niryuu/sni-each-converted huggingface dataset:
Methods We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specifi c serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of Findings 50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specifi c antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies. Interpretation MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from diff erent locations in Oman suggest widespread infection.
Output: Middle East respiratory syndrome coronavirus neutralising serum antibodies in dromedary camels: a comparative serological study
Autophagy is important for a variety for virus life cycles. We sought to determine the role of autophagy in human BK polyomavirus (BKPyV) infection. The addition excess amino acids during viral infection reduced BKPyV infection. Perturbing autophagy levels using inhibitors, 3-MA, bafilomycin A1, and spautin-1, also reduced infection, while rapamycin treatment of host cells increased infection. siRNA knockdown of autophagy genes, ATG7 and Beclin-1, corresponded to a decrease in BKPyV infection. BKPyV infection not only correlated with autophagosome formation, but also virus particles localized to autophagy-specific compartments early in infection. These data support a novel role for autophagy in the promotion of BKPyV infection.
Output: Host cell autophagy promotes BK virus infection
Background. Respiratory illness continues to exert a burden on hajj pilgrims in Makkah. The purpose of this study is to determine the prevalence of respiratory illness and its associated factors among Malaysian hajj pilgrims in 2013 and to describe its preventive measures. Methods. A cross-sectional study was conducted in Makkah and Malaysia during the 2013 hajj season. A self-administered proforma on social demographics, previous experience of hajj or umrah, smoking habits, co-morbid illness and practices of preventive measures against respiratory illness were obtained. Results. A total of 468 proforma were analysed. The prevalence of the respiratory illness was 93.4% with a subset of 78.2% fulfilled the criteria for influenza-like illness (ILI). Most of them (77.8%) had a respiratory illness of <2 weeks duration. Approximately 61.8% were administered antibiotics but only 2.1% of them had been hospitalized. Most of them acquired the infection after a brief stay at Arafat (81.2%). Vaccination coverages for influenza virus and pneumococcal disease were quite high, 65.2% and 59.4%, respectively. For other preventive measures practices, only 31.8% of them practiced good hand hygiene, 82.9% of pilgrims used surgical face masks, N95 face masks, dry towels, wet towels or veils as their face masks. Nearly one-half of the respondents (44.4%) took vitamins as their food supplement. Malaysian hajj pilgrims with previous experience of hajj (OR 0.24; 95% CI 0.10-0.56) or umrah (OR 0.19; 95% CI 0.07-0.52) and those who have practiced good hand hygiene (OR 0.35; 95% CI 0.16-0.79) were found to be significantly associated with lower risk of having respiratory illness. Otherwise, pilgrims who had contact with those with respiratory illness (OR 2.61; 95% CI 1.12-6.09) was associated with higher risk. Conclusions. The prevalence of respiratory illness remains high among Malaysian hajj pilgrims despite having some practices of preventive measures. All preventive measures which include hand hygiene, wearing face masks and influenza vaccination must be practiced together as bundle of care to reduce respiratory illness effectively.
Output: The prevalence and preventive measures of the respiratory illness among Malaysian pilgrims in 2013 hajj season
Background: Femoral head collapse is a key reference point for determining a treatment regimen of femoral head osteonecrosis. However, there are no effective preventive measures and the efficacy of hip-preserving surgery is unsatisfactory due to the unclear mechanism of collapse. This study aimed to identify and validate miRNAs differentially expressed in collapse and non-collapse areas of the osteonecrotic femoral head, and to predict the target genes and pathways of these miRNAs. Results: Nine samples passed the quality control test. A total of 2085 differentially expressed miRNAs were detected, among which 433 miRNAs showed differential expression in the T1 group compared to the W1 group; 344 miRNAs showed differential expression in the T2 group compared to the W2 group; 107 miRNAs showed differential expression in the T3 group compared to the W3 group. After combining data from all three patients, 10 miRNAs showed differential expression in the collapse area (T1+T2+T3) compared to the non-collapse area (W1+W2+W3). Compared to the normal area, has-miR-195-5p showed the most significant downregulation. the collapse area (T1+T2+T3) was significantly lower than that in the non-collapse area (W1+W2+W3) and normal area (Z1+Z2+Z3). 157 genes were perdicted as the target gene of hsa-miR-195-5p. Materials and Methods: Femoral heads of three patients (2 males and 1 female) treated by total hip arthroplasty surgery for steroid-induced femoral head osteonecrosis were selected based on inclusion and exclusion criteria. Bone tissue samples were obtained from the collapse area (T), non-collapse area (W), and normal area (Z) according to the anatomical structure of osteonecrotic femoral heads. Total RNA was extracted from the samples and the microarray chip was scanned. miRNAs showing differential expressions of more than 1.5-fold were selected and was validated by RT-PCR. TargetScan, mirBase and miRanda bioinformatics software was used to predict target genes and identify possible pathways involving these genes. Conclusions: miR-195-5p showed the most significant difference in the collapse area of osteonecrotic femoral heads, suggesting that collapse may be related to the downregulation of miR-195-5p.
