bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alzheimer’s disease susceptibility gene apolipoprotein e (APOE) and blood biomarkers in UK Biobank (N=395,769)
Authors: Ferguson Amy C. , Tank Rachana , Lyall Laura M. , Ward Joey , Celis-Morales Carlos , Strawbridge Rona , Ho Frederick , Whelan Christopher D. , Gill Jason , Welsh Paul , Anderson Jana J. , Mark Patrick B. , Mackay Daniel F. , Smith Daniel J. , Pell Jill P. , Cavanagh Jonathan , Sattar Naveed , Lyall Donald M. 
Published: February 2020

AbstractBackground and objectiveAlzheimer’s disease (AD) is a neurodegenerative condition where the underlying aetiology is still unclear. Investigating the potential influence of apolipoprotein e (APOE), a major genetic risk factor, on common blood biomarkers could provide a greater understanding of the mechanisms of AD and dementia risk. Our objective was to conduct the largest (to date) single-protocol investigation of blood biomarkers in the context of APOE genotype, in UK Biobank.MethodsAfter quality control and exclusions, data on 395,769 participants of White European ancestry were available for analysis. Linear regressions were used to test potential associations between APOE genotypes and biomarkers.ResultsSeveral biomarkers significantly associated with APOE e4 ‘risk’ and e2 ‘protective’ genotypes (vs. neutral e3/e3). Most associations supported previous data: for example, e4 genotype was associated with elevated low-density lipoprotein cholesterol (LDL) (standardized beta [b] = 0.150 standard deviations [SDs] per allele, p<0.001) and e2 with lower LDL (b = −0.456 SDs, p<0.001). There were however instances of associations found in unexpected directions: e.g. e4 and increased insulin-like growth factor (IGF-1) (standardized beta = 0.017, p<0.001) where lower levels have been previously suggested as an AD risk factor.ConclusionsThese findings highlight biomarker differences in non-demented people at genetic risk for dementia. The evidence here in supports previous hypotheses of involvement from cardiometabolic and neuroinflammatory pathways.
Estimating the daily trend in the size of the COVID-19 infected population in Wuhan
Authors: Lin Qiushi , Hu Taojun , Zhou Xiao − Hua 
Published: February 2020

AbstractThere has been an outbreak of coronavirus disease (COVID-19) in Wuhan city, Hubei province, China since December 2019. Cases have been exported to other parts of China and more than 20 countries. We provide estimates of the daily trend in the size of the epidemic in Wuhan based on detailed information of 10,940 confirmed cases outside Hubei province.
Effectiveness of interventions targeting air travellers for delaying local outbreaks of SARS-CoV-2
Authors: Clifford Samuel , Pearson Carl A.B. , Klepac Petra , Van Zandvoort Kevin , Quilty Billy J. ,   CMMID COVID-19 working group, Eggo Rosalind M. , Flasche Stefan 
Published: February 2020

AbstractBackgroundWe evaluated if interventions aimed at air travellers can delay local SARS-CoV-2 community transmission in a previously unaffected country.MethodsWe simulated infected air travellers arriving into countries with no sustained SARS-CoV-2 transmission or other introduction routes from affected regions. We assessed the effectiveness of syndromic screening at departure and/or arrival & traveller sensitisation to the COVID-2019-like symptoms with the aim to trigger rapid self-isolation and reporting on symptom onset to enable contact tracing. We assumed that syndromic screening would reduce the number of infected arrivals and that traveller sensitisation reduces the average number of secondary cases. We use stochastic simulations to account for uncertainty in both arrival and secondary infections rates, and present sensitivity analyses on arrival rates of infected travellers and the effectiveness of traveller sensitisation. We report the median expected delay achievable in each scenario and an inner 50% interval.ResultsUnder baseline assumptions, introducing exit and entry screening in combination with traveller sensitisation can delay a local SARS-CoV-2 outbreak by 8 days (50% interval: 3-14 days) when the rate of importation is 1 infected traveller per week at time of introduction. The additional benefit of entry screening is small if exit screening is effective: the combination of only exit screening and traveller sensitisation can delay an outbreak by 7 days (50% interval: 2-13 days). In the absence of screening, with less effective sensitisation, or a higher rate of importation, these delays shrink rapidly to less than 4 days.ConclusionSyndromic screening and traveller sensitisation in combination may have marginally delayed SARS-CoV-2 outbreaks in unaffected countries.
Early epidemiological assessment of the transmission potential and virulence of coronavirus disease 2019 (COVID-19) in Wuhan City: China, January-February, 2020
Authors: Mizumoto Kenji , Kagaya Katsushi , Chowell Gerardo 
Published: February 2020

