niryuu/sni-each-converted huggingface dataset:
Background. Despite the high burden of respiratory infection and the importance of early and accurate diagnosis, there is no simple diagnostic test to rule in viral infection as a cause of respiratory symptoms. Methods. We performed RNA sequencing on human nasal epithelial cells following stimulation of the intracellular viral recognition receptor RIG-I. Next, we evaluated whether measuring identified host mRNAs and proteins from patient nasopharyngeal swabs could predict the presence of a respiratory virus in the sample. Results. Our first study showed that a signature of 3 mRNAs, CXCL10, IFIT2, and OASL, predicted respiratory virus detection with an accuracy of 97% (95% confidence interval [CI], 0.9-1.0), and identified proteins correlating with virus detection. In a second study, elevated CXCL11 or CXCL10 protein levels identified samples containing respiratory viruses, including viruses not on the initial test panel. Overall area under the curve (AUC) values were: CXCL11 AUC = 0.901 (95% CI, 0.86-0.94); CXCL10 AUC = 0.85 (95% CI, 0.80-0.91). Conclusions. Host antiviral mRNAs and single host proteins detectable using nasopharyngeal swabs accurately predict the presence of viral infection. This approach holds promise for developing rapid, cost-effective tests to improve management of patients with respiratory illnesses.
Output: Antiviral Response in the Nasopharynx Identifies Patients With Respiratory Virus Infection
Nitazoxanide is a broad-spectrum antiviral agent undergoing clinical development for treatment of influenza and other viral respiratory infections. Nitazoxanide exhibits in vitro activity against Middle East respiratory syndrome coronavirus (MERS-CoV) and other coronaviruses, inhibiting expression of the viral N protein. Nitazoxanide also suppresses production of pro-inflammatory cytokines in peripheral blood mononuclear cells and suppresses interleukin 6 production in mice. Having been used extensively in clinical trials and in post-marketing experience, nitazoxanide is an attractive drug candidate for treatment of Middle East respiratory syndrome. Future research should include in vitro mechanism studies, animal models of MERS-CoV infection, clinical trials, including dose-ranging trials, and evaluation of combination therapy with other potential MERS-CoV antivirals.
Output: Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus
Feline calicivirus (FCV) often causes respiratory tract and oral disease in cats and is a highly contagious virus. Widespread vaccination does not prevent the spread of FCV. Furthermore, the low fidelity of the RNA-dependent RNA polymerase of FCV leads to the emergence of new variants, some of which show increased virulence. Currently, few effective anti-FCV drugs are available. Here, we found that germacrone, one of the main constituents of volatile oil from rhizoma curcuma, was able to effectively reduce the growth of FCV strain F9 in vitro. This compound exhibited a strong anti-FCV effect mainly in the early phase of the viral life cycle. The antiviral effect depended on the concentration of the drug. In addition, germacrone treatment had a significant inhibitory effect against two other reference strains, 2280 and Bolin, and resulted in a significant reduction in the replication of strains WZ-1 and HRB-SS, which were recently isolated in China. This is the first report of antiviral effects of germacrone against a calicivirus, and extensive in vivo research is needed to evaluate this drug as an antiviral therapeutic agent for FCV.
Output: In vitro antiviral effect of germacrone on feline calicivirus
The worldwide impact of COVID 19 continues to be felt as hospitals in all countries reduce elective and nonurgent cases to allow staffing and resources to be deployed elsewhere. Urgent gynaecological and cancer procedures are continuing, and it is imperative all theatre staff are protected and risks of SARS-CoV-2 viral transmission reduced when operating on asymptomatic, suspected or confirmed COVID 19 patients. In particular, there are concerns relating to the transmission of COVID 19 during gynaecological laparoscopic surgery, arising from the potential generation of SARS-CoV-2 contaminated aerosols from CO2 leakage and the creation of smoke from the use of energy devices. The aim of this paper is to review all the up to date evidence, including experiences from China and Italy, to guide the safe management of such patients when undergoing gynaecological procedures.
Output: Covid 19 pandemic and gynaecological laparoscopic surgery: knowns and unknowns
The mammalian eye is protected against pathogens and infl ammation in a relatively immune-privileged environment. Stringent mechanisms are activated that regulate external injury, infection, and autoimmunity. The eye contains a variety of cells expressing vasoactive neuropeptides (VNs), and their receptors, located in the sclera, cornea, iris, ciliary body, ciliary process, and the retina. VNs are important activators of adenylate cyclase, deriving cyclic adenosine monophosphate (cAMP) from adenosine triphosphate (ATP). Impairment of VN function would arguably impede cAMP production and impede utilization of ATP. Thus VN autoimmunity may be an etiological factor in retinopathy involving perturbations of purinergic signaling. A sound blood supply is necessary for the existence and functional properties of the retina. This paper postulates that impairments in the endothelial barriers and the blood-retinal barrier, as well as certain infl ammatory responses, may arise from disruption to VN function. Phosphodiesterase inhibitors and purinergic modulators may have a role in the treatment of postulated VN autoimmune retinopathy.
