bluuebunny/crossref_metadata_2025_split huggingface dataset:
An equivalence of prokaryotic pore forming proteins of Plasmodium triggers cellular dysfunction responsible for malaria pathogenesis
Authors: Shivappagowdar Abhishek , Garg Swati , Srivastava Akriti , Hada Rahul S. , Pati Soumya , Garg Lalit , Singh Shailja 
Published: August 2020

AbstractSevere malaria caused byPlasmodium falciparumposes a major global health problem with high morbidity and mortality. TheP. falciparumharbours a family of pore forming proteins (PFPs), known as perforin like proteins (PLPs), which are structurally equivalent to prokaryotic PFPs. These PLPs are secreted from the parasites and by interacting to host cells they contribute to disease pathogenesis. The severe malaria pathogenesis is associated with dysfunction of various barrier cells including endothelial cells. A number of factors, including PLPs, secreted by parasite contribute to the host cell dysfunction. Here in, we tested the hypothesis that the PLPs mediate dysfunction of barrier cells and might have a role in disease pathogenesis. We analysed various dysfunction in barrier cells following rPLP2 exposure and demonstrate that it causes an increase in intracellular Ca2+levels. Additionally, rPLP2 exposed barrier cells displayed features of cell death including Annexin/PI positivity, depolarized mitochondrial membrane potential and ROS generation. We further performed the time lapse video microscopy of barrier cells and found the treatment of rPLP2 triggers their membrane blebbing. The cytoplasmic localization of HMGB1, a marker of necrosis, further confirmed the necrotic type of cell death. This study highlights the role of parasite factor PLP in endothelial dysfunction and provides a rational for the design of adjunct therapies against severe malaria.
The mammalian CLU homologFMTcontrols development and behavior inArabidopsis
Authors: Ralevski Alexandra , Apelt Federico , Olas Justyna J. , Mueller-Roeber Bernd , Rugarli Elena I. , Kragler Friedrich , Horvath Tamas L. 
Published: August 2020

SUMMARYMitochondria in animals are associated with development, as well as physiological and pathological behaviors. Several conserved mitochondrial genes exist between plants and higher eukaryotes. Yet, comparative mitochondrial function among plant and animal species is poorly understood. Here, we show thatFMT(FRIENDLYMITOCHONDRIA) fromArabidopsis thaliana, a highly conserved homolog of the mammalianCLU(CLUSTERED MITOCHONDRIA)gene family encoding mitochondrial proteins associated with developmental alterations and adult physiological and pathological behaviors, affects whole plant morphology and development under salt stress and control conditions.FMTwas found to regulate mitochondrial morphology and dynamics as well as germination, root length, and flowering time. Here, we show that it also affects leaf expansion growth, salt stress-responses and hyponasty. Strikingly, FMT impacted the speed of hyponasty with corresponding change in speed of locomotion of CLU heterozygous knockout mice. These observations indicate that homologous genes affect homologous functions in plants and animals offering the possibility to develop plant models for the study of mammalian behaviors.
The ‘C3aR antagonist’ SB290157 is a partial C5aR2 agonist
Authors: Li Xaria X. , Kumar Vinod , Lee John D. , Woodruff Trent M. 
Published: August 2020

ABSTRACTInnate immune complement activation generates the C3 and C5 protein cleavage products C3a and C5a, defined classically as anaphylatoxins. C3a activates C3a receptors (C3aR), while C5a activates two receptors (C5aR1 and C5aR2) to exert their immunomodulatory activities. The non-peptide compound, SB290157, was originally reported in 2001 as the first C3aR antagonist. In 2005, the first report on non-selective nature of SB290157 was published, where the compound exerted clear agonistic, not antagonistic, activity in variety of cells. Other studies also documented non-selective activities of this drugin vivo. These findings severely hamper data interpretation regarding C3aR when using this compound. Unfortunately, given the dearth of C3aR inhibitors, SB290157 still remains widely used to explore C3aR biology (>70 publications to date). Given these issues, in the present study we aimed to further explore SB290157’s pharmacological selectivity by screening the drug against three human anaphylatoxin receptors, C3aR, C5aR1 and C5aR2, using transfected cells. We first confirmed that SB290157 acts as a potent agonist at human C3aR. We also identified that SB290157 exerts partial agonist activity at C5aR2 by mediating β-arrestin recruitment at higher compound doses. Notably, SB290157’s activity at C5aR2 was more potent and efficacious than the current ‘lead’ C5aR2 agonist P32. Notwithstanding this, SB290157 showed inhibitory effect on C3a-mediated signalling in primary human macrophages. Our results therefore provide even more caution against using SB290157 as a research tool to explore C3aR function. Given the reported immunomodulatory and anti-inflammatory activities of C3aR and C5aR2 agonism, any function observed with SB290157 could be due to these off target activities.
Chromosome painting in cultivated banana and their wild relatives (Musaspp.) reveals differences in chromosome structure
Authors: Šimoníková D , Němečková A , Čížková J , Brown A , Swennen R , Doležel J , Hřibová E 
Published: August 2020

