bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lifespan analysis of repeat expression reveals age-dependent upregulation of HERV-K in the neurotypical human brain
Authors: Evans Taylor A. , Feltrin Arthur S. , Benjamin Kynon J. , Katipalli Tarun , Hyde Thomas , Kleinman Joel E. , Weinberger Daniel R. , Paquola Apua C. , Erwin Jennifer A. 
Published: May 2024

AbstractDNA repetitive sequences (or repeats) comprise over 50% of the human genome and have a crucial regulatory role, specifically regulating transcription machinery. The human brain is the tissue with the highest detectable repeat expression and dysregulations on the repeat activity are related to several neurological and neurodegenerative disorders, as repeat-derived products can stimulate a pro-inflammatory response. Even so, it is unclear how repeat expression acts on the aging neurotypical brain. Here, we leverage a large postmortem transcriptome cohort spanning the human lifespan to assess global repeat expression in the neurotypical brain. We identified 21,696 differentially expressed repeats (DERs) that varied across seven age bins (Prenatal; 0-15; 16-29; 30-39; 40-49; 50-59; 60+) across the caudate nucleus (n=271), dorsolateral prefrontal cortex (n=304), and hippocampus (n=310). Interestingly, we found that long interspersed nuclear elements and long terminal repeats (LTRs) DERs were the most abundant repeat families when comparing infants to early adolescence (0-15) with older adults (60+). Of these differentially regulated LTRs, we identified 17 shared across all brain regions, including increased expression of HERV-K-int in older adult brains (60+). Co-expression analysis from each of the three brain regions also showed repeats from the HERV subfamily were intramodular hubs in its subnetworks. While we do not observe a strong global relationship between repeat expression and age, we identified HERV-K as a repeat signature associated with the aging neurotypical brain. Our study is the first global assessment of repeat expression in the neurotypical brain.
Untargeted Metabolome Atlas for Sleep Phenotypes in the Hispanic Community Health Study/Study of Latinos
Authors: Zhang Ying , Spitzer Brian W , Zhang Yu , Wallace Danielle A , Yu Bing , Qi Qibin , Argos Maria , Avilés-Santa M Larissa , Boerwinkle Eric , Daviglus Martha L , Kaplan Robert , Cai Jianwen , Redline Susan , Sofer Tamar 
Published: May 2024

AbstractSleep is essential to maintaining health and wellbeing of individuals, influencing a variety of outcomes from mental health to cardiometabolic disease. This study aims to assess the relationships between various sleep phenotypes and blood metabolites. Utilizing data from the Hispanic Community Health Study/Study of Latinos, we performed association analyses between 40 sleep phenotypes, grouped in several domains (i.e., sleep disordered breathing (SDB), sleep duration, timing, insomnia symptoms, and heart rate during sleep), and 768 metabolites measured via untargeted metabolomics profiling. Network analysis was employed to visualize and interpret the associations between sleep phenotypes and metabolites. The patterns of statistically significant associations between sleep phenotypes and metabolites differed by superpathways, and highlighted subpathways of interest for future studies. For example, some xenobiotic metabolites were associated with sleep duration and heart rate phenotypes (e.g. 1H-indole-7-acetic acid, 4-allylphenol sulfate), while ketone bodies and fatty acid metabolism metabolites were associated with sleep timing measures (e.g. 3-hydroxybutyrate (BHBA), 3-hydroxyhexanoylcarnitine (1)). Heart rate phenotypes had the overall largest number of detected metabolite associations. Many of these associations were shared with both SDB and with sleep timing phenotypes, while SDB phenotypes shared relatively few metabolite associations with sleep duration measures. A number of metabolites were associated with multiple sleep phenotypes, from a few domains. The amino acids vanillylmandelate (VMA) and 1-carboxyethylisoleucine were associated with the greatest number of sleep phenotypes, from all domains other than insomnia. This atlas of sleep-metabolite associations will facilitate hypothesis generation and further study of the metabolic underpinnings of sleep health.
Shared genetic features between lymphoma pathogenesis and oestrogen levels
Authors: Hill Claire , Muckian Marisa , Garre Marisa Cañadas , Greenfield Graeme , Maxwell Alexander P. , McShane Charlene M. , Anderson Lesley Ann , McKnight Amy Jayne 
Published: May 2024

