bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide association study meta-analysis identifies three novel loci for circulating anti-Müllerian hormone levels in women
Authors: Verdiesen Renée MG , van der Schouw Yvonne T , van Gils Carla H , Verschuren WM Monique , Broekmans Frank JM , Borges Maria C , Soares Ana LG , Lawlor Deborah A , Eliassen A Heather , Kraft Peter , Sandler Dale P , Harlow Sioban D , Smith Jennifer A , Santoro Nanette , Schoemaker Minouk J , Swerdlow Anthony J , Murray Anna , Ruth Katherine S , Onland-Moret N Charlotte 
Published: November 2020

AbstractAnti-Müllerian hormone (AMH) is expressed by antral stage ovarian follicles in women. Consequently, circulating AMH levels are detectable until menopause. Variation in age-specific AMH levels has been associated with breast cancer and polycystic ovary syndrome (PCOS), amongst other diseases. Identification of genetic variants underlying variation in AMH levels could provide clues about the physiological mechanisms that explain these AMH-disease associations. To date, only one variant in MCM8 has been identified to be associated with circulating AMH levels in women. We aimed to identify additional variants for AMH through a GWAS meta-analysis including data from 7049 premenopausal women of European ancestry, which more than doubles the sample size of the largest previous GWAS. We identified four loci associated with AMH levels at p < 5×10−8: the previously reported MCM8 locus and three novel signals in or near AMH, TEX41, and CDCA7. The strongest signal was a missense variant in the AMH gene (rs10417628). Most prioritized genes at the other three identified loci were involved in cell cycle regulation. Genetic correlation analyses indicated a strong positive correlation among SNPs for AMH levels and for age at menopause (rg= 0.82, FDR=0.003). Exploratory Mendelian randomization analyses did not support a causal effect of AMH on breast cancer or PCOS risk, but should be interpreted with caution as they may be underpowered and the validity of genetic instruments could not be extensively explored. In conclusion, we identified a variant in the AMH gene and three other loci that may affect circulating AMH levels in women.
The Association Between Tobacco Exposure During Pregnancy and Newborns’ Birth Weight in DKI Jakarta Community Members
Authors: Phowira Jason , Elvina Felicitas Tania , Wiguna Igor Ian , Bari Wahyudi Fathurohman Ramadhan Hanif , Medise Bernie Endyarni 
Published: November 2020

AbstractLow birth weight (LBW), a major determinant of neonate morbidity and mortality, remains a global public health concern. Intrauterine exposure to tobacco has been discerned as an important risk factor for LBW. This study aims to investigate the association between parental smoking during pregnancy and LBW. An analytical cross-sectional study was conducted from December 2019 - July 2020 on a random sample of parents with child aged 0-5 years old from 5 health centers in DKI Jakarta, Indonesia. A total of 145 subjects met the criteria and were analysed. Data analysis was carried out using IBM SPSS Statistics software. In the study, 11% of infants were born with LBW. The prevalence of smoking in fathers and mothers were 55.2% and 3.4%, respectively. Paternal smoking status was significantly associated with LBW (p < 0.05). Although not statistically significant, there was a dose-response relationship between paternal number of cigarettes/day and duration of smoking with LBW. Maternal smoking status (p = 0.448) was not closely associated with LBW, which might be due limited number of actively smoking mothers. From multivariate logistic regression, paternal smoking status, premature delivery, birth order and inadequate food intake during pregnancy were significant predictors of LBW (p < 0.05).
Feasibility of collecting and processing of COVID-19 convalescent plasma for treatment of COVID-19 in Uganda
Authors: Muttamba Winters , Lusiba John , Namakula Loryndah Olive , Byakika-Kibwika Pauline , Ssali Francis , Ddungu Henry , Mugenyi Levicatus , Kiwanuka Noah , Sekibira Rogers , Kityo Cissy , Keyune Dorothy , Acana Susan , Musinguzi Ambrose , Masasi Ayub , Byamugisha Joseph , Mpanju David , Musoki Walter Jack , Tukamuhebwa Hellen Aanyu , Nakwagala Fred , Bagaya Bernard Sentalo , Kayongo Alex , Kimuli Ivan , Nantanda Rebecca , Katagira Winceslaus , Buregyeya Esther , Byanyima Rosemary , Byarugaba Baterana , Siddharthan Trishul , Mwebesa Henry , Charles Olaro , Joloba Moses Lutaakome , Bazeyo William , Kirenga Bruce 
Published: November 2020

