bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatitis E in Bangladesh: Insights from a National Serosurvey
Authors: Azman Andrew S , Paul Kishor Kumar , Bhuiyan Taufiqur Rahman , Koyuncu Aybüke , Salje Henrik , Qadri Firdausi , Gurley Emily S 
Published: June 2021

AbstractBackgroundHepatitis E virus, typically genotypes 1 and 2, is a major cause of avoidable morbidity and mortality in South Asia. Although case fatality risk among pregnant women can reach as high as 25%, a lack of population-level disease burden data has been cited as a primary factor in key global policy recommendations against the routine use of licensed hepatitis E vaccines, one of the only effective tools available for preventing disease and death.MethodsWe tested serum from a nationally-representative serosurvey in Bangladesh for anti-HEV IgG. We estimated the proportion of the population with evidence of historical HEV infection and used Bayesian geostatistical models to generate high-resolution national maps of seropositivity. We examined variability in seropositivity by individual-level, household-level, and community-level risk factors using spatial logistic regression.ResultsWe tested serum samples from 2924 individuals from 70 communities representing all divisions of Bangladesh and estimated a national seroprevalence of hepatitis E of 20% (95% CI 17-24%). Seropositivity increased with age and male sex (OR: 2.2, 95% CI: 1.8–2.8). Community-level seroprevalence ranged from 0-78% with the seroprevalence in urban areas being higher, including Dhaka, the capital, with 3-fold (95%CrI 2.3-3.7) higher seroprevalence than the rest of the country.ConclusionHepatitis E infections are common throughout Bangladesh, though 90% of women reach reproductive age without any evidence of previous exposure to the virus, thus likely susceptible to infection and disease. Strengthening clinical surveillance for hepatitis E, especially in urban areas may help generate additional evidence needed to appropriately target interventions like vaccines to the populations most likely to benefit.
Gender Balance and Readability of COVID-19 Scientific Publishing: A Quantitative Analysis of 90,000 Preprint Manuscripts
Authors: Celi Leo Anthony , Charpignon Marie-Laure , Ebner Daniel K. , Kaufman Aaron R. , McCoy Liam G. , Millado Maria Cecilia , Park Joel , Salciccioli Justin , Situ Julia 
Published: June 2021

AbstractReleasing preprints is a popular way to hasten the speed of research but may carry hidden risks for public discourse. The COVID-19 pandemic caused by the novel SARS-CoV-2 infection highlighted the risk of rushing the publication of unvalidated findings, leading to damaging scientific miscommunication in the most extreme scenarios. Several high-profile preprints, later found to be deeply flawed, have indeed exacerbated widespread skepticism about the risks of the COVID-19 disease – at great cost to public health. Here, preprint article quality during the pandemic is examined by distinguishing papers related to COVID-19 from other research studies. Importantly, our analysis also investigated possible factors contributing to manuscript quality by assessing the relationship between preprint quality and gender balance in authorship within each research discipline. Using a comprehensive data set of preprint articles from medRxiv and bioRxiv from January to May 2020, we construct both a new index of manuscript quality including length, readability, and spelling correctness and a measure of gender mix among a manuscript’s authors. We find that papers related to COVID-19 are less well-written than unrelated papers, but that this gap is significantly mitigated by teams with better gender balance, even when controlling for variation by research discipline. Beyond contributing to a systematic evaluation of scientific publishing and dissemination, our results have broader implications for gender and representation as the pandemic has led female researchers to bear more responsibility for childcare under lockdown, inducing additional stress and causing disproportionate harm to women in science.
Analysis of the Second COVID-19 Wave in India and the United Kingdom Using a Birth-Death Model
Authors: Viswanath Narayanan C. 
Published: June 2021

