bluuebunny/crossref_metadata_2025_split huggingface dataset:
Loss of neuronal Imp induces seizure behavior through Syndecan function
Authors: Roy Paula R. , Link Nichole 
Published: November 2024

ABSTRACTSeizures affect a large proportion of the global population and occur due to abnormal neuronal activity in the brain. Unfortunately, widespread genetic and phenotypic heterogeneity contribute to insufficient treatment options. It is critical to identify the genetic underpinnings of how seizures occur to better understand seizure disorders and improve therapeutic development. We used theDrosophilamodel to identify that IGF-II mRNA Binding Protein (Imp) is linked to the onset of this phenotype. Specific reduction of Imp in neurons causes seizures after mechanical stimulation. Importantly, gross motor behavior is unaffected, showing Imp loss does not affect general neuronal activity. Developmental loss of Imp is sufficient to cause seizures in adults, thus Imp-modulated neuron development affects mature neuronal function. Since Imp is an RNA-binding protein, we sought to identify the mRNA target that Imp regulates in neurons to ensure proper neuronal activity after mechanical stress. We find that Imp protein bindsSyndecan(Sdc) mRNA, and reduction of Sdc also causes mechanically-induced seizures. Expression of Sdc inImpdeficient neurons rescues seizure defects, showing that Sdc is sufficient to restore normal behavior after mechanical stress. We suggest that Imp protein bindsSdcmRNA in neurons, and this functional interaction is important for normal neuronal biology and animal behavior in a mechanically-induced seizure model. Since Imp and Sdc are conserved, our work highlights a neuronal specific pathway that might contribute to seizure disorder when mutated in humans.
Distinct immune responses to HIV and CMV in Hofbauer cells across gestation highlight evolving placental immune dynamics
Authors: Schuch Viviane , Hossack Daniel , Hailstorks Tiffany , Chakraborty Rana , Johnson Erica L. 
Published: November 2024

AbstractPlacental immune responses to Human Immunodeficiency Virus (HIV) and Human Cytomegalovirus (CMV) vary across gestational stages and may influence postnatal outcomes. This study investigates the innate immunity of Hofbauer cells from placentae obtained at early/mid-gestation (18–21.6 weeks) and term (>37 weeks). RNA sequencing and cytokine profiling reveal that early/mid-gestation HCs exhibit heightened differential gene expression responses compared to term HCs, indicating a distinct transcriptional activity in early pregnancy. Significant overlap in gene expression profiles of early/mid-gestation cells in response to CMV and HIV suggest similar innate immune responses, while term cells exhibit distinct patterns, reflecting the temporal evolution of placental immunity. Integration with Human Protein Atlas database reveals more placental-specific differentially expressed genes in early/mid-gestation HCs exposed to HIV and CMV compared to term cells. Functional analysis reveals downregulation of pathways related to oxygen stress, estrogen response, and KRAS signaling pathway in early/mid-gestation HCs, with HIV uniquely upregulating reactive oxygen species and CMV uniquely disrupting WNT β-Catenin signaling. In term HCs, CMV exposure upregulates antiviral interferon (IFN) signaling and inflammatory pathways. Co-expression analysis highlights distinct molecular pathway enrichments across gestation, particularly with upregulation of IFN signaling and disruption of lipid metabolism in term CMV-exposed HCs. Cytokine profiling shows enhanced expression of GM-CSF, IFN-γ, and Th2-associated cytokines in early/mid-gestation HCs, indicating heightened immune responsiveness. These findings reveal the dynamic nature of placental immunity and underscore the need for targeted interventions to address unique immune and metabolic disruptions caused by viral infections at distinct stages of pregnancy to improve fetal and infant health outcomes.
Variable phylosymbiosis and cophylogeny patterns in wild fish gut microbiota of a large subtropical river
Authors: Liu Yaqiu , Liu Xinhui , Kormas Konstantinos Ar. , Li Yuefei , Li Huifeng , Li Jie 
Published: November 2024

