercial quantitative reverse transcriptase real-time PCR (qRT-PCR) assays to allow 22 prompt initiation of proper medical care and containment of virus spread. 23 24 All rights reserved. No reuse allowed without permission. author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
Output: Development and validation of a rapid, single-step reverse transcriptase loop-mediated isothermal amplification (RT-LAMP) system potentially to be used for reliable and high-throughput screening of COVID-19
Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT > 600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine.
Output: Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals
This article identifies the goals, orientation, planning, and outcomes of international social work student exchanges. It argues that cross-cultural communication is a key skill developed by an exchange. The value base proposed includes belief in global interdependence, a willingness to scrutinize the history of student national and cultural identity, and commitment to evaluation. The knowledge base includes human rights, the history of social and economic development, and models of assessment and social justice.
Output: International Social Work Student Exchanges
Bcl-XL is a pro-survival member of the Bcl-2 family that can be found in the outer mitochondrial membrane and in soluble cytosolic homodimers. Bcl-XL can bind pro-apoptotic members of this family preventing them from activating the execution phase of apoptosis. Bcl-XL has been shown to homodimerize in different ways, although most binding and structural assays have been carried out in the absence of its carboxyl terminal transmembrane domain. We show here that this domain can by itself direct protein oligomerization, which could be related to its previously reported role in mitochondrial morphology alterations and apoptosis inhibition. Vamp2 physically interacts with Vamp2 by blue native page (View interaction) Vamp2 physically interacts with Vamp2 by cross-linking study (View interaction) Bcl-Xl physically interacts with Bcl-Xl by blue native page (View interaction) Bcl-Xl physically interacts with Bcl-Xl by cross-linking study (View interaction) Ó
Output: Protein oligomerization mediated by the transmembrane carboxyl terminal domain of Bcl-XL
To determine the aetiological role and epidemiological profile of common respiratory viruses in adults with acute respiratory tract infections (ARTIs), a 2-year study was conducted in Beijing, China, from May 2005 to July 2007. Nose and throat swab samples from 5808 ARTI patients were analysed by PCR methods for common respiratory viruses, including influenza viruses (IFVs) A, B, and C, parainfluenza viruses (PIVs) 1-4, enteroviruses (EVs), human rhinoviruses (HRVs), respiratory syncytial virus (RSV), human metapneumovirus (HMPV), human coronaviruses (HCoVs) OC43, 229E, NL63, and HKU1, and adenoviruses (ADVs). Viral pathogens were detected in 34.6% of patient samples, and 1.6% of the patients tested positive for more than one virus. IFVs (19.3%) were the dominant agents detected, followed by HRVs (6.5%), PIVs (4.3%), EVs (3.2%), and HCoVs (1.1%). ADVs, RSV and HMPV were also detected (<1%). The viral detection rates differed significantly between infections of the lower and upper respiratory tracts in the sample population: PIVs, the second most commonly detected viral agents in lower acute respiratory tract infections (LRTIs), were more prevalent than in upper acute respiratory tract infections, indicating that the pathogenic role of PIVs in LRTIs should be investigated. Currently, this study is the largest-scale investigation of respiratory virus infections in China with multiple agent detection, providing baseline data for further studies of respiratory virus infections in adults with ARTIs.
Output: Prevalence of human respiratory viruses in adults with acute respiratory tract infections in Beijing, 2005-2007
Q.-W. Jiang). 95% confidence interval (CI): 0.42, 0.66), DARH (OR ¼ 0.73, 95% CI: 0.53, 1.00), and daily average wind velocity (DAWV; OR ¼ 0.81, 95% CI: 0.68, 0.96). Adjustment for the onset time of a primary case led to little change in the results. In addition, in Hebei Province, a major affected area in China, only DAWV (OR ¼ 0.38, 95% CI: 0.20, 0.72) was a significant predictor of secondary attack rate with adjustment for the onset time of primary case. In Inner Mongolia, another major affected area in China, DAWV (OR ¼ 0.50, 95% CI: 0.26, 0.94) and DHS (OR ¼ 0.27, 95% CI: 0.09, 0.81) were significant predictors of secondary attack rate with adjustment for the onset time of primary case. Conclusions: Our results suggest that the SARS outbreak was significantly associated with DAWV, and that DAAP, DARH and DHS may also have influenced the SARS outbreak to some extent. However, because of ecological fallacy and uncontrolled confounding effects that may have biased the results, the association between the SARS outbreak and these meteorological factors and air pollution deserve further investigation.
