bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of predication of Acute Kidney Injury after cardiac surgery by health care providers versus the biomarker [TIMP-2]*[IGFBP7] and scoring systems. Protocol for a prospective single center observational study (PREDICTAKI)
Authors: Vandenberghe Wim , Van Laethem Lien , Zarbock Alexander , Meersch Melanie , Hoste Eric A.J. 
Published: July 2020

AbstractIntroductionAcute kidney injury occurs in up to one third of patients after cardiac surgery and is an important contributor for adverse outcome. Previous research has demonstrated the benefit of a bundle of preventive measurements to reduce AKI in a subgroup of patients with high risk for AKI development. Urinary stress biomarkers [TIMP-2]*[IGFBP7] are used to identify these patients who are at risk for AKI. The trial aims to investigate the potential discrepancy between biomarker results and clinical estimation of occurrence of AKI on ICU in clinical practice.Methods and analysisWe plan to include 100 adult patients after cardiac surgery with cardiopulmonary bypass in a prospective, single center clinical trial. After cardiac surgery, different type of healthcare professional in ICU will provide a prediction of AKI occurrence and severity in the next 48 hours by filling in a questionnaire just before and after [TIMP-2]*[IGFBP7] biomarker analysis. Primary, this trial investigates the potential discrepancy in AKI prediction between clinical estimation by healthcare providers, biomarker results, and previous described score systems. Secondly, the impact of knowledge of the biomarker result on the quality of prediction by healthcare providers will be evaluated.Ethics and disseminationThis prospective, single center study has been approved by the medical ethical committee of the Ghent University Hospital (28th May 2019, trial registration number B670201939991). Informed consent was obtained for patients and healthcare providers.Summary strength and limitations-Influence of knowledge of a kidney biomarker on healthcare providers’ assessment of risk for AKI in clinical setting-Different types of healthcare providers with various expertise-It is a single center study with limited number of patients
SARS-CoV-2 infection induces robust, neutralizing antibody responses that are stable for at least three months
Authors: Wajnberg Ania , Amanat Fatima , Firpo Adolfo , Altman Deena R. , Bailey Mark J. , Mansour Mayce , McMahon Meagan , Meade Philip , Mendu Damodara Rao , Muellers Kimberly , Stadlbauer Daniel , Stone Kimberly , Strohmeier Shirin , Aberg Judith , Reich David L. , Krammer Florian , Cordon-Cardo Carlos 
Published: July 2020

AbstractSARS-CoV-2 has caused a global pandemic with millions infected and numerous fatalities. Questions regarding the robustness, functionality and longevity of the antibody response to the virus remain unanswered. Here we report that the vast majority of infected individuals with mild-to-moderate COVID-19 experience robust IgG antibody responses against the viral spike protein, based on a dataset of 19,860 individuals screened at Mount Sinai Health System in New York City. We also show that titers are stable for at least a period approximating three months, and that anti-spike binding titers significantly correlate with neutralization of authentic SARS-CoV-2. Our data suggests that more than 90% of seroconverters make detectible neutralizing antibody responses and that these titers are stable for at least the near-term future.One Sentence SummaryAntibody responses induced by natural mild-to-moderate SARS-CoV-2 infection are robust, neutralizing and are stable for at least 3 months.
Comparative Effectiveness of Knowledge Graphs- and EHR Data-Based Medical Concept Embedding for Phenotyping
Authors: Lee Junghwan , Liu Cong , Kim Jae Hyun , Butler Alex , Shang Ning , Pang Chao , Natarajan Karthik , Ryan Patrick , Ta Casey , Weng Chunhua 
Published: July 2020

