bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Susceptibility Loci for Cardiovascular Disease in Adults With Hypertension, Diabetes and Dyslipidemia&nbsp;
Authors: Song Youhyun , Choi Ja-Eun , Kwon Yu-Jin , Chang Hyuk-Jae , Kim Jung Oh , Park Da-Hyun , Park Jae-Min , Kim Seong-Jin , Lee Ji Won , Hong Kyung-Won 
Published: September 2020

Abstract
Background: Hypertension (HTN), diabetes mellitus (DM), and dyslipidemia (DL) are well-known risk factors of cardiovascular disease (CVD), but not all patients develop CVDs. Studies have been limited investigating genetic risk of CVDs specific to individuals with metabolic diseases. This study aimed to identify disease-specific and/or common genetic loci associated with CVD susceptibility in chronic metabolic disease patients.Methods: We conducted a genome-wide association study (GWAS) of a multiple case-control design with data from the City Cohort within Health EXAminees subcohort of the Korean Genome and Epidemiology Study (KoGES_HEXA). KoGES_HEXA is a population-based prospective cohort of 173,357 urban Korean adults that had health examinations at medical centers. 42,393 participants (16,309 HTN; 5,314 DM; 20,770 DL) were analyzed, and each metabolic disease group was divided into three CVD case-controls: coronary artery disease (CAD), ischemic stroke (IS), and cardio-cerebrovascular disease (CCD). GWASs were conducted for each case-control group with 7,975,321 imputed single nucleotide polymorphisms using Phase 1/2 Asian panels from 1000 Genomes Project, by logistic regression and controlled for confounding variables. Genome-wide significant levels were implemented to identify important susceptibility loci.Results: Totaling 42,393 individuals, this study included 16,309 HTN (mean age [SD], 57.28 [7.45]; 816 CAD, 398 IS, and 1,185 CCD cases), 5,314 DM (57.79 [7.39]; 361 CAD, 153 IS, and 497 CCD cases), and 20,770 DL patients (55.34 [7.63]; 768 CAD, 295 IS, and 1,039 CCD cases). Six genome-wide significant CVD risk loci were identified, with relatively large effect sizes: 1 locus in HTN (HTN-CAD: 17q25.3/CBX8-CBX4 [OR, 2.607; P = 6.37 × 10−9]), 2 in DM (DM-IS: 4q32.3/MARCH1-LINC01207 [OR, 5.587; P = 1.34 × 10−8], and DM-CCD: 17q25.3/RPTOR [OR, 3.511; P = 1.99 × 10−8]), and 3 in DL (DL-CAD: 9q22.2/UNQ6494-LOC101927847 [OR, 2.282; P = 7.78 × 10−9], DL-IS: 3p22.1/ULK4 [OR, 2.162; P = 2.97 × 10−8], and DL-CCD: 2p22.2/CYP1B1-CYP1B1-AS1 [OR, 2.027; P = 4.24 × 10−8]).Conclusions: This study identified 6 susceptibility loci and positional candidate genes for CVDs in HTN, DM, and DL patients using an unprecedented study design. 1 locus (17q25.3) was commonly associated with CAD. These associations warrant validation in additional studies for potential therapeutic applications.
Important Dispersal Capacity of One Main Species Vector of Bluetongue and Schmallenberg Viruses Culicoides Obsoletus (Diptera: Ceratopogonidae) Revealed by Landscape Genetic Analyses&nbsp;
Authors: Mignotte Antoine , Garros Claire , Dellicour Simon , Jacquot Maude , Gilbert Marius , Gardès Laetitia , Balenghien Thomas , Duhayon Maxime , Rakotoarivony Ignace , de Wavrechin Maïa , Huber Karine 
Published: September 2020

