bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three-month outcomes in hospitalized COVID-19 patients
Authors: Savarraj Jude PJ , Burkett Angela B , Hinds Sarah N , Paz Atzhiry S , Assing Andres , Juneja Shivanki , Colpo Gabriela Delevati , Torres Luis F , Gusdon Aaron , McCullough Louise , Choi H Alex 
Published: October 2020

AbstractCOVID-19 is an ongoing pandemic with a devastating impact on public health. Acute neurological symptoms have been reported after a COVID-19 diagnosis, however there is no data available on the long-term neurological symptoms. Using a prospective registry of hospitalized COVID-19 patients, we assessed the neurological assessments (including functional, cognitive and psychiatric assessments) of several hospitalized patients at 3 months. Our main finding is that 71% of the patients still experienced neurological symptoms at 3 months and the most common symptoms being fatigue (42%) and PTSD (29%). 64% of the patients report pain symptoms we well. Cognitive symptoms were found in 12%. Our preliminary findings suggests the importance of investigating long-term and rationalizes the need for further studies investigating the neurologic outcomes after COVID-19.
Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents
Authors: Viner Russell , Ward Joseph , Hudson Lee , Ashe Melissa , Patel Sanjay , Hargreaves Dougal , Whittaker Elizabeth 
Published: October 2020

AbstractObjectiveTo undertake a systematic review of reviews of the prevalence of symptoms and signs of COVID-19 in those aged under 20 years?DesignNarrative systematic review of reviews. PubMed, medRxiv, Europe PMC and COVID-19 Living Evidence Database were searched on 9 October 2020.SettingAll settings, including hospitalised and community settings.PatientsCYP under age 20 years with laboratory-proven COVID-19.Study review, data extraction and qualityPotentially eligible articles were reviewed on title and abstract by one reviewer. Quality was assessed using the modified AMSTARS criteria and data were extracted from included studies by two reviewers.Main outcome measuresPrevalence of symptoms and signs of COVID-19Results1325 studies were identified and 18 reviews were included. Eight were high quality, 7 medium and 3 low quality. All reviews were dominated by studies of hospitalised children. The proportion who were asymptomatic ranged from 14.6 to 42%. Fever and cough were the commonest symptoms; proportions with fever ranged from 46 to 64.2% and with cough from 32 to 55.9%. All other symptoms or signs including rhinorrhoea, sore throat, headache, fatigue/myalgia and gastrointestinal symptoms including diarrhoea and vomiting are infrequent, occurring in less than 10-20%.ConclusionsFever and cough are the most common symptoms in CYP with COVID-19, with other symptoms infrequent. Further research on symptoms in community samples are needed to inform pragmatic identification and testing programmes for CYP.
Increase in anticholinergic burden in the UK from 1990 to 2015: a UK Biobank study
Authors: Mur J. , Cox S. R. , Marioni R. E. , Muniz-Terrera G. , Russ T. C. 
Published: October 2020

AbstractBackgroundThe use of prescription drugs with anticholinergic properties has been associated with multiple negative health outcomes in older people. Moreover, recent evidence suggests that associated adverse effects may occur even decades after stopping anticholinergic use. Despite the implicated importance of examining longitudinal patterns of anticholinergic prescribing for different age groups, few such data are available.MethodsWe performed an age-period-cohort analysis to study trends in anticholinergic burden between the years 1990 and 2015 utilising data from >220,000 UK Biobank participants with linked prescription data from primary care.ResultsAnticholinergic burden in the sample increased between three- and nine-fold over 25 years and was significant for both period/cohort- and age-effects across all models. When adjusted for total number of prescriptions, the effect of age reversed. Anticholinergic burden was also associated with various lifestyle- and demographic factors.ConclusionsThe increase in anticholinergic prescribing is mostly due to an increase in polypharmacy and is attributable to both ageing of participants, as well as period/cohort-related changes in prescribing practices. There is evidence for deprescribing of anticholinergic medications in older age. Further research is needed to clarify the implications of rising anticholinergic use for public health and to contextualise this rise in light of other relevant prescribing practices.
National Routine Adult Immunization Programs among World Health Organization Member States: An Assessment of Health Systems to Deploy Future SARS-CoV-2 Vaccines
Authors: Williams Sarah R. , Driscoll Amanda J. , LeBuhn Hanna M. , Chen Wilbur H. , Neuzil Kathleen M. , Ortiz Justin R. 
Published: October 2020