AbstractBackgroundSince the first cluster of cases was identified in Wuhan City, China, in December, 2019, coronavirus disease 2019 (COVID-19) rapidly spread around the world. Despite the scarcity of publicly available data, scientists around the world have made strides in estimating the magnitude of the epidemic, the basic reproduction number, and transmission patterns. Accumulating evidence suggests that a substantial fraction of the infected individuals with the novel coronavirus show little if any symptoms, which highlights the need to reassess the transmission potential of this emerging disease. In this study, we derive estimates of the transmissibility and virulence of COVID-19 in Wuhan City, China, by reconstructing the underlying transmission dynamics using multiple data sources.MethodsWe employ statistical methods and publicly available epidemiological datasets to jointly derive estimates of transmissibility and severity associated with the novel coronavirus. For this purpose, the daily series of laboratory–confirmed COVID-19 cases and deaths in Wuhan City together with epidemiological data of Japanese repatriated from Wuhan City on board government–chartered flights were integrated into our analysis.ResultsOur posterior estimates of basic reproduction number (R) in Wuhan City, China in 2019–2020 reached values at 3.49 (95%CrI: 3.39–3.62) with a mean serial interval of 6.0 days, and the enhanced public health intervention after January 23rd in 2020 was associated with a significantly reduced R at 0.84 (95%CrI: 0.81–0.88), with the total number of infections (i.e. cumulative infections) estimated at 1906634 (95%CrI: 1373500–2651124) in Wuhan City, elevating the overall proportion of infected individuals to 19.1% (95%CrI: 13.5–26.6%). We also estimated the most recent crude infection fatality ratio (IFR) and time–delay adjusted IFR at 0.04% (95% CrI: 0.03%–0.06%) and 0.12% (95%CrI: 0.08–0.17%), respectively, estimates that are several orders of magnitude smaller than the crude CFR estimated at 4.06%ConclusionsWe have estimated key epidemiological parameters of the transmissibility and virulence of COVID-19 in Wuhan, China during January-February, 2020 using an ecological modelling approach. The power of this approach lies in the ability to infer epidemiological parameters with quantified uncertainty from partial observations collected by surveillance systems.
The human small intestine contains two subsets of regulatory Foxp3+ CD4+ T cells with very different life span and functional properties
Authors: Chauhan Sudhir Kumar , Casado Raquel Bartolomé , Landsverk Ole J.B. , Johannessen Hanna , Phung Danh , Sætre Frank , Jahnsen Jørgen , Horneland Rune , Yaqub Sheraz , Aandahl Einar Martin , Lundin Knut E.A. , Bækkevold Espen S. , Jahnsen Frode L. 
Published: February 2020

ABSTRACTBackgroundRegulatory CD4 T cells (Tregs) in the mice gut are mainly specific for intestinal antigens and play an important role in the suppression of immune responses against harmless dietary antigens and members of the microbiota. However, information about the phenotype and function of Tregs in the human gut is limited.ObjectiveHere, we performed a detailed characterization of Foxp3+ CD4 Tregs in the human small intestine.MethodsTregs and conventional CD4 T cells derived from normal intestine as well as from transplanted duodenum and celiac disease lesions were subjected to extensive immunophenotyping and their suppressive activity and ability to produce cytokines were assessed.ResultsSmall intestinal Foxp3+ CD4 T cells were CD45RA- CD127- CTLA4+ and suppressed proliferation of autologous T cells. Approximately 60% of the Tregs expressed the transcription factor Helios. When stimulated, Helios- Tregs produced IL-17, IFN-γ and IL-10, whereas Helios+ Tregs produced very low levels of these cytokines. By sampling mucosal tissue from transplanted human duodenum we demonstrated that donor Helios+ Tregs have a short life span whereas Helios- Tregs persisted for at least 1 year post-transplantation. In normal small intestine, Foxp3+ Tregs constituted only 2% of all CD4 T cells, while in active celiac disease both subsets expanded 5-10-fold.ConclusionThe small intestine contains two subsets of Tregs with different functional capacities and very different life span. Both subsets are scarce in the normal situation but increase dramatically in a chronic inflammatory setting.
Codon-usage optimization in the prokaryotic tree of life: How synonymous codons are differentially selected in sequence domains with different expression levels and degrees of conservation
Authors: López José Luis , Lozano Mauricio Javier , Fabre María Laura , Lagares Antonio 
Published: February 2020

