bluuebunny/crossref_metadata_2025_split huggingface dataset:
N95 Filtering Facepiece Respirators Remain Effective After Extensive Reuse During the COVID-19 Pandemic
Authors: Fabre Valeria , Cosgrove Sara E. , Hsu Yea-Jen , Jones George , Helsel Taylor , Bukowski James , Sobota Mark , Sick-Samuels Anna C. , Milstone Aaron M. , Maragakis Lisa L. , Rock Clare ,   for the Centers for Disease Control and Prevention Epicenters Program
Published: December 2020

AbstractIn a cross-sectional evaluation of healthcare worker reuse of their own 3M N95 respirators, 83% (76/92) passed the seal check and the fit-test after a median of 40 repeated donnings. The user seal-check had 31% sensitivity to detect N95 respirator failure but 100% specificity.
Self-harm and the COVID-19 pandemic: a study of factors contributing to self-harm during lockdown restrictions
Authors: Hawton Keith , Lascelles Karen , Brand Fiona , Casey Deborah , Bale Liz , Ness Jennifer , Kelly Samantha , Waters Keith 
Published: December 2020

ABSTRACTIntroductionThe COVID-19 pandemic and resulting public health measures may have major impacts on mental health, including on self-harm. We have investigated what factors related to the pandemic influenced hospital presentations following self-harm during lockdown in England.MethodMental health clinicians assessing individuals aged 18 years and over presenting to hospitals in Oxford and Derby following self-harm during the period March 23rd to 17th May 2020 recorded whether the self-harm was related to the impact of COVID- 19 and, if so, what specific factors were relevant. These factors were organized into a classification scheme. Information was also collected on patients’ demographic characteristics, method of self-harm and suicide intent.ResultsOf 228 patients assessed, in 46.9% (N=107) COVID-19 and lockdown restrictions were identified as influencing self-harm. This applied more to females than males (53.5%, N=68/127 v 38.6%, N=39/101, χ2 = 5.03, p=0.025), but there were no differences in age, methods of self-harm or suicide intent between the two groups. The most frequent COVID-related factors were mental health issues, including new and worsening disorders, and cessation or reduction of services (including absence of face-to-face support), isolation and loneliness, reduced contact with key individuals, disruption to normal routine, and entrapment. Multiple, often inter- connected COVID-related factors were identified in many patients.ConclusionsCOVID-related factors were identified as influences in nearly half of individuals presenting to hospitals following self-harm in the period following introduction of lockdown restrictions. Females were particularly affected. The fact that mental health problems, including issues with delivery of care, predominated has implications for organisation of services during such periods. The contribution of isolation, loneliness and sense of entrapment highlight the need for relatives, friends and neighbours to be encouraged to reach out to others, especially those living alone. The classification of COVID-related factors can be used as an aide-memoire for clinicians.
Fatigue outcomes following coronavirus or influenza virus infection: A systematic review and meta-analysis
Authors: Poole-Wright Kim , Gaughran Fiona , Evans Rachael , Chalder Trudie 
Published: December 2020

ABSTRACTObjectivesFatigue is a pervasive clinical symptom for many infected with respiratory viruses such as influenza or coronaviruses. Prior evidence from influenza and coronavirus epidemics suggest that fatigue symptomology may continue beyond the acute phase, lasting for several months to several years post-discharge. This systematic review aimed to examine long-term fatigue prevalence among survivors and among communities, as well as investigate the current evidence for associated factors.DesignSystematic review and meta-analysis.SettingHospitalised and community samples.ParticipantsPatient populations with a confirmed diagnosis of a named influenza virus or coronavirus.Main outcomes measuredFatigue, fatigue syndromesResultsTen studies met the inclusion criteria for a pooled prevalence analysis and five studies were identified as eligible for a means differences analysis. A fatigue prevalence of 41% (95% CI 0.299-0.488) was found among a total population of 1,310. Using the ‘vitality’ subscale of the SF-36 as a proxy for fatigue, the estimate for means differences indicated a lower mean vitality score for survivors compared to population norms (M -1.523, CI -13.53 – 10.48), although this was not significant (p = 0.803). The most common associations with fatigue were PTSD, depression and anxiety, female gender and higher age.ConclusionsThis study reveals that a significant proportion of survivors (41%) experienced fatigue following their recovery from novel respiratory viruses such as SARS, MERS, SARS-CoV2 or influenza and that this fatigue can be long-lasting. Also, some factors such as female gender and psychological factors may contribute to continuing fatigue outcomes for this population.Strengths and limitations(a) this study provides support for long-term fatigue outcomes in people with a confirmed influenza, SARS, MERS, SARS-CoV2 virus infection (b) the study suggests individual, psychological and social factors are associated with fatigue, (c) findings are limited by the availability of fatigue data and lack of pre-morbid fatigue information; (d) a meta-analysis on the associations was prohibited by the small number of studies investigating long-term fatigue correlates and (e) the heterogeneity of the studies (>75%) suggests the pooled estimates should be interpreted with caution.
Retrospective analysis ofThe Two Sister Studyusing haplotype-based association testing to identify loci associated with early-onset breast cancer
Authors: Gilbert James R. , Cray James J. , Losee Joseph E. , Cooper Gregory M. 
Published: December 2020

