bluuebunny/crossref_metadata_2025_split huggingface dataset:
scReQTL: an approach to correlate SNVs to gene expression from individual scRNA-seq datasets
Authors: Liu Hongyu , Prashant N M , Spurr Liam F. , Bousounis Pavlos , Alomran Nawaf , Ibeawuchi Helen , Sein Justin , Słowiński Piotr , Tsaneva-Atanasova Krasimira , Horvath Anelia 
Published: July 2020

AbstractRecently, pioneering eQTLs studies on single cell RNA-seq (scRNA-seq) data have revealed new and cell-specific regulatory SNVs. Because eQTLs correlate genotypes and gene expression across multiple individuals, they are confined to SNVs with sufficient population frequency. Here, we present an alternative sc-eQTL approach – scReQTL - wherein we substitute the genotypes with expressed Variant Allele Fraction (VAFRNA) at heterozygous SNV sites. Our approach employs the advantage that, when estimated from multiple cells, VAFRNAcan be used to assess effects of rare SNVs in a single individual. ScReQTLs are enriched in known genetic interactions, therefore can be used to identify novel regulatory SNVs.
Linear vector models of time perception account for saccade and stimulus novelty interactions
Authors: Ghaderi Amirhossein , Niemeier Matthias , Crawford John Douglas 
Published: July 2020

AbstractVarious models (e.g., scalar, state-dependent network, and vector models) have been proposed to explain the global aspects of time perception, but they have not been tested against specific visual phenomena like perisaccadic time compression and novel stimulus time dilation. Here, in two separate experiments (N=31), we tested how the perceived duration of a novel stimulus is influenced by 1) a simultaneous saccade, in combination with 2) a prior series of repeated stimuli in human participants. This yielded a novel behavioral interaction: pre-saccadic stimulus repetition neutralizes perisaccadic time compression. We then tested these results against simulations of the above models. Our data yielded low correlations against scalar model simulations, high but non-specific correlations for our feedforward neural network, and correlations that were both high and specific for a vector model based on identity of objective and subjective time. These results demonstrate the power of global time perception models in explaining disparate empirical phenomena and suggest that subjective time has a similar essence to time’s physical vector.
Cell-wall-deficient Bacteria in Oral Biofilm: Association with Periodontitis
Authors: Germano Francesco , Testi Davide , Campagnolo Luisa , Scimeca Manuel , Arcuri Claudio 
Published: July 2020

AbstractCell-wall-deficient bacteria are those that lack cell walls and live in a pleomorphic state. The genus Mycoplasma and L-form bacteria are both members of this group. The aim of this study was to search cell-wall-deficient bacteria in periodontal biofilm and link their presence to periodontal disease. Eighty-nine individuals were recruited and divided into three groups: periodontally healthy individuals, individuals with chronic periodontitis, and those with aggressive periodontitis. The presence of cell-wall-deficient bacteria was detected in freshly collected biofilm by light microscopy, transmission electron microscopy (TEM) with and without electron microscopy in situ hybridization, atomic force microscopy and DNA stain (Hoechst). A new dichotomic index of classification for prevalence and morphologic variants was developed to classify cell-wall-deficient bacteria in periodontal biofilm. Cell-wall-deficient bacteria were found in periodontal biofilm and classified into Protoplastic, Everted, Filament and Intracellular forms, the last one mainly associated with aggressive periodontitis. We also assessed the prevalence of periodontopathic bacteria by means of polymerase chain-reaction (PCR) and found no clear, statistically significant, correlation among periodontal pathogens tested (except T. denticola) that allowed individuals with chronic periodontitis to be distinguished from those with aggressive periodontitis. Association between cell-wall-deficient bacteria and periodontal condition was: periodontally healthy, 3.3% (1/30); individuals with chronic periodontitis, 30.6% (11/36); and those with aggressive periodontitis, 100% (23/23). Cell-wall-deficient bacteria were detected in periodontal biofilm and linked to aggressive periodontitis.
Regional Differences in the Ghrelin-Growth Hormone Secretagogue Receptor Signalling System in Human Heart Disease
Authors: Sullivan Rebecca , Randhawa Varinder K , Lalonde Tyler , Yu Tina , Kiaii Bob , Luyt Leonard , Wisenberg Gerald , Dhanvantari Savita 
Published: July 2020

