bluuebunny/crossref_metadata_2025_split huggingface dataset:
Repetitive but not single blast mild traumatic brain injury increases ethanol responsivity in mice and risky drinking behavior in combat Veterans
Authors: Schindler Abigail G. , Baskin Britahny , Juarez Barbara , Lee Suhjung Janet , Hendrickson Rebecca , Pagulayan Katherine , Zweifel Larry S. , Raskind Murray A. , Phillips Paul E.M. , Peskind Elaine R. , Cook David G. 
Published: November 2020

ABSTRACTMild traumatic brain injury (mTBI) is common in civilians and highly prevalent among military Servicemembers and in contact sports athletes. mTBI, especially within military populations, is often comorbid with posttraumatic stress disorder (PTSD), and can increase health-risk behaviors (e.g., sensation/novelty seeking, impulsivity, risk taking, irritability/aggression) and substance misuse/abuse, but underlying mechanisms remain poorly understood. Using an established mouse model of blast mTBI, here we examined the effects of single (1x) and repetitive (3x) blast exposure on ethanol responsivity using a battery of tests, each associated with distinct aspects of alcohol abuse vulnerability. While both single and repetitive blast exposure increased the sedative properties of high-dose ethanol (with no change in tolerance or metabolism), only repetitive blast exposure potentiated ethanol-induced locomotor stimulation and shifted ethanol intake patterns (i.e., increased consumption ‘front-loading’) during intermittent two bottle choice. To establish translational relevance, we next examined self-report responses to the Alcohol Use Disorders Identification Test-Consumption Questions (AUDIT-C) and used a novel unsupervised machine learning approach to investigate whether a history of blast with acute symptoms and mTBI affected drinking behaviors in Iraq and Afghanistan Veterans. AUDIT-C scores were increased in Veterans with a history of blast exposure and subsequent cluster analysis identified a three-cluster solution: ‘low’ (low intake and low frequency), ‘frequent’ (low intake but high frequency), and ‘risky’ (high intake and high frequency), where Veterans with a history of blast mTBI displayed a shift in cluster assignment from ‘frequent’ to ‘risky’, as compared to Veterans who were deployed to Iraq and/or Afghanistan who had no lifetime history of TBI. Together, these results offer new insight regarding how blast mTBI may give rise to increased substance use/misuse and highlight the increased potential for adverse health-risk behaviors following repetitive blast mTBI exposure.
Short-term forecasts to inform the response to the Covid-19 epidemic in the UK
Authors: Funk S , Abbott S , Atkins BD , Baguelin M , Baillie JK , Birrell P , Blake J , Bosse NI , Burton J , Carruthers J , Davies NG , De Angelis D , Dyson L , Edmunds WJ , Eggo RM , Ferguson NM , Gaythorpe K , Gorsich E , Guyver-Fletcher G , Hellewell J , Hill EM , Holmes A , House TA , Jewell C , Jit M , Jombart T , Joshi I , Keeling MJ , Kendall E , Knock ES , Kucharski AJ , Lythgoe KA , Meakin SR , Munday JD , Openshaw PJM , Overton CE , Pagani F , Pearson J , Perez-Guzman PN , Pellis L , Scarabel F , Semple MG , Sherratt K , Tang M , Tildesley MJ , Van Leeuwen E , Whittles LK ,   CMMID COVID-19 Working Group,   Imperial College COVID-19 Response Team,   ISARIC4C Investigators
Published: November 2020

AbstractBackgroundShort-term forecasts of infectious disease can aid situational awareness and planning for outbreak response. Here, we report on multi-model forecasts of Covid-19 in the UK that were generated at regular intervals starting at the end of March 2020, in order to monitor expected healthcare utilisation and population impacts in real time.MethodsWe evaluated the performance of individual model forecasts generated between 24 March and 14 July 2020, using a variety of metrics including the weighted interval score as well as metrics that assess the calibration, sharpness, bias and absolute error of forecasts separately. We further combined the predictions from individual models into ensemble forecasts using a simple mean as well as a quantile regression average that aimed to maximise performance. We compared model performance to a null model of no change.ResultsIn most cases, individual models performed better than the null model, and ensembles models were well calibrated and performed comparatively to the best individual models. The quantile regression average did not noticeably outperform the mean ensemble.ConclusionsEnsembles of multi-model forecasts can inform the policy response to the Covid-19 pandemic by assessing future resource needs and expected population impact of morbidity and mortality.
The Use of Saliva as a Diagnostic Specimen for SARS CoV-2 Molecular Diagnostic Testing for Pediatric Patients
Authors: Delaney Meghan , Simpson Joelle , Thomas Bobbe , Ralph Christal , Evangalista Michael , Moshgriz Mahdi , Granados Joyce , McGuire Mark , DeBiasi Roberta , Campos Joseph 
Published: November 2020