ABSTRACTBreast cancer is a polygenic disorder and is the leading cause of cancer related mortality among women. Early-onset breast cancer (EOBC) is diagnosed in women prior to 45 years-of-age and is associated with worse clinical outcomes, a more aggressive disease phenotype, and poor prognosis for disease-free survival. While substantial progress has been made in defining the genetics of breast cancer, EOBC remains less well understood. In the current study we perform a retrospective analysis of data derived fromThe Two Sister Study. The use of alternate strategies for handling age-at-diagnosis in conjunction with haplotype-based methods yielded novel findings that help to explain the heritability of EOBC. These findings are validated through comparison against discordant sibs fromThe Two Sister Studyas well as using data derived The Cancer Genome Atlas (TCGA).
PD-L1 expression is associated with higher residual cancer burden in triple-negative breast cancers with residual disease after neoadjuvant chemotherapy
Authors: Grandal Beatriz , Mangiardi-Veltin Manon , Laas Enora , Laé Marick , Meseure Didier , Bataillon Guillaume , El-Alam Elsy , Darrigues Lauren , Dumas Elise , Daoud Eric , Vincent-Salomon Anne , Talagrand Laure-Sophie , Pierga Jean-Yves , Reyal Fabien , Hamy Anne-Sophie 
Published: December 2020

AbstractThe consequences of neoadjuvant chemotherapy (NAC) for PD-L1 activity in triple-negative breast cancers (TNBC) are not well understood. This is an important issue as immune checkpoint inhibitors (ICI) are undergoing rapid development and could be beneficial in patients who do not achieve a pathological complete response. We used immunohistochemistry to assess PD-L1 expression (E1L3N clone, cutoff for positivity: ≥ 1%) on both tumor (PD-L1-TC) and immune cells (PD-L1-IC) from a cohort of surgical specimens of T1-T3NxM0 TNBCs treated with NAC. PD-L1-TC was detected in 17 cases (19.1%) and PD-L1-IC in 14 cases (15.7%). None of the baseline characteristics of the tumor or the patient were associated with PD-L1 positivity, except for pre-NAC stromal TIL levels, which were higher in post-NAC PD-L1-TC-positive than in negative tumors. PD-L1-TC were significantly associated with a higher residual cancer burden (p=0.035) and aggressive post-NAC tumor characteristics, whereas PD-L1-IC were not. PD-L1 expression was not associated with DFS (p=0.38) or OS (p=0.48), but high Ki67 levels after NAC were strongly associated with a poor prognosis (DFS p=0.0014 and OS p=0.001). A small subset of TNBC patients displaying PD-L1 expression in the context of an extensive post-NAC tumor burden could benefit from ICI treatment after standard NAC.
Strong association between Apgar score at 5 minutes and neonatal survival among at-risk neonates
Authors: Dueñas-Espín Iván , Aguilar-Molina Andrea , Aguinaga Fernando , Armijos-Acurio Luciana , Jimbo Ruth , León-Cáceres Ángela , Rivadeneira María F. , Rivera-Guerra Silvana , Sánchez Xavier 
Published: December 2020

