bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and Functional Characterization of Bicaudal-D2 As A Candidate Disease Gene in Autosomal Recessive Consanguineous Family with Dilated Cardiomyopathy
Authors: Luo Kai , Zheng Chenqing , Luo Rong , Cao Xin , Sun Huajun , Ma Huihui , Huang Jichang , Yang Xu , Wu Xiushan , Li Xiaoping 
Published: February 2022

AbstractFamilial Dilated cardiomyopathy (DCM) is a genetic cardiomyopathy with reduced left ventricle function or systolic function. Fifty-one DCM genes have been reported, most of which are inherited in an autosomal dominant manner, while those caused by a recessive manner are rarely observed. Here we identified an autosome recessive and evolutionarily conserved missense variant, c.2429G>A: p.Arg810His, in bicaudal D homolog 2 (BICD2), which was segregated with the disease phenotype in a consanguineous family with DCM. Furthermore, we confirmed the presence of BICD2 variants in 3 of 210 sporadic cases, highlighting its candidate causative role. Interestingly, we discovered that BICD2 expressed higher in cardiomyocytes from DCM than that from control by reanalyzing published scRNA-seq dataset, implicating its possible involvement in cardiac function. We next explored BICD2 function in zebrafish model at both embryonic and adult stages. Knockout of bicd2 resulted in partial embryonic lethality in homozygotes, suggesting a vital role for bicd2 in embryogenesis. We performed zebrafish echocardiography to detect indices of ventricular size at the adult zebrafish stage. Intriguingly, dilated hearts, decreased ejection fraction, cardiac output and stroke volume were observed, suggesting a phenotype similar to human DCM in bicd2-knockout homozygotes. Furthermore, RNA-seq confirmed the largest transcriptome shift in bicd2 homozygotes. Gene Set Enrichment Analysis(GSEA) of bicd2-deficient fish showed altered gene expression enriched in cardiac pathways and mitochondrial energy metabolism. In conclusion, we found for the first time that an autosomal recessive BICD2 variant is associated with familial DCM, providing further insight into the molecular pathological mechanism of DCM.
Humoral Antibody Kinetics with ChAdOx1-nCOV (CovishieldTM) and BBV-152 (CovaxinTM) Vaccine among Indian Healthcare workers: A 6-month Longitudinal Cross-sectional Coronavirus Vaccine-induced Antibody Titre (COVAT) Study
Authors: Singh Awadhesh Kumar , Phatak Sanjeev Ratnakar , Singh Ritu , Bhattacharjee Kingshuk , Singh Nagendra Kumar , Gupta Arvind , Sharma Arvind 
Published: February 2022

AbstractBackground and AimsThere is limited data available on longitudinal humoral antibody dynamics following two doses of ChAdOx1-nCOV (CovishieldTM) and BBV-152 (CovaxinTM) vaccine against SARS-CoV-2 among Indians.MethodsWe conducted a 6-month longitudinal study in vaccinated healthcare workers by serially measuring quantitative anti-spike antibody at 3-weeks, 3-months and 6- months after the completion of second dose. Geometric mean titer (GMT) and linear mixed models were used to assess the dynamics of antibody levels at 6 months.ResultsOf the 481 participants, GMT of anti-spike antibody decreased by 56% at 6- months regardless of demographics and comorbidities in 360 SARS-CoV-2 naive individuals, significantly in hypertensives. Participants with past infection had significantly higher GMT at all time points compared to naive individuals. Among SARS-CoV-2 naive cohorts, a significantly higher GMT was noted amongst the Covishield recipients at all time points, but there was a 44% decline in GMT at 6- month compared to peak titer period. Decline in GMT was insignificant (8%) in Covaxin recipients at 6-month despite a lower GMT at all time points vs. Covishield. There was 5.6-fold decrease in seropositivity rate at 6-month with both vaccines. Participants with type 2 diabetes mellitus have a lower seropositivity rate at all the time points. While seropositivity rate was significantly higher with Covishield vs. Covaxin at all time points except at 6-month where Covaxin recipients had a higher seropositivity, although no difference in seropositivity was noted in propensity-matched analysis.ConclusionsThere is waning humoral antibody response following two doses of either vaccine at six months.Highlights:We assessed humoral antibody dynamics following two doses of the two vaccines used in India until 6 months.Our study of 481 health care workers showed a significant decrease in the anti-spike antibody at 6-months.Reduction in antibody was regardless of demographics, comorbidities and the vaccine type.T2DM cohorts had lowest seropositivity, while hypertensive had significant antibody decline at 6-month.
Vital signs as a source of racial bias
Authors: Velichkovska Bojana , Gjoreski Hristijan , Denkovski Daniel , Kalendar Marija , Mamandipoor Behrooz , Celi Leo Anthony , Osmani Venet 
Published: February 2022