Output: Vasoactive neuropeptides in clinical ophthalmology: An association with autoimmune retinopathy?
Saffold virus (SAFV) is classified into the Cardiovirus genus of the Picornaviridae family. Up to now, eleven genotypes have been identified however, their clinical significance remains unclear. Here, we investigated the presence of SAFV in asymptomatic patients admitted for adenoidectomy. A total of 70 adenoid tissue samples were collected from children with clinical symptoms caused by hypertrophy of adenoids but without symptoms of airway infection. Samples were investigated for SAFV by RT-nested PCR and sequence analysis. Eleven of 70 (15.7%) samples were positive for SAFV. Nasopharyngeal swabs were available from 45 children just before surgery. SAFV was rarely found and only in children with SAFV-positive adenoids 2/8. Our findings indicate that the presence of SAFV seems to be more frequent in adenoid tissue than expected. This could support the notion of a longer than previously anticipated persistence of SAFV nucleic acids in the respiratory tract and possibly a chronic infection. Further investigations are necessary to establish the role of SAFV infection in humans.
Output: Frequent detection of Saffold cardiovirus in adenoids
Without viral envelope proteins, viruses cannot enter cells to start infection. As the major viral proteins present on the surface of virions, viral envelope proteins are a prominent target of the host immune system in preventing and ultimately eliminating viral infection. In addition to the well-appreciated adaptive immunity that produces envelope protein-specific antibodies and T cell responses, recent studies have begun to unveil a rich layer of host innate immune mechanisms restricting viral entry. This review focuses on the exciting progress that has been made in this new direction of research, by discussing various known examples of host restriction of viral entry, and diverse viral countering strategies, in particular, the emerging role of viral envelope proteins in evading host innate immune suppression. We will also highlight the effective cooperation between innate and adaptive immunity to achieve the synergistic control of viral infection by targeting viral envelope protein and checking viral escape. Given that many of the related findings were made with HIV-1, we will use HIV-1 as the model virus to illustrate the basic principles and molecular mechanisms on host restriction targeting HIV-1 envelope protein.
Output: HIV-1 Envelope Glycoprotein at the Interface of Host Restriction and Virus Evasion
Background: Patterns of genetic and genomic variance are informative in inferring population history for human, model species and endangered populations. Results: Here the genome sequence of wild-born African cheetahs reveals extreme genomic depletion in SNV incidence, SNV density, SNVs of coding genes, MHC class I and II genes, and mitochondrial DNA SNVs. Cheetah genomes are on average 95 % homozygous compared to the genomes of the outbred domestic cat (24.08 % homozygous), Virunga Mountain Gorilla (78.12 %), inbred Abyssinian cat (62.63 %), Tasmanian devil, domestic dog and other mammalian species. Demographic estimators impute two ancestral population bottlenecks: one >100,000 years ago coincident with cheetah migrations out of the Americas and into Eurasia and Africa, and a second 11,084-12,589 years ago in Africa coincident with late Pleistocene large mammal extinctions. MHC class I gene loss and dramatic reduction in functional diversity of MHC genes would explain why cheetahs ablate skin graft rejection among unrelated individuals. Significant excess of non-synonymous mutations in AKAP4 (p < 0.02), a gene mediating spermatozoon development, indicates cheetah fixation of five function-damaging amino acid variants distinct from AKAP4 homologues of other Felidae or mammals; AKAP4 dysfunction may cause the cheetah's extremely high (>80 %) pleiomorphic sperm. The study provides an unprecedented genomic perspective for the rare cheetah, with potential relevance to the species' natural history, physiological adaptations and unique reproductive disposition. The African cheetah-the world's fastest land animalis a paradigm of physical prowess that displays numerous physiological adaptations allowing for magnificent high-speed sprints across the African plains. Cheetahs
Output: Genomic legacy of the African cheetah, Acinonyx jubatus Genomic legacy of the African cheetah, Acinonyx jubatus
Historically, research on RNA helicase and translocation enzymes has seemed like a footnote to the extraordinary progress in studies on DNA-remodeling enzymes. However, during the past decade, the rising wave of activity in RNA science has engendered intense interest in the behaviors of specialized motor enzymes that remodel RNA molecules. Functional, mechanistic, and structural investigations of these RNA enzymes have begun to reveal the molecular basis for their key roles in RNA metabolism and signaling. In this chapter, we highlight the structural and mechanistic similarities among monomeric RNA translo-case enzymes, while emphasizing the many divergent characteristics that have caused this enzyme family to become one of the most important in metabolism and gene expression.