AbstractObjectiveTo assess the association between 5-minutes Apgar score and neonatal survival among at-risk neonates.DesignRetrospective survival analysis.SettingEcuadorian neonates who died at ≤28 days of life.PatientsWe analyzed the nationwide neonatal deaths registered by the Ministry of Public Health of Ecuador between January 2014 to September 2017.Main outcome measuresWe performed a survival analysis and estimated adjusted hazard ratios (HR)pereach 5-minutes Apgar scorestratum, by Cox proportional hazards models.ResultsWe included in the study 2893 neonates, 1380 (48%) were female and had a median (P25 to P75) gestational age at birth of 31 (27 to 36) weeks. On univariate analyses, the median survival time in days of life was significantly longer per each increase in the 5-minutes Apgar score, as follows: 0.2 days for ≤4 points, 2 days for 5 points, 2.9 days for 6 points, 3.1 days for 7 points, 3.8 days for 8 points, 4.4 days for 9 points, and 5.5 days for 10 points. On multivariate analyses, and after adjusting for individual and contextual variables, and considering an Apgar score of 9 to 10 points as the reference, the HR was 32% (95% CI: 27% to 37%) higher per each decrease in the Apgar score category of two-to-three points (p-valuefor trend <0.01).ConclusionsThere is a strong direct association between Apgar score at 5 minutes and neonatal survival in neonates considered at-risk. This association is independent of gestational age and other neonatal determinants of neonatal mortality.
GeneTerpret: a customizable multilayer approach to genomic variant prioritization and interpretation
Authors: Manshaei Roozbeh , DeLong Sean , Andric Veronica , Joshi Esha , Okello John B. A. , Dhir Priya , Farncombe Kirsten M. , Kalbfleisch Kelsey , Somerville Cherith , Jobling Rebekah K. , Scherer Stephen W. , Kim Raymond H. , Hosseini S. Mohsen 
Published: December 2020

ABSTRACTVariant interpretation is the main bottleneck in medical genomic sequencing efforts. This usually involves genome analysts manually scouring through a multitude of independent databases, often with the aid of several and mostly independent computational tools.To streamline the variant interpretation process, we developedGeneTerpretplatform that collates data from current interpretation tools and databases, and applies a phenotype-driven query to categorize the variants identified in a given genome. The platform assigns quantitative validity scores to genes by query and assembly of the current genotype-phenotype data, sequence homology, molecular interactions, expression data, and animal models. The platform uses the American College of Medical Genetics (ACMG) criteria to categorize variants into five tiers (from benign to pathogenic). The platform then outputs a prioritized list of potentially causal variants/genes in a given genome for a specific case.GeneTerpretis a flexible and free platform designed to streamline the variant interpretation process through a unique interface, with improved ease, speed and accuracy. This unique integrated system provides effective validity and pathogenicity modules to assess genetic variant data and allows the user to decide which output and impact level should be considered in this process. The platform can be accessed and used online athttps://geneterpret.com.
Ppard Is Essential in Acceleration of Pancreatic Ductal Adenocarcinoma Development by High-Fat Diet in MutantKrasMice
Authors: Liu Yi , Deguchi Yasunori , Wei Daoyan , Moussalli Micheline J. , Li Donghui , Wang Huamin , Valentin Lovie Ann , Colby Jennifer K. , Liu Fuyao , Wang Jing , Zheng Xiaofeng , Ji Baoan , Yao James C. , Zuo Xiangsheng , Shureiqi Imad 
Published: December 2020

AbstractPro-obesity high-fat diet is linked with an increased incidence of pancreatic cancers, but the molecular underpinnings of this association remain poorly understood. Here, we report that PPARD is upregulated in pancreatic intraepithelial neoplasia lesions (PanINs) at early stages of pancreatic tumorigenesis in humans and mutantKrasmice. Transgenic overexpression of Ppard in pancreatic epithelial cells drastically accelerates the development and progression of pancreatic ductal adenocarcinoma in mutantKrasmice when activated by feeding the mice with a high-fat diet or a diet containing GW501516 (50 mg/kg), a selective PPARD agonist. In contrast, pancreatic Ppard genetic deletion significantly suppressed the promotion of pancreatic tumorigenesis by these diets. Mechanistically, we found that this Ppard hyperactivation in pancreatic epithelial cells of mutantKrasmice increased production of chemokines and cytokines (e.g., CcI2, CcI4-5, CxcI5 and II6), leading to the robustly increased recruitment of myeloid-derived suppressor cells and macrophages into pancreata, which fostered an immune suppressive microenvironment and subsequently accelerated pancreatic ductal adenocarcinoma development and progression. Our findings demonstrate that PPARD plays an essential role in the promotion of pancreatic tumorigenesis by a high-fat diet. Targeted inhibition of PPARD activation is a potential interventive strategy for pancreatic cancer prevention and therapy.
Decontamination of Common Healthcare Facility Surfaces Contaminated with SARS-CoV-2 using Peracetic Acid Dry Fogging
Authors: Cutts Todd , Kasloff Samantha , Safronetz David , Krishnan Jay 
Published: December 2020

