bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot study to identify blood-based markers associated with response to treatment with Vedolizumab in patients with Inflammatory Bowel Disease
Authors: Rioux John D. , Boucher Gabrielle , Forest Anik , Bouchard Bertrand , Coderre Lise , Daneault Caroline , Frayne Isabelle Robillard , Legault Julie Thompson , Consortium iGenoMed , Bitton Alain , Ananthakrishnan Ashwin , Lesage Sylvie , Xavier Ramnik J. , Rosiers Christine Des 
Published: September 2024

ABSTRACTThe inflammatory bowel diseases (IBD) known as Crohn’s disease (CD) and ulcerative colitis (UC) are chronic inflammatory diseases of the gastrointestinal tract believed to arise because of an imbalance between the epithelial, immune and microbial systems. It has been shown that biological differences (genetic, epigenetic, microbial, environmental, etc.) exist between patients with IBD, with multiple risk factors been associated with disease susceptibility and IBD-related phenotypes (e.g. disease location). It is also known that there is heterogeneity in terms of response to therapy in patients with IBD, including to biological therapies that target very specific biological pathways (e.g. TNF-alpha signaling, IL-23R signaling, immune cell trafficking, etc.). It is hypothesized that the better the match between the biology targeted by these advanced therapies and the predominant disease-associated pathways at play in each patient will favor a beneficial response. The aim of this pilot study was to identify potential biological differences associated with differential treatment response to the anti α4β7 integrin therapy known as Vedolizumab. Our approach was to measure a broad range of analytes in the serum of patients prior to initiation of therapy and at the first clinical assessment visit, to identify potential markers of biological differences between patients at baseline and to see which biomarkers are most affected by treatment in responders. Our focus on early clinical response was to study the most proximal effects of therapy and to minimize confounders such as loss of response that occurs further distal to treatment initiation. Specifically, we performed targeted analyses of >150 proteins and metabolites, and untargeted analyses of >1100 lipid entities, in serum samples from 92 IBD patients (42 CD, 50 UC) immediately prior to initiation of therapy with vedolizumab (baseline samples) and at their first clinical assessment (14-week samples). We found lower levels of SDF-1a, but higher levels of PDGF-ββ, lactate, lysine, phenylalanine, branched chain amino acids, alanine, short/medium chain acylcarnitines, and triglycerides containing myristic acid in baseline serum samples of responders as compared to non-responders. We also observed an increase in serum levels of CXCL9 and citrate, as well as a decrease in IL-10, between baseline and week 14 samples. In addition, we observed that a group of metabolites and protein analytes was strongly associated with both treatment response and BMI status, although BMI status was not associated with treatment response.
AlphaFold2 and AlphaFold3 leads to significantly different results in human-parasite interaction prediction
Authors: Ozden Burcu , Cuesta-Astroz Yesid , Karaca Ezgi 
Published: September 2024

AbstractParasitic diseases pose a significant global health challenge with substantial socioeconomic impact, especially in developing countries. Combatting these diseases is difficult due to two factors: the resistance developed by parasites to existing drugs and the underfunded research efforts to resolve host-parasite interactions. To address the latter, we focused on 276 human-parasite interaction predictions involving 15 parasitic species known to cause infections in humans. We aimed to validate these interactions by using AlphaFold2-Multimer v2.2 (AF2) and AlphaFold3 (AF3) modeling. Overall, our findings show that, in the context of human-parasite interactions, AF2 and AF3 produce distinct models and score distributions, with no significant correlation between their top-ranked predictions. We recognize that predicting host-parasite interactions is particularly challenging due to the absence of typical coevolutionary signals. Nevertheless, the differences in scores and models between AF2 and AF3 are striking and warrant further investigation, which could only be performed upon the release of AF3.
High-risk neuropsychiatric copy number variants are associated with convergent transcriptomic changes in human brain cells
Authors: Dugan Gabi , Akula Nirmala , Marenco Stefano , Auluck Pavan K , Raznahan Armin , Liu Siyuan , DeCasien Alex , Xu Qing , Feng Ningping , Kolachana Bhaskar , Jiang Xueying , Gregory Michael D , Berman Karen F , Hoffman Gabriel , Roussos Panos , McMahon Francis J , Schulmann Anton 
Published: September 2024