Output: Molecular Mechanics of RNA Translocases
The mammalian RIG-I-like receptors, RIG-I, MDA5 and LGP2, are a family of DExD/H box RNA helicases responsible for the cytoplasmic detection of viral RNA. These receptors detect a variety of RNA viruses, or DNA viruses that express unusual RNA species, many of which are responsible for a great number of severe and lethal diseases. Host innate sentinel proteins involved in pathogen recognition must rapidly evolve in a dynamic arms race with pathogens, and thus are subjected to long-term positive selection pressures to avoid potential infections. Using six codon-based Maximum Likelihood methods, we were able to identify specific codons under positive selection in each of these three genes. The highest number of positively selected codons was detected in MDA5, but a great percentage of these codons were located outside of the currently defined protein domains for MDA5, which likely reflects the imposition of both functional and structural constraints. Additionally, our results support LGP2 as being the least prone to evolutionary change, since the lowest number of codons under selection was observed for this gene. On the other hand, the preponderance of positively selected codons for RIG-I were detected in known protein functional domains, suggesting that pressure has been imposed by the vast number of viruses that are recognized by this RNA helicase. Furthermore, the RIG-I repressor domain, the region responsible for recognizing and binding to its RNA substrates, exhibited the strongest evidence of selective pressures. Branch-site analyses were performed and several species branches on the three receptor gene trees showed evidence of episodic positive selection. In conclusion, by looking for evidence of positive evolutionary selection on mammalian RIG-I-like receptor genes, we propose that a multitude of viruses have crafted the receptors biological function in host defense, specifically for the RIG-I gene, contributing to the innate species-specific resistance/susceptibility to diverse viral pathogens.
Output: Positive Evolutionary Selection On the RIG-I-Like Receptor Genes in Mammals
Air pollution is a severe threat to public health globally, affecting everyone in developed and developing countries alike. Among different air pollutants, particulate matter (PM), particularly combustion-produced fine PM (PM 2.5 ) has been shown to play a major role in inducing various adverse health effects. Strong associations have been demonstrated by epidemiological and toxicological studies between increases in PM 2.5 concentrations and premature mortality, cardiopulmonary diseases, asthma and allergic sensitization, and lung cancer. The mechanisms of PM-induced toxicological effects are related to their size, chemical composition, lung clearance and retention, cellular oxidative stress responses and pro-inflammatory effects locally and systemically. Particles in the ultrafine range (<100 nm), although they have the highest number counts, surface area and organic chemical content, are often overlooked due to insufficient monitoring and risk assessment. Yet, ample studies have demonstrated that ambient ultrafine particles have higher toxic potential compared with PM 2.5 . In addition, the rapid development of nanotechnology, bringing ever-increasing production of nanomaterials, has raised concerns about the potential human exposure and health impacts. All these add to the complexity of PM-induced health effects that largely remains to be determined, and mechanistic understanding on the toxicological effects of ambient ultrafine particles and nanomaterials will be the focus of studies in the near future.
Output: Pulmonary diseases induced by ambient ultrafine and engineered nanoparticles in twenty-first century
Graphical Abstract Highlights d PI4KB activity expedites the formation of coxsackievirus replication organelles (ROs) d PI4KB inhibition impairs polyprotein processing, which is rescued by a 3A mutation d Upon PI4KB inhibition, this mutant replicates at the Golgi in the absence of ROs d Innate immune responses are not enhanced when RO biogenesis is delayed Correspondence m.barcena@lumc.nl (M.B.), f.j.m.vankuppeveld@uu.nl (F. Enteroviruses reorganize cellular endomembranes into replication organelles (ROs) for genome replication. Although enterovirus replication depends on phosphatidylinositol 4-kinase type IIIb (PI4KB), its role, and that of its product, phosphatidylinositol 4-phosphate (PI4P), is only partially understood. Exploiting a mutant coxsackievirus resistant to PI4KB inhibition, we show that PI4KB activity has distinct functions both in proteolytic processing of the viral polyprotein and in RO biogenesis. The escape mutation rectifies a proteolytic processing defect imposed by PI4KB inhibition, pointing to a possible escape mechanism. Remarkably, under PI4KB inhibition, the mutant virus could replicate its genome in the absence of ROs, using instead the Golgi apparatus. This impaired RO biogenesis provided an opportunity to investigate the proposed role of ROs in shielding enteroviral RNA from cellular sensors. Neither accelerated sensing of viral RNA nor enhanced innate immune responses was observed. Together, our findings challenge the notion that ROs are indispensable for enterovirus genome replication and immune evasion.
Output: Escaping Host Factor PI4KB Inhibition: Enterovirus Genomic RNA Replication in the Absence of Replication Organelles
COVID-19 threatens to overwhelm hospital facilities throughout the United States. We created an interactive, quantitative model that forecasts demand for COVID-19 related hospitalization based on county-level population characteristics, data from the literature on COVID-19, and data from online repositories. Using this information as well as user inputs, the model estimates a time series of demand for intensive care beds and acute care beds as well as the availability of those beds. The online model is designed to be intuitive and interactive so that local leaders with limited technical or epidemiological expertise may make decisions based on a variety of scenarios. This complements high-level models designed for public consumption and technically sophisticated models designed for use by epidemiologists. The model is actively being used by several academic medical centers and policy makers, and we believe that broader access will continue to aid community and hospital leaders in their response to COVID-19.
