bluuebunny/crossref_metadata_2025_split huggingface dataset:
Common genetic and clinical risk factors: Association with fatal prostate cancer in the Cohort of Swedish Men
Authors: Huynh-Le Minh-Phuong , Karunamuni Roshan , Fan Chun Chieh , Thompson Wesley K. , Muir Kenneth , Lophatananon Artitaya , Tye Karen , Wolk Alicja , Håkansson Niclas , Mills Ian G. , Andreassen Ole A. , Dale Anders M. , Seibert Tyler M. ,   The PRACTICAL Consortium
Published: September 2020

AbstractBackgroundClinical variables—age, family history, genetics—are used for prostate cancer risk stratification. Recently, polygenic hazard scores (PHS46, PHS166) were validated as associated with age at prostate cancer diagnosis. While polygenic scores are associated with all prostate cancer (not specific for fatal cancers), PHS46 was also associated with age at prostate cancer death. We evaluated if adding PHS to clinical variables improves associations with prostate cancer death.MethodsGenotype/phenotype data were obtained from a nested case-control Cohort of Swedish Men (n=3,279; 2,163 with prostate cancer, 278 prostate cancer deaths). PHS and clinical variables (family history, alcohol intake, smoking, heart disease, hypertension, diabetes, body mass index) were tested via univariable Cox proportional hazards models for association with age at prostate cancer death. Multivariable Cox models with/without PHS were compared with log-likelihood tests.ResultsMedian age at last follow-up/prostate cancer death were 78.0 (IQR: 72.3-84.1) and 81.4 (75.4-86.3) years, respectively. On univariable analysis, PHS46 (HR 3.41 [95%CI 2.78-4.17]), family history (HR 1.72 [1.46-2.03]), alcohol (HR 1.74 [1.40-2.15]), diabetes (HR 0.53 [0.370.75]) were each associated with prostate cancer death. On multivariable analysis, PHS46 (HR 2.45 [1.99-2.97]), family history (HR 1.73 [1.48-2.03]), alcohol (HR 1.45 [1.19-1.76]), diabetes (HR 0.62 [0.42-0.90]) all remained associated with fatal disease. Including PHS46 or PHS166 improved multivariable models for fatal prostate cancer (p<10-15).ConclusionsPHS had the most robust association with fatal prostate cancer in a multivariable model with common risk factors, including family history.ImpactAdding PHS to clinical variables may improve prostate cancer risk stratification strategies.
Dual methylation and hydroxymethylation study of alcohol use disorder
Authors: Clark Shaunna L. , Chan Robin F. , Zhao Min , Xie Lin Y. , Copeland William E. , Penninx Brenda W.J.H. , Aberg Karolina A. , van den Oord Edwin J.C.G. 
Published: September 2020

ABSTRACTUsing an integrative, multi-tissue design we sought to characterize methylation and hydroxymethylation changes in blood and brain associated with alcohol use disorder (AUD). First, we used epigenomic deconvolution to perform cell-type specific methylome-wide association studies within subpopulations of granulocytes/T-cells/B-cells/monocytes in 1,132 blood samples. Blood findings were then examined for overlap with AUD-related associations in methylation and hydroxymethylation in 50 human post-mortem brain samples. Follow-up analyses investigated if overlapping findings mediated AUD-associated transcription changes in the same brain samples. Lastly, we replicated our blood findings in an independent sample of 412 individuals and aimed to replicate published alcohol methylation findings using our results.Cell-type specific analyses in blood identified methylome-wide significant associations in monocytes and T-cells. The monocyte findings were significantly enriched for AUD-related methylation and hydroxymethylation in brain. Hydroxymethylation in specific sites mediated AUD-associated transcription in the same brain samples. As part of the most comprehensive methylation study of AUD to date, this work involved the first cell-type specific methylation study of AUD conducted in blood, identifying and replicating a finding in DLGAP1 that may be involved in AUD-related brain impairment. In this first study to consider the role of hydroxymethylation in AUD, we found evidence for a novel mechanism for cognitive deficits associated with AUD. Our results suggest promising new avenues for AUD research.
How the clinical research community responded to the COVID-19 pandemic: An analysis of the COVID-19 clinical studies in ClinicalTrials.gov
Authors: He Zhe , Erdengasileng Fnu , Luo Xiao , Xing Aiwen , Charness Neil , Bian Jiang 
Published: September 2020

