bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patient and programmatic characteristics, retention and predictors of attrition among patients starting antiretroviral therapy (ART) before and after the implementation of HIV “Treat All” in Zimbabwe
Authors: Makurumidze Richard , Buyze Jozefien , Decroo Tom , Lynen Lutgarde , de Rooij Madelon , Mataranyika Trevor , Sithole Ngwarai , Takarinda Kudakwashe C. , Apollo Tsitsi , Hakim James , Van Damme Wim , Rusakaniko Simbarashe 
Published: July 2020

AbstractBackgroundSince scale-up of the HIV “Treat All”, evidence on its real-world effect on known predictors of attrition (either death or lost to follow-up) is lacking. We conducted a retrospective study using Zimbabwe ART program data to assess the association between “Treat All” and, patient and programmatic characteristics, retention and predictors of attrition.MethodsWe used patient-level data from the electronic patient monitoring system (ePMS) from the nine districts which piloted “Treat All”. We compared patient and programme characteristics, retention and predictors of attrition (lost to follow-up, death or stopping ART) in two cohorts; before (April/May 2016) and after (January/February 2017) “Treat All”. Retention was estimated using survival analysis. Predictors of attrition were determined using a multivariable Cox regression model. Interactions were used to assess the change in predictors.ResultsWe analysed 3787 patients, 1738 (45.9%) and 2049 (54.1%) started ART before and after “Treat All”, respectively. The proportion of men was higher after “Treat All” (39.4.% vs 36.2%, p=0.044). Same-day ART initiation was more frequent after “Treat All” (43.2% vs 16.4%; p<0.001) than before. Retention on ART was higher before “Treat All” (p<0.001). Among non-pregnant women and men, the adjusted hazard ratio (aHR) of attrition after “Treat All” compared to before “Treat All” was 1.73 (95%CI: 1.30 - 2.31). The observed hazard of attrition for women being pregnant at ART initiation decreased by 17% (aHR: 1.73*0.48 = 0.83). Being male (vs female; aHR: 1.45; 95%CI: 1.12 - 1.87) and WHO Stage IV (vs WHO Stage I-III; aHR: 2.89; 95%CI: 1.16 - 7.11) predicted attrition both before and after “Treat All” implementation.ConclusionAttrition was higher after “Treat All”; being male, WHO Stage 4, and pregnancy predicted attrition in both before and after Treat All. However, pregnancy became a less strong risk factor for attrition after “Treat All” implementation.”
Quantifying Respiratory Airborne Particle Dispersion Control Through Improvised Reusable Masks: The Physics of Non-Pharmaceuptical Interventions for Reducing SARS-COV-2 (COVID-19) Airborne Transmision
Authors: Edwards Nathan J. , Widrick Rebecca , Potember Richard , Gerschefske Mike 
Published: July 2020

ABSTRACTBackgroundFor much of the SARS-CoV-2 (COVID-19) pandemic, many countries have struggled to offer definitive guidance on the wearing of masks or face coverings to reduce the highly infectious disease transmission resulting from a lack of compelling evidence on the effectiveness of communities wearing masks, and slow acceptance that aerosols are a primary SARS-CoV-2 disease transmission mechanism. Recent studies have shown that masks have been effective in several countries and populations, leaving only a lack of quantitative data on the control of airborne dispersion from human exhalation. This current study specifically has the objective to quantify the effectiveness of non-medical grade washable masks or face coverings in controlling airborne dispersion from exhalation (both droplet and aerosol) by measuring changes in direction, particle cloud velocities, and concentration.DesignThis randomized effectiveness study used a 10% NaCl nebulized polydisperse particle solution (0.3 μm up to 10 μm in size) delivered by an exhalation simulator to conduct 94 experiment runs with combinations of 8 different fabrics, 5 mask designs, and airflows for both talking and coughing. Multiple particle sensors were instrumented to measure reduction in aerosol dispersion.ResultsThree-way multivariate analysis of variance establishes that fabric, mask design, and exhalation breath level have a statistically significant effect on changing direction, reducing velocity, or concentrations of airborne particles (Fabric: P = < .001, Wilks’ Λ = .000; Mask design: P = < .001, Wilks' Λ = .000; Breath level: P = < .001, Wilks' Λ = .004). There were also statistically significant interaction effects between combinations of all primary factors.Conclusions and RelevanceThe application of facial coverings or masks can significantly reduce the airborne dispersion of aerosolized particles from exhalation by diffusing the particle cloud direction and slow down its travel speed. Consequently, the results indicate that wearing masks when coupled with social distance can decrease the potentially inhaled dose of SARS-CoV-2 aerosols or droplets especially where infectious contaminants may exist in shared air spaces. The conclusion is well aligned with the concept of “time-distance-shielding” from hazardous materials emergency response. However, the effectiveness varies greatly between the specific fabrics and mask designs used.
Evaluation of consensus strategies for haplotype phasing
Authors: Al Bkhetan Ziad , Chana Gursharan , Ramamohanarao Kotagiri , Verspoor Karin , Goudey Benjamin 
Published: July 2020

