bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Onset of COVID-19 with Mobility-Augmented SEIR Model
Authors: Wu Neo , Ben Xue , Green Bradley , Rough Kathryn , Venkatramanan Srinivasan , Marathe Madhav , Eastham Paul , Sadilek Adam , O’Banion Shawn 
Published: July 2020

AbstractTimely interventions and early preparedness of healthcare resources are crucial measures to tackle the COVID-19 disease. To aid these efforts, we developed the Mobility-Augmented SEIR model (MA-SEIR) that leverages Google’s aggregate and anonymized mobility data to augment classic compartmental models. We show in a retrospective analysis how this method can be applied at an early stage in the COVID-19 epidemic to forecast its subsequent spread and onset in different geographic regions, with minimal parameterization of the model. This provides insight into the role of near real-time aggregate mobility data in disease spread modeling by quantifying substantial changes in how populations move both locally and globally. These changes would be otherwise very hard to capture using less timely data.
Transport effect of COVID-19 pandemic in France
Authors: Guan Lina , Prieur Christophe , Zhang Liguo , Prieur Clémentine , Georges Didier , Bellemain Pascal 
Published: July 2020

AbstractAn extension of the classical pandemic SIRD model is considered for the regional spread of COVID-19 in France under lockdown strategies. This compartment model divides the infected and the recovered individuals into undetected and detected compartments respectively. By fitting the extended model to the real detected data during the lockdown, an optimization algorithm is used to derive the optimal parameters, the initial condition and the epidemics start date of regions in France. Considering all the age classes together, a network model of the pandemic transport between regions in France is presented on the basis of the regional extended model and is simulated to reveal the transport effect of COVID-19 pandemic after lockdown. Using the the measured values of displacement of people mobilizing between each city, the pandemic network of all cities in France is simulated by using the same model and method as the pandemic network of regions. Finally, a discussion on an integro-differential equation is given and a new model for the network pandemic model of each age class is provided.
Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Kenyan blood donors
Authors: Uyoga Sophie , M.O. Adetifa Ifedayo , Karanja Henry K. , Nyagwange James , Tuju James , Wanjiku Perpetual , Aman Rashid , Mwangangi Mercy , Amoth Patrick , Kasera Kadondi , Ng’ang’a Wangari , Rombo Charles , Yegon Christine , Kithi Khamisi , Odhiambo Elizabeth , Rotich Thomas , Orgut Irene , Kihara Sammy , Otiende Mark , Bottomley Christian , N. Mupe Zonia , W. Kagucia Eunice , E Gallagher Katherine , Etyang Anthony , Voller Shirine , N. Gitonga John , Mugo Daisy , N. Agoti Charles , Otieno Edward , Ndwiga Leonard , Lambe Teresa , Wright Daniel , Barasa Edwine , Tsofa Benjamin , Bejon Philip , I. Ochola-Oyier Lynette , Agweyu Ambrose , Scott J. Anthony G. , Warimwe George M. 
Published: July 2020

AbstractBackgroundThere are no data on SARS-CoV-2 seroprevalence in Africa though the COVID-19 epidemic curve and reported mortality differ from patterns seen elsewhere. We estimated the anti-SARS-CoV-2 antibody prevalence among blood donors in Kenya.MethodsWe measured anti-SARS-CoV-2 spike IgG prevalence by ELISA on residual blood donor samples obtained between April 30 and June 16, 2020. Assay sensitivity and specificity were 83% (95% CI 59-96%) and 99.0% (95% CI 98.1-99.5%), respectively. National seroprevalence was estimated using Bayesian multilevel regression and post-stratification to account for non-random sampling with respect to age, sex and region, adjusted for assay performance.ResultsComplete data were available for 3098 of 3174 donors, aged 15-64 years. By comparison with the Kenyan population, the sample over- represented males (82% versus 49%), adults aged 25-34 years (40% versus 27%) and residents of coastal Counties (49% versus 9%). Crude overall seroprevalence was 5.6% (174/3098). Population-weighted, test- adjusted national seroprevalence was 5.2% (95% CI 3.7– 7.1%). Seroprevalence was highest in the 3 largest urban Counties - Mombasa (9.3% [95% CI 6.4-13.2%)], Nairobi (8.5% [95% CI 4.9-13.5%]) and Kisumu (6.5% [95% CI 3.3-11.2%]).ConclusionsWe estimate that 1 in 20 adults in Kenya had SARS-CoV-2 antibodies during the study period. By the median date of our survey, only 2093 COVID-19 cases and 71 deaths had been reported through the national screening system. This contrasts, by several orders of magnitude, with the numbers of cases and deaths reported in parts of Europe and America when seroprevalence was similar.
Cell-Free DNA in Blood Reveals Significant Cell, Tissue and Organ Specific injury and Predicts COVID-19 Severity
Authors: Cheng Alexandre Pellan , Cheng Matthew Pellan , Gu Wei , Lenz Joan Sesing , Hsu Elaine , Schurr Erwin , Bourque Guillaume , Bourgey Mathieu , Ritz Jerome , Marty Francisco , Chiu Charles Y. , Vinh Donald Cuong , De Vlaminck Iwijn 
Published: July 2020

