bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence and Risk Factors of Stroke in Bangladesh: A Nationwide Population-Based Survey
Authors: Mondal Md Badrul Alam , Hasibul Hasan A T M , Khan Nushrat , Mohammad Quazi Deen 
Published: June 2021

AbstractBackgroundThis community survey was conducted to estimate the prevalence of stroke and its associated common risk factors among the Bangladeshi population.MethodsThis was a population-based cross-sectional study, carried out in 8 administrative divisions and 64 districts to estimate the prevalence of stroke throughout the country. The study adopted a two-stage cluster random sampling approach. The calculated sample size was 25,287. A semi-structured questionnaire was used to identify suspected stroke patients who were subsequently confirmed by consultant neurologists.ResultIn the first stage, Interviewers identified 561 respondents as suspected stroke in 64 districts. Of the 25,287 respondents, 54.9% were male. The mean age was 39.9 years. In the second stage of the study; among all the respondents, 288 were confirmed as stroke patients which provided a prevalence of 11.39 per 1000 population. The highest stroke prevalence (14.71 per thousand) was found in the Mymensingh division and the lowest (7.62 per thousand) found in the Rajshahi division. It was 30.10 per thousand in the age group of more than 60 years. The prevalence of stroke among males was twice that of females (13.62 versus 8.68 per thousand). The prevalence was slightly higher in rural areas (11.85 versus 11.07). Out of a total of 288 cases, 79.7% (213) patients had an ischemic stroke, 15.7% (42) had hemorrhagic, and 4.6% (12) were diagnosed as subarachnoid hemorrhage. The majority of the stroke patients had hypertension (79.2%), followed by dyslipidemia (38.9%), tobacco use in any form (37.2%), diabetes (28.8%), ischemic heart disease (20.1%).ConclusionWe have found a stroke prevalence of 11.39 per 1000 population, the highest being in the Mymensingh division. The prevalence was much higher in the elderly and male population. More than three fourth had an ischemic stroke. Hypertension, dyslipidemia, tobacco use, diabetes, ischemic heart disease are the most common risk factors observed among stroke patients.Summary BoxAlready Known:▪The prevalence of stroke in Bangladesh was found to be 3 per thousand.▪Hypertension, diabetes, dyslipidemia, smoking, and ischemic heart disease were common risk factors.New Findings:▪This is the first-ever nationwide survey in Bangladesh that revealed a stroke prevalence of 11.39 per thousand.▪There was a wide regional variation of stroke prevalence.▪The prevalence was twice among males.Impact of the study result:▪The study result will help the policymakers in deciding what to do for which regions of this country to handle the stroke burden.▪It will also help the clinicians to identify common risk factors among stroke patients.
An empirical assessment of influenza intensity thresholds obtained from the moving epidemic and WHO methods
Authors: Bracher Johannes , Littek Jonas M. 
Published: June 2021

AbstractThe moving epidemic method (MEM) and the WHO method are widely used to determine intensity levels for seasonal influenza. The two approaches are conceptually similar, but differ in two aspects. Firstly, the MEM involves a log transformation of incidence data, while the WHO method operates on the original scale. Secondly, the MEM uses more than one observation from each past season to compute intensity thresholds, fixing the total number to include. The WHO method uses only the highest value from each season. To assess the impact of these choices on thresholds we perform simulation studies which are based on re-sampling of ILI data from France, Spain, Switzerland and the US. When no transformation is applied, a rather large proportion of season peaks are classified as high or very high intensity. This can be mitigated by a logarithmic transformation. When fixing the total number of included past observations, thresholds increase the more seasons are available. When only few are available, there is a high chance of classifying new season peaks as high or very high intensity. We therefore suggest using one observation per season and a log transformation, i.e. a hybrid of the default settings of the MEM and WHO methods.
Validation of the 4C Deterioration Model for COVID-19 in a UK teaching hospital during Wave 2
Authors: Cowan Sarah L. , Wiegand Martin , Preller Jacobus , Goudie Robert J. B. 
Published: June 2021