Output: Differential expression of miR-195-5p in collapse of steroid- induced osteonecrosis of the femoral head
Healthcare-associated infections Purpose of review Environmental surfaces in healthcare facilities, particularly in a patient room, are a critical pathway for healthcare-associated pathogen transmission. Despite well-established guides and recommendations regarding environmental surface cleaning and disinfection, there are several challenges in resource-limited settings. This viewpoint article will discuss the practice of environmental cleaning in resource-limited settings including challenges and relationship between environment and healthcare-associated infections in this setting and outlines pre-requisites to overcome these challenges. Recent findings Despite several barriers and challenges, environmental cleaning is a crucial component to help reduce transmission of healthcare-associated infections and multidrug-resistant pathogens as well as emerging infectious disease-associated pathogens in resource-limited settings. However, there is a need to develop a multi-modal strategy together with a mechanism for monitor and feedback to improve the practices of environmental cleaning in resource-limited settings. Summary Additional researches on the barriers and implementation gaps and the role of collaborative network as well as how to apply technology would provide significant insights on the practices of environmental cleaning in resource-limited settings.
Output: Environmental Cleaning in Resource-Limited Settings
B cells are one of the key players in the pathogenesis of multiple sclerosis (MS). The peripheral B cell distributions are similar in healthy persons and MS patients. In healthy controls, B cells are rarely present in the cerebrospinal fluid (CSF) while in MS patients, a clonally expanded B cell population is detected. This consists of memory B cells, centroblasts and antibody-secreting plasma blasts and plasma cells that are responsible for intrathecal immunoglobulin G production and oligoclonal band formation in more than 90% of MS patients. Unfortunately, the targets of the autoreactive B cells and antibodies remain largely unknown. Various candidate antigens have been identified but often their involvement in the disease process is still unclear. Most studies characterizing these target antigens examined autoantibodies by analyzing sera or CSF of MS patients. An alternative approach is focusing on the clonally expanded B cells. In this way B cells directed against myelin, astroglia and axons have been denoted in MS patients. B cell immortalization, that is based on the antibody-producing potential of Epstein-Barr virus (EBV) transformed B cells, can be used to expand B cells from MS patients for the production of antibodies, that ultimately can be analysed for target identification.
Output: B cell characterization and reactivity analysis in multiple sclerosis
KEYWORDS Respiratory viruses Laboratory diagnosis Molecular methods Polymerase chain reaction Molecular tests for the detection of respiratory viruses are more sensitive and can detect more viruses than the traditional methods of culture and antigen detection. There are now several molecular assays available, cleared by the Food and Drug Administration, which differ with respect to the viruses detected, instrumentation, throughput, hands-on time, the need for separate nucleic acid extraction, and sensitivity for certain groups of viruses. Issues associated with molecular tests for respiratory viruses include: possible falsenegative results due to sequence variants; the inability of many assays to discriminate rhinoviruses from enteroviruses; the ability to detect viral nucleic acids in asymptomatic individuals; and the increased prevalence of coinfections.
Output: Molecular Detection of Respiratory Viruses
The Golgi apparatus and its resident proteins are utilized and regulated by viruses to facilitate their proliferation. In this study, we investigated Classical swine fever virus (CSFV) proliferation when the function of the Golgi was disturbed. Golgi function was disturbed using chemical inhibitors, namely, brefeldin A (BFA) and golgicide A (GCA), and RNA interfering targets, such as the Golgi-specific BFA-resistance guanine nucleotide exchange factor 1 (GBF1) and Rab2 GTPases. CSFV proliferation was significantly inhibited during RNA replication and viral particle generation after BFA and GCA treatment. CSFV multiplication dynamics were retarded in cells transfected with GBF1 and Rab2 shRNA. Furthermore, CSFV proliferation was promoted by GBF1 and Rab2 overexpression using a lentiviral system. Hence, Golgi function is important for CSFV multiplication, and GBF1 and Rab2 participate in CSFV proliferation. Further studies must investigate Golgi-resident proteins to elucidate the mechanism underlying CSFV replication. [Liang W, Zheng M, Bao C and Zhang Y 2017 CSFV proliferation is associated with GBF1 and Rab2. J. 
Output: CSFV proliferation is associated with GBF1 and Rab2
Attenuated, live viral vaccines have been extraordinarily successful in protecting against many diseases. The main drawbacks in their development and use have been reliance on an unpredictable method of attenuation and the potential for evolutionary reversion to high virulence. Methods of genetic engineering now provide many safer alternatives to live vaccines, so if live vaccines are to compete with these alternatives in the future, they must either have superior immunogenicity or they must be able to overcome these former disadvantages. Several live vaccine designs that were historically inaccessible are now feasible because of advances in genome synthesis. Some of those methods are addressed here, with an emphasis on whether they enable predictable levels of attenuation and whether they are stable against evolutionary reversion. These new designs overcome many of the former drawbacks and position live vaccines to be competitive with alternatives. Not only do new methods appear to retard evolutionary reversion enough to prevent vaccine-derived epidemics, but it may even be possible to permanently attenuate live vaccines that are transmissible but cannot evolve to higher virulence under prolonged adaptation.
