bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimates of the severity of COVID-19 disease
Authors: Verity Robert , Okell Lucy C , Dorigatti Ilaria , Winskill Peter , Whittaker Charles , Imai Natsuko , Cuomo-Dannenburg Gina , Thompson Hayley , Walker Patrick GT , Fu Han , Dighe Amy , Griffin Jamie T , Baguelin Marc , Bhatia Sangeeta , Boonyasiri Adhiratha , Cori Anne , Cucunubá Zulma , FitzJohn Rich , Gaythorpe Katy , Green Will , Hamlet Arran , Hinsley Wes , Laydon Daniel , Nedjati-Gilani Gemma , Riley Steven , van Elsland Sabine , Volz Erik , Wang Haowei , Wang Yuanrong , Xi Xiaoyue , Donnelly Christl A , Ghani Azra C , Ferguson Neil M 
Published: March 2020

SummaryBackgroundA range of case fatality ratio (CFR) estimates for COVID-19 have been produced that differ substantially in magnitude.MethodsWe used individual-case data from mainland China and cases detected outside mainland China to estimate the time between onset of symptoms and outcome (death or discharge from hospital). We next obtained age-stratified estimates of the CFR by relating the aggregate distribution of cases by dates of onset to the observed cumulative deaths in China, assuming a constant attack rate by age and adjusting for the demography of the population, and age- and location-based under-ascertainment. We additionally estimated the CFR from individual line-list data on 1,334 cases identified outside mainland China. We used data on the PCR prevalence in international residents repatriated from China at the end of January 2020 to obtain age-stratified estimates of the infection fatality ratio (IFR). Using data on age-stratified severity in a subset of 3,665 cases from China, we estimated the proportion of infections that will likely require hospitalisation.FindingsWe estimate the mean duration from onset-of-symptoms to death to be 17.8 days (95% credible interval, crI 16.9–19.2 days) and from onset-of-symptoms to hospital discharge to be 22.6 days (95% crI 21.1-24.4 days). We estimate a crude CFR of 3.67% (95% crI 3.56%-3.80%) in cases from mainland China. Adjusting for demography and under-ascertainment of milder cases in Wuhan relative to the rest of China, we obtain a best estimate of the CFR in China of 1.38% (95% crI 1.23%-1.53%) with substantially higher values in older ages. Our estimate of the CFR from international cases stratified by age (under 60 / 60 and above) are consistent with these estimates from China. We obtain an overall IFR estimate for China of 0.66% (0.39%-1.33%), again with an increasing profile with age.InterpretationThese early estimates give an indication of the fatality ratio across the spectrum of COVID-19 disease and demonstrate a strong age-gradient in risk.
Trends in CD4 and viral load testing 2005 to 2018: Multi-cohort study of people living with HIV in Southern Africa
Authors: Zaniewski Elizabeth , Dao Ostinelli Cam Ha , Chammartin Frédérique , Maxwell Nicola , Davies Mary-Ann , Euvrard Jonathan , van Dijk Janneke , Bosomprah Samuel , Phiri Sam , Tanser Frank , Sipambo Nosisa , Muhairwe Josephine , Fatti Geoffrey , Prozesky Hans , Wood Robin , Ford Nathan , Fox Matthew P , Egger Matthias 
Published: March 2020