AbstractObjectiveThe novel coronavirus disease (COVID-19), broke out in December 2019, is a global pandemic. Rapidly in the past few months, a large number of clinical studies have been initiated worldwide to find effective therapeutics, vaccines, and preventive strategies. In this study, we aim to understand the landscape of COVID-19 clinical research and identify the gaps and issues that may cause difficulty in recruitment and the lack of population representativeness.Materials and MethodsWe analyzed 2,034 COVID-19 studies registered in the largest public registry - ClinicalTrials.gov. Leveraging natural language processing, descriptive analysis, association analysis, and clustering analysis, we characterized COVID-19 clinical studies by phase and design features. Particularly, we analyzed their eligibility criteria to understand: (1) whether they considered the reported underlying health conditions that may lead to severe illnesses, and (2) if these studies excluded older adults, either explicitly or implicitly, which may reduce the generalizability of these studies in older adults.ResultsThe 5 most frequently tested drugs are Hydroxychloroquine (N=148), Azithromycin (N=46), Tocilizumab (N=29), Lopinavir (N=20), and Ritonavir (N=20). Most trials did not have an upper age limit and did not exclude patients with common chronic conditions such as hypertension and diabetes that are prevalent in older adults. However, known risk factors that may lead to severe illnesses have not been adequately considered by existing studies.ConclusionsA careful examination of the registered COVID-19 clinical studies can identify the research gaps and inform future COVID-19 trial design towards balanced internal validity and generalizability.
Childhood Vitiligo: A Retrospective Clinico-Epidemiological Study
Authors: Ahmed Ahmed Abdul-Aziz , Ahmed Hayder Saad , Mohammed Mustafa Hameed , Shanshal Mohammed 
Published: September 2020

ABSTRACTBackgroundVitiligo is an acquired depigmentary disorder of the skin, mucous membrane and hair follicle resulting from selective destruction of melanocytes.Aims of StudyIdentify the clinico-epidemiological characteristics of childhood vitiligo.Patients and MethodsA retrospective study carried out at the dermato-venereology clinic of Salah Al-Din Hospital. A total of 120 vitiligo patients, all younger than 17 years old, were enrolled.ResultsAmong included patients, (40%) were male and (60%) were female (M:F=2:3). The mean age of onset was (11.5±6.4 years) with (60.8%) of patients were (11-17) years old, (25%) were (6-11) years and (14.2%) were (0-5) years old. Majority of patients were from urban area (87.5%). Generalized types of vitiligo account for (56.7%) besides (22.5%), (17.5%) and (3.3%) represented focal, acrafacial and segmental vitiligo, respectively. Only (8.3%) have nail changes, presented as longitudinal ridging followed by leukonychia. Family history was positive in (37.5%) of vitiligo patients. Treatment used for vitiligo were topical corticosteroids (92.5%), topical calcineurin inhibitors (55%), NB-UVB (84.2%), and systemic steroids (30.8%).ConclusionsMajority of childhood vitiligo develops after puberty and predominantly affects female. Generalized vitiligo is the most frequent type. Atopic dermatitis is the most common associated disease.
Seroprevalence of SARS-CoV-2 among adults in three regions of France following the lockdown and associated risk factors: a multicohort study
Authors: Carrat Fabrice , de Lamballerie Xavier , Rahib Delphine , Blanché Hélène , Lapidus Nathanael , Artaud Fanny , Kab Sofiane , Renuy Adeline , de Edelenyi Fabien Szabo , Meyer Laurence , Lydié Nathalie , Charles Marie-Aline , Ancel Pierre-Yves , Jusot Florence , Rouquette Alexandra , Priet Stéphane , Saba Villarroel Paola Mariela , Fourié Toscane , Lusivika-Nzinga Clovis , Nicol Jerome , Legot Stephane , Druesne-Pecollo Nathalie , Esseddik Younes , Lai Cindy , Gagliolo Jean-Marie , Deleuze Jean-François , Bajos Nathalie , Severi Gianluca , Touvier Mathilde , Zins Marie ,   for the SAPRIS and SAPRIS-SERO study groups
Published: September 2020

