bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thoracic Multidetector Computed Tomography Findings of Dedicator of Cytokinesis 8 Deficiency in Children
Authors: Lee Edward Y. , Vargas Sara O. , Gaffin Jonathan M. , Chou Janet , Park Halley J. , Winant Abbey J. 
Published: March 2021

Purpose:
To investigate the characteristic thoracic multidetector computed tomography (MDCT) findings of dedicator of cytokinesis 8 (DOCK8) deficiency, a rare autosomal recessive form of hyperimmunoglobulin E syndrome, in children.

Materials and Methods:
All pediatric patients (age 18 y and below) with a known diagnosis of DOCK8 deficiency based on genetic testing who underwent thoracic MDCT studies from November 2004 to November 2020 were included. Two pediatric radiologists independently evaluated MDCT studies for the presence of thoracic abnormalities in the lung [ground-glass opacity (GGO), consolidation, pulmonary nodule, mass, cyst, and bronchiectasis], pleura (pleural effusion and pneumothorax), and mediastinum (lymphadenopathy). When a lung abnormality was present, laterality, distribution (upper, middle, and lower lung zone), and extent were also evaluated. When a pleural abnormality was identified, laterality and size of the abnormality were also assessed. When mediastinal lymphadenopathy was present, its location and size were also evaluated. Interobserver agreement between two independent reviewers was evaluated with κ statistics.

Results:
In all, 17 thoracic MDCT studies from 17 individual pediatric patients [5 males (29%) and 12 females (71%); mean age: 7.4 y; SD: 3.7; range: 1 to 13 y] comprised the final study population. Among 17 thoracic MDCT studies, 11 studies (65%) were performed with intravenous contrast (IV) and the remaining 6 MDCT studies (35%) were obtained without IV contrast. Bilateral bronchiectasis (11/17; 65%) with a middle lung zone predominance (8/11; 73%) was the most frequently detected lung abnormality, followed by GGO in 9/17 patients (53%). Among 11 contrast-enhanced MDCT studies, the majority (9 patients, 82%) had mediastinal lymphadenopathy. There was excellent interobserver κ agreement between 2 independent reviewers for detecting abnormalities on thoracic MDCT studies (κ>0.90).

Conclusion:
Children with DOCK8 deficiency have characteristic thoracic MDCT findings, including bilateral bronchiectasis with a middle lung zone predominance, GGO, and mediastinal lymphadenopathy. When these characteristic thoracic MDCT findings are detected, although rare, DOCK8 deficiency should be considered as a possible underlying diagnosis in the pediatric population.
Genome-Wide Meta-Analysis of Late-Onset Alzheimer’s Disease Using Rare Variant Imputation in 65,602 Subjects Identifies Novel Rare Variant Locus NCK2: The International Genomics of Alzheimer’s Project (IGAP)
Authors: Naj Adam C. , Leonenko Ganna , Jian Xueqiu , Grenier-Boley Benjamin , Dalmasso Maria Carolina , Bellenguez Celine , Sha Jin , Zhao Yi , van der Lee Sven J. , Sims Rebecca , Chouraki Vincent , Bis Joshua C. , Kunkle Brian W. , Holmans Peter , Leung Yuk Yee , Farrell John J. , Chesi Alessandra , Chen Hung-Hsin , Vardarajan Badri , Benchek Penelope , Barral Sandral , Lee Chien-Yueh , Kuksa Pavel , Haut Jacob , Lee Edward B. , Li Mingyao , Zhang Yuanchao , Grant Struan , Phillips-Cremins Jennifer E. , Comic Hata , Pitsillides Achilleas , Xia Rui , Hamilton-Nelson Kara L. , Kuzma Amanda , Valladares Otto , Fulton-Howard Brian , Dupuis Josee , Bush Will S. , Wang Li-San , Below Jennifer E. , Farrer Lindsay A. , van Duijn Cornelia , Mayeux Richard , Haines Jonathan L. , DeStefano Anita L. , Pericak-Vance Margaret A. , Ramirez Alfredo , Seshadri Sudha , Amouyel Philippe , Williams Julie , Lambert Jean-Charles , Schellenberg Gerard D. 
Published: March 2021