AbstractThe persistence and specificity of fish host-microbial interaction during evolution is an important part of exploring the host-microbial symbiosis mechanism. However, it remains unclear how the environmental and host factors shape fish host-microbe symbiotic relationship in subtropical rivers with complex natural environments. Freshwater fish are important consumers in rivers and lakes and considered keystone species in maintaining the stability of food webs there. In this study, patterns and mechanisms shaping gut microbiota community in 42 fish species from the Pearl River, in the subtropical zone of China were investigated. The results showed that fish host specificity is key driver of gut microbiota evolution and diversification. Different taxonomic levels of host showed different degrees of contribution in gut microbiota variation. Geographical location and habitat type were the next most important factors in shaping gut microbiota across the 42 fishes, followed by diet and gut trait. Our results emphasized the contribution of stochastic processes (drift and homogenizing dispersal) in the gut microbial community assembly of freshwater fishes in the middle and lower reach of the Pearl River. Phylosymbiosis is evident at both global and local levels, which are jointly shaped by complex factors including ecological or host physiological filtration and evolutionary process. The core microbiota showed co-evolutionary relationships of varying degrees with different taxonomic groups. We speculate that host genetic isolation or habitat variation facilitate the heterogeneous selection (deterministic process), which occurs and results in different host-core bacterium specificity.
Characterizing 3D RNA structural features from DMS reactivity
Authors: Sanduni Deenalattha D. H. , Jurich Chris P. , Lange Bret , Armstrong Darren , Nein Kaitlyn , Yesselman Joseph D. 
Published: November 2024

AbstractDimethyl sulfate (DMS) chemical mapping probes RNA structure, where low reactivity is generally interpreted as Watson-Crick (WC) base pairs and high reactivity as unpaired nucleotides. Studies examining DMS reactivity of RNAs with known 3D structures have identified nucleotides that deviate from this interpretation with distinct solvent accessibility and hydrogen bonding patterns. Understanding the frequency of these outliers and their recurring structural 3D features remains incomplete. To address this knowledge gap, we systematically analyzed DMS reactivity patterns across a library of 7,500 RNA constructs containing two-way junctions with known 3D structures. We observe DMS reactivity exists on a continuum over four orders of magnitude with approximately 10% overlap in reactivity between WC and non-WC nucleotides. We find that non-WC bases with WC-like DMS protection exhibit increased hydrogen bonding and decreased solvent accessibility, whereas WC pairs exhibiting greater DMS reactivity tend to flank junctions, correlating with weaker base stacking and greater junction dynamics. Furthermore, we discover that DMS reactivity values in non-canonical pairs correlate with atomic distances and base pair geometry, enabling discrimination between different 3D conformations. These DMS reactivity patterns indicate that DMS reactivity provides atomic-scale information about RNA 3D conformations, which can be used to model RNA structures and dynamics.
HiC2Self: self-supervised denoising for bulk and single-cell Hi-C contact maps
Authors: Yang Rui , Karbalayghareh Alireza , Leslie Christina S. 
Published: November 2024

AbstractHi-C is a chromosome conformation capture assay used to study 3D genome organization. The recent development of single-cell Hi-C technologies has further enabled the examination of 3D chromatin organization in individual cells, although these approaches often suffer from low-coverage libraries and data sparsity. Here we introduce HiC2Self, a self-supervised framework for denoising Hi-C contact maps that requires only low-coverage data as input. HiC2Self not only reconstructs key structures (such as TADs and significant loops) from bulk libraries, but its self-supervised training framework also allows it to easily reconstruct cell-type-specific Hi-C structures without the generalization challenges faced by supervised models. HiC2Self can also accurately reconstruct significant loops from Micro-C data at 1 kb resolution. Moreover, when applied to single-nucleus methyl-3C data, HiC2Self successfully reconstructs local TAD structures around specific genes at 10 kb resolution with as few as 50 cells. Finally, HiC2Self enables the examination of single-cell structures at 50 kb resolution in individual cells of the same cell type. HiC2Self thus provides a general tool for denoising bulk, pseudo-bulk, and single-cell 3D contact maps to enable downstream analyses.
Group 2 and 3 ABC-transporter dependant capsular K-loci contribute significantly to variation in the invasive potential ofEscherichia coli
Authors: Gladstone Rebecca A. , Pesonen Maiju , Pöntinen Anna K. , Mäklin Tommi , MacAlasdair Neil , Thorpe Harry , Shao Yan , Mallawaarachchi Sudaraka , Arredondo-Alonso Sergio , Parcell Benjamin J. , Turnbull Jake David , Tonkin-hill Gerry , Johnsen Pål J. , Samuelsen Ørjan , Thomson Nicholas R. , Lawley Trevor , Corander Jukka 
Published: November 2024

