bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal acid-sensing ion channel 1a regulates neuron-to-glioma synapses
Authors: Park Gyeongah , Jin Zhen , Ge Qian , Pan Yuan , Du Jianyang 
Published: September 2023

ABSTRACTNeuronal activity promotes high-grade glioma progression via secreted proteins and neuron-to-glioma synapses, and glioma cells boost neuronal activity to further reinforce the malignant cycle. Whereas strong evidence supports that the activity of neuron-to-glioma synapses accelerates tumor progression, the molecular mechanisms that modulate the formation and function of neuron-to-glioma synapses remain largely unknown. Our recent findings suggest that a proton (H+) signaling pathway actively mediates neuron-to-glioma synaptic communications by activating neuronal acid-sensing ion channel 1a (Asic1a), a predominant H+receptor in the central nervous system (CNS). Supporting this idea, our preliminary data revealed that local acid puff on neurons in high-grade glioma-bearing brain slices induces postsynaptic currents of glioma cells. Stimulating Asic1a knockout (Asic1a-/-) neurons results in lower AMPA receptor-dependent excitatory postsynaptic currents (EPSCs) in glioma cells than stimulating wild-type (WT) neurons. Moreover, glioma-bearing Asic1a-/-mice exhibited reduced tumor size and survived longer than the glioma-bearing WT mice. Finally, pharmacologically targeting brain Asic1a inhibited high-grade glioma progression. In conclusion, our findings suggest that the neuronal H+-Asic1a axis plays a key role in regulating the neuron-glioma synapse. The outcomes of this study will greatly expand our understanding of how this deadly tumor integrates into the neuronal microenvironment.
The eyelid and pupil dynamics underlying stress levels in awake mice
Authors: Zeng Hang 
Published: September 2023

AbstractStress is a natural response of the body to perceived threats, and it can have both positive and negative effects on brain hemodynamics. Stress-induced changes in pupil and eyelid size/shape have been used as a biomarker in several fMRI studies. However, there were limited knowledges regarding changes in behavior of pupil and eyelid dynamics, particularly on animal models. In the present study, the pupil and eyelid dynamics were carefully investigated and characterized in a newly developed awake rodent fMRI protocol. Leveraging deep learning techniques, the mouse pupil and eyelid diameters were extracted and analyzed during different training and imaging phases in the present project. Our findings demonstrate a consistent downwards trend in pupil and eyelid dynamics under a meticulously designed training protocol, suggesting that the behaviors of the pupil and eyelid can be served as reliable indicators of stress levels and motion artifacts in awake fMRI studies. The current recording platform not only enables the facilitation of awake animal MRI studies but also highlights its potential applications to numerous other research areas, owing to the non-invasive nature and straightforward implementation.
A response playbook for early detection and population surveillance of new SARS-CoV-2 variants in a regional public health laboratory
Authors: Barbian Hannah J. , Kittner Alyse , Teran Richard , Bobrovska Sofiya , Qiu Xueting , English Kayla , Green Stefan J. , Ghinai Isaac , Pacilli Massimo , Hayden Mary K. 
Published: September 2023