AbstractThe 4C Deterioration model was developed and validated on data collected in UK hospitals until August 26, 2020, but has not yet been validated in the presence of SARS-CoV-2 variants and novel treatment regimens that have emerged subsequently. In this first validation study of the 4C Deterioration model on patients admitted between August 27, 2020 and April 16, 2021 we found, despite a slightly overestimation of risk, that the discrimination (area under the curve 0.75, 95% CI 0.71-0.78) and calibration of the model remained consistent with the development study, strengthening the evidence for adopting this model into clinical practice.
Effect of Electronic Nicotine Delivery Systems on Cigarette Abstinence in Smokers with no Plans to Quit: Exploratory Analysis of a Randomized Placebo-Controlled Trial
Authors: Foulds Jonathan , Cobb Caroline O. , Yen Miao-Shan , Veldheer Susan , Brosnan Phoebe , Yingst Jessica , Hrabovsky Shari , Lopez Alexa A , Allen Sophia I. , Bullen Christopher , Wang Xi , Sciamanna Chris , Hammett Erin , Hummer Breianna L. , Lester Courtney , Richie John P. , Chowdhury Nadia , Graham Jacob T. , Kang Le , Sun Shumei , Eissenberg Thomas 
Published: June 2021

ABSTRACTIntroductionThe extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking is unclear. This exploratory analysis examined the effects of ENDS delivering different amounts of nicotine on cigarette abstinence up to 24-week follow-up, in comparison to placebo or a behavioral substitute.MethodsThis four-arm parallel-group, randomized placebo-controlled trial took place at two academic medical centers in USA (Penn State Hershey and Virginia Commonwealth University). Participants were current adult smokers (N=520) interested in reducing but not planning to quit. They received brief advice and were randomized to one of four 24-week conditions, receiving either an eGo-style ENDS paired with 0, 8 or 36 mg/ml nicotine liquid (double-blind) or a cigarette-shaped tube, as a cigarette substitute (CS). Self-reported daily cigarette consumption and exhaled carbon monoxide (CO) were measured at all study visits. Outcomes included intent-to-treat, self-reported 7-day cigarette abstinence, biochemically confirmed by exhaled CO at 24 weeks after randomization.ResultsAt 24 weeks, significantly more participants in the 36 mg/ml condition (14/130, 10.8%) than in the 0 mg/ml condition (1/130, 0.8%) and the CS condition (4/130, 3.1%) were abstinent (relative risk = 14 [95% CI=1.9-104.9] and 3.5 [95% CI=1.2-10.4], respectively). The abstinence rate in the 8 mg/ml condition was 4.6% (6/130).ConclusionsWhen smokers seeking to reduce smoking tried ENDS, few quit smoking in the short term. However, if smokers continued to use an ENDS with cigarette-like nicotine delivery, a greater proportion completely switched to ENDS, as compared with placebo or a cigarette substitute.IMPLICATIONSThe extent to which use of electronic nicotine delivery systems (ENDS) for smoking reduction leads to cigarette abstinence in smokers with no plans to quit smoking was unclear. This randomized trial found that ENDS with nicotine delivery approaching that of a cigarette are more effective in helping ambivalent smokers to quit cigarette smoking.
Land-surface evapotranspiration derived from a first-principles primary production model
Authors: Tan Shen , Wang Han , Prentice Iain Colin , Yang Kun 
Published: June 2021