ABSTRACTCOVID-19 primarily affects the lungs, but evidence of systemic disease with multi-organ involvement is emerging. Here, we developed a blood test to broadly quantify cell, tissue, and organ specific injury due to COVID-19, using genome-wide methylation profiling of circulating cell-free DNA in plasma. We assessed the utility of this test to identify subjects with severe disease in two independent, longitudinal cohorts of hospitalized patients. Cell-free DNA profiling was performed on 104 plasma samples from 33 COVID-19 patients and compared to samples from patients with other viral infections and healthy controls. We found evidence of injury to the lung and liver and involvement of red blood cell progenitors associated with severe COVID-19. The concentration of cfDNA correlated with the WHO ordinal scale for disease progression and was significantly increased in patients requiring intubation. This study points to the utility of cell-free DNA as an analyte to monitor and study COVID-19.
RSGSA: a Robust and Stable Gene Selection Algorithm
Authors: Saha Subrata , Soliman Ahmed , Rajasekaran Sanguthevar 
Published: July 2020

AbstractNowadays we are observing an explosion of gene expression data with phenotypes. It enables researchers to efficiently identify genes responsible for certain medical condition as well as classify them for drug target. Like any other phenotype data in medical domain, gene expression data with phenotypes also suffers from being very underdetermined system. In a very large set of features but a very small sample size domains (e.g., DNA microarray, RNA-seq data, GWAS data, etc.), it is often reported that several different spurious feature subsets may yield equally optimal results. This phenomenon is known asinstability. Considering these facts, we have developed a very robust and stable supervised gene selection algorithm to select the most discriminating non-spurious set of genes from the gene expression datasets with phenotypes.Stabilityandrobustnessis ensured by class and instance levels perturbations, respectively.We have performed rigorous experimental evaluations using 10 real gene expression microarray datasets with phenotypes. It revealed that our algorithm outperforms the state-of-the-art algorithms with respect to stability and classification accuracy. We have also done biological enrichment analysis based on gene ontology-biological processes (GO-BP) terms, disease ontology (DO) terms, and biological pathways.
Intersection of structural and functional connectivity of the nucleus basalis of Meynert in Parkinson’s disease dementia and Lewy body dementia
Authors: Oswal Ashwini , Gratwicke James , Akram Harith , Jahanshahi Marjan , Zaborszky Laszlo , Brown Peter , Hariz Marwan , Zrinzo Ludvic , Foltynie Tom , Litvak Vladimir 
Published: July 2020