BackgroundThe SARS-Cov-2 pandemic has highlighted the urgent need for safe and effective surface decontamination methods, particularly in healthcare settings.MethodsThe effectiveness of peracetic acid (PAA) dry fogging in decontaminating common healthcare setting surfaces was evaluated after experimentally contaminating nine surfaces (stainless steel, latex painted wood, unsealed hardwood, melamine countertop, vinyl flooring, clear plastic, faux leather, computer keyboard button and smartphone touch screen) with more than 106 TCID50 of SARS-CoV-2.ResultsWhen fumigated with PAA dry fog for an hour, no infectious SARS-CoV-2 virus was recovered from experimentally inoculated coupons of representing nine different surface types. In contrast, high titer recovery of infectious virus was demonstrated for corresponding untreated drying controls of the same materials.ConclusionStandard surface decontaminating processes, including sprays and wipes, are laborious and often cannot completely decontaminate sensitive electronic equipment. The ease of use, low cost and overall effectiveness of a PAA dry fogging suggest it should be considered for decontaminating settings, particularly intensive care units where severely ill SARS-CoV-2 patients are cared for.
Double Mammary In Situ: Predicting Feasibility of Right Mammary Artery In Situ for Circumflex Coronary Artery System
Authors: Margaryan Rafik , Latta Daniele Della , Bianchi Giacomo , Martini Nicola , Gori Andrea , Solinas Marco 
Published: December 2020

AbstractObjectivesDouble (bilateral) mammary artery in situ revascularization seems less attractive to surgeons because of limited mammary length of right mammary artery, scare, or no means of its length estimation.MethodsWe’ve selected patients who have used bilateral mammary artery for revascularization and divvied them into two groups: in situ and y-graft groups. We have used preoperative chest x-rays to build a predictive model with neural networks that could predict feasibility of in situ bilateral mammary revascularization.ResultsThe predictive model was able to predict a positive outcome with 96% percent accuracy (p < 0.01). Models sensitivity and specificity were 96% and 95% respectively. Neural networks can be used to predict double mammary feasibility using chest x-rays. Model is capable of predicting positive outcomes with 95% accuracy.ConclusionsChest x-ray base model can accurately predict the feasibility of in situ bilateral mammary artery revascularization.
Seroconversion stages COVID19 into distinct pathophysiological states
Authors: Galbraith Matthew D. , Kinning Kohl T. , Sullivan Kelly D. , Baxter Ryan , Araya Paula , Jordan Kimberly R. , Russell Seth , Smith Keith P. , Granrath Ross E. , Shaw Jessica , Dzieciatkowska Monika , Ghosh Tusharkanti , Monte Andrew A. , D’Alessandro Angelo , Hansen Kirk C. , Bennett Tellen D. , Hsieh Elena W.Y. , Espinosa Joaquin M. 
Published: December 2020

ABSTRACTCOVID19 is a heterogeneous medical condition involving a suite of underlying pathophysiological processes including hyperinflammation, endothelial damage, thrombotic microangiopathy, and end-organ damage. Limited knowledge about the molecular mechanisms driving these processes and lack of staging biomarkers hamper the ability to stratify patients for targeted therapeutics. We report here the results of a cross-sectional multi-omics analysis of hospitalized COVID19 patients revealing that seroconversion status associates with distinct underlying pathophysiological states. Seronegative COVID19 patients harbor hyperactive T cells and NK cells, high levels of IFN alpha, gamma and lambda ligands, markers of systemic complement activation, neutropenia, lymphopenia and thrombocytopenia. In seropositive patients, all of these processes are attenuated, observing instead increases in B cell subsets, emergency hematopoiesis, increased markers of platelet activation, and hypoalbuminemia. We propose that seroconversion status could potentially be used as a biosignature to stratify patients for therapeutic intervention and to inform analysis of clinical trial results in heterogenous patient populations.
Genome-Wide Polygenic Scores for Common Traits and Psychiatric Disorders Identify Young Children with Risk for Suicides
Authors: Joo Yoonjung Yoonie , Moon Seo-Yoon , Wang Hee-Hwan , Kim Hyeonjin , Lee Eun-Ji , Jung Seung-Min , Ahn Woo-Young , Choi Incheol , Kim Jae-Won , Cha Jiook 
Published: December 2020