AbstractEdible banana cultivars are diploid, triploid or tetraploid hybrids which originated by natural cross hybridization between subspecies of diploidMusa acuminata, or betweenM. acuminataand diploidM. balbisiana. Participation of two other wild diploid speciesM. schizocarpaandM. textiliswas also indicated by molecular studies. Fusion of gametes with structurally different chromosome sets may give rise to progenies with structural chromosome heterozygosity and reduced fertility due to aberrant chromosome pairing and unbalanced chromosome segregation. Only a few translocations have been classified on the genomic level so far and a comprehensive molecular cytogenetic characterization of cultivars and species of the familyMusaceaeis still lacking. FISH with chromosome-arm specific oligo painting probes was used for comparative karyotype analysis in a set of wildMusaspecies and edible banana clones. The results revealed large differences in chromosome structure discriminating individual accessions. These results permitted identification of putative progenitors of cultivated clones and clarified genomic constitution and evolution of aneuploid banana clones, which seem to be common among the polyploid banana accessions. New insights into the chromosome organization and structural chromosome changes will be a valuable asset in breeding programs, particularly in selection of appropriate parents for cross hybridization.HighlightOligo painting FISH revealed chromosomal translocations in subspecies ofMusa acuminata(A genome), their intra-specific hybrids as well as inM. balbisiana(B genome) and in interspecific hybrid clones originating from cross hybridization betweenM. acuminataandM. balbisiana
Integrated Bioinformatics Analysis Deciphering the microRNA Regulation in Protein-Protein Interaction Network in Lung Adenocarcinoma
Authors: Sengupta Pratyay , Saha Sayoni , Maji Moumita , Ghosh Monidipa 
Published: August 2020

AbstractBackgroundThe architecture of the protein-protein interaction (PPI) network in any organism relies on their gene expression signature. microRNAs (miRNAs) have recently emerged as major post transcriptional regulators that control PPI by targeting mainly untranslated regions of the gene encoding proteins. Here, we aimed to unveil the role of miRNAs in the PPI network for identifying potential molecular targets for lung adenocarcinoma (LUAD).Materials and methodsThe expression profiles of miRNAs and mRNAs were collected from the NCBI Gene Expression Omnibus (GEO) database (GSE74190 and GSE116959). Abnormally expressed mRNAs from the data were appointed to construct a PPI network and hence incorporated with the miRNA-mRNA regulatory network. The miRNAs and mRNAs in this network were subjected to functional enrichment. Through the network analysis, hubs were identified and their mutation rate and probability of cooccurrence were calculated.ResultsWe identified 17 miRNAs and 429 mRNAs signature for differentially altered transcriptome in LUAD. The combined miRNA–mRNA regulatory network exhibited scale-free characteristics. Network analysis showed 5 miRNA (including hsa-miR-486-5p, hsa-miR-200b-5p, and hsa-miR-130b-5p) and 10 mRNA (including ASPM, CCNB1, TTN, TPX2, and BIRC5) which expressively contribute in the LUAD. We further investigated the hub genes and noticed that ASPM and TTN had the maximum rate of mutation and possessed a high tendency of cooccurrence in LUAD.ConclusionThis study provides a unique network approach to the exploration of the underlying molecular mechanism in LUAD. Identified mRNAs and miRNAs may therefore, serve as significant prognostic predictors and therapeutic targets.
Association Between Birth Region and Time to Tuberculosis Diagnosis After US Entry Among Non–US-Born Persons
Authors: Talwar Amish , Li Rongxia , Langer Adam J. 
Published: August 2020