Output: Influence of meteorological factors and air pollution on the outbreak of severe acute respiratory syndrome
Objective: To survey fertility patients' agreement with ASRM recommendations during the pandemic and the emotional impact on them. Design: An online survey was sent to current fertility patients Setting: New York City academic fertility practice at the epicenter of the COVID-19 pandemic Patient(s): Fertility patients seen within the last year Intervention(s): None Main Outcome Measures(s): Patient agreement with the ASRM recommendations during the COVID-19 pandemic and the emotional impact rated on a Likert scale. Result(s): A total of 518 patients completed the survey for a response rate of 17%. Fifty percent of respondents had a cycle canceled due to the COVID-19 pandemic. Of those who had a cycle cancelled, 85% of respondents found it to be moderately to extremely upsetting with 22% rating it to be equivalent to the loss of a child. There was no difference on the emotional impact based on the type of cycle cancelled. Fifty-five percent of patients agreed that diagnostic procedures such as hysterosalpingograms should be cancelled while 36% of patients agreed all fertility cycles should be cancelled. Patients were slightly more likely to agree with the ASRM guidelines if they have an upcoming cycle cancelled (p = 0.041). Of all respondents 82% would have preferred to have the option to start a treatment cycle in consultation with their doctor.
Output: THE EMOTIONAL IMPACT OF THE ASRM GUIDELINES ON FERTILITY PATIENTS DURING THE COVID-19 PANDEMIC
The cellular entry of viruses represents a critical area of study, not only for viral tropism, but also because viral entry dictates the nature of the immune response elicited upon infection. Epidemic keratoconjunctivitis (EKC), caused by viruses within human adenovirus species D (HAdV-D), is a severe, ocular surface infection associated with corneal inflammation. Clathrin-mediated endocytosis has previously been shown to play a critical role in entry of other HAdV species into many host cell types. However, HAdV-D endocytosis into corneal cells has not been extensively studied. Herein, we show an essential role for cholesterol rich, lipid raft microdomains and caveolin-1, in the entry of HAdV-D37 into primary human corneal fibroblasts. Cholesterol depletion using methyl-β-cyclodextrin (MβCD) profoundly reduced viral infection. When replenished with soluble cholesterol, the effect of MβCD was reversed, allowing productive viral infection. HAdV-D37 DNA was identified in caveolin-1 rich endosomal fractions after infection. Src kinase activity was also increased in caveolin-1 rich endosomal fractions after infection, and Src phosphorylation and CXCL1 induction were both decreased in caveolin-1-/-mice corneas compared to wild type mice. siRNA knock down of caveolin-1 in corneal cells reduced chemokine induction upon viral infection, and caveolin-1-/-mouse corneas showed reduced cellular entry of HAdV-D37. As a control, HAdV-C2, a non-corneal pathogen, appeared to utilize the caveolar pathway for entry into A549 cells, but failed to infect corneal cells entirely, indicating virus and cell specific tropism. Immuno-electron microscopy confirmed the presence of caveolin-1 in HAdV-D37-containing vesicles during the earliest stages of viral entry. Collectively, these experiments indicate for the first time that HAdV-D37 uses a lipid raft mediated caveolin-1 associated pathway for entry into corneal cells, and connects the processes of viral entry with downstream proinflammatory cell signaling.