ABSTRACTObjectiveConcept identification is a major bottleneck in phenotyping. Properly learned medical concept embeddings (MCEs) have semantic meaning of the medical concepts, thus useful for feature engineering in phenotyping tasks. The objective of this study is to compare the effectiveness of MCEs learned by using knowledge graphs and EHR data for facilitating high-throughput phenotyping.Materials and MethodsWe investigated four MCEs learned from different data sources and methods. Knowledge-graphs were obtained from the Observational Medical Outcomes Partnership (OMOP) common data model. Medical concept co-occurrence statistics were obtained from Columbia University Irving Medical Center’s (CUIMC) OMOP database. Two embedding methods, node2vec and GloVe, were used to learn embeddings for medical concepts. We used phenotypes with their corresponding concepts generated and validated by the Electronic Medical Records and Genomics (eMERGE) network to evaluate the performance of learned MCEs in identifying phenotype-relevant concepts.ResultsPrecision@k% and Recall@k% in identifying phenotype-relevant concepts based on a single concept and multiple seed concepts were used to evaluate MCEs. Recall@500% and Precision@500% based on a single seed concept of MCE learned using the enriched knowledge graph were 0.64 and 0.13, compared to Recall@500% and Precision@500% of MCE learned using the hierarchical knowledge graph (0.61 and 0.12), 5-year windowed EHR (0.51 and 0.10), and visit-windowed EHR (0.46 and 0.09).ConclusionMedical concept embedding enables scalable identification of phenotype-relevant medical concepts, thereby facilitating high-throughput phenotyping. Knowledge graphs constructed by hierarchical relationships among medical concepts learn more effective MCEs, highlighting the need of more sophisticated use of big data to leverage MCEs for phenotyping.
Psychotic-like experiences and polygenic liability in the ABCD Study®
Authors: Karcher Nicole R. , Paul Sarah E. , Johnson Emma C. , Hatoum Alexander S. , Baranger David AA , Agrawal Arpana , Thompson Wesley K. , Barch Deanna M. , Bogdan Ryan 
Published: July 2020

AbstractBackgroundPsychotic-like experiences (PLEs) during childhood are harbingers for severe psychopathology, including psychotic disorders, and neurodevelopmental impairments in adolescence and adulthood.MethodsData from children of genomically-confirmed European ancestries (n=4,650; ages 9-10; 46.8% female) who completed the baseline Adolescent Brain Cognitive Development⍰ Study session were used to assess whether PLEs (i.e., both total and the presence of significantly distressing) are associated with polygenic scores (PGS) related to psychopathology (i.e., schizophrenia [SCZ], educational attainment [EDU], psychiatric cross-disorder risk [CROSS], PLEs). We also assessed whether variability in global and region indices of brain structure (i.e., volume, cortical thickness, surface area) as well as behaviors proximal to PGS (e.g., cognition for EDU) indirectly linked PGS to PLEs using mediational models.FindingsEDU and CROSS PGS were associated with total and significantly distressing PLEs (all %ΔR2s=0.202-0.660%; ps<0.002). Significantly distressing PLEs were also associated with higher SCZ and PLEs PGS (both %ΔR2=0.120-0.171%; ps<0.02). Global brain volume metrics and cognition indirectly linked EDU PGS to PLEs (proportion mediated: 3.33-32.22%).InterpretationTotal and distressing PLEs were associated with genomic risk indices associated with broad spectrum psychopathology risk (i.e., EDU and CROSS PGS). Significantly distressing PLEs were associated with genomic risk for psychosis (i.e., SCZ, PLEs). Global brain volume metrics and PGS-proximal behaviors represent promising putative intermediary phenotypes that may contribute to genomic risk for psychopathology. Broadly, polygenic scores derived from genome-wide association studies of adult samples can generalize to indices of psychopathology risk among children and aid the identification of putative neural and behavioral intermediaries of risk.FundingNational Institute of Health
Preparedness, Perceived Impact and Concerns of health Care Workers in a Teaching Hospital during Coronavirus Disease 2019 (COVID-19)
Authors: Saurabh Kumar , Ranjan Shilpi 
Published: July 2020