AbstractThe hormone ghrelin and its receptor, the growth hormone secretagogue receptor (GHSR) are expressed in myocardium. GHSR binding activates signalling pathways coupled to cardiomyocyte survival and contractility. These properties have made the ghrelin-GHSR axis a candidate for a biomarker of cardiac function. The dynamics of ghrelin-GHSR are altered significantly in late stages of heart failure and cardiomyopathy, when left ventricular (LV) function is failing. We examined the relationship of GHSR with ghrelin in cardiac tissue from patients with valvular disease with no detectable changes in LV function. Biopsy samples from the LV and left atrium (LA) were obtained from 25 patients with valvular disease (of whom 13 also had coronary artery disease) and preserved LV ejection fraction, and compared control samples obtained via autopsy. Using quantitative confocal fluorescence microscopy, levels of GHSR were determined using a fluorescent peptide analog of ghrelin, Cy5-ghrelin(1-19); ghrelin, the heart failure marker natriuretic peptide type-b (BNP), and contractility marker sarcoplasmic reticulum ATPase pump (SERCA2a) were measured by immunofluorescence. A positive correlation between GHSR and ghrelin was apparent in only diseased tissue. Ghrelin and BNP significantly correlated in the LV and strongly co-localized to the same intracellular compartment in both diseased and control tissue. GHSR, ghrelin and BNP all strongly and significantly correlated with SERCA2a in the LV of diseased tissue only. Our results suggest that the dynamics of the myocardial ghrelin/GHSR axis is altered in cardiovascular disease in the absence of measurable changes in heart function, and may accompany a regional shift in endocrine programming.
Maximizing cooperation in the prisoner’s dilemma evolutionary game via optimal control
Authors: Newton P.K. , Ma Y. 
Published: July 2020

The prisoner’s dilemma (PD) game offers a simple paradigm of competition between two players who can either cooperate or defect. Since defection is a strict Nash equilibrium, it is an asymptotically stable state of the replicator dynamical system that uses the PD payoff matrix to define the fitness landscape of two interacting evolving populations. The dilemma arises from the fact that the average payoff of this asymptotically stable state is sub-optimal. Coaxing the players to cooperate would result in a higher payoff for both. Here we develop an optimal control theory for the prisoner’s dilemma evolutionary game in order to maximize cooperation (minimize the defector population) over a given cycle-timeT, subject to constraints. Our two time-dependent controllers are applied to the off-diagonal elements of the payoff matrix in a bang-bang sequence that dynamically changes the game being played by dynamically adjusting the payoffs, with optimal timing that depends on the initial population distributions. Over multiple cyclesnT(n> 1), the method is adaptive as it uses the defector population at the end of thenthcycle to calculate the optimal schedule over then+ 1stcycle. The control method, based on Pontryagin’s maximum principle, can be viewed as determining the optimal way to dynamically alter incentives and penalties in order to maximize the probability of cooperation in settings that track dynamic changes in the frequency of strategists, with potential applications in evolutionary biology, economics, theoretical ecology, and other fields where the replicator system is used.PACS numbers02.50.Le; 02.30.Yy; 05.45.-a; 87.23.Kg; 87.23.Cc
The National Early Warning Score (NEWS2) systematically underestimates the risk of in-hospital mortality in unplanned COVID-19 admissions to hospital
Authors: Richardson Donald , Faisal Muhammad , Fiori Massimo , Beatson Kevin , Mohammed Mohammed A 
Published: July 2020