AbstractRisk for late-onset Alzheimer’s disease (LOAD) is driven by multiple loci primarily identified by genome-wide association studies, many of which are common variants with minor allele frequencies (MAF)> 0.01. To identify additional common and rare LOAD risk variants, we performed a GWAS on 25,170 LOAD subjects and 41,052 cognitively normal controls in 44 datasets from the International Genomics of Alzheimer’s Project (IGAP). Existing genotype data was imputed using the dense, high-resolution Haplotype Reference Consortium (HRC) r1.1 reference panel. Stage 1 associations of P<10−5 were meta-analyzed with the European Alzheimer’s Disease Biobank (EADB) (n=20,301 cases; 21,839 controls) (stage 2 combined IGAP and EADB). An expanded meta-analysis was performed using a GWAS of parental AD/dementia history in the UK Biobank (UKBB) (n=35,214 cases; 180,791 controls) (stage 3 combined IGAP, EADB, and UKBB). Common variant (MAF≥0.01) associations were identified for 29 loci in stage 2, including novel genome-wide significant associations at TSPAN14 (P=2.33×10−12), SHARPIN (P=1.56×10−9), and ATF5/SIGLEC11 (P=1.03×10−8), and newly significant associations without using AD proxy cases in MTSS1L/IL34 (P=1.80×10−8), APH1B (P=2.10×10−13), and CLNK (P=2.24×10−10). Rare variant (MAF<0.01) associations with genome-wide significance in stage 2 included multiple variants in APOE and TREM2, and a novel association of a rare variant (rs143080277; MAF=0.0054; P=2.69×10−9) in NCK2, further strengthened with the inclusion of UKBB data in stage 3 (P=7.17×10−13). Single-nucleus sequence data shows that NCK2 is highly expressed in amyloid-responsive microglial cells, suggesting a role in LOAD pathology.
Evaluation of pooling of samples for testing SARS-COV- 2 for mass screening of COVID-19
Authors: Mahmoud Sally , Ibrahim Esra , Thakre Bhagyashree , Teddy Juliet , Raheja Preety , Ganesan Subhashini , Zaher Walid 
Published: March 2021

AbstractBackgroundThe current pandemic of SARS- COV- 2 virus, widely known as COVID-19 has affected millions of people around the world. The World Health Organization (WHO) has recommended vigorous testing to differentiate SARS-CoV-2 from other respiratory infections to aid in guiding appropriate care and management. Situations like this have demanded robust testing strategies and pooled testing of samples for SARS- COV- 2 virus has provided the solution to mass screening of people. The pooled testing strategy can be very effective in testing with limited resources, yet it comes with its own limitations. These limitations need critical consideration when it comes to testing of highly infectious disease like COVID −19.MethodsThe study evaluated the pooled testing of nasopharyngeal swabs for SARS- COV- 2 by comparing sensitivity of individual sample testing with 4 and 8 pool sample testing. Median cycle threshold (Ct) values were compared. The precision of pooled testing was assessed by doing an inter and intra assay of pooled samples. Coefficient of variance was calculated for inter and intra assay variability.ResultsThe sensitivity becomes considerably low when the samples are pooled, there is a higher percentage of false negatives with higher pool size and when the patient viral load is low or weak positive samples. High variability was seen in the intra and inter assay, especially in weak positive samples and larger pool size.ConclusionAs COVID - 19 numbers are still high and testing capacity needs to be high, we have to meticulously evaluate the testing strategy for each country depending on its testing capacity, infrastructure, economic strength, and need to make a serious call on cost effective strategy of resource saving and risk/ cost of missing positive patients.
Development of a COVID-19 Application Ontology for the ACT Network
Authors: Visweswaran Shyam , Samayamuthu Malarkodi J. , Morris Michele , Weber Griffin M. , MacFadden Douglas , Trevvett Philip , Klann Jeffrey G. , Gainer Vivian , Benoit Barbara , Murphy Shawn N. , Patel Lav , Mirkovic Nebojsa , Borovskiy Yuliya , Johnson Robert D. , Wyatt Matthew C. , Wang Amy Y. , Follett Robert W. , Chau Ngan , Zhu Wenhong , Abajian Mark , Chuang Amy , Bahroos Neil , Reeder Phillip , Xie Donglu , Cai Jennifer , Sendro Elaina R. , Toto Robert D. , Firestein Gary S. , Nadler Lee M. , Reis Steven E. 
Published: March 2021