ABSTRACTBackgroundChildren are an important population to test for COVID-19 infection, particularly because they may shed the virus without displaying symptoms. Testing children for COVID-19 via sensitive molecular methods is important, although collecting nasopharyngeal (NP) specimens can be challenging. A less invasive mode of specimen collection that yields test results comparable to those from NP specimens would be beneficial to simplify sample collection.MethodsTo demonstrate that saliva is a suitable specimen for collection from children, the clinical usability/acceptability and the analytic performance of saliva were compared to NP specimens suspended in viral transport medium. Four different FDA EUA-approved real-time RT-PCR assays and one EUA approved saliva collection device were investigated.ResultsThe study population included 526 patients between the ages of 3 and 61 years, 461 (88%) were <18 years, 425 were asymptomatic (81.1%), 92 were symptomatic (17.6%). Saliva mixed with saliva stabilizing buffer was found to yield comparable sensitivity to NP specimens when tested on the AllPlex SARS-CoV-2 molecular test (Seegene Inc). The analytic sensitivity of the AllPlex assay during testing of spiked saliva mixed with SpectrumDNA saliva stabilizer was found to be 250 genomic copies/mL.ConclusionsOf the four FDA EUA-approved SARS-CoV-2 PCR assays studied, we found the AllPlex assay to be best suited for testing saliva specimens collected from children 5 years of age or older. The sensitivity of viral detection was equivalent to NP specimens when saliva specimens were mixed with the saliva stabilizer.
Longevity of seropositivity and neutralizing titers among SARS-CoV-2 infected individuals after 4 months from baseline: a population-based study in the province of Trento
Authors: Stefanelli Paola , Bella Antonino , Fedele Giorgio , Fiore Stefano , Pancheri Serena , Benedetti Eleonora , Fabiani Concetta , Leone Pasqualina , Vacca Paola , Schiavoni Ilaria , Neri Arianna , Carannante Anna , Simmaco Maurizio , Santino Iolanda , Zuccali Maria Grazia , Bizzarri Giancarlo , Magnoni Rosa , Benetollo Pier Paolo , Brusaferro Silvio , Rezza Giovanni , Ferro Antonio 
Published: November 2020

SummaryBackgroundThere are conflicting results about the duration of antibodies induced by SARS-CoV-2, but several studies show a rapid decay in a few months after infection. To evaluate antibody decline, we re-evaluated the presence of anti-SARS-CoV-2 antibodies among individuals found seropositive in a first population survey conducted 4 months before.MethodsAll individuals above ten years of age resident in 5 municipalities of the Autonomous Province of Trento, northern Italy, who resulted IgG positive for anti-SARS-CoV-2 nucleocapsid (NC) antibodies in a serosurvey conducted on May 2020 were retested after 4 months. Anti-SARS-CoV-2 antibodies were detected using the Abbott SARS-CoV-2 IgG assay (Abbott Diagnostics, USA) detecting anti-NC antibodies. Samples that gave a negative result were re-tested using the same test plus Liaison SARS-CoV-2 IgG assay (DiaSorin, Italy) to assess anti-spike (S) S1/S2 IgG antibodies. Seroprevalence was calculated as the proportion of positive people on the total number of tested. A neutralizing assay was performed on a subgroup of formerly positives sera using fifty-percent tissue culture infective dose (TCID50) as endpoint dilution to produce a cytopathic effect in 50% of inoculated Vero E6 cells culture. In all the analyses a p value < 0.05 were considered statistically significant. Statistical analysis was performed by STATA version 16.1 (STATA Corp., College Station, Texas, USA).FindingsOverall, 1159 out of 1402 initially anti-NC seropositive participants were enrolled in the study. Of them, 480 (41.1%) became seronegative for anti-NC IgG antibodies. When 479 negative sera were tested for anti-S IgG, 373 samples (77.9%) resulted positives. A functional neutralization assay was performed on 106 sera showing high concordance with anti-S antibodies positivity.InterpretationA decline of anti-NC IgG values was recorded 4 months after the first evaluation. Worth of note, a high proportion of anti-NC seronegative individuals were positive for anti-spike IgG antibodies, which appear to persist longer and to better correlate with neutralization activity.
School-based screening and treatment may reduce P. falciparum transmission
Authors: Cohee Lauren M. , Valim Clarissa , Coalson Jenna E. , Nyambalo Andrew , Chilombe Moses , Ngwira Andrew , Bauleni Andy , Seydel Karl B. , Wilson Mark L. , Taylor Terrie E. , Mathanga Don P. , Laufer Miriam K. 
Published: November 2020