AbstractIntroductionWHO recommends a CD4 cell count before starting antiretroviral therapy (ART) to detect advanced HIV disease, and routine viral load (VL) testing following ART initiation to detect treatment failure. Donor support for CD4 testing has declined to prioritize access to VL monitoring. We examined trends in CD4 and VL testing among adults (≥15 years of age) starting ART in Southern Africa.MethodsWe analysed data from 14 HIV treatment programs with over 300 clinics in Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in years 2005-2018. We examined the frequency of CD4 and VL testing, the percentage of adults with CD4 or VL tests, and among those having a test, the percentage starting ART with advanced HIV disease (CD4 count <200 cells/mm3) or failing to suppress viral replication (>1000 HIV-RNA copies/ml) after ART initiation. We used mixed effect logistic regression to assess time trends adjusted for age and sex.ResultsAmong 502,456 adults, the percentage with CD4 testing at ART initiation decreased from a high of 78.1% in 2008 to a low of 38.0% in 2017. The percentage starting with advanced HIV disease declined from 83.3% in 2005 to 23.5% in 2018. VL testing after starting ART varied; 61.0% of adults in South Africa and 10.7% in Malawi were tested but fewer than 2% were tested in the other four countries. The probability of having a CD4 cell count at ART start declined by 14% each year (odds ratio [OR] 0.86; 95% CI 0.86-0.86); the probability of advanced HIV disease declined by 20% per year (OR 0.80; 95% CI 0.80-0.81). The increase in VL testing after ART start was only modest (OR 1.06; 95% CI 1.05-1.06) and there was no evidence of a decrease in unsuppressed VL over time (OR 1.00; 95% CI 0.99-1.01).ConclusionsCD4 cell counting declined over time, including testing at the start of ART, despite the fact that many patients still initiated ART with advanced HIV disease. Without CD4 testing and expanded VL testing many patients with advanced HIV disease and treatment failure may go undetected, threatening the effectiveness of ART in sub-Saharan Africa.
Modelling the situation of COVID-19 and effects of different containment strategies in China with dynamic differential equations and parameters estimation
Authors: Liu Xiuli , Hewings Geoffrey , Wang Shouyang , Qin Minghui , Xiang Xin , Zheng Shan , Li Xuefeng 
Published: March 2020

AbstractThis paper proposed a quarantine-susceptible-exposed-infectious-resistant (QSEIR) model which considers the unprecedented strict quarantine measures in almost the whole of China to resist the epidemic. We estimated model parameters from published information with the statistical method and stochastic simulation, we found the parameters that achieved the best simulation test result. The next stage involved quantitative predictions of future epidemic developments based on different containment strategies with the QSEIR model, focused on the sensitivity of the outcomes to different parameter choices in mainland China. The main results are as follows. If the strict quarantine measures are being retained, the peak value of confirmed cases would be in the range of [52438, 64090] and the peak date would be expected in the range February 7 to February 19, 2020. During March18-30, 2020, the epidemic would be controlled. The end date would be in the period from August 20 to September 1, 2020. With 80% probability, our prediction on the peak date was 4 days ahead of the real date, the prediction error of the peak value is 0.43%, both estimates are much closer to the observed values compared with published studies. The sensitive analysis indicated that the quarantine measures (or with vaccination) are the most effective containment strategy to control the epidemic, followed by measures to increase the cured rate (like finding special medicine). The long-term simulation result and sensitive analysis in mainland China showed that the QSEIR model is stable and can be empirically validated. It is suggested that the QSEIR model can be applied to predict the development trend of the epidemic in other regions or countries in the world. In mainland China, the quarantine measures can’t be relaxed before the end of March 2020. China can fully resume production with appropriate anti-epidemic measures beginning in early April 2020. The results of this study also implied that other countries now facing the epidemic outbreaks should act more decisively and take in time quarantine measures though it may have negative short-term public and economic consequences.
Paternal body mass index and offspring DNA methylation: findings from the PACE consortium
Authors: Sharp Gemma C , Alfano Rossella , Ghantous Akram , Urquiza Jose , Rifas-Shiman Sheryl L , Page Christian M , Jin Jianping , Fernández-Barrés Silvia , Santorelli Gillian , Tindula Gwen , Yousefi Paul , Kupers Leanne , Ruiz-Arenas Carlos , Jaddoe Vincent WV , DeMeo Dawn , Fossati Serena , Wright John , Huen Karen , Popovic Maja , Nohr Ellen A , Smith George Davey , Lepeule Johanna , Baccarelli Andrea , Magnus Maria C , Nystad Wenche , Casas Maribel , Oken Emily , Håberg Siri E , Vafeiadi Marina , Roumeliotaki Theano , Vrijheid Martine , Munthe-Kaas Monica C , Eskenazi Brenda , Ronfani Luca , Holland Nina , Chatzi Leda , Meltzer Helle Margrete , Herceg Zdenko , Plusquin Michelle , Bustamante Mariona , Hivert Marie-France , Lawlor Deborah A , Sørensen Thorkild IA , London Stephanie J , Felix Janine F , Relton Caroline L 
Published: March 2020