Output: A model to forecast regional demand for COVID-19 related hospital beds
The activity of inosine-5 -monophosphate dehydrogenase (IMPDH) inhibitors, mizoribine and ribavirin, against severe acute respiratory syndrome (SARS)-associated coronavirus (SARS-CoV) was determined by plaque reduction and yield reduction assays. Mizoribine and ribavirin selectively inhibited replication of SARS-CoV. The 50% inhibitory concentration (IC 50 ) of mizoribine for SARS-CoV Frankfurt-1 and SARS-CoV HKU39849, as determined by plaque reduction was 3.5 g/ml and 16 g/ml, respectively, and the IC 50 of ribavirin for SARS-CoV Frankfurt-1 and SARS-CoV HKU39849 was 20 g/ml and 80 g/ml, while the 50% cytotoxic concentration of mizoribine and ribavirin for Vero E6 cells exceeded 200 g/ml. In a yield reduction assay, mizoribine (10 g/ml) and ribavirin (40 g/ml) inhibited the replication of SARS-CoV and reduced the infectious SARS-CoV titers to one-tenth or less. Mizoribine inhibited replication of SARS-CoV more strongly than ribavirin. However, neither drug could completely inhibit replication of SARS-CoV even at concentrations up to 100 g/ml.
Output: Inhibitory effect of mizoribine and ribavirin on the replication of severe acute respiratory syndrome (SARS)-associated coronavirus
The entry of enveloped viruses involves virus adsorption followed by close apposition of the viral and plasma membranes. This multistep process is initiated by specific binding interactions between glycoproteins in the viral envelope and appropriate receptors on the cell surface. In the case of HIV-1, attachment of virions to the cell surface is attributed to a high affinity interaction between envelope spike glycoproteins (Env, composed of the surface protein gp120 and the transmembrane protein gp41) and a complex made of the primary CD4 receptor and a seven-transmembrane co-receptor (e.g., CXCR4 or CCR5) (reviewed in [1]). Then a chain of dynamic events take place that enable the viral nucleocapsid to penetrate within the target cell following the destabilization of membrane microenvironment and the formation of a fusion pore. Although it is generally accepted that HIV-1 attachment to its major cellular reservoirs (i.e., T helper cells and macrophages) occurs through the twostage receptor-interaction pathway, there is accumulating evidence indicating that the initial attachment step is a more complex phenomenon than initially thought. Indeed it seems that adsorption of HIV-1 to the cell surface is modulated by a large variety of interactions between the viral entity and the target cell surface (reviewed in [2] ). This retrovirus may also attach to some cell types by CD4-independent interactions involving highly glycosylated groups or basic residues found on gp120 and polyanionic sulfated chains or lectin-like domains on some specific cell surface receptors (reviewed in [1]). For example, heparan sulfate proteoglycans, which are expressed at high levels on different cell types, such as epithelial and endothelial cells, can interact with the envelope spike glycoprotein and serve as docking structures for HIV-1 [3]. Heparan sulfate proteoglycans such as syndecans serve as the main class of attachment receptors for HIV-1 on different cell types, e.g., macrophages and endothelial cells, and are thought to play a cardinal role in virus transmission Entry Inhibitors in HIV Therapy Edited
Output: Attachment of human immunodeficiency virus to cells and its inhibition
Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based highthroughput screening system, dual envelope pseudovirion (DEP) assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes.
Output: Inhibitors of SARS-CoV entry -Identification using an internally-controlled dual envelope pseudovirion assay
Background: The first cases of influenza A/H1N1 (swine flu) were confirmed in the UK on 27th April 2009, after a novel virus first identified in Mexico rapidly evolved into a pandemic. The swine flu outbreak was the first pandemic in more than 40 years and for many, their first encounter with a major influenza outbreak. This study examines public understandings of the pandemic, exploring how people deciphered the threat and perceived they could control the risks. Methods: Purposive sampling was used to recruit seventy three people (61 women and 12 men) to take part in 14 focus group discussions around the time of the second wave in swine flu cases. Results: These discussions showed that there was little evidence of the public over-reacting, that people believed the threat of contracting swine flu was inevitable, and that they assessed their own self-efficacy for protecting against it to be low. Respondents assessed a greater risk to their health from the vaccine than from the disease. Such findings could have led to apathy about following the UK Governments recommended health protective behaviours, and a sub-optimal level of vaccine uptake. More generally, people were confused about the difference between seasonal influenza and swine flu and their vaccines. Conclusions: This research suggests a gap in public understandings which could hinder attempts to communicate about novel flu viruses in the future. There was general support for the government's handling of the pandemic, although its public awareness campaign was deemed ineffectual as few people changed their current hand hygiene practices. There was less support for the media who were deemed to have over-reported the swine flu pandemic.