AbstractSeveral countries have witnessed multiple waves of the COVID-19 pandemic between 2020 and 21. The method in [8] is applied here to analyze the COVID-19 waves in India and the UK. For this, a birth-death model is fitted to the active and total cases data for 30 days periods called windows starting from 16th March 2020 up to 10th May 2021. Peculiarities of the parameters suggested a classification of the above windows into three categories: (i) whose fitted parameters predicted a rise in the number of active cases before a fall to zero, (ii) which predicted a decrease, without rising, in the active cases to zero and (iii) which predicted an increase in the active cases until the entire susceptible population gets infected. It follows that some of the type (iii) windows are of the same or lesser concern when compared to some type (i) windows. Further analysis of the type (iii) windows leads to the identification of those which could be indicators of the start of a new wave of the pandemic. The study thus proposes a method for using the present data for identifying pandemic waves in the near future.
A personalized network framework reveals predictive axis of anti-TNF response across diseases
Authors: Gerassy-Vainberg Shiran , Starosvetsky Elina , Gaujoux Renaud , Blatt Alexandra , Maimon Naama , Gorelik Yuri , Pressman Sigal , Alpert Ayelet , Bar-Yoseph Haggai , Dubovik Tania , Perets Benny , Katz Adir , Milman Neta , Chowers Yehuda , Shen-Orr Shai S. 
Published: June 2021

AbstractPersonalized treatment of complex diseases has been mostly predicated on biomarker identification of one drug-disease combination at a time. Here, we used a novel computational approach termed Disruption Networks to generate a new data type, contextualized by cell-centered individual-level networks, that captures biology otherwise overlooked when performing standard statistics. The new data-type extends beyond the ‘feature level space’, to the ‘relations space’, by quantifying individual-level breaking or rewiring of cross-feature relations. Applying disruption network to dissect high-dimensional blood data, we discover and validate that the RAC1-PAK1 axis is predictive of anti-TNF response in inflammatory bowel disease. Intermediate monocytes, which correlate with the inflammatory state, play a key role in the RAC1-PAK1 responses, supporting their modulation as a therapeutic target. This axis also predicts response in rheumatoid arthritis, validated in three public cohorts. Our findings support blood-based drug response diagnostics across immune-mediated diseases, implicating common mechanisms of non-response.
Structural organization of the C1b projection within the ciliary central apparatus
Authors: Cai Kai , Zhao Yanhe , Zhao Lei , Phan Nhan , Witman George B. , Nicastro Daniela 
Published: June 2021

Abstract‘9+2’ motile cilia contain 9 doublet microtubules and a central apparatus (CA) composed of two singlet microtubules with associated projections. The CA plays crucial roles in regulating ciliary motility. Defects in CA assembly or function usually result in motility-impaired or paralyzed cilia, which in humans causes disease. Despite their importance, the protein composition and functions of most CA projections remain largely unknown. Here, we combined genetic approaches and quantitative proteomics with cryo-electron tomography and subtomogram averaging to compare the CA of wild-type Chlamydomonas with those of two CA mutants. Our results show that two conserved proteins, FAP42 and FAP246, are localized to the L-shaped C1b projection of the CA. We also identified another novel CA candidate protein, FAP413, which interacts with both FAP42 and FAP246. FAP42 is a large protein that forms the peripheral ‘beam’ of the C1b projection, and the FAP246-FAP413 subcomplex serves as the ‘bracket’ between the beam (FAP42) and the C1b ‘pillar’ that attaches the projection to the C1 microtubule. The FAP246-FAP413-FAP42 complex is essential for stable assembly of both the C1b and C1f projections, and loss of any of these proteins leads to ciliary motility defects. Our results provide insight into the subunit organization and 3D structure of the C1b projection, suggesting that the FAP246-FAP413-FAP42 subcomplex is part of a large interconnected CA-network that provides mechanical support and may play a role in mechano-signaling between the CA and radial spokes to regulate dynein activity and ciliary beating.Summary StatementThe present work provides insight into the subunit organization and 3D structure of the C1b projection of CA and the mechanism by which it regulates dynein activity and ciliary beating.
Single Cell Transcriptomics Reveals Global Markers of Transcriptional Diversity Across Different Forms of Cellular Senescence
Authors: Evans Shane A. , Teo Yee Voan , Clark Kelly , Ito Takahiro , Sedivy John M. , Neretti Nicola 
Published: June 2021