AbstractBackgroundracial bias has been shown to be present in clinical data, affecting patients unfairly based on their race, ethnicity and socio-economic status. This problem has the potential to be significantly exacerbated in the light of Artificial Intelligence-aided clinical decision making. We sought to investigate whether bias can be introduced from sources that are considered neutral with respect to ethnicity and race and consequently routinely used in modelling, specifically vital signs.Methodsto perform our analysis, we extracted vital signs from 49,610 admissions from a cohort of adult patients during the first 24 hours after the admission to the Intensive Care Units (ICU), derived from multi-centre eICU-CRD database and single-centre MIMIC-III database, spanning over 208 hospitals and 335 ICUs. Using heart rate, SaO2, respiratory rate, systolic, diastolic, and mean blood pressure, we develop machine learning models based on Logistic Regression and eXtreme Gradient Boosting and investigate their performance in predicting patients’ self-reported race. To balance the dataset between the three ethno-races considered in our study, we use a matching cohort based on age, gender, and admission diagnosis.Findingsstandard machine learning models, derived solely on six vital signs can be used to predict patients’ self-reported race with AUC of 75%. Our findings hold under diverse patient populations, derived from multiple hospitals and intensive care units. We also show that oxygen saturation is a highly predictive variable, even when measured through methods other than pulse oximetry, namely arterial blood gas analysis, suggesting that addressing bias in routinely collected clinical variables will be challenging.Interpretationour finding that machine learning models can predict self-reported race using solely vital signs creates a significant risk in clinical decision making, further exacerbating racial inequalities, with highly challenging mitigation measures.FundingThe funders had no role in the design of this study.
Chronic fatigue associated with post-COVID syndrome versus transient fatigue caused by high intensity exercise: are they comparable in terms of vascular effects?
Authors: Chudzik Michal , Cender Anna , Mordaka Robert , Zielinski Jacek , Katarzynska Joanna , Marcinek Andrzej , Gebicki Jerzy 
Published: February 2022

AbstractPurposeThe pathophysiology of chronic fatigue associated with post-COVID syndrome is not well recognized. It is assumed that this condition is partly due to vascular dysfunction developed during an acute phase of infection. There is great demand for a diagnostic tool that is able to clinically assess post-COVID syndrome and monitor the rehabilitation process.Patients and MethodsThe Flow Mediated Skin Fluorescence (FMSF) technique appears uniquely suitable for the analysis of basal microcirculatory oscillations and reactive hyperemia induced by transient ischemia. The FMSF was used to measure vascular circulation in 45 patients with post-COVID syndrome. The results were compared with those for a group of 26 amateur runners before and after high intensity exercise, as well as for a control group of 32 healthy age-matched individuals.ResultsBased on the NOI and RHR parameters measured with the FMSF technique, it was found that chronic fatigue associated with post-COVID syndrome is comparable with transient fatigue caused by high-intensity exercise in terms of vascular effects. Both chronic fatigue associated with post-COVID syndrome and transient fatigue caused by high-intensity exercise are associated with vascular stress in the macrocirculation and microcirculation.ConclusionThe NOI and RHR parameters measured with the FMSF technique can be used for non-invasive clinical assessment of post-COVID syndrome, as well as for monitoring the rehabilitation process.
Determinants of Thyroid Dysfunction among Type 2 Diabetes Patients Attending Private Hospitals in Dire Dawa, Eastern Ethiopia
Authors: Tekalign Alemayehu Molla , Habte Fitsum Berhane , Yimer Robel Mekonnen 
Published: February 2022