AbstractBackgroundTimely genomic surveillance is required to inform public health responses to new SARS-CoV-2 variants. However, the processes involved in local genomic surveillance introduce inherent time constraints. The Regional Innovative Public Health Laboratory in Chicago developed and employed a genomic surveillance response playbook for the early detection and surveillance of emerging SARS-CoV-2 variants.MethodsThe playbook outlines modifications to sampling strategies, laboratory workflows, and communication processes based on the emerging variant’s predicted viral characteristics, observed public health impact in other jurisdictions and local community risk level. The playbook outlines procedures for implementing and reporting enhanced and accelerated genomic surveillance, including supplementing whole genome sequencing (WGS) with variant screening by quantitative PCR (qPCR).ResultsThe ability of the playbook to improve the response to an emerging variant was tested for SARS-CoV-2 Omicron BA.1. Increased submission of clinical remnant samples from local hospital laboratories enabled detection of a new variant at 1% prevalence with 95% confidence rather than 2% at baseline. Genotyping qPCR concurred with WGS lineage assignments in 99.9% of 1541 samples with results by both methods, and was more sensitive, providing lineage results in 90.4% of 1833 samples rather than 85.1% for WGS, while reducing the time to lineage result from 27 to 7 days.ConclusionsThe genomic surveillance response playbook provides a structured, stepwise, and data-driven approach to responding to emerging SARS-CoV-2 variants. These pre-defined processes can streamline workflows and expedite the detection and public health response to emerging variants. Based on the processes piloted during the Omicron BA.1 response, this method has been applied to subsequent Omicron subvariants and can be readily applied to future SARS-CoV-2 emerging variants and other public health surveillance activities.
Identification of Novel Genomic Loci for Anxiety and Extensive Genetic Overlap with Psychiatric Disorders
Authors: Tesfaye Markos , Jaholkowski Piotr , Shadrin Alexey A. , van der Meer Dennis , Hindley Guy F.L. , Holen Børge , Parker Nadine , Parekh Pravesh , Birkenæs Viktoria , Rahman Zillur , Bahrami Shahram , Kutrolli Gleda , Frei Oleksandr , Djurovic Srdjan , Dale Anders M. , Smeland Olav B. , O’Connell Kevin S. , Andreassen Ole A. 
Published: September 2023

AbstractBackgroundAnxiety disorders are prevalent and anxiety symptoms co-occur with many psychiatric disorders. We aimed to identify genomic risk loci associated with anxiety, characterize its genetic architecture, and genetic overlap with psychiatric disorders.MethodsWe used the GWAS of anxiety symptoms, schizophrenia, bipolar disorder, major depression, and attention deficit hyperactivity disorder (ADHD). We employed MiXeR and LAVA to characterize the genetic architecture and genetic overlap between the phenotypes. Conditional and conjunctional false discovery rate analyses were performed to boost the identification of genomic loci associated with anxiety and those shared with psychiatric disorders. Gene annotation and gene set analyses were conducted using OpenTargets and FUMA, respectively.ResultsAnxiety was polygenic with 12.9k estimated genetic risk variants and overlapped extensively with psychiatric disorders (4.1-11.4k variants). MiXeR and LAVA revealed predominantly positive genetic correlations between anxiety and psychiatric disorders. We identified 114 novel loci for anxiety by conditioning on the psychiatric disorders. We also identified loci shared between anxiety and major depression (n = 47), bipolar disorder (n = 33), schizophrenia (n = 71), and ADHD (n = 20). Genes annotated to anxiety loci exhibit enrichment for a broader range of biological pathways and differential tissue expression in more diverse tissues than those annotated to the shared loci.ConclusionsAnxiety is a highly polygenic phenotype with extensive genetic overlap with psychiatric disorders. These genetic overlaps enabled the identification of novel loci for anxiety. The shared genetic architecture may underlie the extensive cross-disorder comorbidity of anxiety, and the identified genetic loci implicate molecular pathways that may lead to potential drug targets.
Brain network changes after the first seizure: an insight into medication response?
Authors: Pedersen Mangor , Pardoe Heath R. , Mito Remika , Sethi Moksh , Vaughan David N. , Carney Patrick W. , Jackson Graeme D. 
Published: September 2023

AbstractAfter a first epileptic seizure, anti-seizure medications (ASM) can change the likelihood of having a further event. This prospective study aimed to quantify brain network changes associated with taking ASM monotherapy. We applied graph theoretical network analysis to longitudinal resting-state functional MRI (fMRI) data from 28 participants who had recently experienced their first seizure. Participants were imaged before and during long-term ASM therapy, with a mean inter-scan interval of 6.9 months. After commencing ASM, we observed an increase in the clustering coefficient and a decrease in network path length. Brain changes after ASM treatment were most prominent in the superior frontoparietal and inferior fronto-temporal regions. Participants with recurrent seizures display the most pronounced network changes after ASM treatment. This study shows changes in brain network function after ASM administration, particularly in participants with recurrent seizures. Larger studies that ideally include control cohorts are required to understand further the connection between ASM-related brain network changes and longer-term seizure status.
A One Health approach to pastoral (im)mobility, health, and disease: a qualitative participatory study in Plateau State, Nigeria
Authors: Braam Dorien Hanneke , Bolajoko Muhammad-Bashir , Hammer Charlotte Christiane 
Published: September 2023

