bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review on Multisystem Inflammatory Syndrome in Children (MIS-C) with COVID-19: Development of a scoring system for clinical diagnosis
Authors: Surve Suchitra V , Joseph Shaini , Gajbhiye Rahul K , Mahale Smita D , Modi Deepak N 
Published: April 2021

AbstractBackgroundThere is growing evidence of Multisystem Inflammatory Syndrome in Children (MIS-C) resembling Kawasaki disease in children infected with SARS-CoV-2. The review was undertaken to evaluate the case definition, the spectrum of clinical presentations and current management practices in children with COVID-19 presenting with or without MIS-C.MethodsThe individual patient data from 119 studies accounting for 333 children were analyzed. We devised a scoring system as per WHO criteria to classify the patients as MIS-C or without MIS-C. A score of 3 was given for the presence of fever (>24h) and a score of 1 for lab-confirmed diagnosis of SARS-CoV-2. Additionally, a score of 1 was given for a) rash or conjunctivitis or muco-cutaneous inflammation signs, b) hypotension or shock, c) diarrhea, vomiting or abdominal pain, d) features of myocardial dysfunction as determined by abnormal eco-cardiography or elevated Troponin or N-terminal pro B-type Natriuretic Peptide (NT-proBNP), e) evidence of coagulopathy as evidenced by elevated levels of prothrombin time PT, partial thromboplastin time PTT or D-dimer, f) laboratory evidence of inflammation as determined by elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) or procalcitonin. A negative score of (−3) was given when there was a diagnosis of sepsis, staphylococcal or streptococcal shock syndrome. Based on these criteria, a minimum score of 6 was essential to classify the child as MIS-C.ResultsBased on this score, 18% (52/289) of cases were identified to be MIS-C. A greater proportion of children with MIS-C had cardiac involvement (MIS-C 80% vs Non-MIS-C 20%) and gastrointestinal involvement (MIS-C 71% vs Non-MIS-C 12%). Lymphopenia was commonly reported in MIS-C (MIS-C 54.2% vs Non-MIS-C 29.7%). In addition to routine inflammatory markers, significantly greater proportion of children with MIS-C had elevated Ferritin, LDH, Fibrinogen and IL-6. Children with MIS-C were less likely to have respiratory symptoms like cough (MIS-C 25% vs Non-MIS-C 75%) and rhinorrhea (MIS-C 4% vs Non-MIS-C 22.8%). A greater proportion of children with MIS-C required intensive care and aggressive treatment; and mortality rates were also higher in MIS-C group (MIS-C 10% vs Non-MIS-C 1%).ConclusionThe children with COVID-19 having cardiac and/or gastrointestinal involvement are more likely to develop MIS-C. The children with MIS-C have higher mortality rates. The scoring system developed herein will aid clinicians in patient diagnosis and timely management.
Cross-classification between self-rated health and health status: longitudinal analyses of all-cause mortality and leading causes of death in the UK
Authors: Mutz Julian , Lewis Cathryn M. 
Published: April 2021

AbstractBackgroundRisk stratification is an important public health priority that is central to clinical decision making and resource allocation. The aim of the present study was to examine how different combinations of self-rated and objective health status predict (i) all-cause mortality and (ii) cause-specific mortality from leading causes of death in the UK.MethodsThe UK Biobank study recruited >500,000 participants, aged 37-73, between 2006–2010. The health cross-classification examined incorporated self-rated health (poor, fair, good or excellent) and health status derived from medical history and current disease status, including 81 cancer and 443 non-cancer illnesses. We examined all-cause mortality and six specific causes of death: ischaemic heart disease, cerebrovascular disease, influenza and pneumonia, dementia and Alzheimer’s disease, chronic lower respiratory disease and malignant neoplasm.ResultsAnalyses included>370,000 middle-aged and older adults with a median follow-up of 11.75 (IQR = 1.4) years, yielding 4,320,270 person years of follow-up. Compared to excellent self-rated health and favourable health status, all other levels of the health cross-classification were associated with a greater risk of mortality, with hazard ratios ranging from 1.22 (95% CI 1.15-1.29,pBonf.< 0.001) for good self-rated health and favourable health status to 7.14 (95% CI 6.70-7.60,pBonf.< 0.001) for poor self-rated health and unfavourable health status.ConclusionsOur findings highlight that self-rated health captures additional health-related information and should be more widely assessed across settings. The cross-classification between health status and self-rated health represents a straightforward metric for risk stratification, with applications to population health, clinical decision making and resource allocation.
Regional opening strategies with commuter testing and containment of new SARS-CoV-2 variants in Germany
Authors: Kühn Martin J. , Abele Daniel , Binder Sebastian , Rack Kathrin , Klitz Margrit , Kleinert Jan , Gilg Jonas , Spataro Luca , Koslow Wadim , Siggel Martin , Meyer-Hermann Michael , Basermann Achim 
Published: April 2021