AbstractIntroductionEvidence that supports the use of COVID-19 convalescent plasma (CCP) for treatment of COVID-19 is increasingly emerging. However, very few African countries have undertaken the collection and processing of CCP. The aim of this study was to assess the feasibility of collecting and processing of CCP, in preparation for a randomized clinical trial of CCP for treatment of COVID-19 in Uganda.MethodsIn a cross-sectional study, persons with documented evidence of recovery from COVID-19 in Uganda were contacted and screened for blood donation via telephone calls. Those found eligible were asked to come to the blood donation centre for further screening and consent. Whole blood collection was undertaken from which plasma was processed. Plasma was tested for transfusion transmissible infections (TTIs) and anti-SARS CoV-2 antibody titers. SARS-CoV-2 testing was also done on nasopharyngeal swabs from the donors.Results192 participants were contacted of whom 179 (93.2%) were eligible to donate. Of the 179 eligible, 23 (12.8%) were not willing to donate and reasons given included: having no time 7(30.4%), fear of being retained at the COVID-19 treatment center 10 (43.5%), fear of stigma in the community 1 (4.3%), phobia for donating blood 1 (4.3%), religious issues 1 (4.4%), lack of interest 2 (8.7%) and transport challenges 1 (4.3%). The median age was 30 years and females accounted for 3.7% of the donors. A total of 30 (18.5%) donors tested positive for different TTIs. Antibody titer testing demonstrated titers of more than 1:320 for all the 72 samples tested. Age greater than 46 years and female gender were associated with higher titers though not statistically significant.ConclusionCCP collection and processing is possible in Uganda. However, concerns about stigma and lack of time, interest or transport need to be addressed in order to maximize donations.
Efficacy and safety of levetiracetam versus phenytoin as second line antiepileptic agent in Pediatric convulsive status epilepticus: A systematic review and meta-analysis of randomized controlled trials
Authors: Angurana Suresh Kumar , Suthar Renu 
Published: November 2020

AbstractObjectiveTo evaluate the efficacy and safety of Levetiracetam (LEV) in comparison to phenytoin (PHT) as second line antiseizure medication (ASM) for Pediatric convulsive status epilepticus (SE).Data sourcePubMed, Embase, Google scholar, Scopus, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials.Study selectionRandomized controlled trials (RCTs) assessing LEV and PHT as second line agent for convulsive SE in children <18 years published between 1st January 2000 to 30th September 2020.Data extractionThe data was pooled regarding the proportion of children achieving seizure cessation within 5-60 minutes of completion of study drug infusion (primary outcome); and seizure cessation within 5 minutes, time to achieve seizure cessation, seizure recurrence between 1-24 hours, intubation, and cardiovascular instability (secondary outcomes). Data was analysed using RevMan version 5.4 and quality analysis was done using Cochrane risk-of-bias tool. The study protocol was submitted to PROSPERO for registration.Data synthesisEleven RCTs with 2177 children (1024 received LEV and 988 received PHT) were enrolled. Seizure cessation within 5-60 minutes was similar with both the drugs [81% in LEV vs. 76% in PHT, risk ratio (RR)=1.04, 95% CI 0.9-1.13, p=0.29]. Seizure recurrences within 1-24 hours was higher with PHT as comparison to LEV (15% vs 9%, RR=0.64, 95% CI 0.42-0.99, p=0.04). Seizure cessation within 5 minutes, time to achieve seizure cessation, requirement of intubation/mechanical ventilation, and cardiovascular instability were similar with both the drugs. Three studies had low risk of bias and eight studies had high risk of bias.ConclusionThe efficacy and safety of LEV is not superior to PHT as second line ASM medication for Pediatric convulsive SE. However, the seizure recurrences between 1-24 hours were significantly higher with PHT in comparison to LEV.
A rapid systematic review of measures to protect older people in long term care facilities from COVID-19
Authors: Frazer Kate , Mitchell Lachlan , Stokes Diarmuid , Lacey Ella , Crowley Eibhlin , Kelleher Cecily 
Published: November 2020