Abstract/SummaryBackgroundIn Plateau State, pastoralism has historically been a cost effective and resilient economic system well-suited to the ecological context. However, changes in land use and conflict have increasingly changed patterns of mobility. Pastoralist movement is now often associated with zoonotic disease transmission, environmental degradation and conflict, increasingly resulting in forced sedentarisation. Rather than a direct outcome of population movement however, animal, human and zoonotic disease drivers are complex and influenced by a range of socio-economic and environmental factors. The interlinkages of (im)mobility and health requires better understanding of underlying vulnerabilities to disease, which we aim to address in this study.MethodsUsing a multisite case study methodology we investigated pastoralists’ animal and human health concerns and priorities in Plateau State, Nigeria. We deployed participatory tools, including open-ended Focus Group Discussions, transect walks, mapping exercises, calendars and matrices. Data were analysed using a One Health conceptual framework.ResultsWe interviewed 105 participants, from transhumance, migratory and sedentary households, dependent on livestock and small-scale crops. While transhumance was often preferred, participants had become sedentary as a result of insecurity, loss in livestock, and household characteristics. Humans and animals suffered from several endemic diseases, including zoonoses, however veterinary and human health services are only available in larger towns, and people mostly rely on community (animal) health workers and self-medication. Both transhumance and sedentary livestock keepers face challenges around forage grazing, regularly blocked by landowners, sometimes escalating into conflict.ConclusionsWhile conflict and changes in land use affected animal and human disease patterns, underlying political, social and economic risk factors were important determinants of health. There is a need for more inclusive, transdisciplinary, multilevel approaches to address animal and human disease, based on better contextualization of the challenges, through the participation of affected communities.ImpactsThis study uses participatory approaches to investigate the under researched area of mobility and zoonotic disease dynamics.We found that animal and human mobility may mitigate or exacerbate zoonotic disease risk, impacting conflict, in turn leading to forced migration.Conflict and crime related security challenges need to be addressed simultaneously with mitigating structural inequality, through increasing pastoral social and economic capital, increase access to grazing routes and water, secure land tenure arrangements, and the provision of (veterinary) public health to reduce zoonotic disease risks in the region.
Rural trauma team development amongst medical trainees and traffic law enforcement professionals in a low-income country: A protocol for a prospective multi-center interrupted time series of interventional training
Authors: Lule Herman , Mugerwa Michael , SSebuufu Robinson , Kyamanywa Patrick , Posti Jussi P. , Wilson Michael Lowery 
Published: September 2023