Output: Caveolin-1 Associated Adenovirus Entry into Human Corneal Cells
Background: Upper respiratory tract infection symptoms are a common cause of morbidity. Herbal preparations of the plant Echinacea purpurea have immune-enhancing properties. Objective: To compare the frequency of upper respiratory tract symptoms in individuals receiving E purpurea capsules and those receiving placebo to evaluate the preventive efficacy of echinacea. Methods: In a randomized, double-blind clinical trial, 90 volunteers recruited from hospital personnel were randomly assigned to receive 3 capsules twice daily of either placebo (parsley) or E purpurea for 8 weeks during the winter months. Upper respiratory tract symptoms were reported weekly during this period. Results: Fifty-eight individuals were included in the final data analysis: 28 in the echinacea group and 30 in the placebo group. Individuals in the echinacea group reported 9 sick days per person during the 8-week period, whereas the placebo group reported 14 sick days (z ϭ Ϫ0.42; P ϭ .67). Mild adverse effects were noted by 8% of the echinacea group and 7% of the placebo group (P ϭ .24). Conclusion: Prophylactic treatment with commercially available E purpurea capsules did not significantly alter the frequency of upper respiratory tract symptoms compared with placebo use.
Output: Effects of echinacea on the frequency of upper respiratory tract symptoms: a randomized, double-blind, placebo-controlled trial
Severe viral infections, including hemorrhagic fever and encephalitis, occur throughout the world, but are most prevalent in developing areas that are most vulnerable to infectious diseases. Some of these can also infect related species as illustrated by the threatened extinction of gorillas by Ebola infection in west and central Africa. There are no safe and effective treatments available for these serious infections. In addition to the logistical difficulties inherent in developing a drug for infections that are sporadic and occur mainly in the third world, there is the overwhelming barrier of no hope for return on investment to encourage the pharmaceutical industry to address these unmet medical needs. Therefore, the National Institute of Allergy and infectious Disease (NIAID) has developed and supported a variety of programs and resources to provide assistance and lower the barrier for those who undertake these difficult challenges. The primary programs relevant to the development of therapies for severe viral infections are described and three case studies illustrate how they have been used. In addition, contact information for accessing these resources is supplied. Published by Elsevier B.V.
Output: NIAID resources for developing new therapies for severe viral infections
In the event of a pandemic, the general public would use filters as protective devices. However, most commercial filters only remove airborne viruses physically without inactivating them, allowing reproduction on the surface and yielding the mask as a fomite. The objective of this study was to investigate the inactivation performance of dialdehyde starch (DAS) treated filters against airborne viruses. The viable removal efficiency by and relative survivability on the biocidal filters prepared with dialdehyde starch compared to untreated filters were investigated using MS2 bacteriophage at high relative humidity (80-90%) and room temperature. Experimental results showed no significant difference in viable removal efficiency and pressure drop between the treated and untreated filters for polypropylene filtering facepiece respirators. The pressure drop of DAS treated cellulose filters significantly decreased although there was no significant change in viable removal efficiency; the combination of these two factors resulted in an increase of filter quality. All biocidal filters showed a significantly lower relative survivability than untreated filters, and the relative survivability decreased as the concentration of DAS increased. The biocidal filter treated with 4% DAS presented an average of 30% survivability compared to the baseline of untreated filters. The results demonstrate that dialdehyde starch can be incorporated onto filters to provide an effective means for inactivating MS2 viruses through surface contact.
Output: Use of dialdehyde starch treated filters for protection against airborne viruses
The present study focuses on the neuroprotective effect of glycyrrhizic acid (GA, a major compound separated from Glycyrrhiza Radix, which is a crude Chinese traditional drug) against glutamate-induced cytotoxicity in differentiated PC12 (DPC12) cells. The results showed that GA treatment improved cell viability and ameliorated abnormal glutamate-induced alterations in mitochondria in DPC12 cells. GA reversed glutamate-suppressed B-cell lymphoma 2 levels, inhibited glutamateenhanced expressions of Bax and cleaved caspase 3, and reduced cytochrome C (Cyto C) release. Exposure to glutamate strongly inhibited phosphorylation of AKT (protein kinase B) and extracellular signal-regulated kinases (ERKs); however, GA pretreatment enhanced activation of ERKs but not AKT. The presence of PD98059 (a mitogen-activated protein/extracellular signal-regulated kinase kinase [MEK] inhibitor) but not LY294002 (a phosphoinositide 3-kinase [PI3K] inhibitor) diminished the potency of GA for improving viability of glutamate-exposed DPC12 cells. These results indicated that ERKs and mitochondriarelated pathways are essential for the neuroprotective effect of GA against glutamate-induced toxicity in DPC12 cells. The present study provides experimental evidence supporting GA as a potential therapeutic agent for use in the treatment of neurodegenerative diseases.