AbstractThe global COVID-19 pandemic produced large-scale health and economic complications. Older people and those with comorbidities are particularly vulnerable to this virus, with nursing homes and long term care facilities experiencing significant morbidity and mortality associated with COVID-19 outbreaks. The aim of this rapid systematic review was to investigate measures implemented in long term care facilities to reduce transmission of COVID-19 and their effect on morbidity and mortality of residents, staff, and visitors. Databases (including MedRXiv pre-published repository) were systematically searched to identify studies reporting assessment of interventions to reduce transmission of COVID-19 in nursing homes among residents, staff, or visitors. Outcome measures include facility characteristics, morbidity data, case fatalities, and transmission rates. Due to study quality and heterogeneity, no meta-analysis was conducted. The search yielded 1414 articles, with 38 studies included. Reported interventions include mass testing, use of personal protective equipment, symptom screening, visitor restrictions, hand hygiene and droplet/contact precautions, and resident cohorting. Prevalence rates ranged from 1.2-85.4% in residents and 0.6-62.6% in staff. Mortality rates ranged from 5.3-55.3% in residents. Novel evidence in this review details the impact of facility size, availability of staff and practices of operating between multiple facilities, and for-profit status of facilities as factors contributing to the size and number of COVID-19 outbreaks. No causative relationships can be determined; however, this review provides evidence of interventions that reduce transmission of COVID-19 in long term care facilities.
The prevalence of common mental disorders among health care professionals during the COVID-19 pandemic at a tertiary Hospital in East Africa
Authors: Mulatu Hailu Abera , Tesfaye Muluken , Woldeyes Esubalew , Bayisa Tola , Fesseha Henok , Asrat Rodas 
Published: November 2020

AbstractBackgroundCoronavirus disease 2019 (COVID-19) has resulted in unprecedented morbidity, mortality, and health system crisis leading to a significant psychological distress on healthcare workers (HCWs). The study aimed to determine the prevalence of symptoms of common mental disorders among HCWs during the COVID-19 pandemic at St. Paul’s Hospital, Ethiopia.MethodsA self-administered cross-sectional study was conducted to collect socio-demographic information and symptoms of mental disorders using validated measurement tools. Accordingly, PHQ-9, GAD-7, ISI, and IES-R were used to assess the presence of symptoms of depression, anxiety, insomnia, and distress, respectively. Chi-square test, non-parametric, and logistic regression analysis were used to detect risk factors for common mental disorders.ResultsA total of 420 healthcare workers participated in the survey. The prevalence of depression, anxiety, insomnia, and psychological distress was 20.2%, 21.9%, 12.4%, and 15.5% respectively. Frontline HCWs had higher scores of mental health symptoms than other health care workers. Logistic regression analysis showed that being married was associated with a high level of depression. Working in a frontline position was an independent factor associated with a high-level depression, anxiety, and psychological distress.LimitationsIt is a single-centre cross-sectional study and the findings may not be generalizable or reveal causality.
A tipping point in cancer-immune dynamics leads to divergent immunotherapy responses and hampers biomarker discovery
Authors: Creemers Jeroen H.A. , Lesterhuis W. Joost , Mehra Niven , Gerritsen Winald R. , Figdor Carl G. , de Vries I. Jolanda M. , Textor Johannes 
Published: November 2020