AbstractCellular Senescence is a state of irreversible cell cycle arrest, and the accumulation of senescent cells contributes to age- related organismal decline. The detrimental effects of cellular senescence are due to the senescence associated secretory phenotype (SASP), an array of signaling molecules and growth factors secreted by senescent cells that contribute to the sterile inflammation associated with aging tissues. Recent studies, both in vivo and in vitro, have highlighted the heterogeneous nature of the senescence phenotype. In particular, single cell transcriptomics has revealed that Oncogene Induced Senescence (OIS) is characterized by the presence of subpopulations of cells expressing different SASP profiles. We have generated a comprehensive dataset via single-cell transcriptional profiling of genetically homogenous clonal cell lines from different forms of senescence, including OIS, Replicative Senescence (RS), and DNA Damage Induced Senescence (DDIS). We identified subpopulations of cells that are common to all three major forms of senescence and show that the expression profiles of these subpopulations are driven by markers formerly identified in individual forms of senescence. These common signatures are characterized by chromatin modifiers, inflammation, extracellular matrix remodeling, and Ribosomal protein expression. The expression patterns of these subpopulations recapitulate primary and secondary senescence, a phenomenon where a preexisting (primary) senescent cell induces senescence in a neighboring (secondary) cell through cell-to-cell contact. Since it is still unclear what type of senescence occurs in-vivo with age, it is important to know that the formation of primary and secondary populations is common to multiple types of senescence since this mechanism could help explain how senescent cells accumulate in aged organisms. Finally, we show that these subpopulations show differential susceptibility to the senolytic agent Navitoclax, suggesting that senolytic agents targeting the apoptotic pathways may be clearing only a subset of senescent cells based on their inflammatory profiles in-vivo.
Accurate Protein Function Prediction via Graph Attention Networks with Predicted Structure Information
Authors: Lai Boqiao , Xu Jinbo 
Published: June 2021

AbstractExperimental protein function annotation does not scale with the fast-growing sequence databases. Only a tiny fraction (<0.1%) of protein sequences in UniProtKB has experimentally determined functional annotations. Computational methods may predict protein function in a high-throughput way, but its accuracy is not very satisfactory. Based upon recent breakthroughs in protein structure prediction and protein language models, we develop GAT-GO, a graph attention network (GAT) method that may substantially improve protein function prediction by leveraging predicted inter-residue contact graphs and protein sequence embedding.Our experimental results show that GAT-GO greatly outperforms the latest sequence- and structure-based deep learning methods. On the PDB-mmseqs testset where the train and test proteins share <15% sequence identity, GAT-GO yields Fmax(maximum F-score) 0.508, 0.416, 0.501, and AUPRC(area under the precision-recall curve) 0.427, 0.253, 0.411 for the MFO, BPO, CCO ontology domains, respectively, much better than homology-based method BLAST (Fmax 0.117,0.121,0.207 and AUPRC 0.120, 0.120, 0.163). On the PDB-cdhit testset where the training and test proteins share higher sequence identity, GAT-GO obtains Fmax 0.637, 0.501, 0.542 for the MFO, BPO, CCO ontology domains, respectively, and AUPRC 0.662, 0.384, 0.481, significantly exceeding the just-published graph convolution method DeepFRI, which has Fmax 0.542, 0.425, 0.424 and AUPRC 0.313, 0.159, 0.193.
Spatial structure, phase, and the contrast of natural images
Authors: Rideaux Reuben , West Rebecca K. , Wallis Thomas S. A. , Bex Peter J. , Mattingley Jason B. , Harrison William J. 
Published: June 2021