ABSTRACTPurposeThe purpose of this study is to capture the determinants of thyroid dysfunction in type 2 diabetes mellitus at private hospitals in Dire-Dawa, Eastern Ethiopia. Various studies found that thyroid dysfunction is common in type 2 diabetes and it is associated with poor blood glucose control and chronic diabetic complications responsible for morbidity and mortality. However, only limited studies have assessed determinants of thyroid dysfunctions among type 2 diabetes in Ethiopia.MethodsUnmatched case-control study conducted in two private hospitals found in Dire Dawa town, between May - November 2021. A total of 92 type 2 diabetic patients with thyroid dysfunction as Cases and 183 type 2 diabetes patients with normal thyroid function as controls selected by purposive and systematic random sampling, respectively. Data collected by interview and using checklist, entered into SPSS version 22, and analyzed. Bivariate and multivariate logistic regression analysis employed to identify determinants of thyroid dysfunction with AOR and 95%CI. Independent t-test computed to observe significant mean difference of continuous variables. Variables with P-value < 0.05 declared as significant.ResultFemale gender predominate 65.9% of participants (p= 0.02). The mean glycated hemoglobin level among cases was 10.32 (± 2.4 SD) and 9.249 (± 2.3 SD) among controls, with significant difference (p=0.001). Similarly, the mean LDL cholesterol among cases 116.92 ±45.9 SD and control 102.34 ±43.97SD showed significant difference (p=0.016). Diabetic retinopathy and neuropathy, and ACEI/ARB also significantly associated with thyroid dysfunction (p< 0.05).ConclusionFemale gender, lower educational level, and duration of diabetes associated with thyroid dysfunction. Most patients in both groups had unacceptably elevated HgA1c which need to be addressed. Thus, screening for thyroid dysfunction, especially the female gender, needs to be done.
Measles incidence in South Africa: a six-year review, 2015 - 2020
Authors: Yousif Mukhlid , Hong Heather , Malfeld Susan , Smit Sheilagh , Makhathini Lillian , Motsamai Tshepo , Tselana Dipolelo , Manamela Morubula , Kamupira Mercy , Maseti Elizabeth , Otwombe Kennedy , McCarthy Kerrigan , Suchard Melinda 
Published: February 2022

AbstractIn 2012 the World Health Organization (WHO) aimed to eliminate measles in five regions by 2020. This retrospective descriptive study reviewed measles surveillance data in South Africa for the period 2015 - 2020 to document the epidemiology of measles and the progress made towards meeting the 2020 measles elimination goal.A total of 22,578 specimens were tested over the period 2015 - 2020 yielding 401 (1.8%) confirmed measles cases, 321 (1.4%) compatible and 21,856 (96.8%) discarded cases. The most affected age group was 0-4 year olds. At the provincial level, South Africa achieved adequate surveillance, defined as more than two cases of febrile rash notified annually per 100 000 popoulation, except for KwaZulu-Natal and Limpopo in 2020, probably due to COVID-19 lockdown restrictions. Of confirmed cases, only 26% were vaccinated, 3% were too young to receive vaccines, 5% were not vaccinated, and 65% had vaccination status unknown. Measles vaccine effectiveness amongst 1-4 year olds was 80%. Using the standard case definition, South Africa achieved the measles elimination target of less than one case per one million nationally in years 2015, 2016 and 2020. The years 2017 to 2019 had incidence rates exceeded one per million nationally. Using a narrow case definition, that excluded positive rubella cases, improved the indicators with only the year 2017 having an incidence rate of more than one per million.South Africa displays intermittent measles outbreaks approximately six-yearly interspersed by inter-epidemic periods in which the country meets measles elimination targets. Intense effort is needed to increase the vaccine coverage to avoid periodic outbreaks. Enhanced molecular testing of each case will be required as measles incidence declines regionally.
A longitudinal investigation of blood neurofilament light chain levels in chronic cocaine users
Authors: Bavato F. , Kexel A.K. , Kluwe-Schiavon B. , Maceski A. , Baumgartner M.R , Seifritz E. , Kuhle J. , Quednow B.B. 
Published: February 2022