Output: ERKs and mitochondria-related pathways are essential for glycyrrhizic acid-mediated neuroprotection against glutamate-induced toxicity in differentiated PC12 cells
The growing incidences of new viral diseases and increasingly frequent viral epidemics have strained therapeutic and preventive measures; the high mutability of viral genes puts additional strains on developmental efforts. Given the high cost and time requirements for new drugs development, vaccines remain as a viable alternative, but there too traditional techniques of live-attenuated or inactivated vaccines have the danger of allergenic reactions and others. Peptide vaccines have, over the last several years, begun to be looked on as more appropriate alternatives, which are economically affordable, require less time for development and hold the promise of multi-valent dosages. The developments in bioinformatics, proteomics, immunogenomics, structural biology and other sciences have spurred the growth of vaccinomics where computer assisted approaches serve to identify suitable peptide targets for eventual development of vaccines. In this mini-review we give a brief overview of some of the recent trends in computer assisted vaccine development with emphasis on the primary selection procedures of probable peptide candidates for vaccine development.
Output: Molecular Sciences A Brief Review of Computer-Assisted Approaches to Rational Design of Peptide Vaccines
Background: Early recognition of the signs and symptoms of clinical deterioration could diminish the incidence of cardiopulmonary arrest. The present study investigates outcomes with respect to cardiopulmonary arrest rates in institutions with and without rapid response systems (RRSs) and the current level of cardiopulmonary arrest rate in tertiary hospitals. Methods: This was a retrospective study based on data from 14 tertiary hospitals. Cardiopulmonary resuscitation (CPR) rate reports were obtained from each hospital to include the number of cardiopulmonary arrest events in adult patients in the general ward, the annual adult admission statistics, and the structure of the RRS if present. Results: Hospitals with RRSs showed a statistically significant reduction of the CPR rate between 2013 and 2015 (odds ratio [OR], 0.731; 95% confidence interval [CI], 0.577 to 0.927; P = 0.009). Nevertheless, CPR rates of 2013 and 2015 did not change in hospitals without RRS (OR, 0.988; 95% CI, 0.868 to 1.124; P = 0.854). National university-affiliated hospitals showed less cardiopulmonary arrest rate than private university-affiliated in 2015 (1.92 vs. 2.40; OR, 0.800; 95% CI, 0.702 to 0.912; P = 0.001). High-volume hospitals showed lower cardiopulmonary arrest rates compared with medium-volume hospitals in 2013 (1.76 vs. 2.63; OR, 0.667; 95% CI, 0.577 to 0.772; P < 0.001) and in 2015 (1.55 vs. 3.20; OR, 0.485; 95% CI, 0.428 to 0.550; P < 0.001). Conclusions: RRSs may be a feasible option to reduce the CPR rate. The discrepancy in cardiopulmonary arrest rates suggests further research should include a nationwide survey to tease out factors involved in in-hospital cardiopulmonary arrest and differences in outcomes based on hospital characteristics.