Abstract
Background: In the last two decades, recurrent epizootics of bluetongue virus and Schmallenberg virus have been reported in the western Palearctic region. These viruses affect domestic cattle, sheep, goats and wild ruminants and are transmitted by native hematophagous midges of the genus Culicoides (Diptera: Ceratopogonidae). Culicoides dispersal is known to be stratified, i.e. due to a combination of dispersal processes occurring actively at short distances and passively or semi-actively at long distances, allowing individuals to jump hundreds of kilometers. Methods: Here, we aim to identify the environmental factors that promote or limit gene flows of Culicoides obsoletus, an abundant and widespread vector species in Europe using an innovative framework integrating spatial, population genetics and statistical approaches. A total of 348 individuals were sampled in 46 sites in France and have been genotyped using 11 newly-designed microsatellite markers. Results: We found a low genetic differentiation and population structure for C. obsoletus across the country. Using three complementary inter-individual genetic distances, we did not detect any significant isolation-by-distance, but a significant anisotropic isolation-by-distance on a North-South axis. We have employed a multiple regression approach on distance matrices to investigate the correlation between genetic and environmental distances. Among all the environmental factors that have been tested, only cattle density seems to have an impact on C. obsoletus gene flow. Conclusions: Such a high dispersal capacity of C. obsoletus over land territories calls for a re-evaluation of the impact of Culicoides on virus dispersal and highlights the urgent need to better integrate molecular, spatial and statistical information to guide vector-borne diseases control.
Efficacy of a single oral dose artesunate plus sulfalene/pyrimethamine versus praziquantel in the treatment of Schistosoma mansoni in Kenyan children: randomised, exploratory, open-label trial
Authors: Muok Erick M.O , Were Vincent O. , Obonyo Charles O. 
Published: September 2020

Abstract
Background: The global control strategy for schistosomiasis is the periodic administration of praziquantel. Schistosomes have developed reduced susceptibility to praziquantel. Artemisinin-based drug combinations are promising alternatives to praziquantel, but it is unclear whether a single dose of an artemisinin-based drug combination is as effective and safe as praziquantel. We assessed the efficacy and safety of a single oral dose of artesunate plus sulfalene/pyrimethamine in the treatment of schistosomiasis. Methods: An exploratory, open-label randomized trial, was carried out in Rarieda sub-County, western Kenya to compare the efficacy of a single oral dose of artesunate plus sulfalene/pyrimethamine (12mg/kg of artesunate) to a standard single dose of praziquantel (40mg/kg) in the treatment of school children (aged 6 to 15 years) with S. mansoni infection. The primary outcomes were cure and egg reduction rates on day 28 after treatment in the per-protocol population.Results: A total of 73 S. mansoni infected children were included and randomized to receive either artesunate plus sulfalene/pyrimethamine (n=39) or praziquantel (n=34). 67 children completed the study. The cure rate was 69.4% (25/36) in the artesunate plus sulfalene/pyrimethamine group and 80.6% (25/31) in the praziquantel group (p=0.294). Egg reduction rates were 96.2% in the artesunate plus sulfalene/pyrimethamine group and 82.9% in the praziquantel group (p=0.339). Ten children treated with praziquantel developed adverse events compared with four in the artesunate plus sulfalene/pyrimethamine group. There was no serious adverse event. Conclusion: A single oral dose of artesunate plus sulfalene/pyrimethamine was safe and as efficacious as praziquantel in the treatment of S. mansoni in Kenyan children. These results should be confirmed in larger randomized controlled trials. Combination treatment with praziquantel plus artemisinin-based combination therapies may be a potential alternative for improving praziquantel efficacy and transmission control. Trial Registration: ClinicalTrials.gov, number NCT01054651.
Mortality, Severity, and Hospital Admission Among COVID-19 Patients with ACEI/ARB Use: A Meta-analysis Stratifying Countries Based on Response to the First Wave of the Pandemic
Authors: Alamer Ahmad , Almulhim Abdulaziz , Alrashed Ahmed , Abraham Ivo 
Published: September 2020

Abstract
BackgroundThe use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is controversial for treating COVID-19 patients. We aimed to estimate pooled risks of mortality, disease severity, and hospitalization associated with ACEI/ARB use and stratify them by country and country clusters. MethodsWe conducted a search in various databases through 7/4/2020 and then applied random-effects models to estimate pooled risks (ORp) across stratifications by country cluster. Clusters were chosen to reflect outbreak times (China followed by Korea/Italy, others subsequently) and mobility restrictions (China and Denmark/France/Spain with stricter lockdowns than the UK/US). ResultsOverall analysis showed no increase in mortality; however, a statistical increase in mortality was seen in the US/UK cluster with ORp=1.28[95%CI=1.04; 1.56] and a decrease in China with ORp=0.65[95%CI=0.43; 0.96] and France with OR=0.31[95%CI=0.14; 0.69]. Severity and hospitalization were not statistically significant in the analysis; however, several associations were seen in specific countries but not in country clusters. ConclusionThe country-cluster meta-analysis provided a reasonable explanation for COVID-19 mortality among ACEI/ARB users. The analysis did not explain differences in severity and suggested the involvement of other factors. Hospitalization findings may be considered informative as they may have been subjected to clinical decisions and hospital-bed availability.
Review of Type III Non-Hereditary Angioedema Patients in Manitoba.
Authors: Hinther Kelsey , Kalicinsky Chrystyna 
Published: September 2020