AbstractThe major opportunistic pathogenEscherichia coliis the largest cause of antimicrobial resistance (AMR) associated infections and deaths globally. Considerable antigenic diversity has been documented in Extra-intestinal pathogenicE. coli(ExPEC). Still, the need for systematic genomic surveys of asymptomatic colonisation and invasive disease has precluded the quantification of K-type invasive potential across different ExPEC lineages. We assembled and curated anin-silicocapsular typing database for group 2 and group 3 K-loci from >20,000 genomes and applied it to paired carriage and disease cohorts to investigate K-type epidemiology. The most virulent circulating capsules have estimated odds ratios of >10 for being found in bloodstream infections versus carriage. The invasive potential differed markedly between lineages, and subclades of the global multi-drug resistant ST131, which displayed limited O and H antigens but substantial K-type diversity. We also discovered that insertion sequence elements contribute to the evolutionary dynamics of group 2 and group 3 K-loci by importing new capsular genes. Furthermore, the level of capsule diversity was positively correlated with more recombinogenic lineages that could adapt their antigenic repertoire faster. Our investigation highlights several K-types and lineages that contribute disproportionately to invasive ExPEC disease, which are associated with high levels of AMR. These results have significant translational potential, including improved ExPEC diagnostics, personalised therapy options, and the ability to build predictive regional risk maps by combining genomic surveys with demographic and patient frailty data.
Disparities in Anti-emetic Prophylaxis Care Processes are Predicted by Patient Neighborhood: A Retrospective Cohort and Geospatial Analysis
Authors: Han Jiuying , Wan Neng , Jacobson Cameron K. , Pace Nathan L. , Kartchner Cade K. , Hohl Alexander S. , Schonberger Robert B. , Colquhoun Douglas A. , Dutton Richard P. , Andreae Michael H. , Pearson John F. 
Published: November 2024

AbstractBackgroundSocial Determinants of Health (SDoH) continue to drive persistent disparities in perioperative care. Our team has previously demonstrated racial and socioeconomic disparities in perioperative processes, notably in the administration of antiemetic prophylaxis, in several large perioperative registries. Given how neighborhoods are socially segregated in the US, we examined geospatial clustering of perioperative antiemetic disparities.MethodsWe conducted a retrospective cohort study of anesthetic records from the University of Utah Hospital with 19,477 patients meeting inclusion criteria. We geocoded patient home addresses and combined them with the Census Block Group(CBG) level neighborhood disadvantage (ND), a composite index of from the National Neighborhood Data Archive (NaNDA). We stratified our patients by antiemetic risk score and calculated the number of anti-emetic interventions. We utilized Poisson Spatial Scan Statistics, implemented in SaTScan, to detect geographic clusters of under-treatment.ResultsWe identified one significant cluster (p < .001) of undertreated perioperative antiemetic prophylaxis cases. The relative risk (RR) of the whole cluster is 1.44, implying that patients within the cluster are 1.44 times more likely to receive fewer antiemetics after controlling for antiemetic risk. Patients from more disadvantaged neighborhoods were more likely to receive below median antiemetic prophylaxis after controlling for risk.ConclusionsTo our knowledge, this is the first geospatial cluster analysis of perioperative process disparities; we leveraged innovative geostatistical methods and identified a spatially defined, geographic cluster of patients whose home address census-tract level neighborhood deprivation index predicted disparities in risk adjusted antiemetic prophylaxis.
Cost-effectiveness Analysis of Alternative Infant and Neonatal Rotavirus Vaccination Schedules in Malawi
Authors: Wenger Catherine , Asare Ernest O. , Kwon Jiye , Li Xiao , Mwinjiwa Edson , Chinkhumba Jobiba , Jere Khuzwayo C. , Hungerford Daniel , Cunliffe Nigel A. , Paltiel A. David , Pitzer Virginia E. 
Published: November 2024