AbstractApproximately 90% of US tuberculosis (TB) cases among non–US-born persons are attributable to progression of latent TB infection to TB disease. Using survival analysis, we investigated if birthplace is associated with time of progression to TB disease among non–US-born persons. We derived a Cox regression model comparing differences in time to TB diagnosis after US entry among 19 global birth regions, adjusting for sex, birth year, and age at diagnosis. Compared with persons from Western Europe, the adjusted hazard rate of developing TB was significantly higher (p ≤0.05) for persons from all other regions, except North America and Northern Europe, and highest among persons from Middle Africa (adjusted hazard ratio = 7.0; 95% confidence interval: 6.5–7.4). Time to TB diagnosis among non–US-born persons therefore varied by birth region, which represents an important prognostic indicator for progression to TB disease.
Clinical characteristics and antibody response to SARS-CoV-2 spike 1 protein using the VITROS Anti-SARS-CoV-2 antibody tests in COVID-19 patients in Japan
Authors: Nagura-Ikeda Mayu , Imai Kazuo , Kubota Katsumi , Noguchi Sakiko , Kitagawa Yutaro , Matsuoka Masaru , Tabata Sakiko , Miyoshi Kazuyasu , Ito Toshimitsu , Tamura Kaku , Maeda Takuya 
Published: August 2020

AbstractBackgroundWe evaluated clinical characteristics and the clinical utility of VITROS SARS-CoV-2 antibody tests according to COVID-19 severity in patients in Japan.MethodsWe analyzed 255 serum specimens from 130 COVID-19 patients and examined clinical records and laboratory data. Presence of total (IgA, IgM, and IgG) and specific IgG antibody for the spike 1 antigen of SARS-CoV2 was determined using VITROS Anti-SARS-CoV-2 antibody tests.FindingsOverall, 98 (75.4%) and 32 (24.6%) patients had mild and severe COVID-19, respectively. On admission, 76 (58.5%) and 45 (34.6%) patients were positive for total and IgG antibody assays. Among 91 patients at discharge, 90 (98.9%) and 81 (89.0%) patients were positive for total and IgG antibody, respectively. Clinical background and laboratory findings on admission, but not the prevalence or concentration of total or IgG antibody, were associated with disease prognosis. Total and IgG antibody intensity were significantly higher in severe cases than in mild cases in serum collected after 11 days from onset, but not within 10 days.ConclusionVITROS Anti-SARS-CoV-2 Total and IgG assays will be useful as supporting diagnostic and surveillance tools and for evaluation of humoral immune response to COVID-19. Clinical background and laboratory findings are preferable predictors of disease prognosis.
Assessment of multiplex digital droplet RT-PCR as an accurate diagnosis tool for SARS-CoV-2 detection in nasopharyngeal swabs and saliva samples
Authors: Cassinari Kévin , Alessandri-Gradt Elodie , Chambon Pascal , Charbonnier Françoise , Gracias Ségolène , Beaussire Ludivine , Alexandre Kevin , Sarafan-Vasseur Nasrin , Houdayer Claude , Etienne Manuel , Caron François , Plantier Jean Christophe , Frebourg Thierry 
Published: August 2020

ABSTRACTRT-qPCR on nasopharyngeal swabs is currently the reference COVID-19 diagnosis method. We developed a multiplex RT-ddPCR assay, targeting six SARS-CoV-2 genomic regions, and evaluated it on nasopharyngeal swabs and saliva samples collected from 130 COVID-19 positive or negative ambulatory individuals, who presented symptoms suggestive of mild or moderate Sars-CoV2 infection. The 6-plex RT-ddPCR assay was shown to have 100% sensitivity on nasopharyngeal swabs and a higher sensibility than RT-qPCR on saliva (85% versus 62%). Saliva samples from 2 individuals with negative results on nasopharyngeal swabs were found to be positive. These results show that multiplex RT-ddPCR should represent an alternative and complementary tool for the diagnosis of COVID-19, in particular to control RT-qPCR ambiguous results, and its application to saliva an appropriate strategy for repetitive sampling and testing individuals for whom nasopharyngeal swabbing is not possible.
Effectiveness of Convalescent Plasma for Treatment of COVID-19 Patients
Authors: Chen Shanshan , Lu Chunya , Li Ping , Wang Lei , Wang Huaqi , Yang Qiankun , Chen Liyinghui , Li Jianbin , Ma Hongwei , Sang Qian , Li Jing , Xu Luyang , Song Xiangjin , Li Fangfang , Zhang Yi , Kang Yi , Xing Lihua , Zhang Guojun 
Published: August 2020