AbstractLarge, recurrent copy number variants (CNVs) are among the strongest risk factors for neuropsychiatric conditions, contributing to multiple phenotypes with overlapping psychiatric and cognitive symptoms. However, the molecular basis of this convergent risk remains unknown. We evaluated the human brain transcriptome in carriers of nine high-risk neuropsychiatric CNVs and matched non-carriers using single nucleus RNA-sequencing. Brain tissue from carriers displayed widespread disruptions of gene expression, with deletions showing greater changes than the reciprocal duplications. Functional enrichment analysis revealed changes in mitochondrial energy metabolism and synaptic function that converged across CNVs and cell types. For mirror CNVs, the direction of effects was often reversed between deletions and duplications and showed correlation with CNV gene dosage. These findings suggest that a shared pathophysiology underlies risk for convergent brain phenotypes across CNVs and point toward promising therapeutic targets.
Resolving out of Africa event for Papua New Guinean population using neural network
Authors: Mondal Mayukh , André Mathilde , Pathak Ajai K. , Brucato Nicolas , Ricaut François-Xavier , Metspalu Mait , Eriksson Anders 
Published: September 2024

AbstractThe demographic history of the Papua New Guinean population is a subject of significant interest due to its early settlement in New Guinea, at least 50 thousand years ago, and its relative isolation compared to other out of Africa populations. This isolation, combined with substantial Denisovan ancestry, contributes to the unique genetic makeup of the Papua New Guinean population. Previous research suggested the possibility of admixture with an early diverged modern human population, but the extent of this contribution remains debated. This study re-examines the demographic history of the Papua New Guinean population using newly published samples and advanced analytical methods. Our findings demonstrate that the observed shifts in relative cross coalescent rate curves are unlikely to result from technical artefacts or contributions from an earlier out of Africa population. Instead, they are likely due to a significant bottleneck and slower population growth rate within the Papua New Guinean population. Our analysis positions the Papua New Guinean population as a sister group to other Asian populations, challenging the notion of Papua New Guinean as an outgroup to both European and Asian populations. This study provides new insights into the complex demographic history of the Papua New Guinean population and underscores the importance of considering population-specific demographic events in interpreting relative cross coalescent rate curves.
Mapping snoRNA-target RNA interactions in an RNA binding protein-dependent manner with chimeric eCLIP
Authors: Song Zhuoyi , Bae Bongmin , Schnabl Simon , Yuan Fei , Zoysa Thareendra De , Akinyi Maureen , Roux Charlotte Le , Choquet Karine , Whipple Amanda , Nostrand Eric Van 
Published: September 2024

AbstractSmall nucleolar RNAs (snoRNAs) are non-coding RNAs that function in ribosome and spliceosome biogenesis, primarily by guiding modifying enzymes to specific sites on ribosomal RNA (rRNA) and spliceosomal RNA (snRNA). However, many orphan snoRNAs remain uncharacterized, with unidentified or unvalidated targets, and studies on additional snoRNA-associated proteins are limited. We adapted an enhanced chimeric eCLIP approach to comprehensively profile snoRNA-target RNA interactions using both core and accessory snoRNA binding proteins as baits. Using core snoRNA binding proteins, we confirmed most annotated snoRNA-rRNA and snoRNA-snRNA interactions in mouse and human cell lines and called novel, high-confidence interactions for orphan snoRNAs. While some of these interactions result in chemical modification, others may have modification-independent functions. We then showed that snoRNA ribonucleoprotein complexes containing certain accessory proteins, like WDR43 and NOLC1, enriched for specific subsets of snoRNA-target RNA interactions with distinct roles in ribosome and spliceosome biogenesis. Notably, we discovered that SNORD89 guides 2’-O-methylation at two neighboring sites in U2 snRNA that are important for activating splicing, but also appear to ensure imperfect splicing for a subset of near-constitutive exons. Thus, chimeric eCLIP of snoRNA-associating proteins enables a comprehensive framework for studying snoRNA-target interactions in an RNA binding protein-dependent manner, revealing novel interactions and regulatory roles in RNA biogenesis.
Inferring demographic and selective histories from population genomic data using a two-step approach in species with coding-sparse genomes: an application to human data
Authors: Soni Vivak , Jensen Jeffrey D. 
Published: September 2024