ABSTRACTClinical data networks that leverage large volumes of data in electronic health records (EHRs) are significant resources for research on coronavirus disease 2019 (COVID-19). Data harmonization is a key challenge in seamless use of multisite EHRs for COVID-19 research. We developed a COVID-19 application ontology in the national Accrual to Clinical Trials (ACT) network that enables harmonization of data elements that that are critical to COVID-19 research. The ontology contains over 50,000 concepts in the domains of diagnosis, procedures, medications, and laboratory tests. In particular, it has computational phenotypes to characterize the course of illness and outcomes, derived terms, and harmonized value sets for SARS-CoV-2 laboratory tests. The ontology was deployed and validated on the ACT COVID-19 network that consists of nine academic health centers with data on 14.5M patients. This ontology, which is freely available to the entire research community on GitHub at https://github.com/shyamvis/ACT-COVID-Ontology, will be useful for harmonizing EHRs for COVID-19 research beyond the ACT network.
Impact of COVID-19 on tuberculosis notifications in Blantyre Malawi: an interrupted time series analysis and qualitative study with healthcare workers
Authors: Soko Rebecca Nzawa , Burke Rachael M , Feasey Helena RA , Sibande Wakumanya , Nliwasa Marriott , Henrion Marc YR , Khundi McEwen , Dodd Peter J , Ku Chu Chang , Kawalazira Gift , Choko Augustine T , Divala Titus H , Corbett Elizabeth L , MacPherson Peter 
Published: March 2021

AbstractCOVID-19 may impact on tuberculosis (TB) diagnosis and care. We analysed a city-wide electronic TB register in Blantyre, Malawi and interviewed TB officers. Malawi had no official “lockdown” but closed schools and borders on 23-March 2020. In interrupted time series analysis, there was an immediate 35.9% reduction in TB notifications (95% CI 22.0 to 47.3%) in April, which recovered to near pre-pandemic numbers by December 2020, but with 333 (95% CI 291 to 375) fewer cumulative notifications than anticipated. Women and girls were impacted (30.7% fewer cases, 95% CI 28.4 to 33.0%) more than men and boys (20.9% fewer, 95% CI 18.5 to 23.3). Fear of COVID-19 infection, temporary facility closure, inadequate protective equipment and COVID-19 stigma with similar presenting symptoms to TB were mentioned. Public health measures could benefit both TB and COVID-19, but only if diagnostic services remain accessible and are considered safe to attend.
A Spatiotemporal Analysis of Socio-Environmental Patterns in Severe Maternal Morbidity: A Retrospective Birth Cohort
Authors: Harden Stella , Runkle Jennifer , Sugg Margaret 
Published: March 2021

AbstractObjectivesSevere Maternal Morbidity (SMM) is a group of pregnancy complications in which a woman nearly dies. Despite its increasing prevalence, there is little research that evaluates geographic patterns of SMM and the underlying social determinants that influence excess risk. This study examines the spatial clustering of SMM across South Carolina, US, and its associations with place-based social and environmental factors.MethodsHospitalized deliveries from 1999 to 2017 were analyzed using Kulldorff’s spatial scan statistic to locate areas with abnormally high rates of SMM. Patients inside and outside risk clusters were compared using Generalized Estimating Equations (GEE) to determine underlying risk factors.ResultsFinal models revealed that the odds of living in a high-risk cluster were 84% higher among Black patients (OR=1.84, p<.001), 30% higher among Hispanic and Latina patients (OR=1.3, p<.05), and 1.51 times more likely among women living in highly segregated and poorer minority communities (OR=1.51 p<.001). Odds for residing in a high-risk cluster were 23% higher for those who gave birth during a period with temperatures above 30.65°C/87.3°F (OR=1.23, p<.001).ConclusionsThis study is the first to characterize the geographic clustering of SMM risk in the US. Our geospatial approach contributes a novel understanding to factors which influence SMM beyond patient-level characteristics and identifies the impact of systemic racism on maternal morbidity. Findings address an important literature gap surrounding place-based risk factors by explaining the contextual social and built environment variables that drive SMM risk.SignificanceIt is not entirely clear why SMM is increasing in the US. Underlying health conditions, environmental, and social factors have been linked to higher SMM risk. This study is the first to assess these factors across space to determine the characteristics and locations where SMM likelihood is elevated.HighlightsFirst study to examine spatial patterning of severe maternal morbidity (SMM)SMM is geographically clustered and increasing in South Carolina, USAHighest risk for SMM in racially segregated low-income communitiesObesity and race were significant individual risk factorsHigh ambient temperatures corresponded with high SMM clustering
Within-Day Variability of SARS-CoV-2 RNA in Municipal Wastewater Influent During Periods of Varying COVID-19 Prevalence and Positivity
Authors: Bivins Aaron , North Devin , Wu Zhenyu , Shaffer Marlee , Ahmed Warish , Bibby Kyle 
Published: March 2021