AbstractBackgroundRoad traffic injuries and their resulting mortality disproportionately affect rural communities in low-middle-income countries (LMICs) due to limited human and infrastructural resources for post-crash care. Evidence from high income countries show that trauma team development training could improve the efficiency, care, and outcome of injuries. A paucity of studies has evaluated the feasibility and applicability of this concept in resource constrained settings. The aim of this study protocol is to establish the feasibility of rural trauma team development and training in a cohort of medical trainees and traffic law enforcement professionals in Uganda.MethodsMuti-center interrupted time series of prospective interventional trainings, using the rural trauma team development course (RTTDC) model of the American College of Surgeons. A team of surgeon consultants will execute the training. A prospective cohort of participants will complete a before and after training validated trauma related multiple choice questionnaire (MCQ) during September 2019-November 2023. The difference in mean pre-post training percentage MCQ scores will be compared using ANOVA-test at 95% CI. Time series regression models will be used to test for autocorrelations in performance. Acceptability and relevance of the training will be assessed using 3- and 5-point Likert scales, respectively. All analyses will be performed using Stata 15.0. Ethical approval was obtained from Research and Ethics Committee of Mbarara University of Science and Technology (Ref: MUREC 1/7, 05/05-19) and Uganda National Council for Science and Technology (Ref: SS 5082) prior recruitment. Retrospective registration was accomplished with Research Registry (UIN: researchregistry9490).HighlightsInjury related mortality significantly impact LMICs.Rural trauma teams could improve the efficiency of injury care in LMICs.This study will assess the effect of rural trauma team development training, viewing medical trainees and traffic police as potential human resources for health.The results could inform the implementation of future trauma teams in rural settings.
Prioritizing Cardiovascular Disease-Associated Variants Altering NKX2-5 Binding through an Integrative Computational Approach
Authors: Peña-Martínez Edwin G. , Pomales-Matos Diego A. , Rivera-Madera Alejandro , Messon-Bird Jean L. , Medina-Feliciano Joshua G. , Sanabria-Alberto Leandro , Barreiro-Rosario Adriana C. , Rodriguez-Rios Jessica M. , Rodríguez-Martínez José A. 
Published: September 2023

AbstractCardiovascular diseases (CVDs) are the leading cause of death worldwide and are heavily influenced by genetic factors. Genome-wide association studies (GWAS) have mapped > 90% of CVD-associated variants within the non-coding genome, which can alter the function of regulatory proteins, like transcription factors (TFs). However, due to the overwhelming number of GWAS single nucleotide polymorphisms (SNPs) (>500,000), prioritizing variants for in vitro analysis remains challenging. In this work, we implemented a computational approach that considers support vector machine (SVM)-based TF binding site classification and cardiac expression quantitative trait loci (eQTL) analysis to identify and prioritize potential CVD-causing SNPs. We identified 1,535 CVD-associated SNPs that occur within human heart footprints/enhancers and 9,309 variants in linkage disequilibrium (LD) with differential gene expression profiles in cardiac tissue. Using hiPSC-CM ChIP-seq data from NKX2-5 and TBX5, two cardiac TFs essential for proper heart development, we trained a large-scale gapped k-mer SVM(LS-GKM-SVM) predictive model that can identify binding sites altered by CVD-associated SNPs. The computational predictive model was tested by scoring human heart footprints and enhancers in vitro through electrophoretic mobility shift assay (EMSA). Three variants (rs59310144, rs6715570, and rs61872084) were prioritized for in vitro validation based on their eQTL in cardiac tissue and LS-GKM-SVM prediction to alter NKX2-5 DNA binding. All three variants altered NKX2-5 DNA binding. In summary, we present a bioinformatic approach that considers tissue-specific eQTL analysis and SVM-based TF binding site classification to prioritize CVD-associated variants for in vitro experimental analysis.Graphical Abstract
Association of Common and Rare Variants with Alzheimer’s Disease in over 13,000 Diverse Individuals with Whole-Genome Sequencing from the Alzheimer’s Disease Sequencing Project
Authors: Lee Wan-Ping , Choi Seung Hoan , Shea Margaret G , Cheng Po-Liang , Dombroski Beth A , Pitsillides Achilleas N , Heard-Costa Nancy L , Wang Hui , Bulekova Katia , Kuzma Amanda B , Leung Yuk Yee , Farrell John J , Lin Honghuang , Naj Adam , Blue Elizabeth E , Nusetor Frederick , Wang Dongyu , Boerwinkle Eric , Bush William S , Zhang Xiaoling , De Jager Philip L , Dupuis Josée , Farrer Lindsay A , Fornage Myriam , Martin Eden , Pericak-Vance Margaret , Seshadri Sudha , Wijsman Ellen M , Wang Li-San , Schellenberg Gerard D , Destefano Anita L , Haines Jonathan L , Peloso Gina M 
Published: September 2023