AbstractObjectivesTo explore the hypothesis that plasma levels of neurofilament light chain (NfL), a marker of neuroaxonal pathology, are elevated in chronic cocaine users (CU) and longitudinally associated with changes in cocaine use.MethodsAs part of the Social Stress Cocaine Study (SSCP), we assessed 35 CU and 35 stimulant-naïve healthy controls (HC) at baseline and at a 4-month follow-up. Plasma NfL levels were determined from blood samples using single molecule array (SIMOA) technology. Substance use was subjectively assessed with an extensive interview and objectively measured via toxicological analysis of urine and 4-month hair samples.ResultsIn a generalized linear model corrected for sex, age, and body mass index, NfL plasma levels were elevated in CU compared to HC (p<0.05). A moderate positive correlation between cocaine hair concentration and NfL levels was also found in CU (r(s)=0.36, p=0.03). Changes in cocaine hair concentration (group analysis of increasers vs. decreasers) over the 4-month interval predicted NfL levels at follow-up (p=0.002), indicating a rise in NfL with increased cocaine use and a reduction with decreased use. No associations between use or change of use of other substances (including the cocaine adulterant levamisole) and NfL levels were found (r(s)≤±0.27, p>0.05).ConclusionsOur findings demonstrate that NfL is a sensitive marker for assessing cocaine-related brain pathology, supporting the utility of blood NfL analysis in addiction research. The results also suggest that cocaine use should be considered a potential confounder in diagnostic applications and clinical studies using NfL.
SurvMaximin: Robust Federated Approach to Transporting Survival Risk Prediction Models
Authors: Wang Xuan , Zhang Harrison G , Xiong Xin , Hong Chuan , Weber Griffin M , Brat Gabriel A , Bonzel Clara-Lea , Luo Yuan , Duan Rui , Palmer Nathan P , Hutch Meghan R , Gutiérrez-Sacristán Alba , Bellazzi Riccardo , Chiovato Luca , Cho Kelly , Dagliati Arianna , Estiri Hossein , García-Barrio Noelia , Griffier Romain , Hanauer David A , Ho Yuk-Lam , Holmes John H , Keller Mark S , Klann Jeffrey G , L’Yi Sehi , Lozano-Zahonero Sara , Maidlow Sarah E , Makoudjou Adeline , Malovini Alberto , Moal Bertrand , Moore Jason H , Morris Michele , Mowery Danielle L , Murphy Shawn N , Neuraz Antoine , Ngiam Kee Yuan , Omenn Gilbert S , Patel Lav P , Pedrera-Jiménez Miguel , Prunotto Andrea , Samayamuthu Malarkodi Jebathilagam , Sanz Vidorreta Fernando J , Schriver Emily R , Schubert Petra , Serrano-Balazote Pablo , South Andrew M , Tan Amelia LM , Tan Byorn W.L. , Tibollo Valentina , Tippmann Patric , Visweswaran Shyam , Xia Zongqi , Yuan William , Zöller Daniela , Kohane Isaac S ,   The Consortium for Clinical Characterization of COVID-19 by EHR (4CE), Avillach Paul , Guo Zijian , Cai Tianxi 
Published: February 2022

AbstractObjectiveFor multi-center heterogeneous Real-World Data (RWD) with time-to-event outcomes and high-dimensional features, we propose the SurvMaximin algorithm to estimate Cox model feature coefficients for a target population by borrowing summary information from a set of health care centers without sharing patient-level information.Materials and MethodsFor each of the centers from which we want to borrow information to improve the prediction performance for the target population, a penalized Cox model is fitted to estimate feature coefficients for the center. Using estimated feature coefficients and the covariance matrix of the target population, we then obtain a SurvMaximin estimated set of feature coefficients for the target population. The target population can be an entire cohort comprised of all centers, corresponding to federated learning, or can be a single center, corresponding to transfer learning.ResultsSimulation studies and a real-world international electronic health records application study, with 15 participating health care centers across three countries (France, Germany, and the U.S.), show that the proposed SurvMaximin algorithm achieves comparable or higher accuracy compared with the estimator using only the information of the target site and other existing methods. The SurvMaximin estimator is robust to variations in sample sizes and estimated feature coefficients between centers, which amounts to significantly improved estimates for target sites with fewer observations.ConclusionsThe SurvMaximin method is well suited for both federated and transfer learning in the high-dimensional survival analysis setting. SurvMaximin only requires a one-time summary information exchange from participating centers. Estimated regression vectors can be very heterogeneous. SurvMaximin provides robust Cox feature coefficient estimates without outcome information in the target population and is privacy-preserving.
Express yourself: Quantitative real-time PCR assays for rapid chromosomal antimicrobial resistance detection in Pseudomonas aeruginosa
Authors: Madden Danielle E. , Olagoke Olusola , Baird Timothy , Neill Jane , Ramsay Kay A. , Fraser Tamieka A. , Bell Scott C. , Sarovich Derek S. , Price Erin P. 
Published: February 2022