AbstractIn areas where malaria remains entrenched, novel transmission-reducing interventions are essential for malaria elimination. We report the impact of screening-and-treatment of asymptomatic schoolchildren (N=705) on gametocyte - the parasite stage responsible for human-to-mosquito transmission - carriage and use concomitant household-based surveys to predict the potential reduction in transmission in the surrounding community. Among 179 students with gametocyte-containing infections, 84% had positive malaria rapid diagnostic tests. While gametocyte burden remained constant in untreated children, treatment with artemether-lumefantrine reduced the gametocyte prevalence (p<0.0001) from 51.8% to 9.7% and geometric mean gametocyte density (p=0.008) from 0.52 to 0.05 gametocytes/microliter. Based on these estimates, the gametocyte burden in the community could be reduced by 25-55% depending on the season and the measure used to characterize gametocyte carriage. Thus, school-based interventions to treat asymptomatic infections may be a high-yield approach to not only improve the health and education of schoolchildren, but also decrease malaria transmission.
A computational analysis on Covid-19 transmission raises imuuno-epidemiology concerns
Authors: Kyriakopoulos Anthony M. , Zhao Shi 
Published: November 2020

AbstractFor Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) the investigation of the heterogeneity of individual infectiousness becomes important due to the cross reactive immunity of general population. Using a sample of infected population with SARS-COV-2 in close geographical proximity to the initial Severe Advanced Respiratory Syndrome-1 (SARS-1) outbreak, we explored the association between infector’s age and dispersion (or heterogeneity) of individual infectiousness (k) in order to investigate the relatedness with the age of an individual’s capability to disperse SARS-COV-2. Interestingly, we find a negative association between k and increase of infector’s age. Significantly this becomes more evident for the age group of 20-60 years comparing with the infectors with younger age. This raises important immuno-epidemiology concerns for effectiveness of public health measures to contain the disease.One Sentence SummaryDispersion of Coronavirus Disease-19 in China differed with age.
Plant derived bioactive compounds as potential inhibitors of ZIKA virus: an in silico investigation
Authors: Ahmed Sheikh Rashel , Banik Anik , Anni Sadia Mahjabin , Chowdhury Mohammed Mehadi Hassan 
Published: November 2020

AbstractThe ZIKA virus has caused a heavy concern everywhere the globe because of its high infectivity and mortality rate. Still, there’s no specific drug or preventive medication to treat ZIKA infection despite comprehensive analysis by the researchers. This study was designed to demonstrate the efficacy of some plant derived bioactive compounds against ZIKV by using both structure and ligand based virtual screening methods. A number of 35 plant metabolites were screened against ZIKA NS2B-NS3 protease (5LC0), Envelop protein (5JHM), Capsid protein (5YGH) and NS5 RNA-dependent RNA polymerase protein (5U04) employing molecular docking approach. Results showed that there have been four metabolites, i.e. Chicoric acid, Luteone, Reserpine and Rosmarinic acid provide highest binding affinity to targeted ZIKV proteins. Crucial binding sites and drug surface hotspots are unraveled for every targeted viral protein. The ADME study showed that neither of the candidate compounds had side effects that would reduce their drug-like properties. As compared, the toxicity pattern analysis has unmasked the non-toxic essence of top drug candidates. The RMSD values of ligand-macromolecule complexes were 2 Å apart from Envelop protein- Chicoric Acid, although the RMSF values showed normal atomic fluctuations within the molecular dynamics analysis, with the exception of Envelop protein- Chicoric Acid. The expected majority of the target class the highest drug candidates is enzyme classes (e.g. protease, hydrolase, phosphatase). In addition, the drug similarity prediction revealed several structural analogs from drugbank such as Isoformononetin (DB04202), Deserpidine (DB01089) and Rescinnamine (DB01180) etc. and these analogs could even be an option for the treatment of ZIKV infections. The study can pave the way for the creation of effective ZIKV medications and preventive measures. We highly recommend further in vivo trials for the experimental validation of our findings.
Pangenome-based genome inference
Authors: Ebler Jana , Clarke Wayne E. , Rausch Tobias , Audano Peter A. , Houwaart Torsten , Korbel Jan , Eichler Evan E. , Zody Michael C. , Dilthey Alexander T. , Marschall Tobias 
Published: November 2020