AbstractBackgroundTo estimate the seroprevalence of SARS-CoV-2 infection in May-June 2020 after the lockdown in adults living in three regions in France and to identify the associated risk factors.MethodsParticipants in a survey on COVID-19 from an existing consortium of three general adult population cohorts living in the Ile-de-France (IDF) or Grand Est (GE) - two regions with high rate of COVID-19, or in the Nouvelle-Aquitaine (NA) – with a low rate, were asked to take a dried-blood spot (DBS) for anti-SARS-CoV-2 antibodies assessment.The primary outcome was a positive anti-SARS-CoV-2 ELISA IgG result against the spike protein of the virus (ELISA-S). The secondary outcomes were a positive ELISA IgG against the nucleocapsid protein (ELISA-NP), anti-SARS-CoV-2 neutralizing antibodies titers ≥40 (SN), and predicted positivity obtained from a multiple imputation model (MI). Prevalence estimates were adjusted using sampling weights and post-stratification methods.FindingsBetween May 4, 2020 and June 23, 2020, 16,000 participants were asked to provide DBS, and 14,628 were included in the analysis, 983 with a positive ELISA-S, 511 with a positive ELISA-NP, 424 with SN≥40 and 941±31 with a positive MI. Adjusted estimates of seroprevalence (positive ELISA-S) were 10.0% (95%CI 9.1%;10.9%) in IDF, 9.0% (95%CI 7.7%; 10.2%) in GE and 3.1% (95%CI 2.4%; 3.7%), in NA. The adjusted prevalence of positive ELISA-NP, SN and MI were 5.7%, 5.0% and 10.0% in IDF, 6.0%, 4.3% and 8.6% in GE, and 0.6%, 1.3% and 2.5% in NA, respectively. A higher seroprevalence was observed in younger participants and when at least one child or adolescent lived in the same household. A lower seroprevalence was observed in smokers compared to non-smokers.InterpretationAt the end of the lockdown the prevalence of anti-SARS-CoV-2 IgG or neutralizing antibodies remained low in the French adult population, even in regions with high reported rates of COVID-19.
“Social distancing: barriers to its implementation and how they can be overcome – a rapid systematic review and synthesis of qualitative studies”
Authors: Sadjadi Mahan , Mörschel Katharina Selda , Petticrew Mark 
Published: September 2020

AbstractAimTo systematically review qualitative literature on social distancing in order to identify and describe factors that enable or prevent its implementation.MethodsA rapid systematic qualitative review was conducted in accordance with PRISMA and ENTREQ guidelines. A comprehensive systematic search was carried out in MEDLINE, EMBASE, PsychINFO, Global Health, CINAHL and Web of Science. Included papers (i) report on primary qualitative studies (ii) of the barriers and facilitators to the implementation of social distancing measures (iii) in potentially epidemic infectious diseases. After critical appraisal and standardised data extraction, a meta-ethnographical approach was used for synthesis. Review findings were assessed for strength and reliability using CerQUAL.Results28 papers were included from the systematic search that yielded 5620 results. One additional paper was found by searching references. The review identifies two broad categories of barriers to social distancing measures: individual- or community-level psychological or sociological phenomena, and perceived shortcomings in governmental action. Based on this, 25 themes are identified that can be addressed to improve the implementation of social distancing.ConclusionThere are many barriers, on different levels, to the implementation of social distancing measures. Among other findings, the review identifies the need for good communication as well as the need for authorities to provide comprehensive support as two key opportunities to increase acceptability and adherence. High-quality research is needed during the COVID-19 pandemic to better describe mechanisms by which implementation of social distancing can be improved, and, more importantly, what is already known has to be put into practice.
LDL/Apo B ratio and Lp (a) Each Predict Coronary Artery Disease in Type2 Diabetes Independent of ASCVD Risk Score: A Case-Cohort Study
Authors: Rabizadeh Soghra , Rajab Armin , Mechanick Jeffrey I. , Moosaie Fatemeh , Rahimi Yekta , Nakhjavani Manouchehr , Esteghamati Alireza 
Published: September 2020