AbstractThe demographic history of a population, and the distribution of fitness effects (DFE) of newly arising mutations in functional genomic regions, are fundamental factors dictating both genetic variation and evolutionary trajectories. Although both demographic and DFE inference has been performed extensively in humans, these approaches have generally either been limited to simple demographic models involving a single population, or, where a complex population history has been inferred, without accounting for the potentially confounding effects of selection at linked sites. Taking advantage of the coding-sparse nature of the genome, we propose a 2-step approach in which coalescent simulations are first used to infer a complex multi-population demographic model, utilizing large non-functional regions that are likely free from the effects of background selection. We then use forward-in-time simulations to perform DFE inference in functional regions, conditional on the complex demography inferred and utilizing expected background selection effects in the estimation procedure. Throughout, recombination and mutation rate maps were used to account for the underlying empirical rate heterogeneity across the human genome. Importantly, within this framework it is possible to utilize and fit multiple aspects of the data, and this inference scheme represents a generalized approach for such large-scale inference in species with coding-sparse genomes.
Metabolic Outcomes in Non-Alcoholic and Alcoholic Steatotic Liver Disease in among Korean and Adults: A Population-Based Multi-Cohort Study
Authors: Kim Yeongmin , Lee Taesic , Oh Chang-Myung 
Published: September 2024

ABSTRACTBackground and aimsThis study investigated the prevalence and causal relationships of chronic metabolic diseases (diabetes, hypertension, and dyslipidemia) with steatotic liver disease (SLD), specifically metabolically associated alcoholic liver disease (MetALD).MethodsWe conducted a comprehensive analysis using cross-sectional data from the Korea National Health and Nutrition Examination Survey (KNHANES) from 2011 to 2021 and the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2020. Longitudinal data from 2001 to 2014 from the Korean Genome and Epidemiology Study (KoGES) were used. Participants were categorized into the metabolic dysfunction-associated SLD (MASLD), MetALD, and ALD groups based on their hepatic steatosis index (HSI) and alcohol consumption. Logistic and Cox regression analyses were performed to assess the prevalence and incidence of chronic diseases.ResultsIn both the KNHANES and NHANES cohorts, an increased HSI was significantly associated with a higher prevalence of chronic metabolic diseases. Longitudinal data from the KoGES cohort showed that MASLD and MetALD were significant predictors of chronic metabolic disease in both men and women. MetALD showed a higher hazard ratio for the development of chronic metabolic diseases than MASLD in Cox regression analysis.ConclusionThis study highlighted the intertwined nature of SLD and metabolic health, with an emphasis on the role of MetALD. The significant association between MetALD and chronic metabolic diseases underscores the need for integrated management strategies that address both liver health and metabolic risk factors.
Outcome Dimensions and Measurement Approaches for Evaluating the Impact of China’s Family Doctor Contract Services: A Scoping Review Protocol
Authors: Wang Yang , Jin Hua , Yu Dehua 
Published: September 2024