ABSTRACTBackgroundPredicting treatment response or survival of cancer patients remains challenging in immuno-oncology. Efforts to overcome these challenges focus, among others, on the discovery of new biomarkers. Despite advances in cellular and molecular approaches, only a limited number of candidate biomarkers eventually enter clinical practice.MethodsA computational modeling approach based on ordinary differential equations was used to simulate the fundamental mechanisms that dictate tumor-immune dynamics and to investigate its implications on responses to immune checkpoint inhibition (ICI) and patient survival. Using in silico biomarker discovery trials, we revealed fundamental principles that explain the diverging success rates of biomarker discovery programs.ResultsOur model shows that a tipping point – a sharp state transition between immune control and immune evasion – induces a strongly non-linear relationship between patient survival and both immunological and tumor-related parameters. In patients close to the tipping point, ICI therapy may lead to long-lasting survival benefits, whereas patients far from the tipping point may fail to benefit from these potent treatments.ConclusionThese findings have two important implications for clinical oncology. First, the apparent conundrum that ICI induces substantial benefits in some patients yet completely fails in others could be, to a large extent, explained by the presence of a tipping point. Second, predictive biomarkers for immunotherapy should ideally combine both immunological and tumor-related markers, as a patient’s distance from the tipping point can typically not be reliably determined from solely one of these. The notion of a tipping point in cancer-immune dynamics helps to devise more accurate strategies to select appropriate treatments for cancer patients.
The use of compassionate Ivermectin in the management of symptomatic outpatients and hospitalized patients with clinical diagnosis of COVID-19 at the Medical Center Bournigal and the Medical Center Punta Cana, Rescue Group, Dominican Republic, from may 1 to august 10, 2020
Authors: Morgenstern José , Redondo José N. , De León Albida , Canela Juan Manuel , Torres Nelson , Tavares Johnny , Minaya Miguelina , López Óscar , María Plácido Ana , Castillo Ana , Peña Cruz Rafael , Merette Yudelka , Toribio Marlenin , Francisco Juan Asmir , Roca Santiago 
Published: November 2020

SummaryNo antiviral has been shown to reduce mortality in SARS-COV-2 patients to date. In the present observational and retrospective report, 3,099 patients with a definitive or highly probable diagnosis of infection due to COVID-19 were evaluated between May 1st to August 10th, 2020, at Centro Medico Bournigal (CMBO) and Centro Medico Punta Cana (CMPC), and all received compassionate treatment with Ivermectin. A total of 2,706 (87.3%) were discharged for outpatient treatment, all with mild severity of the infection. In 2,688 (99.33%) with outpatient treatment, the disease did not progress to warrant further hospitalization and there were no deaths. In 16 (0.59%) with outpatient treatment, it was necessary their subsequent hospitalization to a room without any death. In 2 (0.08%) with outpatient treatment, it was necessary their admission to the Intensive Care Unit (ICU) and 1 (0.04%) patient died. There were 411 (13.3%) patients hospitalized, being admitted at a COVID-19 room with a moderate disease 300 (9.7%) patients of which 3 (1%) died; and with a severe to critical disease were hospitalized in the ICU 111 (3.6%), 34 (30.6%) of whom died. The mortality percentage of patients admitted to the ICU of 30.6%, is similar with the percentage found in the literature of 30.9%. Total mortality was 37 (1.2%) patients, which is much lower than that reported in world statistics, which are around 3%.
Endocannabinoid response in acute ischemic stroke: elevated 2-arachidonoylglycerol
Authors: Buciuc Marina , Conte Gian Marco , Scharf Eugene L. 
Published: November 2020

ABSTRACTBackground and purposeEndocannabinoids are hypothesized to have anti-inflammatory and neuroprotective properties and hold therapeutic potential in the acute phase response mechanisms during acute cerebral ischemia and closed head injury. We set to describe the plasma levels of endocannabinoids and related ethanolamides during acute and subacute phases of cerebral ischemia.MethodsWe conducted a prospective observational study of plasma endocannabinoid levels in patients with acute ischemic stroke or transient ischemic attack. Two blood samples were collected: T1 (<12 hours from symptom onset) and T2 (>24 hours from symptom onset). N-arachidonoylethanolamine (AEA), 2-arachidonoylglycerol (2-AG), palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) were quantified by liquid chromatography mass spectrometry.ResultsTwenty-three patients met inclusion criteria. Median (interquartile range): Age – 76 years (60-81); body mass index - 25.6 (23.6-30.4); National Institutes of Health Stroke Scale score-5(3-13); infarct volume - 1.4 cm3 (0.5-8.6). Higher 2-AG levels at T1 were correlated with smaller infarct volumes (Spearman ƿ=-0.48, p=0.0206). Levels of 2-AG were elevated at T2 compared to T1 in 48% of patients (median difference - 310.3nM, 95% CI 194.1-497.3; p=0.001); AEA, PEA and OEA did not differ between T1 and T2, p>0.05. Patients with elevated 2-AG at T2 had larger infarct volumes, p=0.0178, lower frequency of embolectomy performed, p=0.0373, but no difference in neurological disability 90 days after the ischemic event compared to patients without 2-AG elevation.Conclusion2-AG increases significantly in early phases of ischemic stroke. The final mechanistic role of 2-AG in acute ischemic stroke is to be determined in further studies.
Prevalence and expressivity of loss of function mutations in the Melanocortin 4 Receptor (MC4R) in a UK birth cohort
Authors: Wade KH , Lam BYH , Melvin A , Pan W , Corbin LJ , Hughes DA , Rainbow K , Chen JH , Duckett K , Liu X , Mokrosiński J , Mörseburg A , Neaves S , Williamson A , Zhang C , Farooqi IS , Yeo GSH , Timpson NJ , O’Rahilly S 
Published: November 2020