AbstractMotivationHaplotype phasing is a critical step for many genetic applications but incorrect estimates of phase can negatively impact downstream analyses. One proposed strategy to improve phasing accuracy is to combine multiple independent phasing estimates to overcome the limitations of any individual estimate. As such a strategy is yet to be thoroughly explored, this study provides a comprehensive evaluation of consensus strategies for haplotype phasing, exploring their performance, along with their constituent tools, across a range of real and simulated datasets with different data characteristics and on the downstream task of genotype imputation.ResultsBased on the outputs of existing phasing tools, we explore two different strategies to construct haplotype consensus estimators: voting across outputs from multiple phasing tools and multiple outputs of a single non-deterministic tool. We find the consensus approach from multiple tools reduces switch error by an average of 10% compared to any constituent tool when applied to European populations and has the highest accuracy regardless of population ethnicity, sample size, SNP-density or SNP frequency. Furthermore, a consensus provides a small improvement indirectly the downstream task of genotype imputation regardless of which genotype imputation tools were used. Our results provide guidance on how to produce the most accurate phasing estimates and the tradeoffs that a consensus approach may have.AvailabilityOur implementation of consensus haplotype phasing, consHap, is available freely athttps://github.com/ziadbkh/consHap.
STARCH: Copy number and clone inference from spatial transcriptomics data
Authors: Elyanow Rebecca , Zeira Ron , Land Max , Raphael Benjamin J. 
Published: July 2020

AbstractTumors are highly heterogeneous, consisting of cell populations with both transcriptional and genetic diversity. These diverse cell populations are spatially organized within a tumor, creating a distinct tumor microenvironment. A new technology calledspatial transcriptomicscan measure spatial patterns of gene expression within a tissue by sequencing RNA transcripts from a grid of spots, each containing a small number of cells. In tumor cells, these gene expression patterns represent the combined contribution of regulatory mechanisms, which alter the rate at which a gene is transcribed, and genetic diversity, particularly copy number aberrations (CNAs) which alter the number of copies of a gene in the genome. CNAs are common in tumors and often promote cancer growth through upregulation of oncogenes or downregulation of tumor-suppressor genes. We introduce a new method STARCH (Spatial Transcriptomics Algorithm Reconstructing Copy-number Heterogeneity) to infer CNAs from spatial transcriptomics data. STARCH overcomes challenges in inferring CNAs from RNA-sequencing data by leveraging the observation that cells located nearby in a tumor are likely to share similar CNAs. We find that STARCH outperforms existing methods for inferring CNAs from RNA-sequencing data without incorporating spatial information.
Callosal anisotropy predicts attentional network changes after parietal inhibitory stimulation
Authors: Schintu Selene , Cunningham Catherine A. , Freedberg Michael , Taylor Paul , Gotts Stephen J. , Shomstein Sarah , Wassermann Eric M. 
Published: July 2020