Output: Public views of the uk media and government reaction to the 2009 swine flu pandemic
In this study, we aimed to detect viruses in hard ticks using the small RNA sequencing based method. 24 A 235-bp DNA segment was detected in Dermacentor nuttalli (hard ticks) and D. silvarum (hard ticks) from 25 sheep and bovine, respectively. The detected 235-bp segment had an identity of 99% to a 235-bp DNA 26 segment of African Swine Fever Virus (ASFV) and contained three single nucleotide mutations (C38T, 27 C76T and A108C). C38T, resulting in an single amino acid mutation G66D, suggests the existence of a new 28 ASFV strain, which is different from all reported ASFV strains in NCBI GenBank database. These results 29 also suggest that ASFV could have a wide range of hosts or vectors, beyond the well known Suidae family 30 and soft ticks. Our findings pave the way toward further studies of ASFV transmission and development of 31 prevention and control measures.
Output: DNA segment of African Swine Fever Virus 1 first detected in hard ticks from sheep and bovine
Collisson, E.W., Li, J., Sneed, L.W., Peters, M.L. and Wang, L., 1990. Detection of avian infectious bronchitis viral infection using in situ hybridization and recombinant DNA. Vet. Microbiol., 24: A recombinant DNA probe with specificity for the 3' end of genomic RNA from the Ark 99 strain of infectious bronchitis virus (IBV) was found to hybridize with extracted RNA of three strains with the Ark serotype, as well as the Mass41, Ho1152, Gray, JMK, Conn, Fla and SE 17 strains of IBV. Viral infection was detected in the cytoplasm of chicken embryo kidney cells inoculated with Mass41, Ark99, SE17 or two recent field isolates of IBV using in situ cytohybridization and a biotinylated probe. In vivo infections were detected in individual cells of tracheas and lungs 2,4, and 6 days after inoculation of chicks with Mass41 and Ark99. In situ hybridization of Ark99 infected tissue sections using 32p-dATP labelled probe indicated that more viral replication was present in the trachea on day 4 than either days 2 or 6; whereas more viral RNA was found in the lungs on day 6 than days 2 or 4 after inoculation.
Output: Detection of avian infectious bronchitis viral infection using in situ hybridization and recombinant DNA
In eukaryotes, the degradation of cellular mRNAs is accomplished by Xrn1p and 24 the cytoplasmic exosome. Because viral RNAs often lack canonical caps or poly-A tails, 25 they can also be vulnerable to degradation by these host exonucleases. Yeast lack 26 sophisticated mechanisms of innate and adaptive immunity, but do use RNA 27 degradation as an antiviral defense mechanism. One model is that the RNA of yeast 28 viruses is subject to degradation simply as a side effect of the intrinsic exonuclease 29 activity of proteins involved in RNA metabolism. Contrary to this model, we find a highly 30 refined, species-specific relationship between Xrn1p and the "L-A" totiviruses of different 31 Saccharomyces yeast species. We show that the gene XRN1 has evolved rapidly under 32 positive natural selection in Saccharomyces yeast, resulting in high levels of Xrn1p 33 protein sequence divergence from one yeast species to the next. We also show that 34 these sequence differences translate to differential interactions with the L-A virus, where 35 Xrn1p from S. cerevisiae is most efficient at controlling the L-A virus that chronically 36 infects S. cerevisiae, and Xrn1p from S. kudriavzevii is most efficient at controlling the L-37 A-like virus that we have discovered within S. kudriavzevii. All Xrn1p orthologs are 38 equivalent in their interaction with another virus-like parasite, the Ty1 retrotransposon.
Output: Restriction Factor in Yeasts 2 3
IFIT (interferon-induced with tetratricopeptide repeats) proteins are critical mediators of mammalian innate antiviral immunity. Mouse IFIT1 selectively inhibits viruses that lack 2'Omethylation of their mRNA 5' caps. Surprisingly, human IFIT1 does not share this antiviral specificity. Here, we resolve this discrepancy by demonstrating that human and mouse IFIT1 have evolved distinct functions using a combination of evolutionary, genetic and virological analyses. First, we show that human IFIT1 and mouse IFIT1 (renamed IFIT1B) are not orthologs, but are paralogs that diverged >100 mya. Second, using a yeast genetic assay, we show that IFIT1 and IFIT1B proteins differ in their ability to be suppressed by a cap 2'O-methyltransferase. Finally, we demonstrate that IFIT1 and IFIT1B have divergent antiviral specificities, including the discovery that only IFIT1 proteins inhibit a virus encoding a cap 2'O-methyltransferase. These functional data, combined with widespread turnover of mammalian IFIT genes, reveal dramatic species-specific differences in IFIT-mediated antiviral repertoires.