Output: Evolutionary reversion of live viral vaccines: Can genetic engineering subdue it?
Tourism price has been extensively used to predict tourism demand. However, there is no agreement on the proper indicators of its components. Use of different price indicators may be the reason for researchers' apparently inconsistent results. The purpose of this study was to identify proper price indicators for the demand model of Japanese inbound tourism from South Korea. After comparing six models, each with different price indicators, the model with relative price and exchange rate but without transport cost was identified as the best model in which relative price, exchange rate, and per capita income were found to be significant.
Output: Role of tourism price in attracting international tourists: The case of Japanese inbound tourism from South Korea
Epidermal growth factor (EGF) promotes gastrointestinal mucosal recovery by stimulating the mitogenic activity of intestinal crypt epithelial cells. The aim of this study was to determine the effects of EGF on atrophic enteritis induced in piglets by experimental infection with porcine epidemic diarrhoea virus (PEDV) strain Dr13. Two groups of 12 conventional, colostrum-deprived, 1-day-old, large White-Duroc cross breed piglets were inoculated orally with PEDV (3 · 10 5 50% tissue culture infective doses), with or without EGF (10 lg/kg/day, intraperitoneally once daily for 4 days after infection) and compared to 12 uninfected, untreated control piglets. PEDV + EGF piglets had less severe clinical signs than PEDV only piglets at 48 and 60 h post-infection (hpi). Histologically, the ratio of villous height:crypt depth of PEDV + EGF piglets was significantly higher than PEDV only piglets at 36 and 48 hpi. Immunohistochemistry for Ki67 demonstrated increased proliferation in intestinal crypt epithelial cells of PEDV + EGF piglets compared to PEDV only piglets at 36, 48 and 60 hpi. EGF stimulates proliferation of intestinal crypt epithelial cells and promotes recovery from atrophic enteritis in PEDV-infected piglets.
Output: Effects of epidermal growth factor on atrophic enteritis in piglets induced by experimental porcine epidemic diarrhoea virus
Chronic infection and cancer are associated with suppressed T cell responses in the presence of cognate antigen. Recent work identified memory-like CXCR5 + TCF1 + CD8 + T cells that sustain T cell responses during persistent infection and proliferate upon anti-PD1 treatment. Approaches to expand these cells are sought. We show that blockade of interferon type 1 (IFN-I) receptor leads to CXCR5 + CD8 + T cell expansion in an IL-27-and STAT1-dependent manner. IFNAR1 blockade promoted accelerated cell division and retention of TCF1 in virus-specific CD8 + T cells. We found that CD8 + T cell-intrinsic IL-27 signaling safeguards the ability of TCF1 hi cells to maintain proliferation and avoid terminal differentiation or programmed cell death. Mechanistically, IL-27 endowed rapidly dividing cells with IRF1, a transcription factor that was required for sustained division in a cell-intrinsic manner. These findings reveal that IL-27 opposes IFN-I to uncouple effector differentiation from cell division and suggest that IL-27 signaling could be exploited to augment self-renewing T cells in chronic infections and cancer.
Output: IL-27 promotes the expansion of self-renewing CD8 + T cells in persistent viral infection
Virus-like particles (VLPs) are highly organised spheres that self-assemble from virus-derived structural antigens. These stable and versatile subviral particles possess excellent adjuvant properties capable of inducing innate and cognate immune responses. Commercialised VLP-based vaccines have been successful in protecting humans from hepatitis B virus (HBV) and human papillomavirus (HPV) infection and are currently explored for their potential to combat other infectious diseases and cancer. Much insight into VLP-mediated immune stimulation and optimised VLP design has been gained from human immunodeficiency virus (HIV)-derived VLPs presenting promising components of current AIDS vaccine approaches. Owing to their unique features, VLPs and virosomes, the in vitro-reconstituted VLP counterparts, have recently gained ground in the field of nanobiotechnology as organic templates for the development of new biomaterials. Addresses
Output: Virus-like particles-universal molecular toolboxes
The genetic predisposition to severe A(H1N1)2009 (A[H1N1]pdm09) influenza was evaluated in 409 patients, including 162 cases with severe infection and 247 controls with mild infection. We prioritized candidate variants based on the result of a pilot genome-wide association study and a lung expression quantitative trait locus data set. The GG genotype of rs2070788, a higher-expression variant of TMPRSS2, was a risk variant (odds ratio, 2.11; 95% confidence interval, 1.18-3.77; P = .01) to severe A(H1N1)pdm09 influenza. A potentially functional single-nucleotide polymorphism, rs383510, accommodated in a putative regulatory region was identified to tag rs2070788. Luciferase assay results showed the putative regulatory region was a functional element, in which rs383510 regulated TMPRSS2 expression in a genotype-specific manner. Notably, rs2070788 and rs383510 were significantly associated with the susceptibility to A(H7N9) influenza in 102 patients with A(H7N9) influenza and 106 healthy controls. Therefore, we demonstrate that genetic variants with higher TMPRSS2 expression confer higher risk to severe A(H1N1)pdm09 influenza. The same variants also increase susceptibility to human A(H7N9) influenza.