AbstractAimTo evaluate the predictive value of the LDL-C/ApoB ratio for coronary heart disease (CHD) in patients with type2 diabetes (T2D).MethodsIn this case-cohort study, (apo)lipoproteins and glycemic indices were measured in 1058 individuals with T2D from February 2002 to March 2019, with a median duration of follow up of 10 years.ResultsOf 1058 patients with T2D, coronary heart disease occurred in 242 patients. Increased waist circumference, waist-to-hip ratio, and hemoglobin A1c, low-density lipoprotein cholesterol (LDL-C)/Apolipoprotein B (ApoB) ratio, presence of hypertension and metabolic syndrome, and insulin and statin use were more prevalent among patients with CHD (P<0.001). Logistic regression analysis showed that an LDL-C/ApoB ratio equal or lower than 1.2, as well as a Lp(a) cutoff level more than 25.45 mg/dl could each predict CHD independent of ASCVD risk score [adjusted OR:1.841, CI:1.257 – 2.698, P<0.001 and adjusted OR: 1.433, CI:1.014 – 2.026, P=0.041) respectively] when adjusted for multiple confounders.The atherogenic index of plasma (AIP) did not predict CHD.ConclusionThis study showed that LDL-C/ApoB ratio and Lp(a) each, but not the atherogenic index of plasma, may be considered as an indicator of CHD independent of ASCVD risk score in patients with T2D. This finding merits further clarification to optimize preventive strategies for CHD.
Contrasting recruitment of skin-associated adipose depots during cold challenge of mouse and human
Authors: Kasza Ildiko , Kühn Jens-Peter , Völzke Henry , Hernando Diego , Xu Yaohui G. , Siebert John W. , Gibson Angela LF , Yen C.-L. Eric , Nelson David W. , MacDougald Ormond A. , Richardson Nicole E. , Lamming Dudley W. , Kern Philip A. , Alexander CM 
Published: September 2020

ABSTRACTMammalian skin impacts metabolic efficiency system-wide, controlling the rate of heat loss and consequent heat production. Here we compare the unique fat depots associated with mouse and human skin, to determine whether they have corresponding function and regulation. For human, we assay a skin-associated fat (SAF) body-wide depot to distinguish it from the subcutaneous fat pads characteristic of abdomen and upper limbs. We show that the thickness of SAF is not related to general adiposity; it is much thicker (1.6-fold) in women than men, and highly subject-specific. We used molecular and cellular assays of β-adrenergic induced lipolysis and found that dermal white adipose tissue (dWAT) in mice is resistant to lipolysis; in contrast, the body-wide human SAF depot becomes lipolytic, generating heat in response to β-adrenergic stimulation. In mice challenged to make more heat to maintain body temperature (either environmentally or genetically), there is a compensatory increase in thickness of dWAT: A corresponding β-adrenergic stimulation of human skin adipose (in vivoor in explant) depletes adipocyte lipid content. We summarize the regulation of skin-associated adipocytes by age, sex, and adiposity, for both species. We conclude that the body-wide dWAT depot of mice shows unique regulation that enables it to be deployed for heat preservation; combined with the actively lipolytic subcutaneous mammary fat pads they enable thermal defense. The adipose tissue that covers human subjects produces heat directly, providing an alternative to the brown adipose tissues.KEY POINTS SUMMARYSeveral distinct strategies produce and conserve heat to maintain body temperature of mammals, each associated with unique physiologies, with consequence for wellness and disease susceptibilityHighly regulated properties of skin offset the total requirement for heat productionWe hypothesize that the adipose component of skin is primarily responsible for modulating heat flux; here we evaluate the relative regulation of adipose depots in mouse and human, to test their recruitment to heat production and conservationWe found that insulating mouse dermal white adipose tissue accumulates in response to environmentally- and genetically-induced cool stress; this layer is one of two adipose depots closely apposed to mouse skin, where the subcutaneous mammary gland fat pads are actively recruited to heat productionIn contrast, the body-wide adipose depot associated with human skin produces heat directly, potentially creating an alternative to the centrally regulated brown adipose tissue
HieRFIT: Hierarchical Random Forest for Information Transfer
Authors: Kaymaz Yasin , Ganglberger Florian , Tang Ming , Fernandez-Albert Francesc , Lawless Nathan , Sackton Timothy 
Published: September 2020