Output: Evolution-guided functional analyses reveal diverse antiviral specificities encoded by IFIT1 genes in mammals
Adenotonsillectomy (AT) is one of the most common surgical procedures performed in children and adults. We aim to assess the factors associated with changes in the incidence of and indications for AT using population-level data. This retrospective cohort study investigated patients who underwent AT between 1997 and 2010 by using data from the Taiwan National Health Insurance Research Database. We examined surgical rates and indications by the calendar year as well as age, sex, hospital level, and insured residence areas for the correlating factors. The average annual incidence rate of AT was 14.7 per 100,000 individuals during 1997-2010. Pediatric (<18 years) patients represented 48.2% of the total AT population. More than 99% of the patients underwent the AT procedures as an inpatient intervention. Longitudinal data demonstrated an increasing trend in the pediatric AT rates from 1997 (4.3/100,000) to 2010 (5.7/ 100,000) (p = 0.029). In the adult subgroup, a decreasing prevalence of infectious indications (p = 0.014) coincided with an increasing neoplastic indications (p = 0.001). In the pediatric subgroup, the prevalence of obstructive indications increased (p = 0.002). The logistic regression analyses indicated that the significant factors associated with the changing surgical indications for AT were the age in the adult subgroup and hospital level in the pediatric subgroup. This study revealed a low AT rate in Taiwan than that in other countries. Pediatric AT incidence increased during 1997-2010. Although a rising prevalence of obstructive and PLOS ONE | https://doi.
Output: Factors associated with changing indications for adenotonsillectomy: A population-based longitudinal study
θ-defensins constitute a family of macrocyclic peptides expressed exclusively in Old World monkeys. The peptides are pleiotropic effectors of innate immunity, possessing broad spectrum antimicrobial activities and immunoregulatory properties. Here we report that rhesus θdefensin 1 (RTD-1) is highly effective in arresting and reversing joint disease in a rodent model of rheumatoid arthritis (RA). Parenteral RTD-1 treatment of DA/OlaHsd rats with established pristane-induced arthritis (PIA) rapidly suppressed joint disease progression, restored limb mobility, and preserved normal joint architecture. RTD-1 significantly reduced joint IL-1β levels compared with controls. RTD-1 dose-dependently inhibited fibroblast-like synoviocyte (FLS) invasiveness and FLS IL-6 production. Consistent with the inhibition of FLS invasiveness, RTD-1 was a potent inhibitor of arthritogenic proteases including ADAMs 17 and 10 which activate TNFα, and inhibited matrix metalloproteases, and cathepsin K. RTD-1 was non-toxic, non-immunogenic, and effective when administered as infrequently as once every five days. Thus θ-defensins, which are absent in humans, have potential as retroevolutionary biologics for the treatment of RA.
Output: Suppression and resolution of autoimmune arthritis by rhesus θ-defensin-1, an immunomodulatory macrocyclic peptide
Human mobility is a key component of large-scale spatial-transmission models of infectious diseases. Correctly modeling and quantifying human mobility is critical for improving epidemic control, but may be hindered by data incompleteness or unavailability. Here we explore the opportunity of using proxies for individual mobility to describe commuting flows and predict the diffusion of an influenza-like-illness epidemic. We consider three European countries and the corresponding commuting networks at different resolution scales, obtained from (i) official census surveys, (ii) proxy mobility data extracted from mobile phone call records, and (iii) the radiation model calibrated with census data. Metapopulation models defined on these countries and integrating the different mobility layers are compared in terms of epidemic observables. We show that commuting networks from mobile phone data capture the empirical commuting patterns well, accounting for more than 87% of the total fluxes. The distributions of commuting fluxes per link from mobile phones and census sources are similar and highly correlated, however a systematic overestimation of commuting traffic in the mobile phone data is observed. This leads to epidemics that spread faster than on census commuting networks, once the mobile phone commuting network is considered in the epidemic model, however preserving to a high degree the order of infection of newly affected locations. Proxies' calibration affects the arrival times' agreement across different models, and the observed topological and traffic discrepancies among mobility sources alter the resulting epidemic invasion patterns. Results also suggest that proxies perform differently in approximating commuting patterns for disease spread at different resolution scales, with the radiation model showing higher accuracy than mobile phone data when the seed is central in the network, the opposite being observed for peripheral locations. Proxies should therefore be chosen in light of the desired accuracy for the epidemic situation under study.
Output: On the Use of Human Mobility Proxies for Modeling Epidemics
Influenza A viruses continue to emerge and re-emerge, causing outbreaks, epidemics and occasionally pandemics. While the influenza vaccines licensed for public use are generally effective against seasonal influenza, issues arise with production, immunogenicity, and efficacy in the case of vaccines against pandemic and emerging influenza viruses, and highly pathogenic avian influenza virus in particular. Thus, there is need of improved influenza vaccines and vaccination strategies. This review discusses advances in alternative influenza vaccines, touching briefly on licensed vaccines and vaccine antigens; then reviewing recombinant subunit vaccines, virus-like particle vaccines and DNA vaccines, with the main focus on virus-vectored vaccine approaches.