AbstractObjectiveCoronavirus Disease 2019 is a new threat to human lives worldwide. Preparedness of institutions during epidemic outbreak has a pivotal role in saving lives and preventing further spread. At the same time, these pandemics impact badly on professional and personal life of Health care workers. The objective of this study is to find the opinion of Health care workers regarding their level of preparedness, concerns and perceived impact related to this pandemic outbreak.Materials and Methodsin this study, random samples of doctors and nurses was provided with a self-administered questionnaire regarding their preparedness, work and non-work related concerns and impact on their lives during Covid-19 outbreak.ResultsMost of the Health Care Workers believed that their institute preparation to fight Covid-19 pandemic is better than prior to onset of this crisis (p⍰0.001). Work related stress was seen more commonly in nurses whereas higher frequency of non-work related stress was observed among doctors. Nurses (75.55%) faith in their employer was more than doctors faith (46.66%) regarding their medical needs. There was more acceptance of hydroxychloroquine as a prophylactic drug for Covid-19 in doctors compared to nurses (p ⍰0.01).ConclusionsThough this institute was more prepared at the time of pandemic spread, substantial opportunity of improvement remains. The consistency of work and non work related anxiety and stress in health care workers is very high in present study group. Concerns and risks of Health Care Workers should be addressed ethically and adequately by strengthening safety measures and building trust in the system they work.
Outcome of hospitalisation for COVID-19 in patients with Interstitial Lung Disease: An international multicentre study.
Authors: Drake Thomas M , Docherty Annemarie B , Harrison Ewen M , Quint Jennifer K , Adamali Huzaifa , Agnew Sarah , Babu Suresh , Barber Christopher M , Barratt Shaney , Bendstrup Elisabeth , Bianchi Stephen , Villegas Diego Castillo , Chaudhuri Nazia , Chua Felix , Coker Robina , Chang William , Crawshaw Anjali , Crowley Louise E. , Dosanjh Davinder , Fiddler Christine A , Forrest Ian A. , George Peter , Gibbons Michael A , Groom Katherine , Haney Sarah , Hart Simon P , Heiden Emily , Henry Michael , Ho Ling-Pei , Hoyles Rachel K , Hutchinson John , Hurley Killian , Jones Mark , Jones Steve , Kokosi Maria , Kreuter Michael , MacKay Laura , Mahendran Siva , Margaritopoulos George , Molina-Molina Maria , Molyneaux Philip L , O’Brien Aiden , O’Reilly Katherine , Packham Alice , Parfrey Helen , Poletti Venerino , Porter Joanna , Renzoni Elisabetta , Rivera-Ortega Pilar , Russell Anne-Marie , Saini Gauri , Spencer Lisa G , Stella Giulia M. , Stone Helen , Sturney Sharon , Thickett David , Thillai Muhunthan , Wallis Tim , Ward Katie , Wells Athol U , West Alex , Wickremasinghe Melissa , Woodhead Felix , Hearson Glenn , Howard Lucy , Baillie J Kenneth , Openshaw Peter J.M. , Semple Malcolm G , Stewart Iain ,   ISARIC4C Investigators, Jenkins R Gisli 
Published: July 2020

AbstractRationaleThe impact of COVID-19 on patients with Interstitial Lung Disease (ILD) has not been established.ObjectivesTo assess outcomes following COVID-19 in patients with ILD versus those without in a contemporaneous age, sex and comorbidity matched population.MethodsAn international multicentre audit of patients with a prior diagnosis of ILD admitted to hospital with COVID-19 between 1 March and 1 May 2020 was undertaken and compared with patients, without ILD obtained from the ISARIC 4C cohort, admitted with COVID-19 over the same period. The primary outcome was survival. Secondary analysis distinguished IPF from non-IPF ILD and used lung function to determine the greatest risks of death.Measurements and Main ResultsData from 349 patients with ILD across Europe were included, of whom 161 were admitted to hospital with laboratory or clinical evidence of COVID-19 and eligible for propensity-score matching. Overall mortality was 49% (79/161) in patients with ILD with COVID-19. After matching ILD patients with COVID-19 had higher mortality (HR 1.60, Confidence Intervals 1.17-2.18 p=0.003) compared with age, sex and comorbidity matched controls without ILD. Patients with a Forced Vital Capacity (FVC) of <80% had an increased risk of death versus patients with FVC ≥80% (HR 1.72, 1.05-2.83). Furthermore, obese patients with ILD had an elevated risk of death (HR 1.98, 1.13−3.46).ConclusionsPatients with ILD are at increased risk of death from COVID-19, particularly those with poor lung function and obesity. Stringent precautions should be taken to avoid COVID-19 in patients with ILD.
Noise signature in added size suggests bacteria target a commitment size to enable division
Authors: Nieto César , Arias-Castro Juan , Vargas-García César , Sánchez Carlos , Pedraza Juan Manuel 
Published: July 2020

ABSTRACTRecent experiments suggested that sizer-like division strategy, a deviation from the adder paradigm might be produced by additional degradation events of cell division machinery molecules. We revisited single cell size data from a recently microfluidics setup using the above model. We observed that such additional degradation process, although reproduces size observations in the mean sense, it is unable to capture cell size fluctuations. We further extended recently proposed power law models to include commitment size. Our proposal is in agreement of both mean and fluctuation profiles seen in experiments. Our approach suggests further uses of noise profiles on dissecting cell size regulatory mechanisms.SIGNIFICANCEWe contrast cell division models against bacteria cell size data in minimal media. Our results seems to support the idea that division starts once bacteria meet a given commitment size.
Interleukin-10 suppression enhances T-cell antitumor immunity and responses to checkpoint blockade in chronic lymphocytic leukemia
Authors: Rivas J.R. , Liu Y. , Alhakeem S.S. , Eckenrode J.M. , Marti F. , Collard J.P. , Zhang Y. , Shaaban K.A. , Muthusamy N. , Hildebrandt G.C. , Fleischman R.A. , Chen L. , Thorson J.S. , Leggas M. , Bondada S. 
Published: July 2020

