bluuebunny/crossref_metadata_2025_split huggingface dataset:
BioASQ-QA: A manually curated corpus for Biomedical Question Answering
Authors: Krithara Anastasia , Nentidis Anastasios , Bougiatiotis Konstantinos , Paliouras Georgios 
Published: December 2022

ABSTRACTThe BioASQ question answering (QA) benchmark dataset contains questions in English, along with golden standard (reference) answers and related material. The dataset has been designed to reflect real information needs of biomedical experts and is therefore more realistic and challenging than most existing datasets. Furthermore, unlike most previous QA benchmarks that contain only exact answers, the BioASQ-QA dataset also includes ideal answers (in effect summaries), which are particularly useful for research on multi-document summarization. The dataset combines structured and unstructured data. The material linked with each question comprise documents and snippets, which are useful for Information Retrieval and Passage Retrieval experiments, as well as concepts that are useful in concept-to-text Natural Language Generation. Researchers working on paraphrasing and textual entailment can also measure the degree to which their methods improve the performance of biomedical QA systems. Last but not least, the dataset is continuously extended, as the BioASQ challenge is running and new data are generated.
A Versatile Deep Graph Contrastive Learning Framework for Single-cell Proteomics Embedding
Authors: Li Wei , Yang Fan , Wang Fang , Rong Yu , Wu Bingzhe , Zhang Han , Yao Jianhua 
Published: December 2022

AbstractThe advance of single-cell proteomics sequencing technology sheds light on the research in revealing the protein-protein interactions, the post-translational modifications, and the proteoform dynamics of proteins in a cell. However, the uncertainty estimation for peptide quantification, data missingness, severe batch effects and high noise hinder the analysis of single-cell proteomic data. It is a significant challenge to solve this set of tangled problems together, where existing methods tailored for single-cell transcriptome do not address. Here, we proposed a novel versatile framework scPROTEIN, composed of peptide uncertainty estimation based on a multi-task heteroscedastic regression model and cell embedding learning based on graph contrastive learning designed for single-cell proteomic data analysis. scPROTEIN estimated the uncertainty of peptide quantification, denoised the protein data, removed batch effects and encoded single-cell proteomic-specific embeddings in a unified framework. We demonstrate that our method is efficient for cell clustering, batch correction, cell-type annotation and clinical analysis. Furthermore, our method can be easily plugged into single-cell resolved spatial proteomic data, laying the foundation for encoding spatial proteomic data for tumor microenvironment analysis.
Experimental study of modified human tendon stem cells to promote graft ligamentation and tendon-bone healing after anterior cruciate ligament reconstruction
Authors: Zhao Haibo , Chen Jinli , Qi Chao , Wang Tianrui , Liang Tongda , Hao Xiaokun , Li Xiang , Yin Xiangzhi , Yu Tengbo , Zhang Yingze 
Published: December 2022

AbstractRestoring the normal structure and function of injured tendons is one of the biggest challenges faced by the Department of Orthopedics and Sports Medicine. Tendon-derived stem cells (TDSCs), a new type of pluripotent stem cells with multidirectional differentiation potential, are expected to be promising cell seeds for the treatment of tendon injury and tendon-bone healing in the future. In this study, tendon stem cells were successfully isolated from human tissues, which were positive for markers CD44, CD90, and CD105, and exhibited clonality and multilineage differentiation ability. Analysis of single-cell sequencing results and mass spectrometry identification results showed that there were differences in protein expression during CTGF-induced TDSC tendon differentiation. Reverse Co-IP, qPCR, WB, and immunofluorescence detection all confirmed that CTGF directly interacts with KIT, thereby mediating the transcription factor HES1 to regulate the Wnt/β-catenin signaling pathway (GSK3β, β-catenin, TCF4). ChIP-qPCR and dual-luciferase reporter gene assays indicated that HES1 regulates stem cell differentiation by directly regulating the expression of GSK3β in the Wnt/β-catenin pathway. Rats were treated with TDSCs overexpressing the KIT gene after repair surgery. This method had a more ideal recovery effect than other methods through animal behavioral scores, mechanical properties testing, and HE staining tissue observation. This study found that the use of modified human tendon stem cells (hTDSC) could promote graft ligamentization and tendon-bone healing after ACL reconstruction, which could provide an effective way for faster and better recovery from tendon injury.
Non-specific vs specific DNA binding free energetics of a transcription factor domain protein for target search and recognition
Authors: Masri Carmen Al , Wan Biao , Yu Jin 
Published: December 2022