ABSTRACTIntroductionAs the SARS-CoV-2 pandemic disproportionately affects older adults, future pandemic vaccine response will rely on existing adult immunization infrastructures.MethodsWe evaluated the 2018 WHO/UNICEF Joint Reporting Form on Immunization for country reports on adult immunization programs. We described countries with programs and used multivariable regression to identify independent factors associated with having them.ResultsOf 194 WHO Member States, 120 (62%) reported having any adult vaccination program. The Americas and Europe had the most adult immunization programs, most commonly Hepatitis B and influenza vaccines (>45% and >90% of countries). Africa and South-East Asia had the fewest adult immunization programs, with <11% of countries reporting any adult immunization programs for influenza or hepatitis vaccines, and none for pneumococcal vaccines. In bivariate analyses, high- or upper-middle income, introduction of new or underused vaccines, having achieved pediatric vaccine coverage goals, and meeting National Immunization Technical Advisory Groups basic functional indicators were significantly associated (p<0.001) with having any adult immunization programs. In multivariable analyses, the factor most strongly associated with adult immunization programs was country income, with high- or upper-middle income countries significantly more likely to report having a program (aOR 19.3, 95% CI 6.5, 57.7).DiscussionThat 38% of countries lack functional platforms for adult immunization has major implications for future SARS-CoV-2 vaccine deployment. Systems for vaccine storage and handling, delivery, and waste management for adult immunization do not exist in much of the world. Developing countries should strengthen immunization programs to reach adults with SARS-CoV-2 vaccines when they become available.
The dynamic, combinatorial cis-regulatory lexicon of epidermal differentiation
Authors: Kim Daniel , Risca Viviana , Reynolds David , Chappell James , Rubin Adam , Jung Namyoung , Donohue Laura , Kathiria Arwa , Shi Minyi , Zhao Zhixin , Deep Harsh , Chang Howard Y. , Snyder Michael P. , Greenleaf William J. , Kundaje Anshul , Khavari Paul A. 
Published: October 2020

Transcription factors (TFs) bind DNA sequence motif vocabularies in cis-regulatory elements (CREs) to modulate chromatin state and gene expression during cell state transitions. A quantitative understanding of how motif lexicons influence dynamic regulatory activity has been elusive due to the combinatorial nature of the cis-regulatory code. To address this, we undertook multi-omic data profiling of chromatin and expression dynamics across epidermal differentiation to identify 40,103 dynamic CREs associated with 3,609 dynamically expressed genes, then applied an interpretable deep learning framework to model the cis-regulatory logic of chromatin accessibility. This identified cooperative DNA sequence rules in dynamic CREs regulating synchronous gene modules with diverse roles in skin differentiation. Massively parallel reporter analysis validated temporal dynamics and cooperative cis-regulatory logic. Variants linked to human polygenic skin disease were enriched in these time-dependent combinatorial motif rules. This integrative approach reveals the combinatorial cis-regulatory lexicon of epidermal differentiation and represents a general framework for deciphering the organizational principles of the cis-regulatory code in dynamic gene regulation.HIGHLIGHTSAn integrative multi-omic resource profiling chromatin and expression dynamics across keratinocyte differentiationPredictive deep learning models of chromatin dynamics reveal a high-resolution cis-regulatory DNA motif lexicon of epidermal differentiationModel interpretation enables discovery of combinatorial cis-regulatory logic of homotypic and heterotypic motif combinationsMassively parallel reporter experiments validate temporal dynamics and cis-regulatory logic of the combinatorial motif lexicon
Transdermal patch containing physostigmine and procyclidine protects rhesus monkeys against VX intoxication
Authors: Song Young Jo 
Published: October 2020