Output: Experimental vaccines against potentially pandemic and highly pathogenic avian influenza viruses
The two dimensional molecular tagging velocimetry (2D-MTV) has been used to measure velocity fields of the flow in a micro mixer. Instead of commonly used micro particles an optical tagging of the flow has been performed by using a caged dye. The pattern generation is done by imaging a mask for the first time. This allows to generate nearly any imaginable pattern. The flow induces a deformation of the optically written pattern that can be tracked by laser induced fluorescence. The series of raw images acquired in this way were analyzed quantitatively with a novel optical flow based technique. The reference measurements have been carried out allowing to draw conclusions about the accuracy of this procedure. A comparison to the standard technique of lPIV has also been conducted. Apart from measuring flow velocities in microfluidic mixing processes, the spatial distribution of concentration fields for different species has also been measured. To this end, a new technique has been developed that allows spatial measurements from Planar Spontaneous Raman Scattering (PSRS). The Raman stray light of the relevant species has been spectrally selected by a narrow bandpass filter and thus detected unaffectedly by the Raman stray light of other species. The successful operation of this measurement procedure in micro flows will be demonstrated exemplary for a mixing process of water and ethanol.
Output: Micro-flow analysis by molecular tagging velocimetry and planar Raman-scattering
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. The term 'emerging infectious diseases' (EIDs) is a broad one that covers newly recognized human diseases caused by pathogens that have recently jumped species, older pathogens that have emerged in new populations due to human behaviors or modifications to natural habitats, and older pathogens that are exhibiting resurgence in areas once brought under control, usually due to microbiological adaptation and change; this includes previously-identified microorganisms exhibiting new patterns of antimicrobial drug resistance and pathogenic properties. Emerging infectious diseases are those with increasing incidence at local, regional, or international scales, and are spreading from epicenters to new geographic areas. The surveillance, study and control of EIDs is a complex interdisciplinary effort, crossing international borders and involving the collaborative efforts of scientists, clinicians, and political leaders from many disciplines and backgrounds to protect human health. According to a comprehensive literature review performed by Taylor et al. (2001) at the Centre for Tropical Veterinary Medicine at the University of Edinburgh, 1415 species of infectious organisms known to be pathogenic to humans were identified. The human pathogens tabulated by this study included an assortment of 217 viruses and prions, 538 bacteria and rickettsia, 307 fungi, 66 protozoa and 287 helminths. The majority of these (61%) were zoonotic infections transmitted from animals to humans. Of the 175 pathogenic species associated with diseases considered to be 'emerging', 135 (75%) were zoonotic. The study found that protozoan and virus pathogens were particularly likely to emerge, and that the helminths were less likely to do so. Interestingly, no association was found between route of transmission and emergence in this study. An updated literature survey from the Centre for Infectious Diseases at the same institution (University of Edinburgh) was published in 2005 by Woolhouse and Gowtage-Sequeria. This study identified 1407 species of human pathogens, 58% of which were zoonotic. Of the total, 177 were regarded as 'emerging' or 're-emerging' pathogens. The emerging and re-emerging zoonotic pathogens were most likely to have the broadest host ranges. The authors noted that although zoonotic pathogens constitute a significant source for emerging and re-EIDs, only a small minority of them would prove capable of causing major epidemics in the human population -but the H5N1 influenza strain could prove to be an exception. Causal factors contributing to the emergence of new pathogens include human population growth resulting in human encroachment on wildlife habitats, increased human contact with domestic and wild animals, changes in agricultural practices CHAPTER 3 sECTion 1 ä PRE-TRAvEl AdviCE
Output: Emerging Diseases and the International Traveler
Previous studies have suggested that kennelled dogs are more likely to test positive for CECoV than household pets. Here we describe both cross sectional and longitudinal studies in two rescue kennels and two boarding kennels, together with molecular diagnostics, to provide a new insight into the epidemiology of CECoV. Prevalence of CECoV in the cross sectional studies tended to be higher in the rescue kennels (13.8% and 33.3%) than the boarding kennels (5.3% and 13.5%). In each kennel, type I CECoV was more prevalent than type 2 CECoV. The mean quantity of type I detected was equivalent to 6.3 Â 10 8 gc/gm (range = 5 Â 10 6 , 8.5 Â 10 11 ), compared to 1.3 Â 10 8 gc/gm (range = 3 Â 10 6 , 2.4 Â 10 10 ) for type II. In one rescue shelter where dogs were followed longitudinally, infection was significantly associated with accommodation block as well as the length of stay (increased risk of CECoV per week in residence of Â1.9). Of those animals sampled on two or more occasions, none tested positive on arrival, and 54.5% later shed CECoV, suggesting that infection may have been acquired within the kennel. Shedding patterns and sequence analysis suggested both types I and II CECoV were maintained in this population by a combination of introductions into the shelter and within-shelter transmission. The findings suggest that some kennel environments may be important in maintaining CECoV infection in the population. We also propose that the diversity of viruses like CECoV in these populations may provide a novel surrogate marker for the success of biosecurity.