AbstractBackgroundAccumulating evidence links paternal adiposity in the peri-conceptional period to offspring health outcomes. DNA methylation has been proposed as a mediating mechanism, but very few studies have explored this possibility in humans.Methods and findingsIn the Pregnancy And Childhood Epigenetics (PACE) consortium, we conducted a meta-analysis of co-ordinated epigenome-wide association studies (EWAS) of paternal prenatal Body Mass Index (BMI) (with and without adjustment for maternal BMI) in relation to DNA methylation in offspring blood at birth (13 datasets; total n= 4,894) and in childhood (six datasets; total n = 1,982). We found little evidence of association at either time point: for all CpGs, the False Discovery Rate-adjusted P-values were >0.05. In sex-stratified analyses, we found just four CpGs where there was robust evidence of association in female offspring. To compare our findings to those of other studies, we conducted a systematic review, which identified seven studies, including five candidate gene studies showing associations between paternal BMI/obesity and offspring or sperm DNA methylation at imprinted regions. However, in our own study, we found very little evidence of enrichment for imprinted genes.ConclusionOur findings do not support the hypothesis that paternal BMI around the time of pregnancy is associated with offspring blood DNA methylation, even at imprinted regions.Author SummaryPrevious small, mostly candidate gene studies have shown associations between paternal pre-pregnancy BMI and offspring blood DNA methylation. However, in our large meta-analysis of co-ordinated EWAS results from a total of 19 datasets across two timepoints, we found little evidence to support these findings, even at imprinted regions. This does not rule out the possibility of a paternal epigenetic effect in different tissues, at regions not covered by the 450k array, via different mechanisms, or in populations with greater extremes of paternal BMI. More research is warranted to help understand the size and nature of contributions of paternal adiposity to offspring epigenetics and health outcomes.
Factors associated with participation over time in the Avon Longitudinal Study of Parents and Children: a study using linked education and primary care data
Authors: Cornish RP , Macleod J , Boyd A , Tilling K 
Published: March 2020

AbstractBackgroundDropout from studies can lead to biased exposure-outcome estimates if the outcome is associated with continued participation, but this cannot be investigated using incomplete data. Linkage to external datasets provides a means of obtaining outcome – or proxy outcome - data on non-responders.MethodsWe examined the association between baseline socio-demographic factors and participation in the Avon Longitudinal Study of Parents and Children. We investigated whether child and adolescent outcomes measured in linked education and primary care data were associated with participation after accounting for baseline factors. To demonstrate the potential for bias, we examined whether the association between maternal smoking and these outcomes differed in the subsample who completed the 19-year questionnaire.ResultsLower levels of school attainment, lower GP consultation and prescription rates, higher BMI, special educational needs (SEN) status, not having an asthma diagnosis, depression and being a smoker were all associated with lower participation after adjustment for baseline factors. For example, adjusted odds ratio (OR) for participation comparing ever smokers (by 18 years) to non-smokers: 0.65, 95% CI (0.56, 0.75). The association of maternal smoking differed between the subsample of participants at 19 years and the entire sample, although differences were small and confidence intervals overlapped. For example: for SEN status OR=1.19 (1.06, 1.33) (all participants); OR=1.03 (0.79, 1.45) (subsample).ConclusionsLinkage to routine data provides a unique opportunity to compare continuing participators to those who drop out, and the impact this self-selection can have on results. Cohort studies should use linkage to routine data to explore participation and conduct sensitivity analyses.Key messagesEducational and health-related characteristics are strongly associated with ongoing participation in the Avon Longitudinal Study of Parents and Children after adjustment for detailed socio-demographic factors.This could bias analyses using the dataset, with bias dependent on the variables used in the analysis and their impact on participation.Linkage to routine data provides a means of assessing whether factors measured across the life course are associated with ongoing participation in observational studies and the potential impact of this in terms of bias.Researchers can use linkage to external sources of data to make informed decisions about the likely impact of selective participation and to guide their analyses.
Rigidity, normal modes and flexible motion of a SARS-CoV-2 (COVID-19) protease structure
Authors: Wells Stephen A. 
Published: March 2020