AbstractHemispatial neglect is thought to result from disruption of interhemispheric equilibrium. Right hemisphere lesions deactivate the right frontoparietal network and hyperactivate the left via release from interhemispheric inhibition. Support for this theory comes from neuropsychological evidence as well as transcranial magnetic stimulation (TMS) studies in healthy subjects, in whom right posterior parietal cortex (PPC) inhibition causes neglect-like, rightward, visuospatial bias. Concurrent TMS and fMRI after right PPC TMS show task-dependent changes but may fail to identify effects of stimulation in areas not directly activated by the specific task, complicating interpretations. We used resting-state functional connectivity (RSFC) after inhibitory TMS over the right PPC to examine changes in the networks underlying visuospatial attention.In a crossover experiment in healthy individuals, we delivered continuous theta burst TMS to the right PPC and vertex as control condition. We hypothesized that PPC inhibitory stimulation would cause a rightward visuospatial bias, decrease PPC connectivity with frontal areas, and increase PPC connectivity with the attentional network in the left hemisphere. We also expected that individual differences in fractional anisotropy (FA) in white matter connections between the PPCs would account for variability in TMS-induced RSFC changes.As expected, TMS over the right PPC caused a rightward shift in line bisection judgment and increased RSFC between the right PPC and the left superior temporal gyrus. This effect was inversely related to FA in the posterior corpus callosum. Local inhibition of the right PPC reshapes connectivity in the attentional network and depends on interhemispheric connections.
Transcriptional Analysis ofColletotrichum fructicolafrom Different Geographic Regions Inoculated toCamellia oleifera
Authors: Tan Shimeng , Chen Yanying , Zhou Guoying , Liu Junang 
Published: July 2020

AbstractAnthracnose, caused by Colletotrichum. Spp., is an important disease affecting oil tea (Camellia oleifera). Extensive molecular studies have demonstrated thatColletotrichum fructicolais the dominant pathogen of oil tea anthracnose in China. The study aims to investigate differences in molecular processes and regulatory genes at different stages of infection ofC. fructicola, to aide in understanding differences in pathogenic mechanisms ofC. fructicolaof different geographic populations. Materials and Methods: We compared the pathogenicity ofC. fructicolafrom different populations (Wuzhishan, Hainan province and Shaoyang, Hunan province), and gene expression of representative strains of the two populations before and after inoculation in oil tea using RNA sequencing. In results we found thatC. fructicolafrom Wuzhishan has a stronger ability to infect and impact oil tea leaf tissue. Up-regulated genes in oil tea following infection with the two geographic populations were associated with a number of ribosome-related GO terms and ribosome metabolic related KEGG pathways, and were significantly enriched in galactosidase activity, glutamine family amino acid metabolism, arginine and proline metabolism. In addition, up-regulated gene lists associated with infection in the Wuzhishan strains were significantly enriched purine metabolism pathways as well, while Shaoyang strains were not significantly enriched in these processes. Differences in gene expression were indicative of greater active transcription and translation in the Wuzhishan population while more active glycoprotein metabolism was observed following inoculation with strains from Shaoyang. These results indicate thatC. fructicolaobtained sugars and amino acids from oil tea tissue to resist host immune pressure. Moreover, more active in transcriptional and translational activity and the greater regulation of purine metabolism pathway in the Wuzhishan strain might contribute to its stronger pathogenicity.
Analysis of Distributed Neural Synchrony through State-Space Coherence Analysis
Authors: Fard Reza Saadati , Arai Kensuke , Eden Uri T. , Brown Emery N. , Yousefi Ali 
Published: July 2020

AbstractEstablished methods to track the dynamics of neural representations focus at the level of individual neurons for spiking data, and individual or pair of channels for local field potentials. However, our understanding of neural function and computation has moved toward an integrative view, based upon coordinated activity of multiple neural populations across brain areas. To draw network-level inferences of brain function, we propose a new modeling framework that combines the state-space model and cross-spectral matrix estimates – this is called state-space coherence (SSCoh). We define elements of the SSCoh and derive system identification and approximate filter solution for multivariate space processes. We expand SCoh for mixed observation processes, where the observation includes different modalities of neural data including local filed potential and spiking activity. Finally, we show an application of the framework to study neural synchrony across different brain nodes of a task participant performing Stroop task under different distraction levels.
Comparative analysis of chloroplast genomes indicated different origin for Indian Tea (Camellia assamica) cv TV-1 as compared to Chinese tea
Authors: Rawal Hukam C. , Mazumder Abhishek , Borchetia Sangeeta , Bera Biswajit , Soundararajan S. , Ilango R Victor J , Barooah Anoop Kumar , Singh Nagendra Kumar , Mondal Tapan Kumar 
Published: July 2020