ABSTRACTProkaryote genomes exhibit a wide range of GC contents and codon usages, both resulting from an interaction between mutational bias and natural selection. In order to investigate the basis underlying specific codon changes, we performed a comprehensive analysis of 29-different prokaryote families. The analysis of core-gene sets with increasing ancestries in each family lineage revealed that the codon usages became progressively more adapted to the tRNA pools. While, as previously reported, highly-expressed genes presented the more optimized codon usage, the singletons contained the less selectively-favored codons. Results showed that usually codons with the highest translational adaptation were preferentially enriched. In agreement with previous reports, a C-bias in 2- to 3-fold codons, and a U-bias in 4-fold codons occurred in all families, irrespective of the global genomic-GC content. Furthermore, the U-biases suggested that U3-mRNA–U34-tRNA interactions were responsible for a prominent codon optimization in both the more ancestral core and the highly expressed genes. A comparative analysis of sequences that encode conserved-(cr) or variable-(vr) translated products, with each one being under high- (HEP) and low- (LEP) expression levels, demonstrated that the efficiency was more relevant (by a factor of 2) than accuracy to modelling codon usage. Finally, analysis of the third position of codons (GC3) revealed that, in genomes of global-GC contents higher than 35-40%, selection favored a GC3 increase; whereas in genomes with very low-GC contents, a decrease in GC3 occurred. A comprehensive final model is presented where all patterns of codon usage variations are condensed in five-distinct behavioral groups.IMPORTANCEThe prokaryotic genomes—the current heritage of the more ancient life forms on earth— are comprised of diverse gene sets; all characterized by varied origins, ancestries, and spatial-temporal–expression patterns. Such genetic diversity has for a long time raised the question of how cells shape their coding strategies to optimize protein demands (i.e., product abundance) and accuracy (i.e., translation fidelity) through the use of the same genetic code in genomes with GC-contents that range from less than 20 to over 80%. In this work, we present evidence on how codon usage is adjusted in the prokaryote tree of life, and on how specific biases have operated to improve translation. Through the use of proteome data, we characterized conserved and variable sequence domains in genes of either high- or low-expression level, and quantitated the relative weight of efficiency and accuracy—as well as their interaction—in shaping codon usage in prokaryotes.
Trait-based aerial dispersal of arbuscular mycorrhizal fungi
Authors: Chaudhary V. Bala , Nolimal Sarah , Sosa-Hernández Moisés A. , Egan Cameron , Kastens Jude 
Published: February 2020

SUMMARYDispersal is a key process driving local-scale community assembly and global-scale biogeography of plant symbiotic arbuscular mycorrhizal (AM) fungal communities. A trait-based approach could improve predictions regarding how AM fungal aerial dispersal varies by species.We conducted month-long collections of aerial AM fungi for 12 consecutive months in an urban mesic environment at heights of 20 m. We measured functional traits of all collected spores and assessed aerial AM fungal community structure both morphologically and with high-throughput sequencing.Large numbers of AM fungal spores were present in the air over the course of one year and these spores were more likely to exhibit traits that facilitate dispersal. Aerial spores were smaller than average for Glomeromycotinan fungi. Trait-based predictions indicate that nearly 1/3 of described species from diverse genera demonstrate the potential for aerial dispersal. Diversity of aerial AM fungi was relatively high (20 spore species and 17 virtual taxa) and both spore abundance and community structure shifted temporally.The prevalence of aerial dispersal in arbuscular mycorrhizas is perhaps greater than previously indicated and a hypothesized model of AM fungal dispersal mechanisms is presented. Anthropogenic soil impacts may initiate the dispersal of disturbance-tolerating AM fungal species and facilitate community homogenization.
Osprey: Open-Source Processing, Reconstruction & Estimation of Magnetic Resonance Spectroscopy Data
Authors: Oeltzschner Georg , Zöllner Helge J. , Hui Steve C. N. , Mikkelsen Mark , Saleh Muhammad G. , Tapper Sofie , Edden Richard A. E. 
Published: February 2020