Abstract
Introduction: Non-hereditary angioedema with normal C1 esterase inhibitor level and function (NHAE-nC1INH) is a novel entity. The diagnosis of NHAE-nC1INH requires a high index of suspicion, given that there are no laboratory tests to confirm the diagnosis. There is limited evidence on the treatment efficacy for short- and long-term prophylaxis, and acute attacks. The aim of the study is to describe a cohort of NHAE-nC1INH in Manitoba, including an estimate of prevalence, as well as to analyze the response to plasma derived C1esterase inhibitor (pdC1INH), and a bradykinin-2 receptor antagonist (Icatibant).Methods: A retrospective chart review of patients diagnosed with normal C1 esterase level and function angioedema seen at the Clinical Immunology and Allergy Clinic at the Health Sciences Centre in Winnipeg, Manitoba, was done. Inclusion criteria included the following: (1) Reside within Manitoba (2) Aged 18 years and older (3) Angioedema without urticaria (4) Normal C1-INH antigenic level and function (5) No symptom resolution with antihistamines, epinephrine or corticosteroids. (6) No family history. Five patients were included in the study who met the above inclusion criteria. The five patients charts were reviewed. Response to pdC1INH and Icatibant were defined as time to improvement of angioedema symptoms.Results: Four out of five patients had an effective response to pdC1INH for prophylactic treatment and for on-demand treatment for angioedema episodes. pdC1INH was ineffective in 1 patient for prophylaxis and on-demand treatment; tranexamic acid was successful for prophylactic treatment in 1 patient who did not respond to pdC1INH for prophylaxis and for on-demand treatment. 3 of 5 patients have tried Icatibant. All three patients were not responsive to Icatibant.Conclusion: This study suggests that pdC1INH may be an efficacious treatment option for NHAE-nC1INH patients. Larger studies are required to better elucidate the effectiveness of on-demand and prophylactic treatment for NHAE-nC1INH.
Switching First-Line Targeted Therapy After Not Reaching Low Disease Activity Within Six Months is Superior to Conservative Approach: A Propensity Score Matched Analysis From The ATTRA Registry
Authors: Nekvindova Lucie , Vencovský Jiří , Pavelka Karel , Horák Pavel , Křístková Zlatuše , Závada Jakub 
Published: September 2020

Abstract
Background: Treat-to-target (T2T) is a widely accepted strategy for patients with rheumatoid arthritis (RA). It recommends attaining a goal of at least low disease activity (LDA) within six months; otherwise, the current therapy should be modified. We aimed to investigate whether switching a first-line targeted therapy (TT) in patients not reaching LDA within six months leads to a higher probability of meeting LDA at 12‑month visit in daily clinical practice using data from Czech registry ATTRA.Methods: We included patients with RA starting the first-line TT from 1 January 2012 to 31 January 2017 with at least one-year follow-up. We created four mutually exclusive cohorts based on 1) switching to another TT within the first year and 2) reaching a treatment target (DAS28-ESR ≤ 3.2) at the 6‑month visit. The primary outcome was the comparison of odds for reaching remission (REM) or LDA at the 12-month visit between patients switching and not switching TT after not reaching treatment target at six months. Before using logistic regression to estimate the odds ratio, we employed the propensity score to match patients at the 6-month visit.Results: A total of 1275 patients were eligible for the analysis. Sixty-two patients switched within the first five months of the treatment before evaluating treatment response at the 6-month visit (C1); 598 patients reached the treatment target within six months of therapy (C2); 124 patients did not reach treatment response at 6-month visit and switched to another therapy (C3), and 491 patients continued with the same treatment despite not reaching LDA at the 6‑month visit (C4). We matched 75 patients from cohort C3 and 75 patients from C4 using the propensity score. Patients following T2T principle (C3) showed 2.8 (95% CI 1.4–5.8; p=0.005) times increased likelihood of achieving REM/LDA at 12‑month visit compared to patients not following T2T strategy (C4).Conclusions: In daily clinical practice, the application of T2T strategy is underused. Switching TT after not reaching REM/LDA within the first six months leads to a higher probability of achieving REM/LDA in RA patients at the 12-month visit.
Identification of a Novel Nonsense Homozygous Mutation of LINS1&nbsp;Gene in Two Sisters With Moderate Intellectual Disability, Schizophrenia, and Anxiety Disorders and Review of the Literature
Authors: Chen Chia-Hsiang , Huang Yu-Shu , Fang Ting-Hsuan 
Published: September 2020