AbstractBackgroundFamily doctor contract services in mainland China are designed to foster long-term relationships between family doctors and contracted residents, promoting the delivery of primary care services through teamwork and collaboration. By 2035, it is expected that the coverage of these services will exceed 75%, making it a key model for primary care in China. However, the outcome dimensions and measurement approaches used to evaluate the effectiveness of these services remain fragmented and lack a comprehensive framework. This scoping review aims to systematically investigate the outcome dimensions and measurement approaches previously used to evaluate the effectiveness of family doctor contract services in mainland China.MethodsThis scoping review will be conducted in accordance with the JBI methodology for scoping reviews. We will search electronic databases, including CNKI, Wanfang, PubMed, the Cochrane Database of Systematic Reviews, JBI Evidence Synthesis, PROSPERO, and Google Scholar, for literature published since 2006. Eligible sources will include policy documents, quantitative studies, and qualitative studies that assess the outcomes of family doctor contract services. Data extraction will focus on the outcome dimensions and measurement approaches used in these evaluations. Two independent reviewers will screen and extract data from the literature, and any discrepancies will be resolved through group discussions with a third reviewer. Descriptive statistics will be used to analyze the extracted data, and the results will be presented through tables, charts, and a hierarchical tree diagram of outcome dimensions and measurement tools.DiscussionThis scoping review will provide a comprehensive overview of the outcome dimensions and measurement approaches used to evaluate family doctor contract services in mainland China. It will help to identify gaps in the existing literature and offer a clearer framework for future evaluations of these services. By mapping out the outcome dimensions and tools, this review aims to contribute to improving the quality and effectiveness of family doctor contract services in China. The findings will be particularly valuable for policymakers and researchers focused on enhancing primary care systems.Systematic review registrationRegistered in OSF on September 20, 2024 (osf.io/z3eju)
Seroprevalence of teratogenic viruses among women of childbearing age in Botswana
Authors: Gobe I. , Baipoledi K. , Skwenje G. , Ntamo M. , Motswaledi M. 
Published: September 2024

AbstractBackgroundTeratogenic viruses are viruses than can cross the placenta and infect a growing foetus, resulting in malformations and birth defects. Some of the commonly known teratogenic viruses include cytomegalovirus (CMV), rubella, herpes simplex and varicella zoster (VZV) viruses. Most birth defects associated with these infections affect the central nervous system and sensory organs leading to symptoms that include mental retardation, hearing loss and blindness. The economic burden caused by congenital birth defects is high, as many affected children require special care, therapeutic and educational services. Despite the risk posed by teratogenic viruses during pregnancy, there is no national screening for active CMV, Rubella or VZV infection during pregnancy in Botswana and most African countries. Furthermore, data on the seroprevalence of these viruses among women of childbearing age is limited.Methods and settingThis cross-section study used eighty-nine (89) residual plasma samples from Scottish Livingstone Hospital Laboratory in Molepolole-Botswana. Samples were from women between the ages 15-49 years. Samples were tested for antibodies against rubella, VZV and CMV using enzyme linked immunosorbent assay.ResultsOur results show a high seroprevalence of rubella IgG antibodies (97%), even though a small proportion (3%) of women are still susceptible. There was also a high seroprevalence of CMV IgG (100%) which was accompanied by an equally high CMV IgM of 98%. Seroprevalence of VZV IgG was low (63%) and 3% of the samples showed active VZV infection.ConclusionsTeratogenic viruses are a concern in the population. This calls for preventative measures which include prompt screening and vaccination of susceptible eligible women to prevent congenital abnormalities in children.
Wastewater surveillance overcomes socio-economic limitations of laboratory-based surveillance when monitoring disease transmission: the South African experience during the COVID-19 pandemic
Authors: Maree Gillian , Els Fiona , Naidoo Yashena , Naidoo Laven , Mahamuza Phemelo , Macheke Mokgaetji , Ndlovu Nkosenhle , Rachida Said , Iwu-Jaja Chinwe , Taukobong Setshaba , Maposa Sibonginkosi , O’Reilly Kathleen , Yousif Mukhlid , McCarthy Kerrigan 
Published: September 2024