AbstractBackgroundProcessing and quantitative analysis of magnetic resonance spectroscopy (MRS) data are far from standardized and require interfacing with third-party software. Here, we present Osprey, a fully integrated open-source data analysis pipeline for MRS data, with seamless integration of pre-processing, linear-combination modelling, quantification, and data visualization.New MethodOsprey loads multiple common MRS data formats, performs phased-array coil combination, frequency-and phase-correction of individual transients, signal averaging and Fourier transformation. Linear combination modelling of the processed spectrum is carried out using simulated basis sets and a spline baseline. The MRS voxel is coregistered to an anatomical image, which is segmented for tissue correction and quantification is performed based upon modelling parameters and tissue segmentation. The results of each analysis step are visualized in the Osprey GUI. The analysis pipeline is demonstrated in 12 PRESS, 11 MEGA-PRESS, and 8 HERMES datasets acquired in healthy subjects.ResultsOsprey successfully loads, processes, models, and quantifies MRS data acquired with a variety of conventional and spectral editing techniques.Comparison with Existing Method(s)Osprey is the first MRS software to combine uniform pre-processing, linear-combination modelling, tissue correction and quantification into a coherent ecosystem. Compared to existing compiled, often closed-source modelling software, Osprey’s open-source code philosophy allows researchers to integrate state-of-the-art data processing and modelling routines, and potentially converge towards standardization of analysis.ConclusionsOsprey combines robust, peer-reviewed data processing methods into a modular workflow that is easily augmented by community developers, allowing the rapid implementation of new methods.
Anin vitrovesicle formation assay to analyze protein sorting in the secretory transport pathway
Authors: Huang Yan , Yin Haidi , Tang Xiao , Wu Qian , Wang Mo , Poljak Kristina , Li Baiying , Yang Liu , Wu Zhixiao , Jiang Liwen , Miller Elizabeth A. , Yao Zhong-Ping , Guo Yusong 
Published: February 2020

AbstractThe fidelity of protein transport in the secretory transport pathway relies on the accurate sorting of proteins to their correct destination. To deepen our understanding of the underlying molecular mechanisms, it is important to develop a robust approach to systematically reveal cargo proteins that depend on a specific cargo sorting machinery to be efficiently packaged into vesicles. Here, we used anin vitroassay that reconstitutes packaging of human cargo proteins into vesicles to quantify cargo capture. Quantitative mass spectrometry analyses of the isolated vesicles revealed novel cytosolic proteins that are associated with vesicle membranes in a GTP-dependent manner or that interact with GTP-bound Sar1A on vesicle membranes. Functional analysis indicates that two of them, FAM84B and PRRC1, regulate anterograde trafficking. Comparing control cells with cells depleted of the cargo receptors, SURF4 or ERGIC53, we revealed specific clients of each of these two export adaptors. Moreover, our results indicate that vesicles enriched with a specific cargo protein contain specific transmembrane cargo and SNARE proteins. A SNARE protein, Vti1B, is identified to be in vesicles enriched with a planar cell polarity protein, Frizzled6, and promotes vesicular release of Frizzled6. Our results indicate that the vesicle formation assay in combination with quantitative mass spectrometric analysis is a robust and powerful tool to reveal novel cytosolic and transmembrane proteins that regulate trafficking of a specific cargo protein.
Bacterial flagella disrupt host cell membranes and interact with cytoskeletal components
Authors: Wolfson Eliza. B. , Elvidge Johanna , Tahoun Amin , Gillespie Trudi , Mantell Judith , McAteer Sean P. , Rossez Yannick , Paxton Edith , Lane Fiona , Shaw Darren J. , Gill Andrew C. , Stevens Jo , Verkade Paul , Blocker Ariel , Mahajan Arvind , Gally David L. 
Published: February 2020