Output: Identification of TMPRSS2 as a Susceptibility Gene for Severe 2009 Pandemic A(H1N1) Influenza and A(H7N9) Influenza
R-CHOP chemotherapy composed of rituximab, cyclophosphamide, adriamycin, vincristine, and prednisolone which might increase the risk of Pneumocystis pneumonia in patients with non-Hodgkin lymphoma. We estimated the point prevalence of Pneumocystis pneumonia in non-Hodgkin lymphoma patients according to the number of R-CHOP cycles and investigated whether cytoreduction by chemotherapy is associated with Pneumocystis pneumonia development. We retrospectively established a cohort of patients who received R-CHOP for non-Hodgkin lymphoma in our institution. Using this cohort, we estimated the incidence rate and point prevalence of definite and probable Pneumocystis pneumonia. To assess factors associated with Pneumocystis pneumonia development several clinical variables, including absolute neutrophil and lymphocyte count at the time of non-Hodgkin lymphoma diagnosis and when the last R-CHOP cycle was administered, were compared between patients with and without Pneumocystis pneumonia. Of 713 patients in the cohort, 14 and 18 patients were diagnosed with definite and probable Pneumocystis pneumonia, respectively. The overall incidence of definite and definite plus probable PCP in NHL patients receiving R-CHOP were 2.0 % (14/713; 95 % CI, 1.1-3.3 %) and 4.5 % (32/713; 95 % CI, 3.2-6.4 %), respectively. This corresponded to 3.8 (95 % CI, 2.2-6.4) and 8.4 (95 % CI, 5.9-11.9) per 1000 persons. Many cases of Pneumocystis pneumonia (22/32, 68.7 %) developed after administration of the fourth R-CHOP cycle. However, there was no statistical difference in Pneumocystis pneumonia prevalence between patients receiving four or more cycles of R-CHOP and fewer than. Higher absolute neutrophil count (4,742/mm 3 vs. 2,627/ mm 3 ; p<0.01) was associated with Pneumocystis pneumonia development at the last R-CHOP cycle, while absolute lymphocyte count at the time of NHL diagnosis was not. Contrary to expectations, Pneumocystis pneumonia is not a frequent complication of R-CHOP treatment for non-Hodgkin lymphoma. Cytoreduction of R-CHOP might not be a risk factor of Pneumocystis pneumonia development. Universal prophylaxis against Pneumocystis pneumonia during R-CHOP treatment could not be strongly recommended.
Output: Point prevalence of Pneumocystis pneumonia in patients with non-Hodgkin lymphoma according to the number of cycles of R-CHOP chemotherapy
A 69-year-old male with a past medical history of hypertension, diabetes mellitus, and acute myelogenous leukemia (AML) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) presented with recurrent fever and cough. The patient had undergone allogeneic HSCT from a matched unrelated donor 17 months previously, conditioned by fludarabine, melphalan, and alemtuzumab. His posttransplant course was complicated by graft versus host disease and multiple central venous catheter infections with coagulase-negative Staphylococcus spp., vancomycinresistant Enterococcus, Lactobacillus, and alpha-hemolytic Streptococcus. During his initial course, he also developed a nodular pneumonia, and the subsequent workup included a bronchoscopy that was nondiagnostic. The pneumonia resolved with empiric posaconazole treatment. Sixteen months after the transplant, the patient developed fatigue, low-grade fevers, and cough. Chest x-ray (CXR) showed a new, left lower lobe infiltrate. A sputum culture then grew fluoroquinolone-susceptible Pseudomonas, and the Oncology Service subsequently discharged the patient home on moxifloxacin alone. Three weeks later, he presented again with recurrent cough and fever and was readmitted. A CXR showed a new, right lower lobe infiltrate. The patient had a remote history of symptomatic bradycardia for which he had undergone pacemaker placement. He was a former cigarette smoker (40 pack-years), but he denied any intravenous drug use. He was a retired automobile mechanic and lived at home with his wife and a dog. He had traveled recently to Las Vegas for a short trip to visit casinos. His medications on admission included acyclovir, fluconazole, and dapsone prophylaxis. He previously had an adverse reaction to imipenem, which caused a rash, and to voriconazole, which caused visual hallucinations. On physical examination, he was alert and oriented. His temperature was 100.5 °F, heart rate 86 beats per minute, blood pressure 134/94 mmHg, respiratory rate 20 breaths per minute, and oxygen saturation 90% on ambient air. He had mild bilateral crackles at the lung bases and a well-healed, non-tender, nonerythematous surgical scar at the site of the pacemaker pocket on the anterior chest wall. The remainder of his physical examination was unremarkable. Laboratory values were significant for pancytopenia, with WBC count of 3500/μl, (76% neutrophils, 8% lymphocytes, and 12% monocytes), hemoglobin 11.6 g/dL (normal range, 13.5-17.5 g/ dL), and platelet count of 122,000/μL (normal range, 150,000-450,000/μL). Other laboratory
Output: Pulmonary Infection in a Patient After Stem Cell Transplantation
Recent international epidemics of coronavirus-associated illnesses underscore the urgent medical and public health need for vaccine development and regulatory body approved therapies. In particular, the current coronavirus disease 2019 (COVID-19) pandemic has quickly intensified interest in developing treatment options to mitigate impact on human life. Remdesivir (GS-5734™) is a broad-spectrum antiviral drug that is now being tested as a potential treatment for COVID-19 in international, multi-site clinical trials. Currently available evidence about the antiviral effects of remdesivir against coronaviruses is primarily based on in vitro and in vivo studies (including some on a chemically related compound, GS-441524™), which have demonstrated largely favorable findings. As the pandemic progresses, information from human compassionate use cases will continue to accumulate before the clinical trials are concluded. It is imperative for public health practitioners and the One Health community to stay up to date on the most promising potential therapeutic options that are under investigation. Thus, the purpose of this review is to synthesize the knowledge to date about remdesivir as a therapeutic option for coronaviruses, with a special focus on information relevant to the One Health community.