AbstractBackgroundAlthough the National Early Warning Score (NEWS) and its latest version NEWS2 are recommended for monitoring for deterioration in patients admitted to hospital, little is known about their performance in COVID-19 patients. We analysed the performance of National Early Warning Score (NEWS2) during the first phase of the COVID-19 pandemic.MethodsAdult non-elective admissions discharged between 11-March-2020 to 13-June-2020 with an index NEWS2 electronically recorded within ±24 hours of admission are used to predict mortality at four time points (in-hospital, 24hours, 48hours, and 72hours) in COVID-19 versus non-COVID-19 admissions.ResultsOut of 6480 non-elective admissions, 620 (9.6%) had a diagnosis of COVID-19. They were older (73.3 vs 67.7yrs), more often male (54.7% vs 50.1%), had higher index NEWS (4 vs 2.5) and NEWS2 (4.6 vs 2.8) scores and higher in-hospital mortality (32.1% vs 5.8%). The c-statistics for predicting in-hospital mortality in COVID-19 admissions was significantly lower using NEWS (0.64 vs 0.74) or NEWS2 (0.64 vs 0.74), however these differences reduced at 72hours (NEWS: 0.75 vs 0.81; NEWS2: 0.71 vs 0.81), 48 hours (NEWS: 0.78 vs 0.81; NEWS2: 0.76 vs 0.82) and 24hours (NEWS: 0.84 vs 0.84; NEWS2: 0.86 vs 0.84). Increasing NEWS2 values reflected increased mortality, but for any given value the absolute risk was on average 24% higher (e.g.NEWS2=5: 36% vs 9%).InterpretationNEWS2 is a valid predictor of the mortality risk but substantially underestimates the absolute mortality risk in COVID-19 patients. Clinical staff and escalation protocols based on NEWS2 need to make note of this finding.
Assessment and optimization of respiratory syncytial virus prophylaxis regimens in Connecticut, 1996-2013
Authors: Artin Ben , Pitzer Virginia E. , Weinberger Daniel 
Published: July 2020

AbstractBackgroundRespiratory syncytial virus (RSV) causes seasonal respiratory infection, with hospitalization rates of up to 50% in high-risk infants. Palivizumab provides safe and effective, yet costly, immunoprophylaxis. The American Academy of Pediatrics (AAP) recommends palivizumab only for high-risk infants and only during the RSV season. Outside of Florida, the current guidelines do not recommend regional adjustments to the timing of the immunoprophylaxis regimen. We investigate the benefits of adjusting the RSV prophylaxis regimen in Connecticut based on spatial variation in the timing of RSV incidence.MethodsWe obtained weekly RSV-associated hospital admissions by ZIP-code in Connecticut between July 1996 and June 2013. We estimated the fraction of all RSV cases in Connecticut occurring during the period of protection offered by RSV immunoprophylaxis (“preventable fraction”) under the AAP guidelines. We then used the same model to estimate protection conferred by immunoprophylaxis regimens with alternate start dates, but unchanged duration.ResultsThe fraction of RSV hospitalizations preventable by the AAP guidelines varies by county because of variations in epidemic timing. Prophylaxis regimens adjusted for state- or county-level variation in the timing of RSV seasons are modestly superior to the AAP-recommended regimen. The best alternative strategy yielded a preventable fraction of 95.07% (95% CI: 94.69 – 95.44%), compared to 94.07% (95% CI: 93.65 – 94.46%) for the AAP recommendation.ConclusionInitiating RSV prophylaxis based on state-level data may improve protection compared with the standard AAP recommendations. In Connecticut, county-level recommendations would provide only a modest additional benefit while adding complexity.
State-level tracking of COVID-19 in the United States
Authors: Unwin H. Juliette T. , Mishra Swapnil , Bradley Valerie C. , Gandy Axel , Mellan Thomas A. , Coupland Helen , Ish-Horowicz Jonathan , Vollmer Michaela A. C. , Whittaker Charles , Filippi Sarah L. , Xi Xiaoyue , Monod Mélodie , Ratmann Oliver , Hutchinson Michael , Valka Fabian , Zhu Harrison , Hawryluk Iwona , Milton Philip , Ainslie Kylie E. C. , Baguelin Marc , Boonyasiri Adhiratha , Brazeau Nick F. , Cattarino Lorenzo , Cucunuba Zulma , Cuomo-Dannenburg Gina , Dorigatti Ilaria , Eales Oliver D. , Eaton Jeffrey W. , van Elsland Sabine L. , FitzJohn Richard G. , Gaythorpe Katy A. M. , Green William , Hinsley Wes , Jeffrey Benjamin , Knock Edward , Laydon Daniel J. , Lees John , Nedjati-Gilani Gemma , Nouvellet Pierre , Okell Lucy , Parag Kris V. , Siveroni Igor , Thompson Hayley A. , Walker Patrick , Walters Caroline E. , Watson Oliver J. , Whittles Lilith K. , Ghani Azra C. , Ferguson Neil M. , Riley Steven , Donnelly Christl A. , Bhatt Samir , Flaxman Seth 
Published: July 2020