AbstractBackgroundDespite the vaccination process in Germany, a large share of the population is still susceptible to SARS-CoV-2. In addition, we face the spread of novel variants. Until we overcome the pandemic, reasonable mitigation and opening strategies are crucial to balance public health and economic interests.MethodsWe model the spread of SARS-CoV-2 over the German counties by a graph-SIR-type, metapopulation model with particular focus on commuter testing. We account for political interventions by varying contact reduction values in private and public locations such as homes, schools, workplaces, and other. We consider different levels of lockdown strictness, commuter testing strategies, or the delay of intervention implementation. We conduct numerical simulations to assess the effectiveness of the different intervention strategies after one month. The virus dynamics in the regions (German counties) are initialized randomly with incidences between 75-150 weekly new cases per 100,000 inhabitants (red zones) or below (green zones) and consider 25 different initial scenarios of randomly distributed red zones (between 2 and 20 % of all counties). To account for uncertainty, we consider an ensemble set of 500 Monte Carlo runs for each scenario.ResultsWe find that the strength of the lockdown in regions with out of control virus dynamics is most important to avoid the spread into neighboring regions. With very strict lockdowns in red zones, commuter testing rates of twice a week can substantially contribute to the safety of adjacent regions. In contrast, the negative effect of less strict interventions can be overcome by high commuter testing rates. A further key contributor is the potential delay of the intervention implementation. In order to keep the spread of the virus under control, strict regional lockdowns with minimum delay and commuter testing of at least twice a week are advisable. If less strict interventions are in favor, substantially increased testing rates are needed to avoid overall higher infection dynamics.ConclusionsOur results indicate that local containment of outbreaks and maintenance of low overall incidence is possible even in densely populated and highly connected regions such as Germany or Western Europe. While we demonstrate this on data from Germany, similar patterns of mobility likely exist in many countries and our results are, hence, generalizable to a certain extent.
Feedforward mechanisms of masking in mouse V1
Authors: Barbera Dylan , Priebe Nicholas J. , Glickfeld Lindsey L. 
Published: April 2021

AbstractSensory neurons not only encode stimuli that align with their receptive fields but are also modulated by context. For example, the responses of neurons in mouse primary visual cortex (V1) to gratings of their preferred orientation are modulated by the presence of superimposed orthogonal gratings (“plaids”). The effects of this modulation can be diverse: some neurons exhibit cross-orientation suppression while other neurons have larger responses to a plaid than its components. We investigated whether these diverse forms of masking could be explained by a unified circuit mechanism. We report that the suppression of cortical activity does not alter the effects of masking, ruling out cortical mechanisms. Instead, we demonstrate that the heterogeneity of plaid responses is explained by an interaction between stimulus geometry and orientation tuning. Highly selective neurons uniformly exhibit cross-orientation suppression, whereas in weakly-selective neurons masking depends on the spatial configuration of the stimulus, with effects transitioning systematically between suppression and facilitation. Thus, the diverse responses of mouse V1 neurons emerge as a consequence of the spatial structure of the afferent input to V1, with no need to invoke cortical interactions.
6-Month Follow Up of 8679 Hospitalized COVID-19 Patients in Germany: A Nationwide Cohort Study
Authors: Günster Christian , Busse Reinhard , Spoden Melissa , Rombey Tanja , Schillinger Gerhard , Hoffmann Wolfgang , Weber-Carstens Steffen , Schuppert Andreas , Karagiannidis Christian 
Published: April 2021