Output: Rapid Response Systems Reduce In-Hospital Cardiopulmonary Arrest: A Pilot Study and Motivation for a Nationwide Survey
Mitigation of porcine epidemic diarrhea virus (PEDV) was assessed using two feed additives (0.5% inclusion of a benzoic acid [BA] product and 0.02% inclusion of an essential oil [EO] product; DSM Nutritional Products Inc., Parsippany, NJ), and combination of both products (0.5% BA and 0.02% EO) in spray-dried porcine plasma (SDPP) and a swine gestation diet (FEED) as determined by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and bioassay. Viral RNA quantification was performed at 7 sampling days post-laboratory inoculation (d 0, 1, 3, 7, 14, 21, and 42) and infectivity was assessed via bioassay with 10-d-old pigs. There was a tendency for treatment × feed matrix × day interaction (P = 0.094), in which the cycle threshold (Ct) value increased over time in FEED when treated with both feed additives, whereas there was no increase over time observed in SDPP treated with both feed additives. There was a feed matrix × day interaction (P < 0.001) in which Ct increased over time in FEED, whereas very little increase over time was observed in SDPP. A tendency for a treatment × feed matrix effect (P = 0.085) was observed where FEED treated with the combination of EO and BA had a greater (P < 0.05) PEDV Ct value than other FEED treatments, and all SDPP treatments had the lower PEDV Ct values compared to FEED treatments (P < 0.05). Overall, the combination of both feed additives was most effective at reducing the quantity of genetic material as detected by qRT-PCR (P < 0.001) compared to either additive alone or no feed additive. Virus shedding was observed in the d 7 postinoculation SDPP treatment that was treated with both feed additives, as well as d 0 untreated FEED and d 0 FEED treated with both feed additives. No other treatment bioassay room had detectible RNA shed and detected in fecal swabs or cecal contents. In summary, the combination of EO and BA enhanced the degradation of PEDV RNA in feed but had little impact on RNA degradation in SDPP. Both untreated feed and feed treated with the combination of EO and BA resulted in infection at d 0 post-laboratory inoculation; however, neither set of samples was infective at d 1 postinoculation. In addition, SDPP harbored greater levels of quantifiable RNA for a longer duration of time compared to FEED, and these viral particles remained viable for a longer duration of time indicating differences in viral stability exist between different feed matrices.
Output: Determining the impact of commercial feed additives as potential porcine epidemic diarrhea virus mitigation strategies as determined by polymerase chain reaction analysis and bioassay 1
Background: Current prevention options for upper respiratory infections (URIs) are not optimal. We conducted a randomized, double-blinded, placebo-controlled pilot clinical trial to evaluate the safety and efficacy of ARMS-I™ (currently marketed as Halo™) in the prevention of URIs. Methods: ARMS-I is patented novel formulation for the prevention and treatment of influenza, comprising a broadspectrum antimicrobial agent (cetylpyridinium chloride, CPC) and components (glycerin and xanthan gum) that form a barrier on the host mucosa, thus preventing viral contact and invasion. Healthy adults (18-45 years of age) were randomized into ARMS-I or placebo group (50 subjects each). The drug was sprayed intra-orally (3× daily) for 75 days. The primary objectives were to establish whether ARMS-I decreased the frequency, severity or duration of URIs. Secondary objectives were to evaluate safety, tolerability, rate of virus detection, acceptability and adherence; effect on URI-associated absenteeism and medical visits; and effect of prior influenza vaccination on study outcomes. Results: Of the 94 individuals who completed the study (placebo: n = 44, ARMS-I: n = 50), six presented with confirmed URI (placebo: 4, ARMS-I: 2), representing a 55% relative reduction, albeit this was statistically not significant). Influenza, coronavirus or rhinovirus were detected in three participants; all in the placebo group. Moreover, frequency of posttreatment exit visits was reduced by 55% in ARMS-I compared to the placebo group (N = 4 and 2, respectively). Fever was reported only in the placebo group. ARMS-I significantly reduced the frequency and severity of cough and sore throat, and duration of cough (P ≤ .019 for all comparisons). ARMS-I was safe, well tolerated, had high acceptability and high adherence to medication use. Medical visits occurred only in the placebo group while absenteeism did not differ between the two arms. Prior influenza vaccination had no effect on study outcome. Conclusions: This randomized proof-of-concept clinical trial demonstrated that ARMS-I tended to provide protection against URIs in the enrolled study participants, while reducing severity and duration of cough and sore throat. A clinical trial with a larger number of study participants is warranted. Trial registration: ClinicalTrials.gov NCT02644135 (retrospectively registered).