AbstractParkinson’s disease dementia (PDD) and dementia with Lewy bodies (DLB) are related conditions that are associated with cholinergic system dysfunction. Dysfunction of the nucleus basalis of Meynert (NBM), a basal forebrain structure that provides the dominant source of cortical cholinergic innervation, has been implicated in the pathogenesis of both PDD and DLB. Here we leverage the temporal resolution of magnetoencephalography (MEG) with the spatial resolution of MRI tractography in order to explore the intersection offunctionalandstructuralconnectivity of the NBM in a unique cohort of PDD and DLB patients undergoing Deep Brain Stimulation (DBS) of this structure. We observe that NBM-corticalstructuralandfunctionalconnectivity correlate within spatially and spectrally segregated networks including: 1) a beta band network to supplementary motor area (SMA), where activity in the SMA was found to drive activity in the NBM, 2) a delta/theta band network to medial temporal lobe structures encompassing the parahippocampal gyrus and 3) a delta/theta band network to visual areas including lingual gyrus. These findings reveal functional networks of the NBM that are likely to subserve important roles in motor control, memory and visual function respectively. Furthermore, they motivate future studies aimed at disentangling network contribution to disease phenotype.
HIT-scISOseq: High-throughput and High-accuracy Single-cell Full-length Isoform Sequencing for Corneal Epithelium
Authors: Zheng Ying-Feng , Chen Zhi-Chao , Shi Zhuo-Xing , Hu Kun-Hua , Zhong Jia-Yong , Wang Chun-Xiao , Shi Wen , Chen Ying , Xie Shang-Qian , Luo Feng , Bo Xiao-Chen , Tang Chong , Liu Yi-Zhi , Xiao Chuan-Le 
Published: July 2020

AbstractSingle-cell isoform sequencing can reveal transcriptomic dynamics in individual cells invisible to bulk- and single-cell RNA analysis based on short-read sequencing. However, current long-read single-cell sequencing technologies have been limited by low throughput and high error rate. Here we introduce HIT-scISOseq for high-throughput single-cell isoform sequencing. This method was made possible by full-length cDNA capture using biotinylated PCR primers, and by our novel library preparation procedure that combines head-to-tail concatemeric full-length cDNAs into a long SMRTbell insert for high-accuracy PacBio sequencing. HIT-scISOseq yields > 10 million high-accuracy full-length isoforms in a single PacBio Sequel II 8M SMRT Cell, providing > 8 times more data output than the standard single-cell isoform PacBio sequencing protocol. We exemplified HIT-scISOseq by first studying transcriptome profiles of 4,000 normal and 8,000 injured corneal epitheliums from cynomolgus monkeys. We constructed dynamic transcriptome landscapes of known and rare cell types, revealed novel isoforms, and identified injury-related splicing and switching events that are previously not accessible with low throughput isoform sequencing. HIT-scISOseq represents a high-throughput, cost-effective, and technically simple method to accelerate the burgeoning field of long-read single-cell transcriptomics.
Natural Antisense Transcript ofPeriod2, Per2AS, regulates the amplitude of the mouse circadian clock
Authors: Mosig Rebecca A. , Castaneda Allison N. , Deslauriers Jacob C. , Frazier Landon P. , He Kevin L. , Maghzian Naseem , Pokharel Aarati , Schrier Camille T. , Zhu Lily , Koike Nobuya , Tyson John J. , Green Carla B. , Takahashi Joseph S. , Kojima Shihoko 
Published: July 2020

AbstractCircadian transcriptome studies identified a novel transcript at thePeriod2 (Per2)locus, which we namedPer2AS. Per2ASis a long non-coding RNA transcribed from the antisense strand ofPer2, and is expressed rhythmically and anti-phasic toPer2mRNA. Previously, we mathematically tested the hypothesis thatPer2ASandPer2mutually inhibit each other’s expression by forming a double negative feedback loop, and found thatPer2ASexpands the oscillatory domain. In this study, we have experimentally tested this prediction by perturbing the expression ofPer2ASin mouse fibroblasts. We found thatPer2ASrepressesPer2pre-transcriptionallyin cisand regulates the amplitude of the circadian clock, but not period or phase. Unexpectedly, we also found thatPer2positively regulatesPer2ASpost-transcriptionally, indicating thatPer2ASandPer2form a single negative feedback loop. Because knock-down ofPer2does not recapitulate the phenotypes ofPer2ASperturbation andPer2ASalso activatesBmal1 in trans, we propose thatPer2ASregulates the amplitude of the circadian clock without producing a protein by rewiring the molecular clock circuit.
Human thymopoiesis produces polyspecific CD8+α/β T cells responding to multiple viral antigens
Authors: Quiniou Valentin , Barennes Pierre , Mhanna Vanessa , Stys Paul , Vantomme Hélène , Zhou Zhicheng , Martina Federica , Coatnoan Nicolas , Barbié-Sastre Michèle , Pham Hang-Phuong , Clemenceau Béatrice , Vié Henri , Shugay Mikhail , Six Adrien , Brandao Barbara , Mallone Roberto , Mariotti-Ferrandiz Encarnita , Klatzmann David 
Published: July 2020