AbstractBackgroundData on long-term outcomes of hospitalized COVID-19 patients are scarce.ObjectiveTo provide a detailed account of hospitalized COVID-19 patients until 180 days after their initial hospitalization.DesignNationwide cohort study using claims data from the German Local Health Care Funds, the health insurer of one-third of the German population.SettingGermany.PatientsAdult patients hospitalized in Germany between Feb 1 and April 30, 2020 with PCR-confirmed COVID-19 and a related principal diagnosis.MeasurementsPatient characteristics and ventilation status, in-hospital, 30-, 90- and 180- day mortality measured from admission, and 180-day readmission measured from discharge. Multivariable logistic regression model of independent risk factors for 180-day mortality.ResultsOf 8679 patients (median age, 72 years), 2161 (24.9%) died during the index hospitalization. 30-day mortality was 23.9% (2073/8679), 90-day mortality 27.9% (2425/8679), and 180-day mortality 29.6% (2566/8679). The latter was 52.3% (1472/2817) for patients aged ≥ 80 years, and 53.0% for patients who had been ventilated invasively (853/1608). Risk factors for 180-day mortality included coagulopathy, BMI ≥ 40, and age. Female sex was a protective factor. Of 6235 patients discharged alive, 1668 patients were readmitted a total of 2551 times within 180 days, resulting in an overall readmission rate of 26.8%.LimitationsWe could not stratify patients by ICU treatment as it is not coded separately. Furthermore, we cannot exclude residual confounding in our analysis of risk factors nor determine causality between risk factors and long-term mortality given the observational nature of this study.ConclusionThis nationwide cohort study of hospitalized COVID-19 patients in Germany found considerable long-term mortality and readmission rates, especially among patients with coagulopathy. Close follow-up after hospital discharge may improve long-term outcome.
The urgency of resuming disrupted dog rabies vaccination campaigns: a modeling and cost-effectiveness analysis
Authors: Kunkel Amber , Jeon Seonghye , Joseph Haim C , Dilius Pierre , Crowdis Kelly , Meltzer Martin I. , Wallace Ryan 
Published: April 2021

ABSTRACTOBJECTIVEDog vaccination is a cost-effective approach to preventing human rabies deaths. In Haiti, the 2019 dog vaccination campaign did not include the capital city, and the 2020 campaign was cancelled because of COVID-19 lockdown restrictions and redirection of funds. We estimated the number of human lives that could be saved by resuming dog vaccination in 2021 compared to 2022 and compared the cost-effectiveness of these two scenarios.METHODSWe modified a previously published rabies transmission and economic model to estimate trends in dog and human rabies cases in Haiti from 2005-2025. We compared model outputs to surveillance data on human rabies deaths from 2005-2020 and animal rabies cases from 2018-2020. We then estimated the human health and cost implications of restarting dog vaccination programs in either 2021 or 2022.FINDINGSModel predictions and animal surveillance data from Haiti both suggest a 5-to 8-fold increase in animal rabies cases has occurred in the capital city between Fall 2019 and Fall 2020. We estimate that restarting dog vaccination in Haiti in 2021 compared to 2022 could save 285 human lives and prevent 6,541 human rabies exposures over a five-year period and may decrease program costs due to reduced need for human post-exposure prophylaxis.CONCLUSIONSA one-year delay in resuming dog vaccination in Haiti, from 2021 to 2022, could cost hundreds of lives over the next 5 years. Interruptions in dog vaccination campaigns before elimination is achieved can lead to significant human rabies epidemics if not promptly resumed.
A Novel Evidence-Based Predictor Tool for Hospitalization and Length of Stay: Insights from COVID19 Patients in New York City
Authors: Halabi Maan El , Feghali James , Tallón de Lara Paulino , Narasimhan Bharat , Ho Kam , Saabiye Joseph , Huang Judy , Osorio Georgina , Mathew Joseph , Wisnivesky Juan , Steiger David 
Published: April 2021