AbstractAlzheimer’s Disease (AD) is a common disorder of the elderly that is both highly heritable and genetically heterogeneous. Here, we investigated the association between AD and both common variants and aggregates of rare coding and noncoding variants in 13,371 individuals of diverse ancestry with whole genome sequence (WGS) data. Pooled-population analyses identified genetic variants in or nearAPOE, BIN1, andLINC00320significantly associated with AD (p < 5×10-8). Population-specific analyses identified a haplotype on chromosome 14 includingPSEN1associated with AD in Hispanics, further supported by aggregate testing of rare coding and noncoding variants in this region. Finally, we observed suggestive associations (p < 5×10-5) of aggregates of rare coding rare variants inABCA7among non-Hispanic Whites (p=5.4×10-6), and rare noncoding variants in the promoter ofTOMM40distinct ofAPOEin pooled-population analyses (p=7.2×10-8). Complementary pooled-population and population-specific analyses offered unique insights into the genetic architecture of AD.
Maternal obesity shapes the B lymphocyte and antibody repertoires of human colostrum
Authors: Sánchez-Salguero Erick , Bonilla-Ruelas Diana , Alcorta-García Mario René , Lara-Diaz Víctor Javier , López-Villaseñor Claudia Nohemí , Brunck Marion E G 
Published: September 2023

ABSTRACTThe prevalence of obesity is rapidly increasing worldwide and its impact on future generations must be assessed. We recently showed that colostrum from mothers with obesity contained a significantly reduced B lymphocytes (CD19+) fraction. Here, in a subsequent transversal cohort study of 48 mothers, we exhaustively characterize the B lymphocytes subsets present in peripheral blood and colostrum from obese mothers and describe a pervasive alteration of the B lymphocytes compartment of human colostrum accompanied by a dysregulated antibody composition. We describe significant decreases in regulatory B cells and soluble IgA concentrations, combined with increases in soluble IgG and double negative 2 (CD19+, CD27-, IgD-, CD38-, CD24-, CD21-, CD11c+) B lymphocytes. These alterations correlated with maternal BMI and corporal fat %. We provide evidence for possibly autoimmune IgG present in obese colostrum, and for the proinflammatory consequences of obese colostrumin vitro. Beyond the impact of obesity, we evidence the selective presence of B lymphocyte subtypes in colostrum andin situproduction of IgG antibodies, which expands our current understanding of the origin of colostrum IgG. As maternal milk antibodies play a crucial role in regulating neonatal gut immune development, this work uncovers maternal obesity as a potential risk factor for compromised breastmilk immune components, calling for more research on the long-term health of lactating infants.
Development and validation of nomograms for predicting the prognosis of early and late recurrence of advanced gastric cancer after radical surgery
Authors: Liu Chenming , Lu Jialiang , An Liang 
Published: September 2023

AbstractObjectiveIn this study, we aimed to explore the risk factors influencing post recurrence survival (PRS) of early recurrence (ER) and late recurrence (LR) in stage advanced gastric cancer (AGC) patients after radical surgery, respectively, and to develop predictive models in turn.MethodsMedical records of 192 AGC patients who recurred after radical gastrectomy were retrospectively reviewed. They were randomly divided into the training and validation set at a ratio of 2:1. Nomograms were built based on risk factors influencing PRS of ER and LR explored by Cox regression analyses, respectively. Concordance index (C-index) values and calibration curves were used to evaluate predictive power of nomograms.ResultsBody mass index < 18.5 kg/m2, prealbumin level < 70.1 mg/l, positive lymph nodes ratio ≥ 0.486 and palliative treatment after recurrence were independent risk factors for the prognosis of ER. In contrast, prealbumin level < 170.1 mg/l, CEA ≥ 18.32 μg/l, tumor diameter ≥ 5.5 cm and palliative treatment after recurrence were independent risk factors for the prognosis of LR. The C-index value was 0.801 and 0.772 for ER and LR in the training set, respectively. The calibration curves of validation set showed a C-index value of 0.744 and 0.676 for ER and LR, respectively.ConclusionsNomograms which were constructed to predict the prognosis of ER and LR of AGC after surgery showed great predictive power and could provide reference for clinicians’ treatment strategies to some extent.