AbstractT cell receptors (TCRs) are formed by stochastic gene rearrangements, theoretically generating >1019sequences. They are selected during thymopoiesis, which releases a repertoire of about 108unique TCRs per individual. How evolution shaped a process that produces TCRs that can effectively handle a countless and evolving set of infectious agents is a central question of immunology. The paradigm is that a diverse enough repertoire of TCRs should always provide a proper, though rare, specificity for any given need. Expansion of such rare T cells would provide enough fighters for an effective immune response and enough antigen-experienced cells for memory. We show here that human thymopoiesis releases a large population of CD8+T cells harboring α/β paired TCRs that (i) have high generation probabilities and (ii) a preferential usage of some V and J genes, (iii) are shared between individuals and (iv) can each recognize and be activated by multiple unrelated viral peptides, notably from EBV, CMV and influenza. These polyspecific T cells may represent a first line of defense that is mobilized in response to infections before a more specific response subsequently ensures viral elimination. Our results support an evolutionary selection of polyspecific α/β TCRs for broad antiviral responses and heterologous immunity.
Pulmonary function and risk of Alzheimer dementia: two-sample Mendelian randomization study
Authors: Russ Tom C. , Harris Sarah E. , Batty G. David 
Published: July 2020

ABSTRACTDementia is a major global public health concern and in addition to recognised risk factors there is emerging evidence that poorer pulmonary function is linked with subsequent dementia risk. However, it is unclear if this observed association is causal or whether it might result from confounding. Therefore, we present the first two-sample Mendelian randomisation study of the association between pulmonary function and Alzheimer dementia using the most recent genome-wide association studies to produce instrumental variables for both. We found no evidence of a causal effect of reduced Forced Expiratory Volume in 1 second (FEV1) or Forced Vital Capacity (FVC) on Alzheimer dementia risk (both P>0.35). However, the FEV1/FVC ratio was associated with Alzheimer dementia risk with, in fact, superior function predicting an increased dementia risk (OR 1.12, 95%CI 1.02-1.23; P=0.016) which may result from survivor bias. While we can conclude that there is no causal link between impaired pulmonary function and Alzheimer dementia, our study sheds less light on potential links with other types of dementia.
Increasing power in the analysis of responder endpoints in rheumatology: a software tutorial
Authors: McMenamin Martina , Grayling Michael J , Berglind Anna , Wason James MS 
Published: July 2020

AbstractBackgroundComposite responder endpoints feature frequently in rheumatology due to the multifaceted nature of many of these conditions. Current analysis methods used to analyse these endpoints discard much of the data used to classify patients as responders; they are therefore highly inefficient and result in low power.MethodsWe highlight a novel augmented methodology that uses more of the information available to improve the precision of reported treatment effects. Since these methods are more challenging to implement, we have developed free, user friendly software available in a web-based interface. The software consists of two programs: one that supports the analysis of responder endpoints; the second is used for sample size estimation. We demonstrate the augmented analysis method and its software using the MUSE study, a phase IIb trial in patients with systemic lupus erythematosus.ResultsWe show the software can be used to analyse the trial with efficiency gains translating to a reduction in required sample size of 63%. Furthermore, we illustrate how the software can be used to choose the sample size needed in a future trial that will use the novel approach as the primary analysis method.ConclusionWe encourage trialists to utilise the software we have developed to implement augmented methodology in future studies to improve efficiency.
Prevalence of amyloid blood clots in COVID-19 plasma
Authors: Pretorius Etheresia , Venter Chantelle , Laubscher Gert Jacobus , Lourens Petrus Johannes , Steenkamp Janami , Kell Douglas B 
Published: July 2020