AbstractTypical analysis workflows map reads to a reference genome in order to detect genetic variants. Generating such alignments introduces references biases, in particular against insertion alleles absent in the reference and comes with substantial computational burden. In contrast, recent k-mer-based genotyping methods are fast, but struggle in repetitive or duplicated regions of the genome. We propose a novel algorithm, called PanGenie, that leverages a pangenome reference built from haplotype-resolved genome assemblies in conjunction with k-mer count information from raw, short-read sequencing data to genotype a wide spectrum of genetic variation. The given haplotypes enable our method to take advantage of linkage information to aid genotyping in regions poorly covered by unique k-mers and provides access to regions otherwise inaccessible by short reads. Compared to classic mapping-based approaches, our approach is more than 4× faster at 30× coverage and at the same time, reached significantly better genotype concordances for almost all variant types and coverages tested. Improvements are especially pronounced for large insertions (> 50bp), where we are able to genotype > 99.9% of all tested variants with over 90% accuracy at 30× short-read coverage, where the best competing tools either typed less than 60% of variants or reached accuracies below 70%. PanGenie now enables the inclusion of this commonly neglected variant type in downstream analyses.
TIGA: Target illumination GWAS analytics
Authors: Yang Jeremy J , Grissa Dhouha , Lambert Christophe G , Bologa Cristian G , Mathias Stephen L , Waller Anna , Wild David J , Jensen Lars Juhl , Oprea Tudor I 
Published: November 2020

AbstractGenome wide association studies (GWAS) can reveal important genotype–phenotype associations, however, data quality and interpretability issues must be addressed. For drug discovery scientists seeking to prioritize targets based on the available evidence, these issues go beyond the single study. Here, we describe rational ranking, filtering and interpretation of inferred gene–trait associations and data aggregation across studies by leveraging existing curation and harmonization efforts. Each gene–trait association is evaluated for confidence, with scores derived solely from aggregated statistics, linking a protein-coding gene and phenotype. We propose a method for assessing confidence in gene–trait associations from evidence aggregated across studies, including a bibliometric assessment of scientific consensus based on the iCite Relative Citation Ratio, and meanRank scores, to aggregate multivariate evidence. This method, intended for drug target hypothesis generation, scoring and ranking, has been implemented as an analytical pipeline, available as open source, with public datasets of results, and a web application designed for usability by drug discovery scientists, athttps://unmtid-shinyapps.net/tiga/.
Detection and Purification of Lewy Pathology from Formalin Fixed Primary Human Tissue Using Biotinylation by Antigen Recognition
Authors: Killinger BA , Marshall L , Chatterjee D , Chu Y , Kordower JH 
Published: November 2020

AbstractThe intracellular misfolding and accumulation of alpha-synuclein into structures collectively called Lewy pathology is a central phenomenon for the pathogenesis of Parkinson’s disease (PD), Dementia with Lewy Bodies (DLB), and Multiple System Atrophy. Understanding the molecular architecture of Lewy pathology is crucial for understanding disease origins and progression. Here we developed a method to label, extract, and purify molecules from Lewy pathology of formalin fixed PD and DLB brain for blotting and mass spectrometry analysis. Using the biotinylation antibody recognition (BAR) technique, we labeled phosphoserine 129 alpha-synuclein positive pathology and associated molecules with biotin. Formalin crosslinks were then reversed, protein extracted, and pathology associated molecules isolated with streptavidin beads. Results showed superior immunohistochemical staining of Lewy pathology following the BAR protocol when compared to standard avidin biotin complex (ABC) based detection. The enhanced staining was particularly apparent for fibers of the medial forebrain bundle and punctate pathology within the striatum and cortex, which otherwise were weakly labeled or not detected. Subsequent immunoblotting BAR-labeled Lewy pathology extracts revealed the presence of high molecular weight alpha-synuclein, ubiquitin protein conjugates, and phosphoserine 129 alpha-synuclein. Mass spectrometry analysis of BAR-labeled Lewy pathology extracts from PD and DLB patients identified 815 proteins with significant enrichment for many pathways. Notably the most significant KEGG pathway was Parkinson’s disease (FDR = 2.48 × 10−26) and GO Cellular compartment was extracellular exosomes (GO Cellular Compartment; FDR = 2.66× 10−34). We used enrichment data to create a functional map of Lewy Pathology from primary disease tissues, which implicated Vesicle Trafficking as the primary disease associated pathway in DLB and PD. In summary, this protocol can be used to enrich for Lewy pathology from formalin fixed human primary tissues, which allows the determination of molecular signatures of Lewy pathology. This technique has broad potential to help understand the phenomenon of Lewy pathology in primary human tissue and animal models.
Molecular Mimicry Map (3M) of SARS-CoV-2: Prediction of potentially immunopathogenic SARS-CoV-2 epitopes via a novel immunoinformatic approach
Authors: An Hyunsu , Park Jihwan 
Published: November 2020