Abstract
Background: The human LINS1 gene is located at 15q26.3 and encodes the lines homolog 1 protein that contains the Drosophila lines homologous domain. Mutations in the LINS1 gene have been reported to cause a rare recessive form of intellectual disability. A total of seven mutations in six studies have been reported in the literature to our knowledge. Results: Using whole genome sequencing analysis, we identified a novel homozygous nonsense mutation in the LINS1 gene in these two sisters who presented moderate intellectual disability, schizophrenia symptoms, and severe anxiety. The mutation was a C-to-T substitution at the cDNA nucleotide position 274 that changed the amino acid glutamine at the codon 92 to stop codon (Gln92X), resulting in the truncation of LINS1 protein after amino acid 91. This mutation was transmitted from their unrelated parents who were heterozygous carriers. Conclusions: Our findings not only add to the allelic heterogeneity of the LINS1-associated intellectual disability but also expand the spectrum of clinical phenotypes of patients with LINS1 mutations. Our study suggests that the human LINS1 gene mutation may play a role in the pathogenesis of psychosis and anxiety in addition to the intellectual disability.
Effect of porcine immature oocyte vitrification on oocyte-cumulus cell gap junctional intercellular communication.
Authors: Casillas Fahiel , Ducolomb Yvonne , López Alma , Betancourt Miguel 
Published: September 2020

Abstract
Vitrification may severely affect cumulus cells and oocyte morphology and viability, limiting their maturation and developmental potential. The aim of this study was to evaluate the gap junction intercellular communication (GJIC) integrity after the vitrification of porcine immature cumulus-oocyte complexes (COCs). Fresh COCs were randomly distributed in two groups: untreated (control) and vitrified (vitrification), then subjected to in vitro maturation (IVM). Oocyte viability and IVM were measured in both groups. The evaluation of GJIC was expressed as relative fluorescence intensity (RFI). Vitrification significantly decreased oocyte viability and maturation after 44 h of culture compared to control. Also, significantly reduced RFI was observed in vitrified COCs at 4 and 8 h of culture compared to control. This study demonstrates that porcine oocyte viability and maturation after 44 h of culture were compromised after vitrification. GJIC was also affected after the vitrification of GV oocytes, being the possible mechanism by which oocyte maturation decreased.
Radiology Departments as COVID-19 entry-door might improve healthcare efficacy and efficiency, and Emergency Department safety
Authors: Santos José María García , Martínez Juana María Plasencia , Ortega Pablo Fabuel , Ros Marina Lozano , Ayala María Carmen Sánchez , Hernández Gloria Pérez , Martínez Pedro Menchón 
Published: September 2020

Abstract
Background: Possible COVID-19 pneumonia (ppCOVID-19) patients generally overwhelmed EDs during the first COVID-19 wave. Home confinement and primary care phone follow-ups were the first-level regional policies for preventing EDs from collapsing. However, when ppCOVID-19 needed X-ray assessment, the traditional outpatient workflow at the radiology department (RD) was inefficient and raised concerns about potential interpersonal infections. We aimed to assess the efficiency of a primary care high-resolution radiology service (pcHRRS) for ppCOVID-19 in terms of time consumed at the hospital and decision reliability.Methods: We assessed 849 consecutive ppCOVID-19 patients, 418 appointed by general practitioners to the pcHRRS (home-confined ppCOVID-19 cases with negative –group-1- and positive -group-2- X-ray results) and 431 arriving at the ED by themselves (group-3). The pcHRRS provided X-rays and oximetry in an only-one-patient agenda for home-confined ppCOVID-19 patients. Radiologists made next-step decisions (group-1: pneumonia-, home-confinement follow-up; group-2: pneumonia+, ED assessment) according to X-ray results. ANOVA and Bonferroni correction, Student’s t-test, Kruskal-Wallis test, and Chi2 test were used to analyse changes in the ED workload, time-to-decision differences between groups, and pcHRRS performance for discriminating need for admission.Results: The pcHRRS halved ED respiratory patients (49.2%), allowed faster decisions (group-1 vs. home-discharged group-2 and group-3 patients: 0:41±1:05 h vs. 3:50±3:16 h; group-1 vs. all group-2 and group-3 patients: 0:41±1:05 h vs. 5:36±4:36 h; group-2 vs. group-3 admitted patients: 5:27±3:08 h vs. 7:42±5:02 h; P <0.001) and prompted admission in most cases (84/93, 90.3%).Conclusions: A Radiology Department pcHRRS may be a more efficient entry-door for ppCOVID-19 by decreasing ED patients and making expedited decisions while guaranteeing social distance.
Evaluating the interchangeability of infrared and digital devices with the traditional mercury thermometer in hospitalized pediatric patients: an observational study.
Authors: Dante Angelo , Gaxhja Elona , Masotta Vittorio , Cerra Carmen La , Caponnetto Valeria , Petrucci Cristina , Lancia Loreto 
Published: September 2020