AbstractWastewater and environmental surveillance has been promoted as a communicable disease surveillance tool because it overcomes inherent biases in laboratory-based communicable disease surveillance. Yet, little empirical evidence exists to support this notion, and it remains largely an intuitive, though highly plausible hypothesis. Our interdisciplinary uses WES data to show evidence for underreporting of SARS-CoV-2 in the context of measurable and statistically significant associations between economic conditions and SARS-CoV-2 incidence and testing rates. We obtained geolocated, anonymised, laboratory-confirmed SARS-CoV-2 cases, wastewater SARS-CoV-2 viral load data and socio-demographic data for Gauteng Province, South Africa. We spatially located all data to create a single dataset for sewershed catchments served by two large wastewater treatment plants. We conducted epidemiological, persons infected and principal component analysis to explore the relationships between variables. Overall, we demonstrate the co-contributory influences of socio-economic indicators on access to SARS-CoV-2 testing and cumulative incidence, thus reflecting that apparent incidence rates mirror access to testing and socioeconomic considerations rather than true disease epidemiology. These analyses demonstrate how WES provides valuable information to contextualise and interpret laboratory-based epidemiological data. Whilst it is useful to have these associations established for SARS-CoV-2, the implications beyond SARS-CoV-2 are legion for two reasons, namely that biases inherent in clinical surveillance are broadly applicable across pathogens and all pathogens infecting humans will find their way into wastewater albeit in varying quantities. WES should be implemented to strengthen surveillance systems, especially where economic inequalities limit interpretability of conventional surveillance data.
Allosteric mechanism of membrane fusion activation in a herpesvirus
Authors: González-Del Pino Gonzalo L. , Walsh Richard M. , Atanasiu Doina , Cairns Tina M. , Saw Wan Ting , Cohen Gary H. , Heldwein Ekaterina E. 
Published: September 2024

ABSTRACT/SUMMARYHerpesviridaeinfect nearly all humans for life, causing diseases that range from painful to life-threatening1. These viruses penetrate cells by employing a complex apparatus composed of separate receptor-binding, signal-transmitting, and membrane-fusing components2. But how these components coordinate their functions is unknown. Here, we determined the 4.19-angstrom cryoEM reconstruction of the central signal-transmitting component from herpes simplex virus 2, the gH/gL complex, in its elusive pre-activation state. Analysis of the continuum of conformational ensembles observed in cryoEM data revealed a series of structural rearrangements in gH/gL that allosterically transmit the fusion-triggering signal from the receptor-binding glycoprotein gD to the membrane fusogen gB. Furthermore, we identified a structural “switch” element in gH/gL that refolds and flips 180 degrees during the transition from pre-activation to activated form. Conservation of this “switch” in gH/gL homologs suggests that the proposed fusion triggering mechanism may apply to allHerpesviridaeand points to a new target for subunit-based vaccines and treatment efforts.
Lower limb pointing to assess intersegmental dynamics after incomplete spinal cord injury and the associated role of proprioceptive impairments
Authors: Malik Raza N. , Marigold Daniel S. , Chow Mason , Eginyan Gevorg , Lam Tania 
Published: September 2024

ABSTRACTBackgroundDisorders in the recovery of gait strategies in individuals with incomplete spinal cord injury (SCI) suggest difficulties in controlling lower limb intersegmental dynamics, which could relate to proprioceptive impairments. To probe discrete aspects of lower limb interjoint coordination, we present here a novel protocol to assess lower limb motor strategies and evaluate the influence of proprioceptive impairments following SCI.MethodsTwelve able-bodied controls and 16 participants with SCI performed lower limb pointing to three targets that involved combined hip and knee flexion, or hip or knee flexion only while standing, with either full or obstructed visual feedback. We quantified lower limb proprioceptive sense in individuals with SCI using a robotic gait device. We used motion analysis to determine lower limb joint angles and foot trajectory, computed inverse dynamics to quantify joint and intersegmental dynamics, and derived muscle torque as an indicator of the motor strategies produced to control the motion to each target. We used linear mixed-effects models to assess differences between the control and SCI groups on end-point performance and muscle torque, and to assess the relationship of muscle torque with end-point performance and proprioceptive sense.ResultsGroups differed in motor strategies, but not end-point performance, when pointing to all three targets. Compared to controls, the SCI group had difficulty controlling knee muscle torque when performing the hip-flexion-only target (p = 0.008) or when flexing the hip and knee simultaneously (p = 0.0004). To complete the knee-flexion-only target, the SCI group had difficulties generating the required hip extensor muscle torque to maintain the thigh in neutral (p = 0.0001). These altered motor strategies in individuals with SCI were associated with proprioceptive impairments and end-point performance.ConclusionThis novel lower limb pointing task can identify disordered motor strategies in individuals with SCI, especially at the knee, and are associated with proprioceptive impairment. Variations of this paradigm can be employed to further understand differences in motor strategies between controls and individuals with SCI, and the impact of proprioceptive deficits.