AbstractAs of 1st June 2020, the US Centers for Disease Control and Prevention reported 104,232 confirmed or probable COVID-19-related deaths in the US. This was more than twice the number of deaths reported in the next most severely impacted country. We jointly modelled the US epidemic at the state-level, using publicly available death data within a Bayesian hierarchical semi-mechanistic framework. For each state, we estimate the number of individuals that have been infected, the number of individuals that are currently infectious and the time-varying reproduction number (the average number of secondary infections caused by an infected person). We used changes in mobility to capture the impact that non-pharmaceutical interventions and other behaviour changes have on the rate of transmission of SARS-CoV-2. Nationally, we estimated 3.7% [3.4%-4.0%] of the population had been infected by 1st June 2020, with wide variation between states, and approximately 0.01% of the population was infectious. We also demonstrated that good model forecasts of deaths for the next 3 weeks with low error and good coverage of our credible intervals.
Modelling suggests blood group incompatibility may substantially reduce SARS-CoV-2 transmission
Authors: Ellis Peter J. I. 
Published: July 2020

AbstractSeveral independent datasets suggest blood type A is over-represented and type O under-represented among COVID-19 patients. Here, I model a scenario in which ABO transfusion incompatibility reduces the chance of a patient transmitting the virus to an incompatible recipient. Comparison of model outputs to published data on COVID-19 prevalence indicates that if this scenario holds true, ABO incompatibility may reduce virus transmissibility by 60% or more. Paradoxically, however, targeted vaccination of either high-susceptibility type A or “super-spreader” type O individuals is less effective than random vaccination at blocking community spread of the virus. Instead, the key is to maintain blood type diversity amongst the remaining susceptible individuals. I stress that these results illustrate a theoretical model of ABO blood group interaction with virus transmission and require confirmation by observation.
Evaluation of the Practicability of a Finger-Stick Whole-Blood SARS-Cov-2 Self-Test Adapted for the General Population
Authors: Prazuck Thierry , Van Jean Phan , Sinturel Florence , Levray Fredrique , Elie Allan , Camera Denise , Pialoux Gilles 
Published: July 2020

AbstractBackgroundCOVID-19 (COronaVIrus Disease 2019) is an infectious respiratory disease caused by the novel SARS-CoV-2 virus. Rapid Diagnostic Tests (RDTs) have been developed to detect specific antibodies, IgG and IgM, to SARS-CoV-2 virus in human whole blood and easily usable by the general population are needed in order to alleviate the lockdown that many countries have initiated in response to the growing COVID-19 pandemic. A real-life study has been conducted in order to evaluate the performance of the COVID-PRESTO® RDT and the results have been submitted for publication and are currently under review. Even if this test showed very high sensitivity and specificity in a laboratory setting when used by trained professionals, it needs to be further evaluated for practicability when used by common folk in order to be approved by health authorities for in-home useMethods142 participants were recruited between March 2020 and April 2020 among non-medical populations in central France (nuclear plants workers, individuals attending the Orleans University Hospital vaccination clinic and Orleans University Hospital non-medical staff). Instructions for use with or without a tutorial video was made available to the volunteers. Two separate objectives were pursued: evaluation of the capability of participants to obtain an interpretable result, and evaluation of the users’ ability to read the results.Results88.4 % of the test users judged the instruction for use leaflet to be clear and understandable. 99.3 % of the users obtained a valid results and according to the supervisors 92.7% of the tests were properly performed by the user. Overall, 95% of the users gave positive feedback toward the COVID PRESTO® as a potential self-test. No influence of age and education was observed.ConclusionCOVID-PRESTO® was successfully used by an overwhelming majority of participants and its utilization was judged very satisfactory, therefore showing a promising potential as a self-test to be used by the general population. This RDT can become an easy-to-use tool to help know whether individuals are protected or not, particularly in the perspective of a second wave or a mass vaccination program.
Interest in COVID-19 vaccine trials participation among young adults in China: Willingness, reasons for hesitancy, and demographic and psychosocial determinants
Authors: Sun Shufang , Lin Danhua , Operario Don 
Published: July 2020