AbstractTranscription factor (TF) proteins regulate gene expression by binding to specific sites on the genome. In the facilitated diffusion model, an optimized search process is achieved by the TF protein alternating between 3D diffusion in the bulk and 1D diffusion along DNA. While undergoing 1D diffusion, the protein can switch from a search mode for fast diffusion along non-specific DNA to a recognition mode for stable binding to specific DNA. It was recently noticed that for a small TF domain protein, re-orientations on DNA other than conformational changes happen between the non-specific and specific DNA binding. We here conducted all-atom molecular dynamics simulations with steering forces to reveal the protein-DNA binding free energetics, with a difference between the non-specific and specific binding about 10kBT, confirming that the search and recognition modes are distinguished only by protein orientations on the DNA. As the binding free energy difference differs from that being estimated from experimental measurements about 4-5kBTon 15-bp DNA constructs, we hypothesize that the discrepancy comes from DNA sequences flanking the 6-bp central binding sites impacting on the dissociation kinetics measurements. The hypothesis is supported by a simplified spherical protein-DNA model along with stochastic simulations and kinetic modeling.
Identification of plant exclusive lipid transfer SMP proteins at membrane contact sites in Arabidopsis and Tomato
Authors: Huercano Carolina , Percio Francisco , Sanchez-Vera Victoria , Morello-López Jorge , Botella Miguel A , Ruiz-Lopez Noemi 
Published: December 2022

ABSTRACTMembrane contact sites (MCS) are regions where two membranes of different organelles are close but not fused; they coordinate non-vesicular communication between organelles and are involved in a wide variety of physiological functions, including membrane lipid homeostasis. Amongst proteins localized at MCS are those containing a lipid transport domain known as synaptotagmin-like mitochondrial-lipid binding protein (SMP), being the mammalian Extended Synaptotagmins, the yeast Tricalbins and the plant Synaptotagmin 1 (SYT1) the best SMP proteins characterized so far. They are all localized at endoplasmic reticulum-plasma membrane contact sites (ER-PM CS). We have carried outin-silicogenome-wide identification of genes encoding SMP proteins in Arabidopsis and tomato. We have identified the plant exclusive NTMC2T5 proteins as ER-chloroplast CS components which make them extremely interesting as the route for lipid trafficking into and out of chloroplasts remains unknown. Additionally,NTMC2T5over-expressions caused a significant clustering of chloroplast around nucleus. Moreover, SYT6, NTMC2T6 and TEX2 have been identified as ER-Trans-Golgi Network CS proteins. These proteins associated between them and with the exocytosis related proteins VAMP721 and VAMP727. Since the functional roles of many of these genes are unknown, this gene collection provides a useful resource for future studies.HIGHLIGHTPlant exclusive lipid transport proteins were identified at membrane contact sites. SYT6, TEX2 and NTMC2T6 proteins are localized at ER-TGN. NTMC2T5 proteins are localized at ER-Chloroplast and induced chloroplast-nucleus clustering.
Processing and evaluating the quality of genome-wide nascent transcription profiling libraries
Authors: Scott Thomas G. , Martins André L. , Guertin Michael J. 
Published: December 2022

AbstractPrecision genomic run-on assays (PRO-seq) quantify nascent RNA at single nucleotide resolution with strand specificity. Here we deconstruct a recently published genomic nascent RNA processing pipeline (PEPPRO) into its components and link the analyses to the underlying molecular biology. PRO-seq experiments are evolving and variations can be found throughout the literature. The analyses are presented as individual code chunks with comprehensive details so that users can modify the framework to accommodate different protocols. We present the framework to quantify the following quality control metrics: library complexity, nascent RNA purity, nuclear run-on efficiency, alignment rate, sequencing depth, and RNA degradation.
Experimental Data Connector (XDC): Integrating the Capture of Experimental Data and Metadata Using Standard Formats and Digital Repositories
Authors: Samineni Sai P. , Vidal Gonzalo , Vidal-Céspedes Carlos , Yañez-Feliú Guillermo , Rudge Timothy J. , Myers Chris J. , Mante Jeanet 
Published: December 2022