AbstractBackgroundSuicide is the leading cause of death in youth worldwide.1 Identifying children with high risk for suicide remains challenging.2 Here we test the extents to which genome-wide polygenic scores (GPS) for common traits and psychiatric disorders are linked to the risk for suicide in young children.MethodsWe constructed GPSs of 24 traits and psychiatric disorders broadly related to suicidality from 8,212 US children with ages of 9 to 10 from the Adolescent Brain Cognitive Development study. We performed multiple logistic regression to test the association between childhood suicidality, defined as suicidal ideation or suicidal attempt, and the GPSs. Machine learning techniques were used to test the predictive utility of the GPSs and other phenotypic outcomes on suicide and suicidal behaviors in the youth.OutcomesWe identified three GPSs significantly associated with childhood suicidality: Attention deficit hyperactivity disorder (ADHD) (P = 2.83×10−4; odds ratio (OR) = 1.12, FDR correction), general happiness with belief that own life is meaningful (P = 1.30×10−3; OR = 0.89) and autism spectrum disorder (ASD) (P = 1.81×10−3; OR = 1.14). Furthermore, the ASD GPS showed significant interaction with ELS such that a greater polygenic score in the presence of a greater ELS has even greater likelihood of suicidality (with active suicidal ideation, P = 1.39×10−2, OR = 1.11). In machine learning predictions, the cross validated and optimized model showed an ROC-AUC of 0.72 and accuracy of 0.756 for the hold-out set of overall suicidal ideation prediction, and showed an ROC-AUC of 0.765 and accuracy of 0.750 for the hold-out set of suicidal attempts.InterpretationOur results show that childhood suicidality is linked to the GPSs for psychiatric disorders, ADHD and ASD, and for a common trait, general happiness, respectively; and that GPSs for ASD and insomnia, respectively, have synergistic effects on suicidality via an interaction with early life stress. By providing the quantitative account of the polygenic and environmental factors of childhood suicidality in a large, representative population, this study shows the potential utility of the GPS in investigation of childhood suicidality for early screening, intervention, and prevention.
Features and outcomes of secondary sepsis and urinary tract infections in COVID-19 patients treated with stem cell nebulization
Authors: Torres Zambrano Gina M. , Rivero Rene Antonio , Villegas Valverde Carlos A. , Carmenate Yendry Ventura 
Published: December 2020

AbstractBackgroundCOVID-19 is the defining global crisis of our time. Secondary complication such as urinary tract infections and sepsis, worsen the already established problem, creating a new challenge.ObjectiveTo characterize the features and outcomes in COVID-19 patients with sepsis and urinary tract infection.MethodsAn observational and analytical study was conducted within the framework of the SENTAD COVID clinical trial at the Abu Dhabi Stem Cells Center, were the patients received a nebulization therapy with the use of autologous stem cells (group A). Those patients were compared with a not stem cells treated control arm (group B), and both received the UAE COVID 19 standard management. An analysis of the culture samples, antimicrobial agents and the efficacy of the therapy on patient’s outcomes was done.ResultsA significant difference between the groups was found in the UTI incidence (p=*0.0206). Patients in group A showed a lower tendency to sepsis in comparison with group B (7% vs 21%), HR=0.35, (95% Confidence Interval: 0.13 – 0.91), p=0.0175. It was calculated a NNT=7.3. Candida albicans was the most frequently agent causing sepsis and UTI. The massive use of broad-spectrum antimicrobials was striking.ConclusionsWe found a protective factor of stem cells against secondary infection in COVID 19 cases, in terms of sepsis and UTI. The suggested immunomodulatory effect of stem cells offers a therapeutic strategy to manage the disease and avoid several complications. Antimicrobial agents can lead to increased opportunistic infections, so a rational approach to these treatments must be considered.
Visualizing subcellular structures in neuronal tissue with expansion microscopy
Authors: Campbell Logan A. , Pannoni Katy E. , Savory Niesha A. , Lal Dinesh , Farris Shannon 
Published: December 2020

ABSTRACTProtein expansion microscopy (proExM) is a powerful technique that crosslinks proteins to a swellable hydrogel to physically expand and optically clear biological samples. The resulting increased resolution (~70 nm) and physical separation of labeled proteins make it an attractive tool for studying the localization of subcellular organelles in densely packed tissues, such as the brain. However, the digestion and expansion process greatly reduces fluorescence signals making it necessary to optimize ExM conditions per sample for specific end goals. Here we describe a proExM workflow optimized for resolving subcellular organelles (mitochondria and the Golgi apparatus) and reporter-labeled spines in fixed mouse brain tissue. By directly comparing proExM staining and digestion protocols, we found that immunostaining before proExM and using a proteinase K based digestion for 8 hours consistently resulted in the best fluorescence signal to resolve subcellular organelles while maintaining sufficient reporter labeling to visualize spines and trace individual neurons. With these methods, we more accurately quantified mitochondria size and number and better visualized Golgi ultrastructure in reconstructed CA2 neurons of the hippocampus.