ABSTRACTVX is an organophosphate cholinesterase inhibitor known as a chemical warfare agent. This study was designed 1) to determine the acute toxicity of VX in male rhesus monkeys by subcutaneous administration, 2) to evaluate the efficacy of a transdermal patch containing physostigmine and procyclidine. The median lethal dose (LD50) of the subcutaneous injection of VX was 15.409 ug/kg, which was calculated using the up-and-down dose selection procedure based on deaths occurring within 48 h. To test the efficacy of the transdermal patch, rhesus monkeys were treated with a patch (5×5 cm2) alone or in combination with post-exposure therapy comprising atropine plus 2-pralidoxime (2-PAM), and then administered subcutaneous injection of VX at various doses. The rhesus monkeys pretreated with the patch alone were 100% protected against 1.5×LD50of VX, while the rhesus monkeys treated with the patch, atropine, and 2-PAM were 100% protected against 50×LD50of VX. This study demonstrated that patch pretreatment in conjunction with atropine and 2-PAM treatment is an effective regimen against high doses of VX.
NetworkExtinction: an R package to simulate extinction’s propagation and rewiring potential in ecological networks
Authors: Ávila-Thieme M.Isidora , Corcoran Derek , Kusch Erik , Castillo Simón P. , Valdovinos Fernanda S. , Navarrete Sergio A. , Marquet Pablo A. 
Published: October 2020

AbstractEarth’s biosphere is currently undergoing drastic reorganisation as a consequence of the sixth mass extinction brought on by the Anthropocene. Impacts of local and regional extirpation of species have been demonstrated to propagate through the complex interaction networks they are part of, subsequently leading to secondary extinctions, exacerbating biodiversity loss. Contemporary ecological theory has developed several measures to analyse the structure and robustness of ecological networks under biodiversity loss. However, a toolbox for direct simulation and quantification of extinction cascades and the creation of novel interactions (i.e. rewiring) remains absent.Here, we presentNetworkExtinction- a novel R package which we have developed to explore the propagation of species extinctions sequences through ecological networks as well as quantify the effects of rewiring potential in response to primary species extinctions. WithNetworkExtinctionwe have integrated ecological theory and computational simulations to develop functionality with which users may analyze and visualize the structure and robustness of ecological networks. The core functions introduced withNetworkExtinctionfocus on simulations of sequential primary extinctions and associated secondary extinctions while allowing for user-specified secondary extinction thresholds and realisation of rewiring potential.With the packageNetworkExtinction,users can estimate the robustness of ecological networks after performing species extinction routines based on several algorithms. Moreover, users can compare the number of simulated secondary extinctions against a null model of random extinctions. In-built visualizations enable graphing topological indices calculated by the deletion sequence functions after each simulation step. Finally, the user can define the degree distribution of the network by fitting different common distributions. Here, we illustrate the use of the package and its outputs by analyzing a Chilean coastal marine food web.NetworkExtinctionis a compact and easy-to-use R package with which users can quantify changes in ecological network structure in response to different patterns of species loss, thresholds, and rewiring potential. Therefore, this package is particularly useful to evaluate ecosystem responses to anthropogenic and environmental perturbations that produce non-random species extinctions.
CD4 and CD8 co-receptors modulate functional avidity of CD1b-restricted T cells
Authors: James Charlotte A. , Xu Yuexin , Aguilar Melissa S. , Jing Lichen , Layton Erik D. , Gilleron Martine , Minnaard Adriaan J. , Scriba Thomas J. , Day Cheryl L. , Warren Edus H. , Koelle David M. , Seshadri Chetan 
Published: October 2020