AbstractWe propose an application of eco-evolutionary optimality theory in the context of monitoring and modelling physical land-surface processes. Evapotranspiration (ET) links the water and carbon cycles in the atmosphere, hydrosphere, and biosphere. We develop an ET modelling framework based on the hypothesis that canopy conductance acclimates to plant growth conditions so that the total costs of maintaining carboxylation and transpiration capacities are minimized. This is combined with the principle of co-ordination between the light- and Rubisco-limited rates of photosynthesis to predict gross primary production (GPP). Transpiration (T) is predicted from GPP via canopy conductance. No plant type- or biome-specific parameters are required. ET is estimated from T by calibrating a site-specific (but time-invariant) ratio of modelled average T to observed average ET. Predicted seasonal cycles of GPP were well supported by (weekly) GPP data at 20 widely distributed eddy-covariance flux sites (228 site-years), with correlation coefficients (r) = 0.81 and root-mean-square error (RMSE) = 18.7 gC/week and Nash-Sutcliffe efficiency coefficient (NSE) = 0.61. Seasonal cycles of ET were also well supported, withr= 0.85, RMSE = 5.5 mm week−1and NSE = 0.66. Estimated T/ET ratios (0.52–0.92) showed significant positive relationships to radiation, precipitation and green vegetation cover and negative relationships to temperature and modelled T (r= 0.84). Although there are still uncertainties to be improved in the current framework, particularly in estimating T/ET, we see the application of eco-evolutionary principles as a promising direction for water resources research.HighlightsBuilding an evapotranspiration estimation framework based ona prioriprimary productivity model (the P model).Assessing the contribution of environmental indicators to the ratio of transpiration to evapotranspiration.Proving the reliability of this approach to estimate evapotranspiration.
Sustained TREM2 stabilization accelerates microglia heterogeneity and Aβ pathology in a mouse model of Alzheimer’s disease
Authors: Dhandapani Rahul , Neri Marilisa , Bernhard Mario , Brzak Irena , Schweizer Tatjana , Rudin Stefan , Joller Stefanie , Berth Ramon , Waldt Annick , Cuttat Rachel , Naumann Ulrike , Keller Caroline Gubser , Roma Guglielmo , Feuerbach Dominik , Shimshek Derya R. , Neumann Ulf , Gasparini Fabrizio , Galimberti Ivan 
Published: June 2021

SummaryTREM2 is a transmembrane protein expressed exclusively in microglia in the brain that regulates inflammatory responses to pathological conditions. Proteolytic cleavage of membrane TREM2 affects microglial function and is associated with Alzheimer’s disease, but the consequence of reduced TREM2 proteolytic cleavage has not been determined. We generated a transgenic mouse model of reduced TREM2 shedding (Trem2-IPD) through amino acid substitution of ADAM-protease recognition site. We found that Trem2-IPD mice displayed increased TREM2 cell surface receptor load, survival and function in myeloid cells. Using single cell transcriptomic profiling of mouse cortex we show that sustained TREM2 stabilization induces a shift of fate in microglial maturation and accelerates microglial responses to Aβ pathology in a mouse model of Alzheimer’s disease. Our data indicate that reduction of TREM2 proteolytic cleavage aggravates neuroinflammation during the course of AD pathology suggesting that TREM2 shedding is a critical regulator of microglial activity in pathological states.
Structural analysis of 3’UTRs in insect flaviviruses reveals novel determinant of sfRNA biogenesis and provides new insights into flavivirus evolution
Authors: Slonchak Andrii , Parry Rhys , Pullinger Brody , Sng Julian D.J. , Wang Xiaohui , Buck Teresa F , Torres Francisco J , Harrison Jessica J , Colmant Agathe M G , Hobson-Peters Jody , Hall Roy A , Tuplin Andrew , Khromykh Alexander A 
Published: June 2021

AbstractInsect-specific flaviviruses (ISFs) circulate in nature due to vertical transmission in mosquitoes and do not infect vertebrates. ISFs include two distinct lineages – classical ISFs (cISFs) that evolved independently and dual host associated ISFs (dISFs) that are proposed to diverge from mosquito-borne flaviviruses (MBFs). Compared to pathogenic flaviviruses, ISFs are relatively poorly studied, and their molecular biology remains largely unexplored. In this study we focused on the characterisation of ISF 3’UTRs and their ability to produce subgenomic flaviviral RNAs – noncoding viral RNAs that are known as important determinants of transmission and replication of pathogenetic flaviviruses. We demonstrated that cISFs and dISFs produce sfRNAs by employing a highly conserved mechanism of resistance to degradation by the cellular 5’-3’ exoribonuclease XRN1. We determined the secondary structures of complete 3’UTRs and experimentally identified structured RNA elements that resist degradation by XRN1 (xrRNAs) in divergent representatives of cISF and dISF clades. We discovered a novel class of xrRNAs in dISFs and identified structurally divergent xrRNA in Anopheles-associated cISFs. Phylogenetic analyses based on sequences and secondary structures of xrRNAs and complete 3’UTRs reveal that xrRNAs of cISFs and MBFs/dISFs evolved from a common xrRNA ancestor similar to the xrRNA of Anopheles-associated cISFs. Additionally, we found that duplications of xrRNAs occurred independently in ISF and MBF clades. Using ISF mutants deficient in the production of sfRNAs, we found that individual sfRNAs of ISFs have redundant functions. We conclude that duplicated xrRNAs were selected in the evolution of flaviviruses to ensure that sfRNA is produced if one of the xrRNAs lose XRN1 resistance due to mutations or misfolding.
Protein crosslinking as a therapeutic strategy for SOD1-related ALS
Authors: Hossain Md Amin , Sarin Richa , Donnelly Daniel P. , Miller Brandon C. , Salisbury Joseph P. , Conway Jeremy B. , Watson Samantha , Winters Jenifer N. , Alam Novera , Sivasankar Durgalakshmi , Ponmudiyan Aparna C. , Gawde Tanvi , Kannapadi Sunanda , Auclair Jared R. , Makowski Lee , Petsko Gregory A. , Ringe Dagmar , Greenblatt David J. , Ondrechen Mary Jo , Chen Yunqiu , Manetsch Roman , Agar Jeffrey N. 
Published: June 2021