AbstractAccelerating the development of synthetic biology applications requires reproducible experimental findings. Different standards and repositories exist to exchange experimental data and metadata. However, the associated software tools often do not support a uniform data capture, encoding, and exchange of information. A connection between digital repositories is required to prevent siloing and loss of information. To this end, we developed the Experimental Data Connector (XDC). It captures experimental data and related metadata by encoding it in standard formats and storing the converted data in digital repositories. Experimental data is then uploaded to Flapjack and the metadata to SynBioHub in a consistent manner linking these repositories. This produces complete connected experimental datasets that are exchangeable. The information is captured using a single template Excel Workbook, which can be integrated into existing experimental workflow automation processes.TOC Graphic
Comparative transcriptome revealed potential genes related with drug resistance in Melanoma
Authors: Zhao Bei , Liu Yinghua , Tang Xuemei , Cheng Shi 
Published: December 2022

AbstractChemotherapy remains a relatively ineffective and unsatisfactory treatment because of drug resistance in melanoma (whether due to intrinsic resistance or the use of cytostatic drugs). In order to explore the genes and signaling pathways related to melanoma drug resistance, the study presented here obtained drug-resistant melanoma cell lines of A375 and M14 by gradually increasing the concentration of dacarbazine (DTIC), followed by comparative transcriptomics studies (RNA-seq) and real-time quantitative PCR (RT-qPCR) and Western Blotting validation. The results showed that after 8 months of continuous treatment, the IC50 values of A375 and M14 to DTIC were increased by more than 5 folds. Meanwhile, flow cytometry analysis found that drug-resistant melanoma cells have a significant ability to resist apoptosis induced by DTIC. Subsequently, RNA-seq revealed high expression ofSENP1and abnormal activation of the Hippo signaling pathway in drug-resistant cells. Finally, we found that compared with wild-type cells, the expressions ofSENP1andYAPwere both up-regulated in drug-resistant cells via RT-qPCR and Western Blotting. Roles of SENP1 in drug resistance was finally verified via its overexpression in normal A375 cell lines. Therefore, this paper infers that there is a positive correlation between the ubiquitin-specific protease SENP1 and the drug resistance of melanoma. Meanwhile, the up-regulation of its expression may lead to changes in the Hippo signaling pathway and increase the resistance of melanoma to DTIC.
Streptococcus pneumoniaere-emerges as a cause of community-acquired pneumonia, including frequent co-infection with SARS-CoV-2, in Germany, 2021
Authors: Ankert Juliane , Hagel Stefan , Schwarz Claudia , Pan Kaijie , Wang Liz , Eiff Christof von , Gessner Bradford D. , Theilacker Christian , Pletz Mathias W. 
Published: December 2022

AbstractBackgroundThe COVID-19 pandemic and the associated containment measures had a substantial impact on pathogens causing pneumonia in adults. The objective of this study was to determine the etiology of hospitalized community-acquired pneumonia (CAP) among adults in Germany in 2021, the second year of the COVID-19 pandemic.MethodsSince January 2021, this on-going, prospective, population-based surveillances study enrolled adult patients with clinically and radiographically confirmed CAP at three hospitals in Thuringia, Germany, serving a population of approximately 280,000. Urine samples were collected from patients and tested forS. pneumoniaeusing the pneumococcal urinary antigen test (PUAT, BinaxNOWS. pneumoniae) and the proprietary serotype-specific urinary antigen detection (UAD) assays. Nasopharyngeal swabs were tested for 10 respiratory viruses by PCR.ResultsA total of 797 patients were enrolled, of whom 760 were included in the analysis. The median age of patients with CAP was 67 years; in-hospital case-fatality rate was 8.4%. A respiratory pathogen was detected in 553 (72.8%) patients. The most common pathogen was SARS-CoV-2 (n=498, 68.2%), followed byS. pneumoniae(n=40, 6.4%). Serotypes contained in the 13-valent, 15-valent and 20-valent pneumococcal conjugate vaccine were detected in 42.5%, 45.0%, and 70.0% of the pneumococcal CAP cases. Between the first and second half of 2021, the proportion of CAP cases associated withS. pneumoniaeincreased from 1.1% to 5.6% in patients aged 18-59 years and from 2.5% to 12.4% in those aged ≥60 years; coinfection of SARS-CoV-2 andS. pneumoniaeamong COVID-19 patients increased from 0.7% (2/283 cases) to 6.0% (13/215) in patients aged ≥18 years, and from 1.0% (2/195) to 8.7% (11/127) in those aged ≥60 years.ConclusionIn Germany, the proportion of CAP cases associated withS. pneumoniaerebounded to a near-pandemic level in the second half of 2021 and many pneumococcal infections occurred in patients with COVID-19. Vaccination uptake against respiratory pathogens, includingS. pneumoniae, should be strengthened.
Clinical Characteristic of a Haitian Stroke Cohort and a scoping review of the literature of stroke among the Haitian population
Authors: Paul Axler Jean , Charles Jude Hassan , Gedner Gandhi Marius Edwitch , Roche Richardson , Andre Wislet , Saint Croix Garly Rushler , Perue Gillian Gordon 
Published: December 2022