AbstractBackgroundCoronavirus disease 2019 (COVID-19) has evolved into a true global pandemic infecting more than 30 million people worldwide. Predictive models for key outcomes have the potential to optimize resource utilization and patient outcome as outbreaks continue to occur worldwide. We aimed to design and internally validate a web-based calculator predictive of hospitalization and length of stay (LOS) in a large cohort of COVID-19 positive patients presenting to the Emergency Department (ED) in a New York City health system.MethodsThe study cohort consisted of consecutive adult (>18 years) patients presenting to the ED of one of the Mount Sinai Health System hospitals between March, 2020 and April, 2020 who were diagnosed with COVID-19. Logistic regression was utilized to construct predictive models for hospitalization and prolonged (>3 days) LOS. Discrimination was evaluated using area under the receiver operating curve (AUC). Internal validation with bootstrapping was performed, and a web-based calculator was implemented.ResultsThe cohort consisted of 5859 patients with a hospitalization rate of 65% and a prolonged LOS rate of 75% among hospitalized patients. Independent predictors of hospitalization included older age (OR=6.29; 95% CI [1.83-2.63], >65 vs. 18-44), male sex (OR=1.35 [1.17-1.55]), chronic obstructive pulmonary disease (OR=1.74; [1.00-3.03]), hypertension (OR=1.39; [1.13-1.70]), diabetes (OR=1.45; [1.16-1.81]), chronic kidney disease (OR=1.69; [1.23-2.32]), elevated maximum temperature (OR=4.98; [4.28-5.79]), and low minimum oxygen saturation (OR=13.40; [10.59-16.96]). Predictors of extended LOS included older age (OR=1.03 [1.02-1.04], per year), chronic kidney disease (OR=1.91 [1.35-2.71]), elevated maximum temperature (OR=2.91 [2.40- 3.53]), and low minimum percent oxygen saturation (OR=3.89 [3.16-4.79]). AUCs of 0.881 and 0.770 were achieved for hospitalization and LOS, respectively. A calculator was made available under the following URL: https://covid19-outcome-prediction.shinyapps.io/COVID19_Hospitalization_Calculator/ConclusionThe prediction tool derived from this study can be used to optimize resource allocation, guide quality of care, and assist in designing future studies on the triage and management of patients with COVID-19.
Single-cell landscapes of primary glioblastomas and matched organoids and cell lines reveal variable retention of inter- and intra-tumor heterogeneity
Authors: LeBlanc VG , Trinh DL , Aslanpour S , Hughes M , Livingstone D , Blough MD , Cairncross JG , Chan JA , Kelly JJ , Marra MA 
Published: April 2021

SummaryGlioblastomas (GBMs) are aggressive primary malignant brain tumors characterized by extensive levels of inter- and intra-tumor genetic and phenotypic heterogeneity. Patient-derived organoids (PDOs) have recently emerged as useful models to study such heterogeneity. Here, we present bulk exome as well as single-cell genome and transcriptome profiles of primaryIDHwild type GBMs from ten patients, including two recurrent tumors, as well as PDOs and brain tumor-initiating cell (BTIC) lines derived from these patients. We find that PDOs are genetically similar to and variably retain gene expression characteristics of their parent tumors. At the phenotypic level, PDOs appear to exhibit similar levels of transcriptional heterogeneity as their parent tumors, whereas BTIC lines tend to be enriched for cells in a more uniform transcriptional state. The datasets introduced here will provide a valuable resource to help guide experiments using GBM-derived organoids, especially in the context of studying cellular heterogeneity.
Senolytics and the compression of late-life mortality
Authors: Kowald Axel , Kirkwood Thomas B L 
Published: April 2021

AbstractSenescent cells play an important role in mammalian ageing and in the etiology of age-related diseases. Treatment of mice with senolytics – drugs that selectively remove senescent cells – causes an extension of median lifespan but has little effect on maximum lifespan. Postponement of some mortality to later ages, without a corresponding increase in maximum mortality, can be termed ‘compression of mortality’. When we fit the standard Gompertz mortality model to the survival data following senolytic treatment, we find an increase in the slope parameter, commonly described as the ‘actuarial ageing rate’. These observations raise important questions about the actions of senolytic treatments and their effects on health and survival, which are not yet sufficiently understood. To explore how the survival data from senolytics experiments might be explained, we combine recent exploration of the evolutionary basis of cellular senescence with theoretical consideration of the molecular processes that might be involved. We perform numerical simulations of senescent cell accumulation and senolytic treatment in an ageing population. The simulations suggest that while senolytics diminish the burden of senescent cells, they may also impair the general repair capacity of the organism, leading to a faster accumulation post-treatment of new senescent cells. Our results suggest a framework to address the benefits and possible side effects of senolytic therapies, with the potential to aid the design of optimal treatment regimens.
Uncertainty drives deviations in normative foraging decision strategies
Authors: Kilpatrick Zachary P , Davidson Jacob D , Hady Ahmed El 
Published: April 2021