Output: Randomized, double-blind, placebo- controlled clinical trial to assess the safety and effectiveness of a novel dual-action oral topical formulation against upper respiratory infections
Prior studies have shown that complement plays a critical role in controlling WNV infection in complement (C) 3 −/− and complement receptor 1/2 −/− mice. Here, we dissect the contributions of the individual complement activation pathways to the protection from WNV disease. Genetic defi ciencies in C1q, C4, factor B, or factor D all resulted in increased mortality in mice, suggesting that all activation pathways function together to limit WNV spread. In the absence of alternative pathway complement activation, WNV disseminated into the central nervous system at earlier times and was associated with reduced CD8 + T cell responses yet near normal anti-WNV antibody profi les. Our results suggest that individual pathways of complement activation control WNV infection by priming adaptive immune responses through distinct mechanisms.
Output: The Journal of Experimental Medicine Protective immune responses against West Nile virus are primed by distinct complement activation pathways
Flaviviridae family that has been known to circulate for decades causing mild febrile illness. the more recent ZiKV outbreaks in the Americas and the caribbean associated with congenital malformations and Guillain-Barré syndrome in adults have placed public health officials in high alert and highlight the significant impact of ZIKV on human health. New technologies to study the biology of ZIKV and to develop more effective prevention options are highly desired. in this study we demonstrate that direct delivery in mice of an infectious ZiKV cDnA clone allows the rescue of recombinant (r)ZiKV in vivo. A bacterial artificial chromosome containing the sequence of ZIKV strain Paraiba/2015 under the control of the cytomegalovirus promoter was complexed with a commercial transfection reagent and administrated using different routes in type-I interferon receptor deficient A129 mice. Clinical signs and death associated with ZIKV viremia were observed in mice. the rZiKV recovered from these mice remained fully virulent in a second passage in mice. interestingly, infectious rZiKV was also recovered after intraperitoneal inoculation of the rZiKV cDnA in the absence of transfection reagent. further expanding these studies, we demonstrate that a single intraperitoneal inoculation of a cDnA clone encoding an attenuated rZiKV was safe, highly immunogenic, and provided full protection against lethal ZiKV challenge. this novel in vivo reverse genetics method is a potentially suitable delivery platform for the study of wild-type and liveattenuated ZiKV devoid of confounding factors typical associated with in vitro systems. Moreover, our results open the possibility of employing similar in vivo reverse genetic approaches for the generation of other viruses and, therefore, change the way we will use reverse genetics in the future. Zika virus (ZIKV), a member of the Flaviviridae family, became a global public concern because of the correlation of Zika virus epidemic with fetal developmental defects, including highly publicized cases of microcephaly 1 . The viral genome is made of a positive sense, single-stranded RNA molecule (~10.8 kb) that contains a single open reading frame flanked by 5′ and 3′ untranslated regions 2-4 . The viral RNA is translated as a single polyprotein that is co-and post-translationally processed by viral and cellular proteases into three major structural proteins (capsid, pre-membrane and envelope) involved in viral entry, fusion and assembly 5 , and seven non-structural (NS) proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B and NS5) that are involved in viral RNA replication and transcription, assembly and evasion of the host antiviral responses [6] [7] [8] [9] . Although the majority of ZIKV infections are asymptomatic or associated with a mild febrile illness, infection during pregnancy has been associated with miscarriage and severe congenital malformations, including fetal
Output: In vivo rescue of recombinant Zika virus from an infectious cDnA clone and its implications in vaccine development
The aim of the workshop was to discuss the latest trends in using high-throughput sequencing, bioinformatics, and allied technologies to analyze immune and pathogen repertoires and their interplay within the host, bringing together key international players in the field and Singapore-based researchers and clinicianscientists. The focus was in particular on the application of these technologies for the improvement of patient diagnosis, prognosis and treatment, and for other broad public health outcomes. The presentations by scientists and clinicians showed the potential of deep sequencing technology to capture the coevolution of adaptive immunity and pathogens. For clinical applications, some key challenges remain, such as the long turnaround time and relatively high cost of deep sequencing for pathogen identification and characterization and the lack of international standardization in immune repertoire analysis.