ABSTRACTCD4 and CD8 co-receptors define distinct lineages of T cells restricted by major histocompatibility complex (MHC) Class II and I molecules, respectively. Co-receptors interact with the T cell receptor (TCR) at the surface of MHC-restricted T cells to facilitate antigen recognition, thymic selection, and functional differentiation. T cells also recognize lipid antigens presented by CD1 molecules, but the role that CD4 and CD8 play in lipid antigen recognition is unknown. We studied the effect of CD4 and CD8 on the avidity, activation, and function of T cells specific for two CD1b-presented mycobacterial lipid antigens, glucose monomycolate (GMM) and diacylated sulfoglycolipids (SGL). In a human cohort study using SGL-loaded CD1b tetramers, we discovered a hierarchy among SGL-specific T cells in which T cells expressing the CD4 or CD8 co-receptor stain with a higher tetramer mean fluorescence intensity (MFI) than CD4-CD8- T cells. To determine the role of the TCR co-receptor in lipid antigen recognition, we exogenously expressed GMM and SGL-specific TCRs in Jurkat or polyclonal T cells and quantified tetramer staining and activation thresholds. Transduced CD4+ primary T cells bound the lipid-loaded CD1b tetramer with a higher MFI than CD8+ primary T cells, and transduced CD8+ Jurkat cells bound the SGL-CD1b tetramer with higher MFI than CD4-CD8- Jurkat cells. The presence of either co-receptor also decreased the threshold for IFN-γ secretion. Further, co-receptor expression increased surface expression of CD3ε, suggesting a mechanism for increased tetramer binding and activation. Finally, we used single-cell sequencing to define the TCR repertoire andex vivofunctional profiles of SGL-specific T cells from individuals with M.tb disease. We found that CD8+ T cells specific for SGL express canonical markers associated with cytotoxic T lymphocytes, while CD4+ T cells could be classified as T regulatory or T follicular helper cells. Among SGL-specific T cells, only those expressing the CD4 co-receptor also expressed Ki67, suggesting that they were actively proliferating at the time of sample collection. Together, these data reveal that expression of CD4 and CD8 co-receptor modulates TCR avidity for lipid antigen, leading to functional diversity and differences inin vivoproliferation during M.tb disease.
Cardiovascular Disease Related Proteomic Biomarkers of Alcohol Consumption
Authors: Sun Xianbang , Ho Jennifer E. , Gao He , Evangelou Evangelos , Yao Chen , Huan Tianxiao , Hwang Shih-Jen , Courchesne Paul , Larson Martin G. , Levy Daniel , Ma Jiantao , Liu Chunyu 
Published: October 2020

AbstractThe relationship between alcohol consumption, circulating proteins, and cardiovascular disease (CVD) risk has not been well studied. We performed association analyses of alcohol consumption with three CVD risk factors and 71 CVD-related circulating proteins measured in 6,745 Framingham Heart Study participants (mean age, 49 years; 53% women). We found that an increase in alcohol consumption was associated with a higher risk of incident hypertension (P=7.2E-3) but a lower risk of incident obesity (P=5.7E-4) and type 2 diabetes (P=1.4E-5) in a 14-year of follow-up. Using independent discovery (n=4,348) and validation (n=2,397) samples, we identified 20 alcohol-associated proteins (FDR<0.05 in discovery and P<0.05/n in validation), with majority (18 of 20 proteins) inversely associated with alcohol consumption. The alcohol-protein associations remained similar after removing heavy drinkers. Four proteins demonstrated consistent triangular relationships, as expected, with alcohol consumption and CVD risk factors. For example, a greater level of APOA1, which was associated with a higher alcohol consumption (P=1.2E-65), was associated with a lower risk of type 2 diabetes (P=3.1E-5). However, several others showed inconsistent triangular relationships, e.g., a greater level of GDF15, which was associated with a lower alcohol consumption (P=1.0E-13), was associated with an increased risk of hypertension (P=2.4E-4). In conclusion, we identified 20 alcohol-associated proteins and demonstrated complex relationships between alcohol consumption, circulating proteins and CVD risk factors. Future studies with integration of more proteomic markers and larger sample size are warranted to unravel the complex relationship between alcohol consumption and CVD risk.
Safe linkage of cohort and population-based register data in a genome-wide association study on health care expenditure
Authors: de Zeeuw Eveline L. , Voort Lykle , Schoonhoven Ruurd , Nivard Michel G. , Emery Thomas , Hottenga Jouke-Jan , Willemsen Gonneke A.H.M. , Dykstra Pearl A. , Zarrabi Narges , Kartopawiro John D. , Boomsma Dorret I. 
Published: October 2020