AbstractThe rapid detection of COVID-19 uses genotypic testing for the presence of SARS-Cov-2 virus in nasopharyngeal swabs, but it can have a poor sensitivity. A rapid, host-based physiological test that indicated whether the individual was infected or not would be highly desirable. Coagulaopathies are a common accompaniment to COVID-19, especially micro-clots within the lungs. We show here that microclots can be detected in the native plasma of COVID-19 patient, and in particular that such clots are amyloid in nature as judged by a standard fluorogenic stain. This provides a rapid and convenient test (P<0.0001), and suggests that the early detection and prevention of such clotting could have an important role in therapy.
MAPS integrates overlooked regulation of actin-targeting effector SteC into the virulence control network ofSalmonellasmall RNA PinT
Authors: Santos Sara Correia , Bischler Thorsten , Westermann Alexander J. , Vogel Jörg 
Published: July 2020

ABSTRACTA full understanding of the contribution of small RNAs (sRNAs) to bacterial virulence demands knowledge of their target suites under infection-relevant conditions. Here, we take an integrative approach to capturing targets of the Hfq-associated sRNA PinT, a known post-transcriptional timer of the two major virulence programs ofSalmonella enterica. Using MS2 affinity purification and RNA-sequencing (MAPS), we identify PinT ligands in bacteria underin-vitroconditions mimicking specific stages of the infection cycle, and in bacteria growing inside macrophages. This reveals PinT-mediated translational inhibition of the secreted effector kinase SteC, which had gone unnoticed in previous target searches. Using genetic, biochemical, and microscopic assays, we provide evidence for PinT-mediated repression ofsteCmRNA, eventually preventing actin rearrangements in infected host cells. Our findings support the role of PinT as a central post-transcriptional regulator inSalmonellavirulence and illustrate the need for complementary methods to reveal the full target suites of sRNAs.
SARS-CoV-2 in-vitro neutralization assay reveals inhibition of virus entry by iota-carrageenan
Authors: Morokutti-Kurz Martina , Graf Philipp , Grassauer Andreas , Prieschl-Grassauer Eva 
Published: July 2020

AbstractIn the absence of a vaccine and other effective prophylactic or therapeutic countermeasures the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) remains a significant public health threat. Attachment and entry of coronaviruses including SARS-CoV-2 is mediated by the spike glycoprotein (SGP). Recently, a SARS-CoV-2 Spike Pseudotyped Lentivirus (SSPL) was developed that allows studying spike-mediated cell entry via luciferase reporter activity in a BSL2 environment. Here, we show that iota-carrageenan can inhibit the cell entry of SSPL in a dose dependent manner. SSPL particles were efficiently neutralized with an IC50value of 2.6 µg/ml iota-carrageenan. In vitro data on iota-carrageenan against various Rhino- and Coronaviruses showed similar IC50values and translated readily into clinical effectiveness when a nasal spray containing iota-carrageenan demonstrated a reduction in severity and duration of symptoms of common cold caused by various respiratory viruses. Accordingly, our in vitro data on SSPL suggest that administration of iota-carrageenan may be an effective and safe prophylaxis or treatment for SARS-CoV-2 infections.
Concerted but segregated actions of oxytocin and vasopressin within the ventral and dorsal lateral septum determine female aggression
Authors: de Moura Oliveira Vinícius Elias , Lukas Michael , Wolf Hannah Nora , Durante Elisa , Lorenz Alexandra , Mayer Anna-Lena , Bludau Anna , Bosch Oliver J. , Grinevich Valery , Egger Veronica , de Jong Trynke R. , Neumann Inga D. 
Published: July 2020

ABSTRACTIn contrast to males, aggression in females has been rarely studied. Here, we established a rat model of enhanced female aggression using a combination of social isolation and aggression-training to specifically investigate the involvement of the oxytocin (OXT) and vasopressin (AVP) systems within the lateral septum (LS). Using neuropharmacological, optogenetic, chemogenetic as well as microdialyses approaches, we revealed that enhanced OXT release within the ventral LS (vLS), combined with reduced AVP release within the dorsal LS (dLS), are required for female aggression. Accordingly, increased excitability of OXT-responsive neurons in the vLS and decreased excitability of AVP-responsive neurons in the dLS were essential to evoke female aggression. Finally,in vitroactivation of OXT receptors in the vLS increased tonic GABAergic inhibition of dLS neurons. Overall, our data demonstrate that septal release of OXT and AVP affects female aggression by differential regulation of the excitatory-inhibitory balance within subnetworks of the LS.