AbstractT-cell dysfunction is a hallmark of B-cell Chronic Lymphocytic Leukemia (CLL), where CLL cells downregulate T-cell responses through regulatory molecules including programmed death ligand-1 (PD-L1) and Interleukin-10 (IL-10). Immune checkpoint blockade (ICB) aims to restore T-cell function by preventing the ligation of inhibitory receptors like PD-1. However, most CLL patients do not respond well to this therapy. Thus, we investigated whether IL-10 suppression could enhance antitumor T-cell activity and responses to ICB. Since CLL IL-10 expression depends on Sp1, we utilized a novel, better tolerated analogue of the Sp1 inhibitor mithramycin (MTMox32E) to suppress CLL IL-10. MTMox32Etreatment inhibited mouse and human CLL IL-10 production and maintained T-cell effector functionin vitro. In the Eμ-Tcl1 mouse model, treatment reduced plasma IL-10 and CLL burden and increased CD8+T-cell proliferation, effector and memory cell prevalence, and interferon-γ production. When combined with ICB, suppression of IL-10 improved responses to anti-PD-L1 as shown by a 4.5-fold decrease in CLL cell burden compared to anti-PD-L1 alone. Combination therapy also produced more interferon-γ+, cytotoxic effector KLRG1+, and memory CD8+T-cells, and fewer exhausted T-cells. Since current therapies for CLL do not target IL-10, this provides a novel strategy to improve immunotherapies.
Artificial feeding of invasive grey squirrels (Sciurus carolinensis) at urban parks: a social norms approach to understand its drivers and to guide behavioral interventions
Authors: Cerri Jacopo , Martinelli Elena , Bertolino Sandro 
Published: July 2020

AbstractArtificial wildlife feeding might contribute to the successful establishment of some invasive alien species, like the Eastern grey squirrel (Sciurus carolinensis) in Europe and the UK. Reducing squirrel feeding at urban parks can be important to reduce squirrel populations while avoiding social conflicts. From April to October 2018, we conducted interviews and administered factorial surveys to two samples of visitors at the Valentino urban park in Torino (Italy). We established whether squirrel feeding can be regarded as an independent or an interdependent behavior, by eliciting visitors’ moral beliefs, and their empirical and normative expectations.Most respondents did not regard artificial feeding as something neither intrinsically positive nor negative. Satisfaction, the need for a connection with nature and the presence of children were its main causes. On the other hand, feeding squirrels was deemed to be potentially dangerous for squirrel health, and leading to high squirrel densities and to confident squirrels.Factorial surveys indicated that empirical expectations about the behavior of other visitors, altogether with their past behavior, lead visitors to feed squirrels, while the availability of suboptimal food types (e.g. sweets), was deemed to made people less prone to forage squirrels. Our findings indicate that supplementary feeding is an interdependent behavior, governed by descriptive norms. It might be reduced by means of informative panels containing descriptive information about the fact that most visitors indeed do not feed squirrels, as well as by panels emphasizing the potential damage that squirrels could suffer from eating suboptimal food provided by humans.
Nef enhances HIV-1 replication and infectivity independently of SERINC3 and SERINC5 in CEM T cells
Authors: Ramirez Peter W. , Vollbrecht Thomas , Acosta Francisco M. , Suarez Marissa , Angerstein Aaron A. , Wallace Jared , Connell Ryan M. O’ , Guatelli John 
Published: July 2020