ABSTRACTWastewater surveillance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is being used to monitor Coronavirus Disease 2019 (COVID-19) trends in communities; however, within-day variation in primary influent concentrations of SARS-CoV-2 RNA remain largely uncharacterized. In the current study, grab sampling of primary influent was performed every 2 hours over two different 24-hour periods at two wastewater treatment plants (WWTPs) in northern Indiana, USA. In primary influent, uncorrected, recovery-corrected, and pepper mild mottle virus (PMMoV)-normalized SARS-CoV-2 RNA concentrations demonstrated ordinal agreement with increasing clinical COVID-19 positivity, but not COVID-19 cases. Primary influent SARS-CoV-2 RNA concentrations exhibited greater variation than PMMoV RNA concentrations as expected for lower shedding prevalence. The bovine respiratory syncytial virus (BRSV) process control recovery efficiency was low (mean: 0.91%) and highly variable (coefficient of variation: 51% - 206%) over the four sampling events with significant differences between the two WWTPs (p <0.0001). The process control recovery was similar to the independently assessed SARS-CoV-2 RNA recovery efficiency, which was also significantly different between the two WWTPs (p <0.0001). Recovery-corrected SARS-CoV-2 RNA concentrations better reflected within-day changes in primary influent flow rate and fecal content, as indicated by PMMoV concentrations. These observations highlight the importance of assessing the process recovery efficiency, which is highly variable, using an appropriate process control. Despite large variations, both recovery-corrected and PMMoV-normalized SARS-CoV-2 RNA concentrations in primary influent demonstrate potential for monitoring COVID-19 positivity trends in WWTPs serving peri-urban and rural areas.
Calculating variant penetrance using family history of disease and population data Authorship
Authors: Spargo Thomas P , Opie-Martin Sarah , Lewis Cathryn M , Iacoangeli Alfredo , Al-Chalabi Ammar 
Published: March 2021

AbstractPurposeGenetic penetrance is the probability of a phenotype manifesting if one harbours a specific pathogenic variant. For most Mendelian genes, penetrance is incomplete and may be age-dependent. Accurate penetrance estimates are important in many biomedical fields including genetic counselling, disease research, and for gene therapy. The main methods for its estimation are limited in situations where large family pedigrees are not available, the disease is rare, late onset, or complex.MethodsHere we present a novel method for penetrance estimation in autosomal dominant phenotypes. It uses population-scale data regarding the distribution of a variant among unrelated people affected (cases) and unaffected (controls) by an associated phenotype and can be operated using samples of affected people only by considering family disease history.ResultsThe method is validated within simulation studies. Candidate variant-disease case studies yield estimates which align with existing disease knowledge and estimates derived using established methods.ConclusionWe have presented a valid method for penetrance estimation in autosomal dominant traits which avoids kinship-specific penetrance estimates and the ascertainment biases that can arise when sampling rare variants among control populations. It can be accessed from our public web server (https://adpenetrance.rosalind.kcl.ac.uk) and is available as an open-source R library (https://github.com/ThomasPSpargo/adpenetrance).
Systemic cytokines and GlycA discriminate inflammaging, disease progression and corticosteroid response in HTLV-1-associated neuroinflammation
Authors: Assone Tatiane , Menezes Soraya Maria , de Toledo Gonçalves Fernanda , Folgosi Victor Angelo , da Silva Prates Gabriela , Dierckx Tim , Braz Marcos , Smid Jerusa , Haziot Michel E. , Marcusso Rosa M N , E. Dahy Flávia , Bruhn Roberta , Murphy Edward L. , de Oliveira Augusto César Penalva , Daelemans Dirk , Vercauteren Jurgen , Casseb Jorge , Van Weyenbergh Johan 
Published: March 2021

ABSTRACTBackgroundHTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is an incapacitating neuroinflammatory disorder for which no disease-modifying therapy is available, but corticosteroids provide some clinical benefit.ObjectiveTo investigate systemic cytokines and GlycA as possible biomarkers of immunopathogenesis and therapeutic response to corticosteroid pulse therapy in HAM/TSP.MethodsWe prospectively followed 110 People living with HTLV-1 (PLwHTLV-1, 67 asymptomatic individuals and 43 HAM/TSP patients), for a total of 906 person-years. Plasma cytokine levels (IL-2/4/6/10/17A, IFN-γ, TNF) and GlycA were quantified by Cytometric Bead Array and 1NMR, respectively. Cytokine signaling and prednisolone response were validated in an independent cohort by nCounter digital transcriptomics. We applied logistic regression and machine learning algorithms to predict disease progression and glucocorticoid response.ResultsIL-6 was positively correlated with age and GlycA in asymptomatics but not HAM/TSP patients. Systemic IFN-γ and IL-17A levels were increased in HAM/TSP patients, as compared to asymptomatics. All patients significantly decreased IL-17A levels post-treatment but only prednisolone-responders decreased IFN-γ levels post-treatment. Higher pre-treatment GlycA and TNF levels significantly predicted a negative therapeutic outcome, which was associated with higher post-treatment IFN-γ levels. Low IL-4 and IL-10 levels in incident HAM/TSP can be reverted to increased IL-10 and IL-4/IL-13 signaling by prednisolone in vitro.Conclusions1) An age-related increase in systemic IL-6/GlycA levels reveals inflammaging in PLwHTLV-1. 2) IFN-γ and IL-17A are biomarkers of untreated, active HAM/TSP disease, while pre-treatment GlycA and TNF predict therapeutic response to prednisolone pulse therapy. 3) Low IL-4/IL-10 and high IFN-γ signaling in incident HAM/TSP can be normalized by prednisolone.
How safe is Covishield (ChAdOx1nCoV-19) vaccine? Experience from a tertiary care hospital in South India
Authors: Inbaraj Leeberk Raja , George Carolin Elizabeth , Franklyn Nirupama Navamani 
Published: March 2021

AbstractBackgroundCOVID vaccine has been recently rolled out for Health care workers in India. Though vaccine trials and data are available, people, including HCWs, need more real-life data from their contexts to get over the vaccine hesitancy. We aimed to determine the incidence of Adverse Event Following Immunisation (AEFI) among HCWs after their first dose of ChAdOx1nCoV-19 vaccineMethodsWe conducted a cross-sectional study among 218 staff of a tertiary care hospital. We circulated a google form with informed consent on the hospital WhatsApp platform and asked them to self-report their vaccination experience.ResultsTwo thirds (69.7% (152/218), 95% CI: 63.1-75.7) had minor AEFI, and none had severe AEFI. Body ache (46.8% (102/218), 95% CI :40 – 53.6) was the most common symptom followed by headache (30.3% (66/218), 95% CI :24.2 – 36.8) and fever (22% 948/218), 95% CI :16.7 – 28.1). Most of them (39.4% (87/218) 95% CI:32.9 – 46.2) experienced symptoms within 4-24 hours after taking the vaccine while 22.3% (49/218) (95% CI: 17.1 – 28.6) experienced it after a day. Majority of the HCWs (78.9% (172/218), 95% CI: 72.8 – 84.1) were anxious before the vaccination. Younger age group and female gender were significantly associated with AEFI compared to their counterparts.ConclusionHCWs experienced minor, self-limiting AEFI with the first dose of ChAdOx1nCoV-19. The hospital reported no serious AEFI following the vaccination
Occupational risk of COVID-19 by country of birth. A register-based study
Authors: Kjøllesdal M , Magnusson K 
Published: March 2021

AbstractAimTo assess the role of occupation in the spread of COVID-19 among immigrants in Norway.MethodsIn 2.729.627 residents in Norway aged 20-70 years and born in Norway, Somalia, Pakistan, Iraq, Afghanistan and Turkey (mean [SD] age 44 (14) years and 51% men), we examined whether persons employed as taxi drivers, bus- and tram drivers, child care workers, nurses, personal care workers in health, food service counter attendants, waiters/bartenders, cleaners and shop sale persons had a higher risk of COVID-19, from April 1st 2020 to December 2nd 2020, compared to 1) Norwegian-born in the same occupational group and 2) all others with the same birth country and aged 20-70 years, using logistic regressions.ResultsWithin each of the included occupational groups, immigrants had a greatly increased odds of COVID-19 when compared to Norwegian-born (OR ∼ 1.66-12.72). However, immigrants working in the selected occupations had the same odds of COVID-19 as person with same birth country not having the same occupation (OR∼1). Exceptions were Somalian-, Afghani- and Iraqi personal care workers in health services who had an increased odds of COVID-19 (OR 1.61 (95% CI 1.31, 1.98), OR 1.46 (1.06, 2.02) and OR 1.40 (1.03, 1.91), respectively) compared to others from the same country.ConclusionImmigrants holding various occupations implying close contact with others did not have higher odds of notified infection than others with the same country of birth, except for health care workers. Our study indicates that occupation is not an important driver of the high rates of COVID-19 among immigrants from Somalia, Pakistan, Iraq, Afghanistan and Turkey.