Output: deep sequencing in infectious diseases: immune and pathogen repertoires for the improvement of patient outcomes The inaugural workshop "Deep Sequencing in Infectious Diseases: Immune and Pathogen Repertoires for the Improvement of Patient Outcomes" was held in Singapore
Intravascular-thrombosis and extravascular-lipid-deposit are the two key pathogenic events considered to interrupt intraosseous blood supply during development of steroid-associated osteonecrosis (ON). However, there are no clinically employed agents capable of simultaneously targeting these two key pathogenic events. The present experimental study demonstrated that constitutional flavonoid glycosides derived from herb Epimedium (EF, composed of seven flavonoid compounds with common stem nuclear) exerted dose-dependent effect on inhibition of both thrombosis and lipiddeposition and accordingly reducing incidence of steroid-associated ON in rabbits, which was not via direct action by themselves rather by their common metabolite on potential cellular targets involved in the two pathogenic pathways. The underlying mechanism could be explained by counteracting endothelium injury and excessive adipogenesis. These findings encourage designing clinical trials to investigate potential of EF in prevention of steroid-associated ON.
Output: Constitutional Flavonoids Derived from Epimedium Dose-Dependently Reduce Incidence of Steroid- Associated Osteonecrosis Not via Direct Action by Themselves on Potential Cellular Targets
Purpose Antigens were conjugated on the surface of Ntrimethylaminoethylmethacrylate chitosan (TMC) nanoparticles to induce systemic and mucosal immune responses after nasal immunization. Methods TMC was synthesized by free radical polymerization and blank nanoparticles were prepared by ionic crosslinking of TMC and sodium tripolyphosphate. The model antigen (ovalbumin) was conjugated on the surface of blank nanoparticles (OVA-NP) through thioester bond formation. The cellular uptake of OVA-NP was investigated in Raw 264.7 macrophages and biodistribution of antigens was studied by the radioiodine labeling method. The immunological effects were evaluated by nasal administration of OVA-NP to Balb/C mice. The transport mechanism and nasal toxicity of OVA-NP were studied in rats. The cellular uptake of OVA-NP was significantly higher than that of ovalbumin-encapsulated nanoparticles (NPe) after 30 min. Nasally administered OVA-NP showed higher transport of antigens to cervical lymph nodes with higher targeting efficiency than all other groups. Compared with NPe, OVA-NP induced much higher levels of systemic and mucosal immune responses in Balb/C mice after three nasal immunizations. Ex vivo culturing of nasopharynx-associated lymphoid tissue (NALT) confirmed its participation in nasal immunization. The transport mechanism study revealed that OVA-NP can be transported across the nasal epithelium through glands and may be taken up in NALT through M cells. OVA-NP did not induce obvious toxicity to nasal mucosa or hemolysis in animals. The present study demonstrated that the conjugation of TMC nanoparticles with antigens is an effective strategy for nasal vaccination.
Output: Antigen-conjugated N-trimethylaminoethylmethacrylate Chitosan Nanoparticles Induce Strong Immune Responses After Nasal Administration
Food technology is a burgeoning field of applied science, invading many areas of the food industry and making contributions to economic advancement; however, little research has focused on ethical aspects in this field. This article attempts to fill this knowledge gap by revisiting the tainted milk event in China in 2008, followed by a detailed discussion of the application of food technology ethics in industrial contexts. Through the lesson learnt in the Chinese food industry, it is hoped that more global concerns on ethical issues in food technology will be raised, thereby creating a more humane food production industry.