AbstractBackgroundWith the demand for rapid COVID-19 vaccine development and evaluation, this paper aimed to describe the prevalence and correlates of willingness to participate in COVID-19 vaccine trials among university students in China.MethodsA cross-sectional survey with 1,912 Chinese university students was conducted during March and April 2020. Bivariate and multivariate analyses were performed to identify variables associated with willingness to participate.ResultsThe majority of participants (64.01%) indicated willingness to participate in COVID-19 vaccine trials. Hesitancy over signing informed consent documents, concerns over time necessary for participating in a medical study, and perceived COVID-19 societal stigma were identified as deterrents, whereas lower socioeconomic status, female gender, perception of likely COVID-19 infection during the pandemic, and COVID-19 prosocial behaviors were facilitative factors. Further, public health mistrust and hesitancy over signing informed consent documents had a significant interactive effect on vaccine trial willingness.ConclusionsHigh standards of ethical and scientific practice are needed in COVID-19 vaccine research, including providing potential participants full and accurate information and ensuring participation free of coercion, socioeconomic inequality, and stigma. Attending to the needs of marginalized groups and addressing psychosocial factors including stigma and public health mistrust may also be important to COVID-19 vaccine development and future uptake.
Prostaglandin catabolism inSpodoptera exigua, a lepidopteran insect
Authors: Ahmed Shabbir , Kim Yonggyun 
Published: July 2020

ABSTRACTSeveral prostaglandins (PGs) and PG-synthesizing enzymes have been identified from insects. PGs can mediate cellular and humoral immune responses. However, uncontrolled and prolonged immune responses might have adverse effects on survival. PG catabolism in insects has not been reported. Here, using a transcriptomic analysis, we predicted two PG-degrading enzymes,PG dehydrogenase(SePGDH) andPG reductase(SePGR), inSpodoptera exigua, a lepidopteran insect.SePGDHandSePGRexpression levels were upregulated after immune challenge. However, their expression peaks occurred after those of PG biosynthesis genes such as PGE2synthase or PGD2synthase. Indeed,SePGDHandSePGRexpression levels were upregulated after injection with PGE2or PGD2. In contrast, such upregulated expression was not detected after injection with leukotriene B4, an eicosanoid inflammatory mediator. RNA interference (RNAi) using double-stranded RNAs specific toSePGDHorSePGRsuppressed their expression levels. The RNAi treatment resulted in an excessive and fatal melanization of larvae even after a non-pathogenic bacterial infection. Phenoloxidase (PO) activity mediating the melanization in larval plasma was induced by bacterial challenge or PGE2injection. Although the induced PO activity decreased after 8 h in control, larvae treated with dsRNAs specific to PG-degrading enzyme genes kept the high PO activities for a longer period compared to control larvae. These results suggest that SePGDH and SePGR are responsible for PG degradation at a late phase of immune responses.
Neural Network Poisson Models for Behavioural and Neural Spike Train Data
Authors: Khajehnejad Moein , Habibollahi Forough , Nock Richard , Arabzadeh Ehsan , Dayan Peter , Dezfouli Amir 
Published: July 2020

AbstractOne of the most important and challenging application areas for complex machine learning methods is to predict, characterize and model rich, multi-dimensional, neural data. Recent advances in neural recording techniques have made it possible to monitor the activities of a large number of neurons across different brain regions as animals perform behavioural tasks. This poses the critical challenge of establishing links between neural activity at a microscopic scale, which might for instance represent sensory input, and at a macroscopic scale, which then generates behaviour. Predominant modeling methods apply rather disjoint techniques to these scales; by contrast, we suggest an end-to-end model which exploits recent developments of flexible, but tractable, neural network point-process models to characterize dependencies between stimuli, actions, and neural data. We apply this model to a public dataset collected using Neuropixel probes in mice performing a visually-guided behavioural task as well as a synthetic dataset produced from a hierarchical network model with reciprocally connected sensory and integration circuits intended to characterize animal behaviour in a fixed-duration motion discrimination task. We show that our model outperforms previous approaches and contributes novel insights into the relationships between neural activities and behaviour.