AbstractThe rise of antimicrobial-resistant (AMR) bacteria is a global health emergency. One critical facet in tackling this epidemic is more rapid AMR diagnosis in serious multi-drug resistant pathogens like Pseudomonas aeruginosa. Here, we designed and then validated two multiplex quantitative real-time PCR (qPCR) assays to simultaneously detect differential expression of the resistance-nodulation-division efflux pumps MexAB-OprM, MexCD-OprJ, MexEF-OprN, MexXY-OprM, the AmpC β-lactamase, and the porin OprD, which are commonly associated with chromosomally-encoded AMR. Next, qPCRs were tested on 15 sputa from 11 participants with P. aeruginosa respiratory infections to determine AMR profiles in vivo. We confirm multiplex qPCR testing feasibility directly on sputa, representing a key advancement in in vivo AMR diagnosis. Notably, comparison of sputa with their derived isolates grown in Luria-Bertani broth (±2.5% NaCl) or a 5-antibiotic cocktail showed marked expression differences, illustrating the difficulty in replicating in vivo expression profiles in vitro. Cystic fibrosis sputa showed significantly reduced mexE and mexY expression when compared with chronic obstructive pulmonary disease sputa, despite harbouring fluoroquinolone- and aminoglycoside-resistant strains, indicating that these loci are not contributing to AMR in vivo. oprD was also significantly downregulated in cystic fibrosis sputa, even in the absence of contemporaneous carbapenem use, suggesting a common adaptive trait in chronic infections that may affect carbapenem efficacy. Sputum ampC expression was highest in participants receiving carbapenems (6.7-15x), some of whom were simultaneously receiving cephalosporins, the latter of which would be rendered ineffective by the upregulated ampC. Our qPCR assays provide valuable insights into the P. aeruginosa resistome, and their use on clinical specimens will permit timely treatment alterations that will improve patient outcomes and antimicrobial stewardship measures.
Genetic population structure across Brittany and the downstream Loire basin provides new insights on the demographic history of Western Europe
Authors: Alves Isabel , Giemza Joanna , Blum Michael , Bernhardsson Carolina , Chatel Stéphanie , Karakachoff Matilde , Pierre Aude Saint , Herzig Anthony F. , Olaso Robert , Monteil Martial , Gallien Véronique , Cabot Elodie , Svensson Emma , Bacq-Daian Delphine , Baron Estelle , Berthelier Charlotte , Besse Céline , Blanché Hélène , Bocher Ozvan , Boland Anne , Bonnaud Stéphanie , Charpentier Eric , Dandine-Roulland Claire , Férec Claude , Fruchet Christine , Lecointe Simon , Floch Edith Le , Ludwig Thomas , Marenne Gaëlle , Meyer Vincent , Quellery Elisabeth , Racimo Fernando , Rouault Karen , Sandron Florian , Schott Jean-Jacques , Suarez Lourdes Velo , Violleau Jade , Willerslev Eske , Coativy Yves , Jézéquel Mael , Bris Daniel Le , Nicolas Clément , Pailler Yvan , Goldberg Marcel , Zins Marie , Marec Hervé Le , Jakobsson Mattias , Darlu Pierre , Génin Emmanuelle , Deleuze Jean-François , Redon Richard , Dina Christian 
Published: February 2022

AbstractEuropean genetic ancestry originates from three main ancestral populations - Western hunter-gatherers, early European farmers and Yamnaya Eurasian herders - whose edges geographically met in present-day France. Despite its central role to our understanding of how the ancestral populations interacted and gave rise to modern population structure, the population history of France has remained largely understudied. Here, we analysed the high-coverage whole-genome sequences and genome-wide genotype profiles of respectively 856 and 3,234 present-day individuals from the northern half of France, and merged them with publicly available present-day and ancient Europe-wide genotype datasets. We also explored, for the first time, the whole-genome sequences of six mediaeval individuals (300-1100 CE) from Western France to gain insights into the genetic impact of what is commonly known as the Migration Period in Europe. We found extensive fine-scale population structure across Brittany and the downstream Loire basin, emphasising the need for investigating local populations to better understand the distribution of rare and putatively deleterious variants across space. Overall, we observed an increased population differentiation between the northern and southern sides of the river Loire, which are characterised by different proportions of steppe vs. Neolithic-related ancestry. Samples from Western Brittany carry the largest levels of steppe ancestry and show high levels of allele sharing with individuals associated with the Bell Beaker complex, levels that are only comparable with those found in populations lying on the northwestern edges of Europe. Together, our results imply that present-day individuals from Western Brittany retain substantial legacy of the genetic changes that occurred in Northwestern Europe following the arrival of the Bell Beaker people c. 2500 BCE. Such genetic legacy may explain the sharing of disease-related alleles with other present-day populations from Western Britain and Ireland.