Output: Current knowledge about the antivirals remdesivir (GS-5734) and GS- 441524 as therapeutic options for coronaviruses
Introduction: More than 93,000 cases of coronavirus disease have been reported worldwide. We describe the epidemiology, clinical course, and virologic characteristics of the first 12 U.S. patients with COVID-19. We collected demographic, exposure, and clinical information from 12 patients confirmed by CDC during January 20-February 5, 2020 to have COVID-19. Respiratory, stool, serum, and urine specimens were submitted for SARS-CoV-2 rRT-PCR testing, virus culture, and whole genome sequencing. Results: Among the 12 patients, median age was 53 years (range: 21-68); 8 were male, 10 had traveled to China, and two were contacts of patients in this series. Commonly reported signs and symptoms at illness onset were fever (n=7) and cough (n=8). Seven patients were hospitalized with radiographic evidence of pneumonia and demonstrated clinical or laboratory signs of worsening during the second week of illness. Three were treated with the investigational antiviral remdesivir. All patients had SARS-CoV-2 RNA detected in respiratory specimens, typically for 2-3 weeks after illness onset, with lowest rRT-PCR Ct values often detected in the first week. SARS-CoV-2 RNA was detected after reported symptom resolution in seven patients. SARS-CoV-2 was cultured from respiratory specimens, and SARS-CoV-2 RNA was detected in stool from 7/10 patients. In 12 patients with mild to moderately severe illness, SARS-CoV-2 RNA and viable virus were detected early, and prolonged RNA detection suggests the window for diagnosis is long. Hospitalized patients showed signs of worsening in the second week after illness onset. for use under a CC0 license.
Output: Title: First 12 patients with coronavirus disease
High-throughput screening (HTS) of large compound libraries has become a commonly used method for the identification of drug leads, and non-physiological reducing agents have been widely used for HTS. However, a comparison of the difference in the HTS results based on the choice of reducing agent used and potency comparisons of selected inhibitors has not been done with the physiological reducing agent, reduced glutathione (GSH). Here, we compared the effects of three reducing agents: dithiothreitol (DTT), β-mercaptoethanol (β-MCE), and tris-(2carboxyethyl)-phosphine (TCEP), in addition to GSH, against three drug target proteins. Approximately 100,000 compounds were computationally screened for each target protein, and experimental testing of high scoring compounds (~560 compounds) with the four reducing agents surprisingly produced many non-overlapping hits. More importantly, we find that various reducing agents alter inhibitor potency (IC 50 ) from ~10 µM with one reducing agent to complete loss (IC 50 > 200 µM) of inhibitory activity with another reducing agent. Therefore, the choice of reducing agent in a HTS is critical as this may lead to the pursuit of falsely identified active compounds or failure to identify the true active compounds. We demonstrate the feasibility of using GSH for in vitro HTS assays with these three target enzymes. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Contributions H.L. performed all experiments with assistance of J.T. and L.T., R.C. performed computational selection of inhibitors for PLpro and NS3/4A, A.M. performed computational selection of inhibitors for 3CLpro, and H.L. and M.E.J. designed the experiments and wrote the manuscript.
Output: Reducing agents affect inhibitory activities of compounds: Results from Multiple Drug Targets
Porcine reproductive and respiratory syndrome virus (PRRSV) represents a significantly economical challenge to the swine industry worldwide. In this study, we investigated the importance of cellular and viral lipid rafts in PRRSV infection. First, we demonstrated that PRRSV glycoproteins, Gp3 and Gp4, were associated with lipid rafts during viral entry, and disruption of cellular lipid rafts inhibited PRRSV entry. We also showed the raft-location of CD163, which might contribute to the glycoproteins-raft association. Subsequently, raft disruption caused a significant reduction of viral RNA production. Moreover, Nsp9 was shown to be distributed in rafts, suggesting that rafts probably serve as a platform for PRRSV replication. Finally, we confirmed that disassembly of rafts on the virus envelope may affect the integrity of PRRSV particles and cause the leakage of viral proteins, which impaired PRRSV infectivity. These findings might provide insights on our understanding of the mechanism of PRRSV infection.