AbstractBacterial flagella have many established roles beyond swimming motility. Despite clear evidence of flagella-dependent adherence, the specificity of ligands and mechanisms of binding are still debated. In this study, the molecular basis ofE. coliO157:H7 andS. Typhimurium flagella binding to epithelial cell cultures was investigated. Flagella interactions with host cell surfaces were intimate and crossed cellular boundaries as demarcated by actin and membrane labelling. SEM revealed flagella disappearing into cellular surfaces and TEM ofS. Typhiumurium indicated host membrane deformation and disruption in proximity to flagella. Motor mutants ofE. coliO157:H7 andS. Typhimurium caused reduced haemolysis compared to wild-type, indicating that membrane disruption was in part due to flagella rotation. Flagella fromE. coliO157 (H7), EPEC O127 (H6), andS. Typhimurium (P1 & P2 flagella) were shown to bind to purified intracellular components of the actin cytoskeleton and directly increase in vitro actin polymerisation rates.
Fatigue behavior of trabecular bone orientation
Authors: Januddi Fatihhi Szali , Harun M.N , Abdullah Jaafar , Mostakhdemin Mohammad , Syahrom Ardiyansyah 
Published: February 2020

AbstractThe present study reports the anisotropy effects of uniaxial and multiaxial loading on cancellous bone in order to mimic true physiological conditions as well as pathological reactions and thereby provides improved data that represents clinical and real life conditions. Cancellous bone samples were CT-scanned for morphological analysis and model construction. The models were then computationally loaded on three different directions; horizontal, vertical, and at 45°. Lower BV/TV, Tb.Th, and Conn.D resulted in lower number of cycles to failure, regardless to the loading conditions. However, the number of cycles to failure was found to be negatively correlated to the value of structural model index. Dramatic increased in effective plastic strain and decrease in cycles to failure were demonstrated by the cancellous bone models under multiaxial loading. The reduction of fatigue life was five times lower in multiaxial condition in comparison to the fatigue life under uniaxial loading. Off-axis orientation effect on the fatigue life of the trabecular bone was demonstrated the worst in horizontal trabecular bone model. Effective plastic strain was recorded the highest in horizontal model, while the model at 45° demonstrated 1.6 times higher effective plastic strain than the vertical ones. This is due to several numbers of thin trabeculae which are susceptible to fatigue at higher stress concentration. In conclusion, the anisotropic effect of uniaxial and multiaxial loading onto the mechanical behaviour of bovine cancellous bone was demonstrated throughout this study. It is apparent that multiaxial with off-axis forces are important to be considered as the loading direction manifests the fatigue lifetime of cancellous bone.
Incidence of atrial septal defects in children attended the Cardiac Center of Ethiopia during January 2016 to December 2018
Authors: Musa Abdu Hassen , Afework Mekbeb , Bedru Mohammed , Tamirat Shibikom ,   on behalf of Cardiac Center of Ethiopia record screener
Published: February 2020

AbstractBackgroundAlthough it appears that an atrial septal defect (ASD) occurs frequently in Ethiopia there are only a few published studies available so far on this matter. This study is therefore aimed to evaluate the prevalence and echocardiographic characteristics of ASDs in children (aged ≤ 15 years) attended a cardiac referral center in Ethiopia.MethodsThis retrospective study reviewed the sociodemographic data and the initial echocardiographic findings of the children with ASDs who were diagnosed at the Cardiac Center of Ethiopia (CCE), Addis Ababa, from January 2016 to December 2018.ResultsA total of 116 children (56.9% females and 43.1% males) with a mean age of 3.47± 3.72 years (range: 15 days to 15 years) were diagnosed with ASDs. The most prevalent age groups were infancy (50%) and early childhood (29.3%). All the studied cases were diagnosed with ostium secundum ASD while there were no cases with ostium primum, sinus venosus and coronary sinus defects. The most frequent ostium secundum ASD was large size (61.2%) and was more frequent in infants (23.3%) and young children (21.6% of all cases).ConclusionOstium secundum ASD is the most prevalent IAS defect and more common among female cases. Large size ostium secundum ASD is more frequent in the studied children and is more prevalent in infants and young children. This survey may provide data for the currently lacking statistics on ASDs at the CCE and might be helpful for the management and follow-up of children with ASDs. Scheduled follow-up and intervention studies are required to evaluate the incidence and patterns of spontaneous and surgical closure of ASD and their outcomes.