Abstract
A gradual replacement of the mercury thermometers with alternative devices is ongoing around the world as effect of the global strategies to reduce mercury pollution. However, to reduce the risks of misdiagnosis, unnecessary treatments, and omission of care in the pediatric population, more evidence on the reliability and validity of alternative thermometers are needed. The aim of this comparative observational study was to detect any differences in temperature measurements between the gold-standard axillary mercury thermometer (AXLMER) and the alternative devices. Temperature values in Celsius (°C) were simultaneously measured in a group of Albanian children aged up to 14 years using both (AXLMER) and digital axillary thermometers (AXLDGT), as well as forehead and tympanic infra-red thermometers. The AXLDGT device, compared with the AXLMER, showed no clinically significant difference in the mean values (-0.04 ± 0.29 °C) and the narrowest 95% Level of Agreement (+0.53 °C to -0.62 °C) in the paired comparisons. For cut-off points of 37.0 °C and 37.5 °C, the AXLDGT showed the highest levels of sensitivity (67.4% and 72.5%) and specificity (95.3% and 99.1%) in detecting fever. This study indicates that the AXLDGT thermometer may prove the better option since it adequately balances accuracy, safety and children’s comfort.
The role of complementary feeding in India’s enigma of high child malnutrition rates: Findings from a comprehensive national study
Authors: Petrikova Ivica 
Published: September 2020

Abstract
Relative to its economic growth and poverty levels, Indian children suffer from higher levels of malnutrition than children in most other low- or lower-middle-income countries. The current Covid-19 pandemic is likely to further exacerbate the situation. Research presented in this article has examined the effects of infant and young child feeding practices on the rates of stunting, underweight, wasting, and anaemia amongst Indian children and concluded that feeding children between 6 and 23 months old (semi)solid food of sufficient variety, and particularly animal-source foods, has a significant positive effect on their nutritional outcomes. The study further assessed the effects of the Integrated Child Development Services and district-level livestock ownership on the helpful feeding practices and found that the Integrated Child Development Services encouraged beneficial dietary behaviour amongst children but did not improve their nutritional outcomes. In contract, district-level poultry ownership appeared to have both augmented the beneficial feeding practices and improved children’s nutritional outcomes.
Contexts and mechanisms that promote access to healthcare for populations experiencing homelessness: a realist review
Authors: Siersbaek Rikke , Ford John , Burke Sara , Cheallaigh Clíona Ní , Thomas Steve 
Published: September 2020

Abstract
Objective: The objective of this study was to identify and understand the health system contexts and mechanisms that allow for homeless populations to access appropriate healthcare when needed.Design: A realist review.Data sources: Ovid MEDLINE, embase.com, CINAHL, ASSIA and grey literature until April 2019. Eligibility criteria for selecting studies: The purpose of the review was to identify health system patterns which enable access to healthcare for people who experience homelessness. Peer reviewed articles were first identified through a systematic search, grey literature searching, citation tracking and expert recommendations. Studies meeting the inclusion criteria were assessed for rigour and relevance and coded to identify data relating to contexts, mechanisms and/or outcomes.Analysis: Inductive coding was used to generate Context-Mechanism-Outcome configurations which were refined and then used to build several iterations of the overarching programme theory.Results: Searching identified 330 review articles, of which 24 were included. Additional searching of grey literature yielded 50 records of which 12 were included. An additional 11 grey literature and primary sources were identified through citation tracking and expert recommendation for a total of 47 included sources. The analysis found that healthcare access for populations experiencing homelessness is improved when services are coordinated and delivered in a way that is organised around the person with a high degree of flexibility and a culture that rejects stigma generating trusting relationships between patients and staff/providers. Health systems should provide long-term, dependable funding for services to ensure sustainability and staff retention. Conclusions: With homelessness on the rise internationally, this study will inform health systems policy-making and implementation. It contributes to our understanding how healthcare systems can be more accessible for populations experiencing homelessness by providing long-term stable funding, promoting inclusive cultures and limiting stigma. Health systems should be flexible, timely and connected.