AbstractMutations in the gene encoding Cu-Zn superoxide dismutase 1 (SOD1) cause a subset of familial amyotrophic lateral sclerosis (fALS). One effect of these mutations is that SOD1, which is normally a stable dimer, dissociates into toxic monomers. Considerable research efforts have been devoted to developing compounds that stabilize the dimer of fALS SOD1 variants, but these have not yet resulted in an approved drug. We demonstrate that a cyclic thiosulfinate cross-linker can stabilize prevalent disease-causing SOD1 variants. The degree of stabilization afforded by cyclic thiosulfinates (up to 24 °C) is unprecedented. We show this compound works rapidly in vivo with a half-life of ~3 days. The efficacy, low toxicity, and pharmacodynamics of cross-linker mediated stabilization make it a promising therapeutic approach for SOD1-related fALS.Significance statementCyclic thiosulfinate S-XL6 enables the kinetic stabilization of ALS-associated SOD1 variants, in vivo.
Ire1α-Regulated mRNA Translation Rate Controls the Identity and Polarity of Upper Layer Cortical Neurons
Authors: Ambrozkiewicz Mateusz C. , Borisova Ekaterina , Newman Andrew G. , Kraushar Matthew L. , Schaub Theres , Dannenberg Rike , Brockmann Marisa , Rosário Marta , Turko Paul , Jahn Olaf , Kaplan David R. , Iwawaki Takao , Spahn Christian M. T. , Rosenmund Christian , Tarabykin Victor 
Published: June 2021

SUMMARYEvolutionary expansion of the neocortex is associated with the increase in upper layer neurons. Here, we present Inositol-Requiring Enzyme 1α, Ire1α, as an essential determinant of upper layer fate, neuronal polarization and cortical lamination. We demonstrate a non-canonical function of Ire1α in the regulation of global translation rates in the developing neocortex through its dynamic interaction with the ribosome and regulation of eIF4A1 and eEF-2 expression. Inactivation of Ire1α engenders lower protein synthesis rates associated with stalled ribosomes and decreased number of translation start sites. We show unique sensitivity of upper layer fate to translation rates. Whereas eEF-2 is required for cortical lamination, eIF4A1 regulates acquisition of upper layer fate downstream of Ire1α in a mechanism of translational control dependent on 5’UTR-embedded structural elements in fate determinant genes. Our data unveil developmental regulation of ribosome dynamics as post-transcriptional mechanisms orchestrating neuronal diversity establishment and assembly of cortical layers.HIGHLIGHTSSmall molecule screening reveals Ire1α upstream of upper layer neuronal identityPolarization and proper lamination of layer II/III neurons require Ire1αDevelopment of upper layers requires high translation rates driven by eIF4A1 and eEF-2 downstream of Ire1αeIF4A1-dependent Satb2 mRNA translation initiation is a mechanism of upper layer fate acquisition
3D UNet with GAN discriminator for robust localisation of the fetal brain and trunk in MRI with partial coverage of the fetal body
Authors: Uus Alena , Grigorescu Irina , van Poppel Milou , Hughes Emer , Steinweg Johannes , Roberts Thomas , Lloyd David , Pushparajah Kuberan , Deprez Maria 
Published: June 2021