AbstractRotavirus is the leading cause of severe diarrhea among children under five worldwide, especially in low- and middle-income countries (LMICs). Although vaccination is the best strategy for preventing rotavirus infection, obstacles leading to poor vaccine effectiveness undermine its impact in LMICs. This study aimed to evaluate the impact and cost-effectiveness of the current two-dose Rotarix vaccine schedule in Malawi compared to two alternative vaccine delivery schedules and a next-generation neonatal vaccine (RV3-BB) from 2025-2034. The cost-effectiveness of rotavirus vaccine strategies in Malawi was evaluated from both the government and societal perspectives using estimates of moderate-to-severe and non-severe rotavirus cases derived from a mathematical model of rotavirus transmission dynamics and published estimates of health-seeking behaviors and costs as inputs. A probabilistic sensitivity analysis was performed to evaluate the robustness of our results to parameter uncertainty. Over a ten-year time horizon, the current two-dose strategy was predicted to avert over 1.5 million cases and 90,000 disability-adjusted life-years (DALYs) and cost $104.87 per DALY averted compared to no vaccination from the government perspective. Adding a third dose at 14 weeks could avert about 1 million more cases and cost $5 million more than the current strategy. The neonatal RV3-BB vaccine could avert 1.1 million cases and 41,000 DALYs due to rotavirus and save about $3.7 million compared to the current strategy. The current rotavirus vaccine program in Malawi is cost-effective and saves lives compared to no vaccination. However, adding a third dose is likely to be cost-effective at a willingness to pay (WTP) of $138.38 per DALY averted, while switching to the neonatal RV3-BB vaccine when available is likely to be cost-effective at a WTP above $45.89 per DALY averted.
Knowledge, attitude, and practices of reporting adverse events following immunization among healthcare providers in Simiyu Region, Tanzania: A cross sectional study
Authors: Kambona Raphael C. , Marealle Alphonce I. , Kilonzi Manase , Masunga Emmanuel , Kunambi Peter , Ilomo Helfrid B. , Mutagonda Ritah 
Published: November 2024

AbstractIntroductionImmunization is the most cost effective health intervention in the history of mankind. Its role in reducing the morbidities and mortality due to vaccine-preventable diseases is significant. Despite vaccines being important in saving lives; adverse events following immunization (AEFI) do occur that need prompt detection, management, and then reported, analyzed, and the findings being shared with all stakeholders to ensure vaccine safety. The reporting of AEFI in Tanzania is still low. Health Care Providers (HCPs) are obliged to collect and report AEFI. This study assessed the knowledge, attitude, and practices of reporting AEFI among HCPs in Simiyu region, Tanzania.MethodologyThis cross-sectional study was conducted between May and June 2024. A total of 180 HCPs were enrolled, structured questionnaire was used to assess the knowledge, attitude, and practices of reporting AEFI among HCPs at primary health facilities. Statistical Package for Social Science (SPSS) was used for entry and data analysis, and the findings were summarized using frequency and percentages. Chi-square test was used to screen for factors associated with AEFI reporting while Poisson regression model was used to confirm the determinants.ResultsThe median age of study participants was 32 (Inter Quartile Range; 29, 38) years. Among the HCPs, more than one quarter (28.89%) had adequate knowledge of reporting AEFI, and more than half (68.89%) had positive attitudes and good practices (62.22%) of reporting AEFI. Less than half of HCPs (48.3%) had encountered AEFI cases, and about two-thirds (69%) reported it.Conclusions and recommendationsDespite the inadequacy of knowledge on reporting AEFI among HCPs, the attitude and practices of reporting AEFI among HCPs were promising. Based on the study findings, we recommend more training on vaccine surveillance, routine follow-up, and supportive supervision of AEFI surveillance for optimal AEFI reporting and vaccine safety surveillance in Tanzania.
How early family activities predict life satisfaction among parents with adult children
Authors: Peterson M. Nils , Bordewieck Kathleen , Velluti-Fry Elijah , Jansson Julia L. , Peterson Gwen E. , Peterson Tarla R. 
Published: November 2024

AbstractLife satisfaction represents a relatively universal social goal. Research suggests familiar interactions of diverse types may shape life satisfaction, but many questions remain about the valence and relative importance of variables shaping life satisfaction. In this exploratory study, we examined the relationships between frequency of shared parent-child activities in early life stages and self-reported parental life-satisfaction after children leave home using a case study of NC State University and University of Texas at El Paso students’ parents (n=92). Frequency of shared housework with young children was the most important, and positive, predictor of life satisfaction among parents after the children left home, and shared religious activities were also a positive predictor. Conversely, frequency of playing sports with young children was a negative predictor of later life satisfaction among parents. We did not detect a relationship for shared visits to local parks. Current activity level and income level both positively predicted life satisfaction, but we did not detect relationships for gender or marital status. This preliminary research highlights several novel ways shared family activities may affect later life satisfaction among older parents, but requires larger scale research to assess if an how findings apply in other contexts.
Examining and classifying reasons for missing viral loads among adults living with HIV: An extended outcome investigation and ascertainment approach in Western Kenya
Authors: Adhiambo Harriet Fridah , Lewis-Kulzer Jayne , Nyagesoa Edwin , Gimbel Sarah , Akama Eliud , Mangale Dorothy , Montonya Lina , Eshun-Wilson Ingrid , Iguna Sarah , Nyandieka Everlyne , Bukusi Elizabeth , Abuogi Lisa , Odeny Thomas , Petersen Maya L. , Geng Elvin H. 
Published: November 2024