AbstractBackgroundThere are research questions whose answers require record linkage of multiple databases which may be characterized by limited options for full data sharing. For this purpose, the Open Data Infrastructure for Social Science and Economic Innovations (ODISSEI) consortium has supported the development of the ODISSEI Secure Supercomputer (OSSC) platform that allows researchers to link cohort data to data from Statistics Netherlands and run analyses in a high performance computing (HPC) environment.MethodsAfter successful record linkage genome-wide association (GWA) analyses were carried out on expenditure for total health, mental health, primary and hospital care and medication. Record linkage for genotype data from 16,726 participants from the Netherlands Twin Register (NTR) with data from Statistics Netherlands was accomplished in the secure OSSC platform, followed by gene-based tests and estimation of total and SNP-based heritability.ResultsThe total heritability of expenditure ranged between 29.4 (SE 0.8) and 37.5 (SE 0.8) per cent, but GWA analyses did not identify single SNPs or genes that were genome-wide significantly associated with health care expenditure. SNP-based heritability was between 0.0 (SE 3.5) and 5.4 (SE 4.0) per cent and was different from zero for mental health care and primary care expenditure.ConclusionsWe successfully linked genotype data to administrative health care expenditure data from Statistics Netherlands and performed a series of analyses on health care expenditure. The OSSC platform offers secure possibilities for analysing linked data in large-scale and realizing sample sizes required for GWA studies, providing invaluable opportunities to answer many new research questions.Key messagesCohort data of the Netherlands Twin Register were safely linked to population-based register data of Statistics NetherlandsOn the ODISSEI Secure Supercomputer (OSSC) platform genome-wide association analyses were carried out on linked genotype and health care expenditure dataVariation in health care expenditure was for approximately one third explained by family-based heritability, but SNP-heritability based on genetic similarity across unrelated individuals explained only a very small proportion of varianceThe newly developed platform can serve as a prototype for realizing genome-wide association studies with sensitive data
ALS-linked mutations impair UBQLN2 stress-induced biomolecular condensate assembly in cells
Authors: Riley Julia F. , Hehnly Heidi , Castañeda Carlos A. 
Published: October 2020

AbstractMutations in Ubiquilin-2 (UBQLN2), a ubiquitin-binding shuttle protein involved in several protein quality control processes, can lead to amyotrophic lateral sclerosis (ALS). We previously found that wild-type UBQLN2 forms dynamic, membraneless biomolecular condensates upon cellular stress, and undergoes liquid-liquid phase separationin vitro. However, the impact of ALS-linked mutations on UBQLN2 condensate formation in cells is unknown. Here, we employ live-cell imaging with photokinetic analysis to investigate how five patient-derived ALS-linked mutations in UBQLN2 impact stress-induced UBQLN2 condensate assembly and condensate material properties. Both wild-type and mutant UBQLN2 condensates are generally cytoplasmic and liquid-like. However, cells transfected with mutant UBQLN2 contain fewer stress-induced UBQLN2 condensates than those with wild-type UBQLN2. Most strikingly, ectopically expressed P506T UBQLN2 forms the lowest number of stress-induced condensates of all UBQLN2 mutants, and these condensates are significantly smaller than those of wild-type UBQLN2. Fluorescence recovery after photobleaching (FRAP) analysis of UBQLN2 condensates revealed higher immobile fractions for UBQLN2 mutants, especially P506T. P497S and P497H mutations differentially impact condensate properties, demonstrating that the effects of ALS-linked mutations are both position- and amino acid-dependent. Collectively, our data show that disease mutations hinder assembly and alter viscoelastic properties of stress-induced UBQLN2 condensates, potentially leading to aggregates commonly observed in ALS.
The Almond plumage color pattern is associated with eye pigmentation defects in the domestic pigeon (Columba livia)
Authors: Bruders Rebecca , Sidesinger Max , Shapiro Michael D. 
Published: October 2020

AbstractChanges in epidermal pigmentation are associated with eye defects in humans and other vertebrates. In the rock pigeon (Columba livia), the sex-linked Almond color pattern is characterized by hypopigmentation of epidermal structures. The trait is controlled by the classicalStipper(St) locus, and homozygous (ZStZSt) Almond males often have severe eye defects. Heterozygous (ZStZ+) and hemizygous (ZStW) pigeons do not typically have obvious eye defects, suggesting that higher dosage of the mutant allele is deleterious. Because Almond pigeons have pronounced hypopigmentation in epidermal structures, we hypothesized that they might also have reduced eye pigmentation. Here, we examined pigmentation in the iris, ciliary body, anterior retinal pigmented epithelium (RPE), and posterior RPE in pigeons with and without Almond alleles. We found that pigmentation of anterior segment structures was reduced in birds with at least one Almond allele. However, posterior eye pigmentation was substantially reduced only in homozygous Almond birds. We postulate that the gradient of effects on eye pigmentation is due to the different embryological origins of anterior and posterior eye pigment-producing cells.