AbstractBackgroundThere is staggering evidence of stroke care disparities in Low- and Middle-Income countries compared to developed countries. Haiti like those countries suffer from lack of resources for acute stroke management. To our knowledge, we conducted the first study reporting the epidemiological profile of the Haitian population presenting with stroke symptoms in the largest academic hospital of the nation.MethodsThis is an observational study conducted over a period of five months from April to August 2021 in the Internal Medicine Department of the State University Hospital of Haiti including 51 consecutive patients suspected to have acute stroke. Descriptive statistical analysis was conducted. A scoping review of the literature on Haitian population stroke was also conducted.ResultMore than 50% of our patients are in the age range [19-65] years, 96.1% are older than 35 years. Mean age at presentation was 61 years, predominantly female (64.74 %). Severe motor deficit was more prevalent 96 %, with presenting NIHSS of 12 on average. Only 15% of patients (8/51) had a CT scan during their hospitalization. The majority were delays with a median time to CT of 84 hours after symptoms onset. About 80% of those with complications took more than 24 hours to arrive at the hospital after the onset of symptoms. There was a significant association between the modified Rankin Score and the occurrence of complications (F=6.33; p=0.016). 11% of the patient had complications with a mortality rate of 3.9%. NIHSS score has a very highly significant association with the Glasgow score (p<0.001) where an inverse proportional correlation was measured (r=-0.7; p<0.001) and a proportional correlation with the Rankin prediction score (r=0.3, p=0.04).ConclusionStroke affect the most economically active portion of the Haitian population and there is a salient lack of equipped healthcare facilities and appropriate treatment for stroke management in Haiti. Urgent assistance in both personnel and infrastructural resources dedicated to stroke care is needed. Neurological assessment based on NIHSS and Rankin score should be systematic in stroke Evaluation.
Investigating social deprivation and comorbid mental health diagnosis as predictors of treatment access among patients with an opioid use disorder using substance use services: a prospective cohort study
Authors: Adams Emma A , Yang Justin C , O’Donnell Amy , Minot Sarah , Osborn David , Kirkbride James B 
Published: December 2022

ABSTRACTPurposeWe investigated the role of social deprivation and comorbid mental health diagnoses in predicting re-engagement with substance use services or contact with crisis and inpatient services for individuals with opioid use disorder in secondary mental health care in inner-city London.MethodsWe conducted a prospective cohort study which followed individuals diagnosed with a first episode of opioid use disorder who accessed substance use services between September 2015 and May 2020 for up to 12 months, using anonymised electronic health records. We employed Poisson regression and Cox proportional survival analyses to assess associations between exposures and outcomes.ResultsComorbid mental health diagnoses were associated with higher contact rates with crisis/inpatient services among people with opioid use disorder: incidence rate ratios (IRR) and 95% confidence intervals (CI) were 3.37 (2.11-5.53) for non-opioid substance use comorbidity, 7.02 (3.63-13.31) for a single comorbid mental health diagnosis, and 11.68 (7.53-18.71) for multiple comorbid mental health diagnoses. Social deprivation was not associated with contact rates with crisis/inpatient services. Similar patterns were found with time to first crisis/inpatient contact. Social deprivation and comorbid mental health diagnoses were not associated with re-engagement with substance use services.ConclusionComorbid substance and mental health difficulties amongst people who use opioids led to earlier and more frequent contact with crisis/inpatient services during the first 12 months of follow up. Given the common co-occurrence of mental health and substance use disorders among those who use opioids, a better understanding of their needs will ensure they are supported in their treatment journeys.
Genetic modifiers of rare variants in monogenic developmental disorder loci
Authors: Kingdom Rebecca , Beaumont Robin N. , Wood Andrew R. , Weedon Michael N. , Wright Caroline F. 
Published: December 2022