AbstractThe rigidity and flexibility of two recently reported crystal structures (PDB entries 6Y2E and 6LU7) of a protease from the SARS-CoV-2 virus, the infectious agent of the COVID-19 respiratory disease, has been investigated using pebble-game rigidity analysis, elastic network model normal mode analysis, and all-atom geometric simulations. This computational investigation of the viral protease follows protocols that have been effective in studying other homodimeric enzymes. The protease is predicted to display flexible motions in vivo which directly affect the geometry of a known inhibitor binding site and which open new potential binding sites elsewhere in the structure. A database of generated PDB files representing natural flexible variations on the crystal structures has been produced and made available for download from an institutional data archive. This information may inform structure-based drug design and fragment screening efforts aimed at identifying specific antiviral therapies for the treatment of COVID-19.
Prolonged presence of SARS-CoV-2 in feces of pediatric patients during the convalescent phase
Authors: Xing Yuhan , Ni Wei , Wu Qin , Li Wenjie , Li Guoju , Tong Jianning , Song Xiufeng , Xing Quansheng 
Published: March 2020

AbstractBackgroundSevere acute respiratory coronavirus 2 (SARS-CoV-2) is a newly identified virus which mainly spreads from person-to-person. Presence of SARS-CoV-2 has been constantly reported in stools of patients with coronavirus disease 2019 (COVID-19). However, there is a paucity of data concerning fecal shedding of the virus in pediatric patients.ObjectiveTo investigate dynamic changes of SARS-CoV-2 in respiratory and fecal specimens in children with COVID-19.MethodsFrom January 17, 2020 to February 23, 2020, three pediatric cases of COVID-19 were reported in Qingdao, Shandong Province, China. Epidemiological, clinical, laboratory, and radiological characteristics and treatment data of these children were collected. Real-time fluorescence reverse-transcriptase-polymerase-chain reaction (RT-PCR) was performed to detect SARS-CoV-2 RNA in throat swabs and fecal specimens. Patients were followed up to March 10, 2020, the final date of follow-up, and dynamic profiles of RT-PCR results were closely monitored.ResultsAll the three pediatric cases were household contacts of adults whose symptoms developed earlier. Severity of disease was mild to moderate and fever was the most consistent and predominant symptom at onset of illness of these children (two cases had body temperature higher than 38.5°C). All children showed increased lymphocytes (>4.4×109 /L) with normal white blood cell counts on admission. Radiological changes were not typical for COVID-19. All children showed good response to supportive treatment. Clearance of SARS-CoV-2 in respiratory tract occurred within two weeks after abatement of fever, whereas viral RNA remained positive in stools of pediatric patients for longer than 4 weeks. Two children had fecal SARS-CoV-2 turned negative 20 days after throat swabs showing negative, while that of another child lagged behind for 8 days.InterpretationSARS-CoV-2 may exist in gastrointestinal tract for a longer time than respiratory system. Persistent shedding of SARS-CoV-2 in stools of infected children indicates the potential for the virus to be transmitted through fecal excretion. Massive efforts should be made at all levels to prevent spreading of the infection among children after reopening of kindergartens and schools.
A device for exploring the full angular excitation space - Can more angular projections improve determination of a molecules 3D-orientation in the presence of noise?
Authors: Pfennig Dominik , Albrecht Andreas , Nowak Julia , Walla Peter Jomo 
Published: March 2020