Output: Lipid rafts both in cellular membrane and viral envelope are critical for PRRSV efficient infection
Nonsynonymous-synonymous substitution rate ratio (d N /d S ) is an important measure for evaluating selective pressure based on the protein-coding sequences. Maximum likelihood (ML) method with codon-substitution models is a powerful statistic tool for detecting amino acid sites under positive selection and adaptive evolution. We analyzed the hepatitis C virus (HCV) envelope protein-coding sequences from 18 general geno/ subtypes worldwide, and found 4 amino acid sites under positive selection. Since these sites are located in different immune epitopes, it is reasonable to anticipate that our study would have potential values in biomedicine. It also suggests that the ML method is an effective way to detect adaptive evolution in virus proteins with relatively high genetic diversity.
Output: Using maximum likelihood method to detect adaptive evolution of HCV envelope protein-coding genes
The known genetic diversity of the hepaciviruses and pegiviruses has increased greatly in recent years through the discovery of viruses related to hepatitis C virus and human pegivirus in bats, bovines, equines, primates, and rodents. Analysis of these new species is important for research into animal models of hepatitis C virus infection and into the zoonotic origins of human viruses. Here, we provide the first systematic phylogenetic and evolutionary analysis of these two genera at the wholegenome level. Phylogenies confirmed that hepatitis C virus is most closely related to viruses from horses whereas human pegiviruses clustered with viruses from African primates. Within each genus, several well-supported lineages were identified and viral diversity was structured by both host species and location of sampling. Recombination analyses provided evidence of interspecific recombination in hepaciviruses, but none in the pegiviruses. Putative mosaic genome structures were identified in NS5B gene region and were supported by multiple tests. The identification of interspecific recombination in the hepaciviruses represents an important evolutionary event that could be clarified by future sampling of novel viruses. We also identified parallel amino acid changes shared by distantly related lineages that infect similar types of host. Notable parallel changes were clustered in the NS3 and NS4B genes and provide a useful starting point for experimental studies of the evolution of Hepacivirus host-virus interactions.
Output: Evolutionary and Phylogenetic Analysis of the Hepaciviruses and Pegiviruses
The increase of complexity of livestock production and the associated value chains has led to changes in the food systems that feed us, which in turn carry new challenges from zoonotic diseases in particular their impact, and the costs of surveillance, control and prevention. Direct losses to the animal and public health sectors, connected mainly to value losses due to morbidity and mortality in humans and animals, and indirect losses, such as the economic cost caused by the reaction to disease and the limiting of its negative effects, all contribute to this negative impact. Its full assessment can be challenging, but economic tools and frameworks can be used to estimate zoonotic disease impact and the economic efficiency of possible technical ways of dealing with these diseases. In this chapter, we review the impact of zoonoses across sectors, also in the context of an increasingly complex value chain, address the economic concepts behind the balance between losses due to direct costs of disease and expenditures in reaction to disease presence, and identify possible economic tools and frameworks to assess the impact of zoonoses and interventions. 1107 
Output: Economic Aspects of Zoonoses: Impact of Zoonoses on the Food Industry Impact of Zoonoses on the Food Industry
Computational (in silico) methods have been developed and widely applied to pharmacology hypothesis development and testing. These in silico methods include databases, quantitative structure-activity relationships, similarity searching, pharmacophores, homology models and other molecular modeling, machine learning, data mining, network analysis tools and data analysis tools that use a computer. Such methods have seen frequent use in the discovery and optimization of novel molecules with affinity to a target, the clarification of absorption, distribution, metabolism, excretion and toxicity properties as well as physicochemical characterization. The first part of this review discussed the methods that have been used for virtual ligand and target-based screening and profiling to predict biological activity. The aim of this second part of the review is to illustrate some of the varied applications of in silico methods for pharmacology in terms of the targets addressed. We will also discuss some of the advantages and disadvantages of in silico methods with respect to in vitro and in vivo methods for pharmacology research. Our conclusion is that the in silico pharmacology paradigm is ongoing and presents a rich array of opportunities that will assist in expediating the discovery of new targets, and ultimately lead to compounds with predicted biological activity for these novel targets.
Output: In silico pharmacology for drug discovery: applications to targets and beyond
The aim of this study was to explore the role of the Diffusion of Innovations framework in adopting an infection prevention and control program (IPCP) in a low and middle income (LMI) country, the Republic of Kiribati. Methods: Case-study methodology was used to examine and contextualise the analysis of the Republic of Kiribati's adoption of the IPCP from 2003 to 2010. Data were collected from multiple sources including semi-structured interviews, IPCP documentation, program evaluation and a healthcare worker survey. Data were subjected to thematic analysis and descriptive statistics where relevant to the study design. Results: It was found that the self-initiated progression of activities and stimuli has resulted in the successful adoption of a comprehensive IPCP. The process followed the staged model of the classic Diffusion of Innovations process in organisations described by Everett Rogers. Conclusion: This case study provides an illustration of how a comprehensive IPCP can be adopted in a LMI country setting with little involvement from external agencies. It identifies key stimuli, opportunities and activities which could be similarly adopted and implemented by other LMI countries.