AbstractThe emergence of single-cell RNA sequencing (scRNA-seq) has led to an explosion in novel methods to study biological variation among individual cells, and to classify cells into functional and biologically meaningful categories. Here, we present a new cell type projection tool, HieRFIT (HierarchicalRandomForest forInformationTransfer), based on hierarchical random forests. HieRFIT usesa prioriinformation about cell type relationships to improve classification accuracy, taking as input a hierarchical tree structure representing the class relationships, along with the reference data. We use an ensemble approach combining multiple random forest models, organized in a hierarchical decision tree structure. We show that our hierarchical classification approach improves accuracy and reduces incorrect predictions especially for inter-dataset tasks which reflect real life applications. We use a scoring scheme that adjusts probability distributions for candidate class labels and resolves uncertainties while avoiding the assignment of cells to incorrect types by labeling cells at internal nodes of the hierarchy when necessary. Using HieRFIT, we re-analyzed publicly available scRNA-seq datasets showing its effectiveness in cell type cross-projections with inter/intra-species examples. HieRFIT is implemented as an R package and it is available at (https://github.com/yasinkaymaz/HieRFIT/releases/tag/v1.0.0)
Selecting pharmacies for COVID-19 testing to ensure access
Authors: Risanger Simon , Singh Bismark , Morton David , Meyers Lauren Ancel 
Published: September 2020

AbstractRapid diagnostic testing for COVID-19 is key to guiding social distancing orders and containing emerging disease clusters by contact tracing and isolation. However, communities throughout the US do not yet have adequate access to tests. Pharmacies are already engaged in testing, but there is capacity to greatly increase coverage. Using a facility location optimization model and willingness-to-travel estimates from US National Household Travel Survey data, we find that if COVID-19 testing became available in all US pharmacies, an estimated 94% of the US population would be willing to travel to obtain a test, if warranted. Whereas the largest chain provides high coverage in densely populated states, like Massachusetts, Rhode Island, New Jersey, and Connecticut, independent pharmacies would be required for sufficient coverage in Montana, South Dakota, and Wyoming. If only 1,000 pharmacies in the US are selected to provide testing, judicious selection, using our optimization model, provides estimated access to 29 million more people than selecting pharmacies simply based on population density. COVID-19 testing through pharmacies can improve access across the US. Even if only few pharmacies offer testing, judicious selection of specific sites can simplify logistics and improve access.
Examining Health Sector Stakeholder Perceptions on the Efficiency of County Health Systems in Kenya
Authors: Nyawira Lizah , Mbau Rahab , Jemutai Julie , Hanson Kara , Molyneux Sassy , Normand Charles , Tsofa Benjamin , Maina Isabel , Mulwa Andrew , Barasa Edwine 
Published: September 2020

AbstractEfficiency gains is a potential strategy to expand Kenya’s fiscal space for health. We explored health sector stakeholders’ understanding of efficiency and their perceptions of the factors that influence the efficiency of county health systems in Kenya. We collected data during a stakeholder engagement workshop. Workshop participants included health sector stakeholders from the national ministry of health and 10 (out 47) county health departments, and non-state actors in Kenya. We divided stakeholders into three groups and carried out facilitated group discussions followed by whole group feedback and discussion session. A total of 25 health sector stakeholders participated. We analysed data using a thematic approach. Health sector stakeholders indicated the need for the outputs and outcomes of a health system to be aligned to community health needs. They felt that both hardware aspects of the system (such as the financial resources, infrastructure, human resources for health) and software aspects of the system (such as health sector policies, public finance management systems, actor relationships) should be considered as inputs in the analysis of county health system efficiency. They also felt that while traditional indicators of health system performance such as intervention coverage or outcomes for infectious diseases, and reproductive, maternal, neonatal and child health (RMNCH) are still relevant, emerging epidemiological trends characterized by an increase in the burden of non-communicable diseases (NCDs) should also be considered. The stakeholders identified public finance management, human resources for health, political interests, corruption, management capacity, and poor coordination as factors that influence the efficiency of county health systems. An in-depth examination of the factors that influence the efficiency of county health systems could illuminate potential policy levers for generating efficiency gains. Mixed methods approaches could facilitate the study of both hardware and software factors that are considered inputs, outputs or factors that influence health system efficiency.