Output: Revisiting the melamine contamination event in China: implications for ethics in food technology
Alveolar Type II (ATII) cells are important targets for seasonal and pandemic influenza. To investigate the influenza-induced innate immune response in those cells, we measured the global gene expression profile of highly differentiated ATII cells infected with the influenza A virus at a multiplicity of infection of 0.5 at 4 hours and 24 hours after inoculation. Infection with influenza stimulated a significant increase in the mRNA concentrations of many host defense-related genes, including pattern/pathogen recognition receptors, IFN, and IFN-induced genes, chemokines, and suppressors of cytokine signaling. We verified these changes by quantitative real-time RT-PCR. At the protein level, we detected a robust virusinduced secretion of the three glutamic acid-leucine-arginine (ELR)negative chemokines CXCL9, CXCL10, and CXCL11, according to ELISA. The ultraviolet inactivation of virus abolished the chemokine and cytokine response. Viral infection did not appear to alter the differentiation of ATII cells, as measured by cellular mRNA and concentrations of surfactant proteins. However, viral infection significantly reduced the secretion of surfactant protein (SP)-A and SP-D. In addition, influenza A virus triggered a time-dependent activation of phosphatidylinositol 3-kinase signaling in ATII cells. The inhibition of this pathway significantly decreased the release of infectious virus and the chemokine response, but did not alter virusinduced cell death. This study provides insights into influenzainduced innate immunity in differentiated human ATII cells, and demonstrates that the alveolar epithelium is a critical part of the initial innate immune response to influenza.
Output: Innate Immune Response to Influenza A Virus in Differentiated Human Alveolar Type II Cells
Bactericidal action of demonstrated a stronger bactericidal activity than Al 2 O 3 . The colony-forming ability of E. coli was completely lost in 0.5 min on both of Ag/Al 2 O 3 and AgCl/Al 2 O 3 at room temperature in air. The configuration of the bacteria on the catalyst surface was observed using scanning electron microscopy (SEM). Reactive oxygen species (ROS) play an important role in the expression of the bactericidal activity on the surface of catalysts by assay with O 2 /N 2 bubbling and scavenger for ROS. Furthermore, the formation of CO 2 as an oxidation product could be detected by diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and be deduced by total carbon analysis. These results strongly support that the bactericidal process on the surface of Ag/Al 2 O 3 and AgCl/Al 2 O 3 was caused by the catalytic oxidation.
Output: Catalytic sterilization of Escherichia coli K 12 on Ag/Al 2 O 3 surface on pure culture of Escherichia coli K 12 was studied
We have previously reported that the apathogenic Tula hantavirus induces apoptosis in Vero E6 epithelial cells. To assess the molecular mechanisms behind the induced apoptosis we studied the effects of hantavirus infection on cellular signaling pathways which promote cell survival. We previously also observed that the Tula virus-induced cell death process is augmented by external TNF-α. Since TNF-α is involved in the pathogenesis of hantavirus-caused hemorrhagic fever with renal syndrome (HFRS) we investigated its effects on HFRS-causing hantavirus-infected cells. We studied both apathogenic (Tula and Topografov) and pathogenic (Puumala and Seoul) hantaviruses for their ability to regulate cellular signaling pathways and observed a direct virusmediated down-regulation of external signal-regulated kinases 1 and 2 (ERK1/2) survival pathway activity, which was dramatically enhanced by TNF-α. The fold of ERK1/2 inhibition correlated with viral replication efficiencies, which varied drastically between the hantaviruses studied. We demonstrate that in the presence of a cytokine TNF-α, which is increased in HFRS patients, hantaviruses are capable of inactivating proteins that promote cell survival (ERK1/ 2). These results imply that hantavirus-infected epithelial cell barrier functions might be compromised in diseased individuals and could at least partially explain the mechanisms of renal dysfunction and the resulting proteinuria seen in HFRS patients.
Output: Virology Journal Hantaviruses and TNF-alpha act synergistically to induce ERK1/2 inactivation in Vero E6 cells