ABSTRACTMutations in the melanocortin 4 receptor gene (MC4R) have frequently been reported in severe early-onset human obesity but the prevalence and extent of phenotypic impact of such mutations are unclear. In a large UK birth cohort, we found that 17 of 5724 unrelated participants (∼1/337; 0.30%) were heterozygous for functionally deleterious mutations. At age 18 years, the mean difference in body weight, body mass index (BMI) and fat mass was 17.76kg (95% CI: 9.41, 26.10), 4.84kg/m2(95% CI: 2.19, 7.49) and 14.78kg (95% CI: 8.56, 20.99), respectively, in carriers of loss of function (LoF) mutations compared to non-LoF carriers. Carriage of LoF mutations increased adiposity from as early as 5 years.MC4RLoF was associated with an impact on BMI at age 18 years that was approximately double that of a genome-wide polygenic risk score (comparing the upper 10thand lower 90thpercentile). An extrapolation of incidence forMC4RLoF mutations from this birth cohort suggests that up to ∼200,000 people in the UK are likely to carry such mutations. This frequency, combined with the substantial impact of these variants on adiposity, has implications for public health, and drug development.
Prevalence of missing data in the National Cancer Database and association with overall survival
Authors: Yang Daniel X. , Khera Rohan , Miccio Joseph A. , Jairam Vikram , Chang Enoch , Yu James B. , Park Henry S. , Krumholz Harlan M. , Aneja Sanjay 
Published: November 2020

AbstractImportanceCancer registries are important real-world data (RWD) sources that rely on data abstraction from the medical record, however, patients with unknown or missing data are under-represented in studies that use such data sources.ObjectiveTo determine the prevalence of missing data and its associated overall survival among cancer patientsDesign, Setting, and ParticipantsIn this retrospective cohort study, all variables within the National Cancer Database (NCDB) were reviewed for missing or unknown values for the three most common cancers in the United States diagnosed from 2006 to 2015. Prevalence of patient records with missing data and their associated overall survival were determined. Data analysis was performed from February to August 2020.ExposuresAny missing data field within a patient record among 63 variables of interest, from over 130 variables total in the NCDB.Main Outcome and MeasurePrevalence of cancer patient records with missing data and associated two-year overall survivalResultsA total of 1,198,749 non-small cell lung cancer (NSCLC) patients (mean [SD] age, 68.5 [10.9] years; 569,938 [47.5%] women), 2,120,775 breast cancer patients (mean [SD] age, 61.0 [13.3] years; 2,101,758 [99.1%] women), and 1,158,635 prostate cancer patients (mean [SD] age, 65.2 [9.0] years; 0 [0%] women) were included for analysis. For NSCLC, there were 851,295 (71.0%) patients with missing data in variables of interest; 2-year overall survival was 33.2% for patients with missing data and 51.6% for patients with complete data (p<0.001). For breast cancer, there were 1,161,096 (54.7%) patients with missing data; 2-year overall survival was 93.2% for patients with missing data and 93.9% for patients with complete data (p<0.001). For prostate cancer, there were 460,167 (39.7%) patients with missing data; 2-year overall survival was 91.0% for patients with missing data and 95.6% for patients with complete data (p<0.001).Conclusions and RelevanceWithin a large cancer registry-based RWD source, missing data that was unable to be ascertained from the medical record was highly prevalent. Missing data among cancer patients was associated with heterogeneous differences in overall survival. Improving documentation and data quality are needed to best leverage RWD for clinical advancements.