ABSTRACTNearly all animals forage, as it is essential to acquire energy for survival through efficient search and resource harvesting. Patch exploitation is a canonical foraging behavior, but a systematic treatment of how animals cope with uncertainty is lacking. To address these shortcomings, we develop a normative theory of patch foraging decisions, proposing mechanisms by which foraging behaviors emerge in the face of uncertainty. Our model foragers statistically and sequentially infer patch resource yields using Bayesian updating based on their resource encounter history. A decision to leave a patch is triggered when the certainty of the patch type or the estimated yield of the patch fall below a threshold. The timescale over which uncertainty in resource availability persists strongly impacts behavioral variables like patch residence times and decision rules determining patch departures. When patch depletion is slow, as in habitat selection, departures are characterized by a reduction of uncertainty, suggesting the forager resides in a low-yielding patch. Uncertainty leads patch-exploiting foragers to overharvest (underharvest) patches with initially low (high) resource yields in comparison to predictions of the marginal value theorem. These results extend optimal foraging theory and motivate a variety of behavioral experiments investigating patch foraging behavior.
A comparative analysis of computational tools for the prediction of epigenetic DNA methylation from long-read sequencing data
Authors: Pai Shruta Sandesh , Mathew Aimee Rachel , Anindya Roy 
Published: April 2021

AbstractRecent development of Oxford Nanopore long-read sequencing has opened new avenues of identifying epigenetic DNA methylation. Among the different epigenetic DNA methylations, N6-methyladenosine is the most prevalent DNA modification in prokaryotes and 5-methylcytosine is common in higher eukaryotes. Here we investigated if N6-methyladenosine and 5-methylcytosine modifications could be predicted from the nanopore sequencing data. Using publicly available genome sequencing data ofSaccharomyces cerevisiae, we compared the open-access computational tools, including Tombo, mCaller, Nanopolish and DeepSignal for predicting 6mA and 5mC. Our results suggest that Tombo and mCaller can predict DNA N6-methyladenosine modifications at a specific location, whereas, Tombo dampened fraction, Nanopolish methylation likelihood and DeepSignal methylation probability have comparable efficiency for 5-methylcytosine prediction from Oxford Nanopore sequencing data.
A Phylogenetic Independent Contrast Method under the Ornstein-Uhlenbeck Model and its Applications in Correlated Evolution
Authors: Liang Cong , Deng Yingjun 
Published: April 2021

AbstractPhylogenetic comparative methods are essential in studying the evolution of traits across a phylogeny. Felsenstein’s phylogenetic independent contrast (PIC) method and the generalized least squares (GLS) regression were often utilized to study whether evolutionary changes between traits were correlated. However, a neutral Brownian model is assumed in the PIC method, which impacts the performance of the PIC method when the trait is subject to adaptation. In recent years, the Ornstein-Uhlenbeck (OU) model has attracted increasing attention in studying the evolution of traits with stabilizing selection. In this study, we extended Felsenstein’s PIC method under the OU model, which we termed OU-PIC. We simulated trait evolution under the OU model on phylogenetic trees with 8, 10, and 55 species. Compared to the PIC method, the OU-PIC method with correct stabilizing selection parameters achieved an appropriate type I error rate, the highest test power, and the lowest mean squared error. We presented a concise proof of the intrinsic connection between the OU-PIC and the generalized least squares (GLS) regression method in evaluating correlated evolution under the OU model. The OU-PIC method has a broad range of applications when trait evolution could be sufficiently modeled by the OU process. Compared with other phylogenetic comparative methods, OU-PIC avoids the inverse of the covariance matrix and would facilitate the analysis of correlated evolution on large phylogenies.