AbstractTea is an important plantation crop of some Asian and African countries. Based upon the morphological characteristics, tea is classified botanically into 2 main types i.e. Assam and China, which are morphologically very distinct. Further, they are so easily pollinated among themselves, that a third category, Cambod type is also described. Although the general consensus of origin of tea is India, Burma and China joining area, yet specific origin of China and Assam tea are not yet clear. In the present study, we made an attempt to understand the origin of Indian tea through the comparative analysis of different chloroplast (cp) genomes under the Camellia genus. Cp genome based phylogenetic analysis indicated that Indian Assam Tea, TV-1 formed a different group from that of China tea, indicating that TV-1 might have undergone different domestication and hence owe different origin. The simple sequence repeats (SSRs) analysis and codon usage distribution pattern also supported the clustering order in the cp genome based phylogenetic tree.
Ex vivoobservation of granulocyte activity during thrombus formation
Authors: Morozova Daria S. , Martyanov Alexey A. , Obydennyi Sergei I. , Korobkin Julia-Jessica D. , Sokolov Alexey V. , Shamova Ekaterina V. , Gorudko Irina V. , Shcherbina Anna , Panteleev Mikhail A. , Sveshnikova Anastasia N. 
Published: July 2020

AbstractInfiltration of growing thrombi by leukocytes, being the key part of the thromboinflammation, is well establishedin vivo. The study was aimed at the development of anex vivosimulation of this phenomenon. Thrombus formation in anticoagulated whole blood from healthy volunteers and patients was visualized by fluorescent microscopy in parallel-plate flow chambers with fibrillar collagen type I coverslips.Moving CD66b-positive cells (granulocytes) were observed in hirudinated or recalcified blood under low wall shear rate conditions (<200 s−1). These cells crawled around thrombi in a step-wise manner with an average rate of 70 nm/s. Pre-incubation of blood with leukocyte priming agents lead to a significant increase in average cell velocity. On the contrary, leukocytes from Wiskott-Aldrich syndrome patients demonstrated a 1.5-fold lower average velocity, in line with their impaired actin polymerization.Thereby, the observed features of granulocytes crawling are consistent with the neutrophil chemotaxis phenomenon. We conclude that the proposedex vivoexperimental setting allows us to observe granulocytes activity in near-physiological conditions.
A simple and efficient metric quantifying druggable property of chemical small molecules
Authors: Huang Chuanbo , Yang Jichun , Cui Qinghua 
Published: July 2020

AbstractOne big class of drugs are chemical small molecules (CSMs), but the majority of CSMs are in very low druggable potential. Therefore, it is quite important to predict drug-related properties (druggable properties) for candidate CSMs. Currently, although a number of druggable properties (e.g. logP and pKa) can be calculated by in silico methods, the identification of druggable CSMs is still at high risk and new quantitative metrics for the druggable potential of CSMs are increasingly needed. Here, we presented normalized bond energy (NBE), a new metric for the above purpose. By applying NBE to the DrugBank CSMs whose properties are largely known, we revealed that NBE is able to describe a number of critical druggable properties including logP, pKa, membrane permeability, blood-brain barrier penetration, and human intestinal absorption. Moreover, given that the human endogenous metabolites could be served as an important resource for drug discovery, we applied NBE to the metabolites in the Human Metabolome Database. As a result, NBE shows a significant difference in metabolites from various body fluids and is correlated with some important properties including melting point and water solubility.
IP6K1 upregulates the formation of processing bodies by promoting proteome remodeling on the mRNA cap
Authors: Shah Akruti , Bhandari Rashna 
Published: July 2020