ABSTRACTRare damaging variants in a large number of genes are known to cause monogenic developmental disorders (DD), and have been shown to cause milder sub-clinical phenotypes in population cohorts. To investigate potential genetic modifiers, we identified individuals in UK Biobank with predicted deleterious variants in 599 autosomal dominant DD genes, and found that carrying multiple rare variants in these genes had an additive adverse effect on numerous cognitive and socio-economic traits, which could be partially counterbalanced by a higher educational attainment polygenic score (EA-PGS). Amongst rare DD variant carriers, those with a DD-related clinical diagnosis had a substantially lower EA-PGS and more severe phenotype than those without. Our results suggest that the overall burden of both rare and common variants can modify the expressivity of a phenotype, which may influence whether an individual reaches the threshold for clinical disease.
Invasive Mechanical Ventilation Duration Prediction using Survival Analysis
Authors: Kobara Yawo , Rodrigues Felipe F. , de Souza Camila P. E. , Wismer Megan 
Published: December 2022

AbstractInvasive mechanical ventilation is one of the leading life support machines in the intensive care unit (ICU). By identifying the predictors of ventilation time upon arrival, important information can be gathered to improve decisions regarding capacity planning.In this study, first-day ventilated patients’ ventilation time was analyzed using survival analysis. The probabilistic behaviour of ventilation time duration was analyzed and the predictors of ventilation time duration were determined based on available first-day covariates.A retrospective analysis of ICU ventilation time in Ontario was performed with data from ICU patients obtained from the Critical Care Information System (CCIS) in Ontario between July 2015 and December 2016. As part of the protocol for inclusion, a patient must have been connected to an invasive ventilator upon arrival to the ICU. Parametric survival methods were used to characterize ventilation time and to determine associated covariates. Parametric and non-parametric methods were used to determine predictors of ventilation duration for first-day ventilated patients.A total of 128,030 patients visited the ICUs between July 2015 and December 2016. 51,966 (40.59%) patients received invasive mechanical ventilation on arrival. Analysis of ventilation duration suggested that the log-normal distribution provided the best fit to ventilation time, whereas the log-logistic Accelerated Failure Time model best describes the association between the covariates and ventilation duration. ICU site, admission source, admission diagnosis, scheduled admission, scheduled surgery, referring physician, central venous line treatment, arterial line treatment, intracranial pressure monitor treatment, extra-corporeal membrane oxygen treatment, intraaortic balloon pump treatment, other interventions, age group, pre-ICU LOS, and MODS score were significant predictors of the ICU ventilation time.The results show substantial variability in ICU ventilation duration for different ICUs, patient’s demographics, and underlying conditions, and highlight mechanical ventilation as an important driver of ICU costs.The predictive performance of the proposed model showed that both the model and the data can be used to predict an individual patient’s ventilation time and to provide insight into predictors.
Human retina trades single-photon detection for high-fidelity contrast encoding
Authors: Kilpeläinen Markku , Westö Johan , Laihi Anton , Takeshita Daisuke , Rieke Fred , Ala-Laurila Petri 
Published: December 2022

SUMMARYWe lack a fundamental understanding of how the spike output of the retina enables human visual perception. Here we show that human vision at its ultimate sensitivity limit depends on the spike output of ON but not OFF parasol (magnocellular) ganglion cells. Surprisingly, nonlinear signal processing in the retinal ON pathway precludes perceptual detection of single photons in darkness, but enables quantal-resolution discrimination of differences in light intensity.