AbstractIntroductionGaps in HIV RNA monitoring persist globally impeding the ability to determine clinical progress and outcomes. This study systematically evaluated provider (e.g., guideline non- adherence), system (e.g., laboratory error) and patient-based (e.g., refusal) drivers of missed viral load (VL) monitoring measurements among adults living with HIV in Kenya.MethodsAdults aged 18-65 years were followed across five health facilities in Kenya as part of a clinical trial (NCT#02338739) where HIV RNA monitoring was done routinely. Instances of missed VL despite being indicated per Kenyan guidelines were identified. An algorithm for assessing root causes of missing HIV RNA was developed and generalized linear models estimated the risk ratios (RR) for patient-level characteristics associated with missed viral load.ResultsAmong 1,754 patients (66% female), the prevalence of missed viral load in year one and two was 24.4% and 29.4%, respectively. Drivers for missed viral load measurements included loss to follow up (51.5% in year one and 57.8% in year two), clinician non-adherence with guidelines (36.7% in year one and 32.2% in year two), unknown (10.3% in year one and 8.6% in year two), and requested but not collected (1.5% in year one and 1.3% in year two). Patients aged < 24 years (RR 2.27, 95% CI: 1.66-3.12), those with higher socioeconomic status (RR 1.47, 95% CI: 1.03- 1.91), receiving HIV treatment at a rural clinic (RR 1.22, 95% CI: 1.02-1.46) and with advanced HIV disease (RR 2.39, 95% CI: 1.52-3.73) were more likely to miss VL monitoring.ConclusionsMissed routine viral load monitoring remains high, primarily due to loss to follow- up, and may substantially alter suppression estimates. Sustainable approaches to keep people living with HIV engaged in care, alongside strengthening providers’ clinical practices and alignment with national guidelines, are necessary for optimizing viral monitoring and accurately assessing viral suppression within public health systems.
Integration of single cell omics with biobank data discoverstranseffects ofSREBF1abdominal obesity risk variants on adipocyte expression of more than 100 genes
Authors: Sukhatme Mihir G. , Kar Asha , Arasu Uma Thanigai , Lee Seung Hyuk T. , Alvarez Marcus , Garske Kristina M. , Gelev Kyla Z. , Rajkumar Sandhya , Das Sankha Subhra , Kaminska Dorota , Männistö Ville , Peltoniemi Hilkka , Heinonen Sini , Säiläkivi Ulla , Saarinen Tuure , Juuti Anne , Pietiläinen Kirsi H. , Pihlajamäki Jussi , Kaikkonen Minna U. , Pajukanta Päivi 
Published: November 2024

AbstractGiven the fast-increasing prevalence of obesity and its comorbidities, it would be critical to improve our understanding of the cell-type level differences between the two key human adipose tissue depots, subcutaneous (SAT) and visceral adipose tissue (VAT), in their depot-specific contributions to cardiometabolic health. We integrated cell-type level RNA- and ATAC-seq data from human SAT and VAT biopsies and cell-lines to comprehensively elucidate transcriptomic, epigenetic, and genetic differences between the two fat depots. We identify cell-type marker genes for tissue specificity and functional enrichment, and show through genome-wide association study (GWAS) and partitioned polygenic risk score (PRS) enrichment analyses that the marker genes upregulated in SAT adipocytes have more prominent roles in abdominal obesity than those of VAT. We also identifySREBF1, a master transcription factor (TF) of fatty acid synthesis and adipogenesis, as specifically upregulated in SAT adipocytes and present in numerous SAT functional pathways. By integrating multi-omics data from an independent human cohort, we further show that the risk allele carrier status of seven abdominal obesity GWAS variants in thecisregion ofSREBF1affects the adipocyte expression of 146 SAT adipocyte marker genes intrans. We replicate this finding independently in the UK Biobank by showing that the partitioned abdominal obesity PRSs of thetransgene sets differ by the regionalSREBF1risk allele carrier status. In summary, we discover the master TF,SREBF1, driving the SAT adipocyte expression profiles of more than a hundred of adipocyte marker genes intrans, a finding that indicates that humantransgenes can be identified by integrating single cell omics with biobank data.