AbstractInositol hexakisphosphate kinases (IP6Ks) are ubiquitously expressed small molecule kinases that catalyze the conversion of the inositol phosphate IP6 to 5-IP7. IP6Ks have been reported to influence cellular functions by protein-protein interactions independent of their enzymatic activity. Here, we show that IP6K1 regulates the formation of processing bodies (P-bodies), which are cytoplasmic ribonucleoprotein granules that serve as sites for storage of translationally repressed mRNA. Cells with reduced levels of IP6K1 display a dramatic reduction in the number of P-bodies, which can be restored by the expression of active or catalytically inactive IP6K1. IP6K1 does not localize to P-bodies, but instead facilitates the formation of P-bodies by promoting translation suppression. We demonstrate that IP6K1 is present on ribosomes, where it interacts with proteins that constitute the mRNA decapping complex – the scaffold protein EDC4, activator proteins DCP1A/B, and the decapping enzyme DCP2. IP6K1 also interacts with components of the eIF4F translation initiation complex – the scaffolding protein eIF4G1, the RNA helicase eIF4A2, and the cap binding protein eIF4E. The RNA helicase DDX6 and the eIF4E binding protein 4E-T are known to promote translation suppression to facilitate P-body formation. We show that IP6K1 binds to DDX6 and promotes the interaction of DDX6 and 4E-T with the cap binding protein eIF4E, and also enhances the binding between DDX6 and EDC4, thus acting to suppress mRNA translation and promote mRNA decapping. Our findings unveil IP6K1 as a novel facilitator of proteome remodelling on the mRNA cap, tipping the balance in favour of translation repression over initiation, and thus leading to the formation of P-bodies.
Intraneuronal chloride accumulation via NKCC1 is not essential for hippocampal network developmentin vivo
Authors: Graf Jürgen , Zhang Chuanqiang , Marguet Stephan Lawrence , Herrmann Tanja , Flossmann Tom , Hinsch Robin , Rahmati Vahid , Guenther Madlen , Frahm Christiane , Urbach Anja , Neves Ricardo Melo , Witte Otto W. , Kiebel Stefan J. , Isbrandt Dirk , Hübner Christian A. , Holthoff Knut , Kirmse Knut 
Published: July 2020

AbstractNKCC1 is the primary transporter mediating chloride uptake in immature principal neurons, but its role in the development ofin vivonetwork dynamics and cognitive abilities remains unknown. Here, we address the function of NKCC1 in developing mice using electrophysiological, optical and behavioral approaches. We report that NKCC1 deletion from telencephalic glutamatergic neurons decreasesin-vitroexcitatory GABA actions and impairs neuronal synchrony in neonatal hippocampal brain slices.In vivo, it has a minor impact on correlated spontaneous activity in the hippocampus and does not affect network activity in the intact visual cortex. Moreover, long-term effects of the developmental NKCC1 deletion on synaptic maturation, network dynamics and behavioral performance are subtle. Our data reveal a neural network function of depolarizing GABA in the hippocampusin vivo, but challenge the hypothesis that NKCC1 is essential for major aspects of hippocampal development.
How robust are cross-population signatures of polygenic adaptation in humans?
Authors: Refoyo-Martínez Alba , Liu Siyang , Jørgensen Anja Moltke , Jin Xin , Albrechtsen Anders , Martin Alicia R. , Racimo Fernando 
Published: July 2020

AbstractOver the past decade, summary statistics from genome-wide association studies (GWASs) have been used to detect and quantify polygenic adaptation in humans. Several studies have reported signatures of natural selection at sets of SNPs associated with complex traits, like height and body mass index. However, more recent studies suggest that some of these signals may be caused by biases from uncorrected population stratification in the GWAS data with which these tests are performed. Moreover, past studies have predominantly relied on SNP effect size estimates obtained from GWAS panels of European ancestries, which are known to be poor predictors of phenotypes in non-European populations. Here, we collated GWAS data from multiple anthropometric and metabolic traits that have been measured in more than one cohort around the world, including the UK Biobank, FINRISK, Chinese NIPT, Biobank Japan, APCDR and PAGE. We then evaluated how robust signals of polygenic score overdispersion (which have been interpreted as suggesting polygenic adaptation) are to the choice of GWAS cohort used to identify associated variants and their effect size estimates. We did so while using the same panel to obtain population allele frequencies (The 1000 Genomes Project). We observe many discrepancies across tests performed on the same phenotype and find that association studies performed using multiple different cohorts, like meta-analyses and mega-analyses, tend to produce polygenic scores with strong overdispersion across populations. This results in apparent signatures of polygenic adaptation which are not observed when using effect size estimates from biobank-based GWASs of homogeneous ancestries. Indeed, we were able to artificially create score overdispersion when taking the UK Biobank cohort and simulating a meta-analysis on multiple subsets of the cohort. Finally, we show that the amount of overdispersion in scores for educational attainment - a trait with strong social implications and high potential for misinterpretation - is also strongly dependent on the specific GWAS used to build them. This suggests that extreme caution should be taken in the execution and interpretation of future tests of polygenic score overdispersion based on population differentiation, especially when using summary statistics from a GWAS that combines multiple cohorts.