AbstractIn fetal MRI, automated localisation of the fetal brain or trunk is a prerequisite for motion correction methods. However, the existing CNN-based solutions are prone to errors and may require manual editing. In this work, we propose to combine a multi-label 3D UNet with a GAN discriminator for localisation of both fetal brain and trunk in fetal MRI stacks. The proposed method is robust for datasets with both full and partial coverage of the fetal body.
High quality, phased genomes of Phytophthora ramorum clonal lineages NA1 and EU1
Authors: Carleson Nicholas C. , Press Caroline M. , Grünwald Niklaus J. 
Published: June 2021

AbstractPhytophthora ramorum is the causal agent of sudden oak death in West Coast forests and currently two clonal lineages, NA1 and EU1, cause epidemics in Oregon forests. Here, we report on two high-quality genomes of individuals belonging to the NA1 and EU1 clonal lineages respectively, using PacBio long-read sequencing. The NA1 strain Pr102, originally isolated from coast live oak in California, is the current reference genome and was previously sequenced independently using either Sanger (P. ramorum v1) or PacBio (P. ramorum v2) technology. The EU1 strain PR-15-019 was obtained from tanoak in Oregon. These new genomes have a total size of 57.5 Mb, with a contig N50 length of ~3.5-3.6 Mb and encode ~15,300 predicted protein-coding genes. Genomes were assembled into 27 and 28 scaffolds with 95% BUSCO scores and are considerably improved relative to the current JGI reference genome with 2,575 or the PacBio genomes with 1,512 scaffolds. These high-quality genomes provide a valuable resource for studying the genetics, evolution, and adaptation of these two clonal lineages.
A critical period of translational control during brain development at codon resolution
Authors: Harnett Dermot , Ambrozkiewicz Mateusz C. , Zinnall Ulrike , Rusanova Alexandra , Borisova Ekaterina , Dannenberg Rike , Imami Koshi , Münster-Wandowski Agnieszka , Fauler Beatrix , Mielke Thorsten , Selbach Matthias , Landthaler Markus , Spahn Christian M.T. , Tarabykin Victor , Ohler Uwe , Kraushar Matthew L. 
Published: June 2021

AbstractTranslation modulates the timing and amplification of gene expression after transcription. Brain development requires uniquely complex gene expression patterns, but large-scale measurements of translation directly in the prenatal brain are lacking. We measure the reactants, synthesis, and products of translation spanning mouse neocortex neurogenesis, and discover a transient window of dynamic regulation at mid-gestation. Timed translation upregulation of chromatin binding proteins like Satb2, which is essential for neuronal subtype differentiation, restricts protein expression in neuronal lineages despite broad transcriptional priming in progenitors. In contrast, translation downregulation of ribosomal proteins sharply decreases ribosome number, coinciding with a major shift in protein synthesis dynamics at mid-gestation. Changing levels of eIF4EBP1, a direct inhibitor of ribosomal protein translation, are concurrent with ribosome downregulation and controls Satb2 fate acquisition during neuronal differentiation. Thus, the refinement of transcriptional programs by translation is central to the molecular logic of brain development. Modeling of the developmental neocortex translatome is provided as an open-source searchable resource: https://shiny.mdc-berlin.de/cortexomics/.
SLC1A5provides glutamine and asparagine necessary for bone development in mice
Authors: Sharma Deepika , Yu Yilin , Shen Leyao , Zhang Guo-Fang , Karner Courtney 
Published: June 2021

AbstractOsteoblast differentiation is sequentially characterized by high rates of proliferation followed by increased protein and matrix synthesis, processes that require substantial amino acid acquisition and production. How osteoblasts obtain or maintain intracellular amino acid production is poorly understood. Here we identifySlc1a5as a critical amino acid transporter during bone development. Using a genetic and metabolomic approach, we showSlc1a5acts cell autonomously in osteoblasts to import glutamine and asparagine. DeletingSlc1a5or reducing either glutamine or asparagine availability prevents protein synthesis and osteoblast differentiation. Mechanistically, glutamine and asparagine metabolism support amino acid biosynthesis. Thus, osteoblasts depend onSlc1a5to provide glutamine and asparagine, which are subsequently used to produce non-essential amino acids and support osteoblast differentiation and bone development.