AbstractBackground and objectiveThe outbreak of COVID-19 has become a global health concern. In this study, we evaluate the effectiveness and safety of convalescent plasma therapy in patients with severe and critically ill COVID-19.MethodsSixteen COVID-19 patients received transfusion of anti-COVID-19 antibody-positive convalescent plasma. The main outcome was time for viral nucleic acid amplification (NAA) test turning negative. Clinical laboratory parameters were measured at the baseline (d0) before plasma transfusion, and day 1 (d1), day 3 (d3) after transfusion as well.ResultsAmong the 16 patients, 10 of them had a consistently positive result of viral NAA test before convalescent plasma transfusion. Eight patients (8/10) became negative from day 2 to day 8 after transfusion. Severe patients showed a shorter time for NAA test turning negative after transfusion (mean rank 2.17 vs 5·90, P = 0.036). Two critically ill patients transfused plasma with lower antibody level remained a positive result of NAA test. CRP level demonstrated a decline 1 day after convalescent plasma treatment, compared with the baseline (P = 0.017). No adverse events were observed during convalescent plasma transfusion.ConclusionsViral NAA test of most patients with COVID-19 who received convalescent plasma transfusion turned negative on the 2nd to 8th days after transfusion, and the negative time of severe patients was shorter than that of critically ill patients.Trial RegistrationChinese Clinical Trial Registry; No.: ChiCTR2000030627 URL:http://www.chictr.org
A multi-centre prospective study of COVID-19 transmission following outpatient Gastrointestinal Endoscopy in the United Kingdom
Authors: Hayee Bu’Hussain ,   The SCOTS project group, East James E. , Rees Colin , Penman Ian 
Published: August 2020

MessageThe COVID-19 pandemic has severely curtailed the practice of endoscopy (as an exemplar for outpatient diagnostic procedures) worldwide. Restart and recovery processes will be influenced by the need to protect patients and staff from disease transmission, but data on the risk of COVID-19 transmission after endoscopy are sparse. This is of particular importance in later pandemic phases when the risk of harm from delayed or missed significant diagnoses is likely to far outweigh the risk of infection. The British Society of Gastroenterology (BSG) guidance for restarting endoscopy included stratification of diagnostic procedures according to aerosol generation or assessment of infectious risk as well as pragmatic guidance on the use of personal protective equipment (PPE). We sought to document the risk of COVID-19 transmission after endoscopy in this “COVID-minimised” environment. Prospective data were collected from 18 UK centres for n=6208 procedures. Pre-endoscopy, 3/2611 (0.11% [95% CI: 0.00-0.33%]) asymptomatic patients tested positive for SARS-CoV-2 on nasopharyngeal swab. Based on follow-up telephone symptom screening of patients at 7 and 14 days, no cases of COVID-19 were detected by any centre after endoscopy in either patients or staff. While these data cannot determine the relative contribution of each component of a COVID-minimised pathway, they provide clear support for such an approach. The rational use of PPE and infection control policies should be continued and will aid planning for outpatient diagnostics in the COVID-19 recovery phase.
The Lebanese Cohort for COVID-19; A Challenge for the ABO Blood Group System
Authors: Khalil Athar , Feghali Rita , Hassoun Mahmoud 
Published: August 2020