AbstractThe sensitivity of the human visual system is thought to be shaped by environmental statistics. A major endeavour in vision science, therefore, is to uncover the image statistics that predict perceptual and cognitive function. When searching for targets in natural images, for example, it has recently been proposed that target detection is inversely related to the spatial similarity of the target to its local background. We tested this hypothesis by measuring observers’ sensitivity to targets that were blended with natural image backgrounds. Targets were designed to have a spatial structure that was either similar or dissimilar to the background. Contrary to masking from similarity, we found that observers were most sensitive to targets that were most similar to their backgrounds. We hypothesised that a coincidence of phase-alignment between target and background results in a local contrast signal that facilitates detection when target-background similarity is high. We confirmed this prediction in a second experiment. Indeed, we show that, by solely manipulating the phase of a target relative to its background, the target can be rendered easily visible or undetectable. Our study thus reveals that, in addition to its structural similarity, the phase of the target relative to the background must be considered when predicting detection sensitivity in natural images.
The contributions of extracellular matrix and sarcomere properties to passive muscle stiffness in cerebral palsy
Authors: Konno Ryan N. , Nigam Nilima , Wakeling James M. , Ross Stephanie A. 
Published: June 2021

AbstractCerebral palsy results from an upper motor neuron lesion and has significant effects on skeletal muscle stiffness throughout the body. The increased stiffness that occurs is partly a result of changes in the microstructural components of muscle. In particular, alterations in extracellular matrix, sarcomere length, fibre diameter, and fat content have been reported; however, experimental studies have shown wide variability in the degree to which each component is altered. Many studies have reported alterations in the extracellular matrix, while others have reported no changes. A consistent finding throughout the literature is increased sarcomere length in cerebral palsy muscle. Often more than one component is altered, making it difficult to determine the individual effects on stiffness. The purpose of this study is to use a modeling approach to isolate individual effects of microstructural alterations that typically occur during cerebral palsy on whole muscle behavior; in particular, the extracellular matrix volume fraction, stiffness, and sarcomere length. These microstructural effects can be captured using a three dimensional model of muscle. We found that the extracellular matrix volume fraction has a larger effect on stiffness compared to sarcomere length, even when coupled with decreased extracellular matrix stiffness. Additionally, the effects of sarcomere length in passive stiffness are mitigated by the increased extracellular matrix volume fraction. Using this model, we can achieve a better understanding of the possible combinations of microstructural changes that can occur during cerebral palsy. Developing these insights into diseased muscle tissue will help to direct future clinical and experimental procedures.
Non-serotype 2 isolates from healthy pigs are a potential zoonotic reservoir ofStreptococcus suisgenetic diversity and antimicrobial resistance
Authors: Kittiwan Nattinee , Calland Jessica K. , Mourkas Evangelos , Hitchings Matthew D. , Murray Susan , Tadee Pakpoom , Tadee Pacharaporn , Duangsonk Kwanjit , Méric Guillaume , Sheppard Samuel K. , Patchanee Prapas , Pascoe Ben 
Published: June 2021

SummaryStreptococcus suisis a leading cause of bacterial meningitis in SE Asia, with frequent zoonotic transfer to humans associated with close contact with pigs. A small number of invasive lineages are responsible for endemic infection in the swine industry causing considerable global economic losses. A lack of surveillance and a rising trend in clinical treatment failure has raised concerns of growing antimicrobial resistance (AMR) among invasiveS. suis. The source-sink dynamics between healthy and disease isolates is poorly understood and, in this study, we sample and sequence a collection of isolates predominantly from healthy pigs in Chiang Mai province, Northern Thailand. Pangenome comparisons with a selection of invasive serotype 2 isolates identified increased genetic diversity and more frequent AMR carriage in isolates from healthy pigs. Multiple antimicrobial resistance genes were identified conferring resistance to aminoglycosides, lincosamides, tetracycline and macrolides. All isolates were non-susceptinle to three or more different antimicrobial classes, and 75% of non-serotype 2 isolates were non-susceptible to 6 or more classes (compared to 37.5% of serotype 2 isolates). Antimicrobial resistance genes were found on integrative and conjugative elements (ICE) previously observed in other species, suggesting mobile gene pool which can be accessed by invasive disease isolates.Significance statementThe zoonotic pathogenStreptococcus suiscauses respiratory disease in pigs and is among the most common causative agents of human clinical bacterial meningitis in SE Asia. We collected isolates from farmed healthy pigs in Northern Thailand, representing a source population from which invasive isolates have recently emerged – linked to the pork production industry. Pangenome characterisation of the isolates revealed a reservoir of genetic diversity and antimicrobial resistance suggesting that One Health approaches may be beneficial in tackling the increase in antimicrobial resistance.
Tau interactome mapping reveals dynamic processes in synapses and mitochondria associated with neurodegenerative disease
Authors: Tracy Tara E. , Madero-Pérez Jesus , Swaney Danielle , Chang Timothy S. , Moritz Michelle , Konrad Csaba , Ward Michael E. , Stevenson Erica , Hüttenhain Ruth , Kauwe Grant , Mercedes Maria , Sweetland-Martin Lauren , Chen Xu , Mok Sue-Ann , Telpoukhovskaia Maria , Min Sang-Won , Wang Chao , Sohn Peter Dongmin , Martin Jordie , Zhou Yungui , Manfredi Giovanni , Coppola Giovanni , Krogan Nevan J. , Geschwind Daniel H. , Gan Li 
Published: June 2021