Output: Success in the South Pacific: a case study of successful diffusion of an infection prevention and control program
Purpose of review-New respiratory viruses have been discovered in recent years and new molecular diagnostic assays have been developed that improve our understanding of respiratory virus infections. This article will review the changing epidemiology of these viruses after hematopoietic stem cell and solid organ transplantation. Recent findings-Respiratory viruses are frequently detected in transplant recipients. A number of viruses have been newly discovered or emerged in the last decade, including human metapneumovirus, human bocavirus, new human coronaviruses and rhinoviruses, human polyomaviruses, and a new 2009 pandemic strain of influenza A/H1N1. The potential for these viruses to cause lower respiratory tract infections after transplantation varies, and is greatest for human metapneumovirus and H1N1 influenza, but appears to be limited for the other new viruses. Acute and long term complications in hematopoietic and solid organ transplant recipients are active areas of research. Summary-Respiratory viral infections are frequently associated with significant morbidity following transplantation and are therefore of great clinical and epidemiologic interest. As new viruses are discovered, and more sensitive diagnostic methods are developed, defining the full impact of emerging respiratory viruses in transplant recipients must be elucidated by welldesigned clinical studies.
Output: Changing Epidemiology of Respiratory Viral Infections in Hematopoietic Cell Transplant Recipients and Solid Organ Transplant Recipients
Isopeptide bond-tethered triple-stranded coiled coils of HIV-1 gp41 N-terminal heptad repeat (NHR) peptides have been designed with de novo auxiliaries to guide site-directed trimerized cross-linking. The presence of isopeptide bridges in the rationally designed trimerization motifs provides extraordinary stability to withstand thermal and chemical denaturation. As a result, these ultra-stable and well-folded trimeric coiled coils direct and yield proteolysis-resistant and remarkably potent N-peptide chimeric trimers with HIV-1 fusion inhibitory activities in the low nanomolar range, much more effective than the corresponding unstructured N-peptide monomers and reaching the potency of clinically used T20 peptide (enfuvirtide). Thus, these isopeptide bond-crosslinked de novo coiled coils may also be used as attractive scaffolds for isolating NHR-trimers in other class I enveloped viruses for therapeutic intervention. Furthermore, this isopeptide bridge-tethering strategy could be extendable to the construction of ultra-stable proteins interfering with certain biological processes.
Output: De novo design of isopeptide bond-tethered triple- stranded coiled coils with exceptional resistance to unfolding and proteolysis: implication for developing antiviral therapeutics †
A high proportion of dogs suffer from respiratory disease when they are placed in kennels for vacation or re-homing. The role of Mycoplasma cynos as an initiating agent in canine infectious respiratory disease was investigated by examining the serological response of dogs to this organism at the time of entry into a large re-homing kennel. Forty-two paired serum samples from dogs (21-day interval) were examined for antibody to M. cynos using Western blotting. The development of antibody in the serum was related to clinical disease recorded over the same period. Sixty seven per cent of the dogs showed a two-fold or greater rise in antibody to M. cynos during the first 3 weeks in the kennel. Reactivity with a 45 kDa antigen was dominant. Of those showing a positive serological reaction, 80% had recorded clinical respiratory disease while 20% remained healthy. The findings of this study show that an antibody response to M. cynos is common in dogs entering the re-homing kennel and is positively related to the development of clinical respiratory disease. #
Output: Serological evidence of Mycoplasma cynos infection in canine infectious respiratory disease
Danhong injection (DHI) is a widely used Chinese Materia Medica standardized product for the clinical treatment of ischemic encephalopathy and coronary heart disease. The bindings of eight natural components in DHI between bovine serum albumin (BSA) were studied by fluorescence spectroscopy technology and molecular docking. According to the results, the quenching process of salvianolic acid B and hydroxysafflor yellow A was a static quenching procedure through the analysis of quenching data by the Stern-Volmer equation, the modified Stern-Volmer equation, and the modified Scatchard equation. Meanwhile, syringin (Syr) enhanced the fluorescence of BSA, and the data were analyzed using the Lineweaver-Burk equation. Molecular docking suggested that all of these natural components bind to serum albumin at the site I location. Further competitive experiments of SaB confirmed the result of molecular docking studies duo to the displacement of warfarin by SaB. Base on these studies, we selected SaB as a research target because it presented the strongest binding ability to BSA and investigated the influence of the multi-components coexisting in DHI on the interaction between the components of the SaB-BSA binding system. The participation of these natural components in DHI affected the interaction between the components of the SaB-BSA system. Therefore, when DHI is used in mammals, SaB is released from serum albumin more quickly than it is used alone. This work would provide a new experiment basis for revealing the scientific principle of compatibility for Traditional Chinese Medicine.