Output: Cross sectional and longitudinal surveys of canine enteric coronavirus infection in kennelled dogs: A molecular marker for biosecurity
The number of patients presenting to the Emergency Department (ED) with meticillin-resistant Staphylococcus aureus (MRSA) is increasing, but few studies focus on patients with bacteraemia. From January 2001 to June 2006 the clinical characteristics and outcome of 177 consecutive patients with MRSA bacteraemia visiting an ED of a university hospital were studied. The average age of the patients was 65.8 years. Healthcareassociated MRSA bacteraemia comprised 76.3% of all cases. Catheter-related bacteraemia was the most common type of infection (22.6%), followed by soft tissue infection (20.9%) and primary bacteraemia (15.3%). Different types of infection were significantly related to different outcome. In-hospital mortality was 33.3%, but the mortality decreased to 17.7% when patients with rapidly fatal disease and mortality within 3 days were excluded. All isolates exhibited lower susceptibility to vancomycin (minimum inhibitory concentration (MIC) 1-2 g/mL). Factors associated with mortality included severity of underlying illness, severity of bacteraemia and persistent bacteraemia. A detrimental effect of elevated MIC could not be demonstrated despite applying several definitions of patient outcome. Patients admitted to the ED with MRSA bacteraemia carry high overall mortality; however, the severity of underlying illness, severity of bacteraemia and persistent bacteraemia are correlated with mortality, but not vancomycin MICs (2 g/mL) of MRSA isolates.
Output: Outcome of patients with meticillin-resistant Staphylococcus aureus bacteraemia at an emergency department of a medical centre in Taiwan
Background: Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CL pro ), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection. Methodology/Principal Findings: Here, we profiled the substrate specificities of 3CL pro from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS-CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 1968 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CL pro prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CL pro from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CL pro prefers P4-Pro and SARS-CoV 3CL pro prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences 'VARLQQSGF' that can be cleaved efficiently by all 3CL pro with relative activity of 1.7 to 3.2, and 'VPRLQQSGF' that can be cleaved specifically by IBV 3CL pro with relative activity of 4.3. Conclusions/Significance: The comprehensive substrate specificities of 3CL pro from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases.
Output: Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses
Background We investigated the temporal progression of the clinical, radiological, and virological changes in a community outbreak of severe acute respiratory syndrome (SARS). We followed up 75 patients for 3 weeks managed with a standard treatment protocol of ribavirin and corticosteroids, and assessed the pattern of clinical disease, viral load, risk factors for poor clinical outcome, and the usefulness of virological diagnostic methods. Findings Fever and pneumonia initially improved but 64 (85%) patients developed recurrent fever after a mean of 8·9 (SD 3·1) days, 55 (73%) had watery diarrhoea after 7·5 (2·3) days, 60 (80%) had radiological worsening after 7·4 (2·2) days, and respiratory symptoms worsened in 34 (45%) after 8·6 (3·0) days. In 34 (45%) patients, improvement of initial pulmonary lesions was associated with appearance of new radiological lesions at other sites. Nine (12%) patients developed spontaneous pneumomediastinum and 15 (20%) developed acute respiratory distress syndrome (ARDS) in week 3. Quantitative reverse-transcriptase (RT) PCR of nasopharyngeal aspirates in 14 patients (four with ARDS) showed peak viral load at day 10, and at day 15 a load lower than at admission. Age and chronic hepatitis B virus infection treated with lamivudine were independent significant risk factors for progression to ARDS (p=0·001). SARS-associated coronavirus in faeces was seen on RT-PCR in 65 (97%) of 67 patients at day 14. The mean time to seroconversion was 20 days. Interpretation The consistent clinical progression, shifting radiological infiltrates, and an inverted V viral-load profile suggest that worsening in week 2 is unrelated to uncontrolled viral replication but may be related to immunopathological damage.
Output: Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study
Autophagy, a vital catabolic process that degrades cytoplasmic components within the lysosome, serves as an essential cytoprotective response to pathologic stresses that occur during diseases such as cancer, ischemia, and infection. In addition to its role as a stress response pathway, autophagy plays an essential quality control function in the cell by promoting basal turnover of long-lived proteins and organelles as well as selectively degrading damaged cellular components. This homeostatic function protects against a wide variety of diseases including neurodegeneration, myopathy, liver disease, and diabetes. This review discusses our current understanding of these two principal functions for autophagy as a physiologic stress response and quality control mechanism within mammalian cells and details how alterations in autophagy promote human disease.
Output: Autophagy As A Stress Response And Quality Control Mechanism-Implications for Cell Injury and Human Disease
Herein we present the synthesis of a novel type of peptidomimetics composed of repeating diaminopropionic acid residues modified with structurally diverse heterobifunctional polyethylene glycol chains (abbreviated as DAPEG). Based on the developed compounds, a library of fluorogenic substrates was synthesized. Further library deconvolution towards human neutrophil serine protease 4 (NSP4) yielded highly sensitive and selective internally quenched peptidomimetic substrates. In silico analysis of the obtained peptidomimetics revealed the presence of an interaction network with distant subsites located on the enzyme surface.
Output: PEGylated substrates of NSP4 protease: A tool to study protease specificity OPEN