ABSTRACTCurrently, more than 33 million peoples have been infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and more than a million people died from coronavirus disease 2019 (COVID-19), a disease caused by the virus. There have been multiple reports of autoimmune and inflammatory diseases following SARS-CoV-2 infections. There are several suggested mechanisms involved in the development of autoimmune diseases, including cross-reactivity (molecular mimicry). A typical workflow for discovering cross-reactive epitopes (mimotopes) starts with a sequence similarity search between protein sequences of human and a pathogen. However, sequence similarity information alone is not enough to predict cross-reactivity between proteins since proteins can share highly similar conformational epitopes whose amino acid residues are situated far apart in the linear protein sequences. Therefore, we used a hidden Markov model-based tool to identify distant viral homologs of human proteins. Also, we utilized experimentally determined and modeled protein structures of SARS-CoV-2 and human proteins to find homologous protein structures between them. Next, we predicted binding affinity (IC50) of potentially cross-reactive T-cell epitopes to 34 MHC allelic variants that have been associated with autoimmune diseases using multiple prediction algorithms. Overall, from 8,138 SARS-CoV-2 genomes, we identified 3,238 potentially cross-reactive B-cell epitopes covering six human proteins and 1,224 potentially cross-reactive T-cell epitopes covering 285 human proteins. To visualize the predicted cross-reactive T-cell and B-cell epitopes, we developed a web-based application “Molecular Mimicry Map (3M) of SARS-CoV-2” (available athttps://ahs2202.github.io/3M/). The web application enables researchers to explore potential cross-reactive SARS-CoV-2 epitopes alongside custom peptide vaccines, allowing researchers to identify potentially suboptimal peptide vaccine candidates or less ideal part of a whole virus vaccine to design a safer vaccine for people with genetic and environmental predispositions to autoimmune diseases. Together, the computational resources and the interactive web application provide a foundation for the investigation of molecular mimicry in the pathogenesis of autoimmune disease following COVID-19.
Identification of a Putative Sensor Protein Involved in Regulation of Vesicle Production by a Hypervesiculating Bacterium,Shewanella vesiculosaHM13
Authors: Yokoyama Fumiaki , Imai Tomoya , Aoki Wataru , Ueda Mitsuyoshi , Kawamoto Jun , Kurihara Tatsuo 
Published: November 2020

AbstractBacteria secrete and utilize nanoparticles, called extracellular membrane vesicles (EMVs), for survival in their growing environments. Therefore, the amount and components of EMVs should be tuned in response to the environment. However, how bacteria regulate vesiculation in response to the extracellular environment remains largely unknown. In this study, we identified a putative sensor protein, HM1275, involved in the induction of vesicle production in a hypervesiculating Gram-negative bacterium,Shewanella vesiculosaHM13. This protein was predicted to possess typical sensing and signaling domains of sensor proteins, such as methyl-accepting chemotaxis proteins. Comparison of vesicle production between thehm1275-disrupted mutant and the parent strain revealed that HM1275 is involved in lysine-induced hypervesiculation. Moreover, HM1275 has sequence similarity to a biofilm dispersion protein, BdlA, ofPseudomonas aeruginosaPAO1, andhm1275disruption increased the amount of biofilm. Thus, this study showed that the induction of vesicle production and suppression of biofilm formation in response to lysine concentration are under the control of the same putative sensor protein.