Output: Interaction between the Natural Components in Danhong Injection (DHI) with Serum Albumin (SA) and the Influence of the Coexisting Multi-Components on the SaB-BSA Binding System: Fluorescence and Molecular Docking Studies
publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active. 852 • Head and/or body tremor. • Twitching. • Tremor is an involuntary, rhythmic, oscillatory movement of all or part of the body. It results from the alternate or synchronous contraction of reciprocally innervated, antagonistic muscles. • Disease of the nervous system (central and peripheral) and muscle may result in tremor, shaking or twitching. • Usually tremors with increased amplitudes and slower frequencies (coarse tremor) are associated with cerebellar disorders. Those tremors with decreased amplitudes and faster frequencies (fine tremor) are associated with diffuse central nervous system disease or muscle weakness. • Tremor can have differing amplitudes (the distance traveled during the movement) and frequencies (how fast the tremor is).
Output: 39. The cat with tremor or twitching Diseases causing tremor or twitching COARSE TREMOR AND TWITCHING (INTENTIONAL)
Cryptosporidium species are coccidian parasites with a large capacity to reproduce and to disseminate. Several species are known to infect farm animals, although the economic importance of cryptosporidiosis is highly host species dependent. This paper reviews the impact of cryptosporidial infections in livestock and poultry. For dierent farm animals, the Cryptosporidium spp. that occur, as well as their clinical and pathological features, and their interactions with other pathogens, are described. In addition, data concerning the prevalence, the transmission and the epidemiology of the disease are mentioned and a description of the economic losses associated with cryptosporidiosis in each of the hosts is given. Cryptosporidiosis seems to be mainly a problem in neonatal ruminants. Cryptosporidium parvum is considered to be an important agent in the aetiology of the neonatal diarrhoea syndrome of calves, lambs and goat kids, causing considerable direct and indirect economic losses. Avian cryptosporidiosis is an emerging health problem in poultry, associated with respiratory disease in chickens and other Galliformes, and with intestinal disease in turkeys and quails. Because of limited availability of eective drugs, the control of cryptosporidiosis relies mainly on hygienic measures and good management. #
Output: A review of the importance of cryptosporidiosis in farm animals
The infection by the new coronavirus (SARS-CoV-2) has taken the dimension of a pandemic, affecting more than 160 countries in a few weeks. In Colombia, despite the implementation of the rules established by the national government, exists an elevate concern both for mortality and for the limited capacity of the health system to respond effectively to the needs of patients infected. For Colombia, assuming a case fatality rate among people infected with SARS-CoV-2 of 0.6% (average data from the information reported for Latin American countries for March 18) (Table 1) , the number of deaths, in one or two weeks, could be 16 and 243, respectively. These estimates differ markedly from those documented in countries such as Spain and Italy, in which COVID-19 case fatality rates exceed 8% (case of Italy) and from the percentage of patients who have required intensive care, which has ranged from 9% to 11% of patients in Mediterranean European countries. These differences could be explained due to: a) the percentage of the population at risk (individuals older than 60 years); b) a higher epidemiological exposure to viral respiratory infections associated with more frequent exposure to them, due to geographic and climatic conditions; c) less spread of the virus by location in the tropical zone; and d) earlier preventive measures to contain the spread of SARS-CoV-2 infection. Therefore, it is possible to establish that the situation in this country will be different from in European Mediterranean and that Colombia could have different endpoints from Spain and Italy. * Corresponding author. Street 67 # 53 -108 Office 2-118,
Output: COVID-19 in Colombia endpoints. Are we different, like Europe?
Reactive oxygen species (ROS) and reactive nitrogen species (RNS) produced by the oxidative burst in activated macrophages and neutrophils cause oxidative stressimplicated diseases. Quercetin is flavonoid that occurs naturally in plants and is widely used as a nutritional supplement due to its antioxidant and anti-inflammatory properties. In this study, we investigated antioxidant activities and mechanisms of action in zymosan-induced macrophages of quercetin and quercetin-related flavonoids such as quercitrin, isoquercitrin, quercetin 3-O-β-(2′′-galloyl)rhamnopyranoside (QGR) and quercetin 3-O-β-(2′′-galloyl)glucopyranoside (QGG) as well as gallic acid, a building moiety of QGR and QGG. QGR and QGG exhibited stronger antioxidant activities compared with quercetin, whereas quercitrin, isoquercitrin and gallic acid exhibited weak-tono antioxidant activities, assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, superoxide production, superoxide scavenging, nitric oxide (NO) production, peroxynitrite (ONOO -) scavenging and myeloperoxidase (MPO) activity. Regarding mechanisms, the quercetincontaining flavonoids QGR and QGG differentially targeted compared with quercetin in the NF-κB signaling pathway that inhibited the DNA binding activity of the NF-κB complex without affecting the degradation and phosphorylation of IκBα and NF-κB phosphorylation. In addition, QGR and QGG inhibited CRE and activator protein (AP-1) transcriptional activity and JNK phosphorylation by inhibiting the cAMP/protein kinase A (PKA) and protein kinase C (PKC) signaling in a different manner than quercetin. Our results showed that although QGR and QGG exhibited stronger antioxidant activities than querce-tin in macrophages, their mechanisms of action in terms of the NF-κB, PKA and PKC signaling pathways were different. al.,
Output: Relative Antioxidant Activities of Quercetin and Its Structurally Related Substances and Their Effects on NF-κB/CRE/AP-1 Signaling in Murine Macrophages