SUMMARYTau (MAPT) drives neuronal dysfunction in Alzheimer’s disease (AD) and other tauopathies. To dissect the underlying mechanisms, we combined an engineered ascorbic acid peroxidase (APEX) approach with quantitative affinity purification mass spectrometry (AP-MS) followed by proximity ligation assay (PLA) to characterize Tau interactomes modified by neuronal activity and mutations that cause frontotemporal dementia (FTD) in human induced pluripotent stem cell (iPSC)-derived neurons. We established activity-dependent interactions of Tau with presynaptic vesicle proteins during Tau secretion and mapped the exact APEX-tau-induced biotinylated tyrosines to the cytosolic domains of the interacting vesicular proteins. We showed that FTD mutations impair bioenergetics and markedly diminished Tau’s interaction with mitochondria proteins, which were downregulated in AD brains of multiple cohorts and correlated with disease severity. These multi-modal and dynamic Tau interactomes with unprecedented spatiotemporal resolution shed novel insights into Tau’s role in neuronal function and disease-related processes with potential therapeutic targets to block Tau-mediated pathogenesis.
No evidence for changes in GABA concentration, functional connectivity, or working memory following continuous theta burst stimulation over dorsolateral prefrontal cortex
Authors: Thapa Tribikram , Hendrikse Joshua , Thompson Sarah , Suo Chao , Biabani Mana , Morrow James , Hoy Kate E , Fitzgerald Paul B , Fornito Alex , Rogasch Nigel C 
Published: June 2021

AbstractContinuous theta burst stimulation (cTBS) is thought to reduce cortical excitability and modulate functional connectivity, possibly by altering cortical inhibition at the site of stimulation. However, most evidence comes from the motor cortex and it remains unclear whether similar effects occur following stimulation over other brain regions. We assessed whether cTBS over left dorsolateral prefrontal cortex altered gamma aminobutyric acid (GABA) concentration, functional connectivity and brain dynamics at rest, and brain activation and memory performance during a working memory task. Seventeen healthy individuals participated in a randomised, sham-controlled, cross-over experiment. Before and after either real or sham cTBS, magnetic resonance spectroscopy was obtained at rest to measure GABA concentrations. Functional magnetic resonance imaging (fMRI) was also recorded at rest and during an n-back working memory task to measure functional connectivity, regional brain activity (low-frequency fluctuations), and task-related patterns of brain activity. We could not find evidence for changes in GABA concentration (P=0.66, Bayes factor [BF10]=0.07), resting-state functional connectivity (P(FWE)>0.05), resting-state low-frequency fluctuations (P=0.88, BF10=0.04), blood-oxygen level dependent activity during the n-back task (P(FWE) >0.05), or working memory performance (P=0.13, BF10=0.05) following real or sham cTBS. Our findings add to a growing body of literature suggesting the effects of cTBS are highly variable between individuals and question the notion that cTBS is a universal ‘inhibitory’ paradigm.