AbstractA sudden outbreak of pneumonia caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has rapidly spread all over the world facilitating the declaration of the resultant disease as a pandemic in March,2020. In Lebanon, the fast action of announcing a state of emergency with strict measures was among the factors that helped in achieving a successful containment of the disease in the country. Predisposing factors for acquiring COVID-19 and for developing a severe form of this disease were postulated to be related to epidemiological and clinical characteristics as well as the genomics signature of a given population or its environment. Biological markers such as the ABO blood group system was amongst those factors that were proposed to be linked to the variability in the disease course and/or the prevalence of this infection among different groups. We therefore conducted the first retrospective case-control study in the Middle-East and North Africa that tackles the association between the blood group types and the susceptibility as well as the severity of SARS-CoV2 infection. Opposing to the current acknowledged hypothesis, our results have challenged the association significance of this system with COVID-19. Herein, we highlighted the importance of studying larger cohorts using more rigorous approaches to diminish the potential confounding effect of some underlying comorbidities and genetic variants that are known to be associated with the ABO blood group system.
A Voting Ensemble Approach for Hepatitis Disease Detection
Authors: Dutta Shawni , Bandyopadhyay Samir Kumar 
Published: August 2020

AbstractThe inflammation of the liver is termed as Hepatitis. Several different types of hepatitis are from A to G. For example, Hepatitis A is caused by the hepatitis A virus. Similarly, other type of Hepatitis virus is formed by the name, say Hepatitis G. Some types of virus will not create any serious problems. LongAlasting and cause scarring of the liver, loss of liver function and in some cases, liver cancer are also caused by this disease. Voting ensemble based approach is proposed in this paper as final phase classification that accepts top two classifier models obtained from first and second phase classification respectively. The reason of using the proposed classifier is to enhance the prediction performance so that patients with hepatitis disease are identified correctly.
Introducing causal inference to the medical curriculum using temporal logic to draw directed acyclic graphs
Authors: Ellison George T.H. 
Published: August 2020

AbstractDirected acyclic graphs (DAGs) might yet transform the statistical modelling of observational data for causal inference. This is because they offer a principled approach to analytical design that draws on existing contextual, empirical and theoretical knowledge, but ultimately relies on temporality alone to objectively specify probabilistic causal relationships amongst measured (and unmeasured) covariates, and the associated exposure and outcome variables. While a working knowledge of phenomenology, critical realism and epistemology seem likely to be useful for mastering the application of DAGs, drawing a DAG appears to require limited technical expertise and might therefore be accessible to even inexperienced and novice analysts. The present study evaluated the inclusion of a novel four-task directed learning exercise for medical undergraduates, which culminated in temporality-driven covariate classification, followed by DAG specification itself. The exercise achieved high levels of student engagement, although the proportion of students completing each of the exercise’s four key tasks declined from close to 100% in tasks 1 and 2 (exposure and outcome specification; and covariate selection) to 83.5% and 77.6% in the third and fourth tasks, respectively. Fewer than 15% of the students successfully classified all of their covariates (as confounders, mediators or competing exposures) using temporality-driven classification, but this improved to more than 35% following DAG specification – an unexpected result given that all of the DAGs displayed at least one substantive technical error. These findings suggest that drawing a DAG, in and of itself, increases the utility of temporality-driven covariate classification for causal inference analysis; although further research is required to better understand: why even poorly specified DAGs might reduce covariate misclassification; how ‘wrong but useful’ DAGs might be identified; and how these marginal benefits might be enhanced with or without improvements in DAG specification.
Optimal seasonal routines across animals and latitudes
Authors: Thygesen Uffe H. , Visser Andy W. , Heilmann Irene , Andersen Ken H. 
Published: August 2020

AbstractMost animals face seasonal fluctuations in food availability and need to develop an annual routine that maximizes their lifetime reproductive success. Two particularly common strategies are reducing energy expenditure and building storage to sustain the animal in meager periods (winters). Here, we pose a simple and generic model for an animal that can decide, at each time during the season, on its level of foraging effort and on building energy stores. Using dynamic optimization, we identify the optimal annual routines that maximize the trade-off between energy and mortality over a life-long horizon. We investigate how the optimal strategies depend on the body size and longevity of the animal, and upon the seasonal variability in the environment. We find that with large fluctuations, the optimal annual routine for small animals is to develop a surviving egg/spore stage rather than to attempt to survive the winter. Medium sized animals invest heavily in reserves to allow long hibernation, while larger animals only need smaller reserves and a shorter hibernation period. In environments with smaller fluctuations, organisms do not need energy stores or hibernation but reduce foraging activities during spring and summer where their fitness is highest. Our optimization model can be used as a null hypothesis to explain the annual routines of animals of all body sizes across the globe.