AbstractThe lentiviralnefgene encodes several discrete activities aimed at co-opting or antagonizing cellular proteins and pathways to defeat host defenses and maintain persistent infection. Primary functions of Nef include downregulation of CD4 and MHC class-I from the cell surface, disruption or mimicry of T-cell receptor signaling, and enhancement of viral infectivity by counteraction of the host antiretroviral proteins SERINC3 and SERINC5. In the absence of Nef, SERINC5 incorporates into virions and inhibits viral fusion with target cells, decreasing infectivity. However, whether Nef’s counteraction of SERINC5 is the cause of its positive influence on viral growth-rate in CD4-positive T cells is unclear. Here, we utilized CRISPR/Cas9 to knockout SERINC3 and SERINC5 in a leukemic CD4-positive T cell line (CEM) that displays relatively robustnef-related infectivity and growth-rate phenotypes. As previously reported, viral replication was attenuated in CEM cells infected with HIV-1 lacking Nef (HIV-1ΔNef). This attenuated growth-rate phenotype was observed regardless of whether the coding regions of theserinc3orserinc5genes were intact. Moreover, knockout ofserinc3orserinc5failed to restore the infectivity of HIV1ΔNef virions produced from infected CEM cells. Taken together, our results corroborate a similar study using another T-lymphoid cell line (MOLT-3) and indicate that the antagonism of SERINC3 and SERINC5 cannot fully explain the virology of HIV-1 lacking Nef.
CRAG:De novocharacterization of cell-free DNA fragmentation hotspots in plasma whole-genome sequencing
Authors: Zhou Xionghui , Zheng Haizi , Fu Hailu , Dillehay McKillip Kelsey L. , Pinney Susan M. , Liu Yaping 
Published: July 2020

AbstractNon-random cell-free DNA fragmentation is a promising signature for cancer diagnosis. However, its aberration at the fine-scale in early-stage cancers is poorly understood. Here, we developed an approach tode novocharacterize the cell-free DNA fragmentation hotspots from whole-genome sequencing. In healthy, hotspots are enriched in gene-regulatory elements, including open chromatin regions, promoters, hematopoietic-specific enhancers, and, interestingly, 3’end of transposons. Hotspots identified in early-stage hepatocellular carcinoma patients showed overall hypo-fragmentation patterns compared to healthy controls. These cancer-specific hypo-fragmented hotspots are associated with genes enriched in gene ontologies and KEGG pathways that are related to the initiations of hepatocellular carcinoma and cancer stem cells. Further, we identified the fragmentation hotspots at 297 cancer samples across 8 different cancer types (92% in stage I to III), 103 benign samples, and 247 healthy samples. The fine-scale fragmentation level at most variable hotspots showed cancer-specific fragmentation patterns across multiple cancer types and non-cancer controls. With the fine-scale fragmentation signals alone in a machine learning model, we achieved 48% to 95% sensitivity at 100% specificity in different early-stage cancer. We further validated the model at independent datasets we generated at a small number of early-stage cancers and healthy plasma samples with matched age, gender, and lifestyle. In cancer-positive cases, we further localized cancer to a small number of anatomic sites with a median of 80% accuracy. The results highlight the significance ofde novocharacterizing the cell-free DNA fragmentation hotspots for detecting early-stage cancers and dissection of gene-regulatory aberrations in cancers.
Anti-SARS-CoV-2 IgG antibodies in adolescent students and their teachers in Saxony, Germany (SchoolCoviDD19): very low seropraevalence and transmission rates
Authors: Armann Jakob P. , Unrath Manja , Kirsten Carolin , Lück Christian , Dalpke Alexander H. , Berner Reinhard 
Published: July 2020

AbstractBackgroundSchool closures are part of the SARS-CoV-2 pandemic control measures in many countries, based on the assumption that children play a similar role in transmitting SARS-CoV-2 as they do in transmitting influenza. We therefore performed a SARS-CoV-2 seropraevalence-study in students and teachers to assess their role in the SARS-CoV-2 transmission.MethodsStudents grade 8–11 and their teachers in 13 secondary schools in eastern Saxony, Germany, were invited to participate in the SchoolCoviDD19 study. Blood samples were collected between May 25th and June 30th, 2020. Anti-SARS-CoV-2 IgG were assed using chemiluminescence immunoassay technology and all samples with a positive or equivocal test result were re-tested with two additional serological tests.Findings1538 students and 507 teachers participated in this study. The seropraevalence for SARS-CoV-2 was 0.6%. Even in schools with reported Covid-19 cases before the Lockdown of March 13th no clusters could be identified. 23/24 participants with a household history of COVID-91 were seronegative. By using a combination of three different immunoassays we could exclude 16 participants with a positive or equivocal results after initial testing.InterpretationStudents and teachers do not play a crucial role in driving the SARS-CoV-2 pandemic in a low prevalence setting. Transmission in families occurs very infrequently, and the number of unreported cases is low in this age group, making school closures not appear appropriate as a strategy in this low prevalence settings.FundingThis study was supported by a grant from the state of Saxony