AbstractIn the past, different methods have been presented to determine the 3D orientation of single molecules in a microscopic set-up by excitation polarization modulation. Using linearly polarized illumination from different directions and thereby measuring different 2D projections enables reconstructing the full 3D orientation. Theoretically, two projections suffice for a full 3D orientation determination if the intensities are properly calibrated. If they are not, a third projection will enable unambiguous orientation measurements. The question arises if three projections already contain the maximum information on the 3D orientation when also considering the limited number of available photons and shot noise in an experiment, or if detecting more projections or even continuously changing the projection direction during a measurement provides more information with an identical number of available photons. To answer this principle question, we constructed a simple device allowing for exploring any projection direction available with a particular microscope objective and tested several different excitation modulation schemes using simulated as well as experimental single molecule data. We found that three different projections in fact already do provide the maximum information also for noisy data. Our results do not indicate a significant improvement in angular precision in comparison to three projections, both when increasing the number of projections and when modulating the projection direction and polarization simultaneously during the measurement.In fluorescence microscopy polarized illumination from different directions enables the determination of the 3D orientation of single molecules by combining the 2D information of different projection directions. Ambiguities that emerge when using only two projections can be eliminated using a third projection. In a systematic study we show that – also considering the limited number of available photons and shot noise in an experiment – three projection directions already contain the maximum information on the 3D orientation. Our results do not indicate a significant improvement in angular precision in comparison to three projections, both when increasing the number of projections and when modulating the projection direction and polarization simultaneously during the measurement.
Altered kinetics of circulating progenitor cells in cardiopulmonary bypass (CPB) associated vasoplegic patients: A pilot study
Authors: Nandi Sanhita , Potunuru Uma Rani , Kumari Chandrani , Nathan Abel Arul , Gopal Jayashree , Menon Gautam I , Siddharthan Rahul , Dixit Madhulika , Thangaraj Paul Ramesh 
Published: March 2020

AbstractVasoplegia observed post cardiopulmonary bypass (CPB) is associated with substantial morbidity, multiple organ failure and mortality. Circulating counts of hematopoietic stem cells (HSCs) and endothelial progenitor cells (EPC) are potential markers of neo-vascularization and vascular repair. However, the significance of changes in the circulating levels of these progenitors in perioperative CPB, and their association with post-CPB vasoplegia, are currently unexplored. We enumerated HSC and EPC counts, via flow cytometry, at different time-points during CPB in 19 individuals who underwent elective cardiac surgery. These 19 individuals were categorized into two groups based on severity of post-operative vasoplegia, a clinically insignificant vasoplegic Group 1 (G1) and a clinically significant vasoplegic Group 2 (G2). Differential changes in progenitor cell counts during different stages of surgery were compared across these two groups. Machine-learning classifiers (logistic regression and gradient boosting) were employed to determine if differential changes in progenitor counts could aid the classification of individuals into these groups. Enumerating progenitor cells revealed an early and significant increase in the circulating counts of CD34+and CD34+CD133+hematopoietic stem cells (HSC) in G1 individuals, while these counts were attenuated in G2 individuals. Additionally, EPCs (CD34+VEGFR2+) were lower in G2 individuals compared to G1. Gradient boosting outperformed logistic regression in assessing the vasoplegia grouping based on the fold change in circulating CD 34+levels. Our findings indicate that a lack of early response of CD34+cells and CD34+CD133+HSCs might serve as an early marker for development of clinically significant vasoplegia after CPB.
Patterns of gene-body-methylation conservation and its divergent association with gene expression in Pigeonpea and Soybean
Authors: Junaid Alim , Singh N.K. , Gaikwad Kishor 
Published: March 2020

AbstractPigeonpea and Soybean are closely related agronomically important legumes that diverged ∼23 million years ago followed by a whole genome duplication event in Soybean. However, the impact of divergence on their epigenomes is not known. Comparative epigenomics is a powerful tool to understand shaping of epigenomes and its functional consequences during evolution. In this study, we investigated the conservation and divergence of Gene body methylation (GbM) and gene-expression patterns between the two species. We compared their genome-wide DNA methylation landscape at single-base resolution and studied the influence of GbM on duplicate gene retention. Our results indicate that during the divergence of Pigeonpea and Soybean, the effects of methylation on gene expression evolved in a heterogeneous manner. GbM features-slow evolution rate and increased length remained conserved in Pigeonpea and Soybean. We also found that contrary to high CG-methylation conservation, non-CG methylated genes remained diverged during evolution due to transposons insertion in adjacent sequences. The methylation differences in paralogs were associated with expression divergence. Notably, we found that variably methylated marks are less likely to target evolutionary conserved sequences. Finally, our findings identify conservation of nitrogen-related genes during evolution, which are promising candidates for epi-alleles for crop improvement.