AbstractIn the last decade, genetic analysis has aided lymphoma classification, alongside traditional phenotypic subdivision. Lymphomas exhibit sex differences in disease incidence and prevalence; therefore, scope existed to explore sex-specific genetic variation.Harnessing UK Biobank genetic data (185,000 females, 176,000 males), sex-specific genome-wide genetic variation significantly associated with lymphoma subtypes was determined in both autosomal and sex chromosome genes. Sex-specific genetic variation significantly associated with sex-related characteristics was also identified. Functional predictions for those genes containing significant (p<5×10-5) genetic variation was carried out via ViSEAGO. For each lymphoma subtype, approximately 10-12% of the genes containing significantly associated genetic variants were shared between the sexes, highlighting largely sex-specific profiles for lymphoma subtypes.Significantly associated X chromosome genetic variants were identified for Non-Hodgkin’s lymphoma (NHL) and Diffuse large B-cell lymphoma (DLBCL), such as variants withinSYTL5(in males) andPPP2R3B(in females); genes previously implicated in haematological malignancy biological processes. Additionally, in female NHL patients, a genetic variant mapped toESR1, the gene coding for oestrogen receptor-α was identified, adding to the body of evidence highlighting the relevance of oestrogen regulation for haematological malignancy subtypes.Indeed, up to 9.1% of overlap was observed between those genes containing significant genetic variation associated with specific lymphoma subtypes, and those significantly associated with oestrogen level determination. Gene ontology analysis further emphasised functional overlaps between lymphoma and oestrogen level determination in females, highlighting predicted involvement in epigenetic modification, gene expression, and signalling.This study revealed sex-specific genetic variation significantly associated with lymphoma, as well as hormone level determination, and revealed biological pathways potentially disrupted during lymphoma pathogenesis which are influenced by oestrogen. Exploring these pathways may advance our understanding of the sex-specificities of lymphoma, and may reveal therapeutic targets to advance patient care.
Predictors of Postviral Symptoms Following Epstein-Barr Virus-Associated Infectious Mononucleosis in Young People – Data from the IMMUC Study
Authors: Bodenhausen Maren , Geisperger Jonas , Lange de Luna Julia , Wendl Johannes , Hapfelmeier Alexander , Schulte-Hillen Lina , Pricoco Rafael , Körber Nina , Bauer Tanja , Mautner Josef , Hoffmann Dieter , Luppa Peter , Egert-Schwender Silvia , Nößner Elfriede , Delecluse Henri-Jacques , Delecluse Susanne , Hauck Fabian , Falk Christine , Schulz Thomas , Steinborn Marc-Matthias , Bietenbeck Andreas , Nieters Alexandra , Mihatsch Lorenz , Gerrer Katrin , Behrends Uta ,   the IMMUC Study Group
Published: May 2024

ABSTRACTBackgroundEpstein-Barr virus-associated Infectious Mononucleosis (EBV-IM) is a common disease following primary EBV infection in children and adolescents. While EBV-IM is mostly self-limiting, symptoms like fatigue may persist over several months or even result in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This large clinical observational study aimed at identifying risk factors for protracted courses of EBV-IM in young people.MethodsA cohort of N=200 children, adolescents, and young adults with acute primary EBV infection was recruited from hospitals and private practices. Data on the patients’ medical history as well as clinical and laboratory parameters were collected at a baseline visit (V1) within four weeks after symptom onset (Tonset) and at two follow-up visits (V2 and V3) one and six months after Tonset. Risk factors for protracted symptoms at V3 were modeled using multivariable logistic regressions.ResultsProtracted symptoms were observed in 55/183 (30.1%) and protracted fatigue in 34/181 (18.8%) patients at V3. A medical history indicating an increased susceptibility to infectious diseases as well as distinct severe IM symptoms, e.g. severe gastrointestinal symptoms, were significantly associated with protracted disease [OR: 2.31; P=0.011 and OR: 3.42; P=0.027] and with chronic fatigue [OR: 2.98; P=0.006 and OR: 3.54; P=0.034], respectively. Occurrence of twelve or more clinical and laboratory parameters until and including V1 discriminated between fatigue and no fatigue at V3 [OR 2.43, P=0.033].ConclusionA clinical history of immune dysregulation as well as distinct severe IM symptoms might predict protracted post-viral disease and thus help in the identification of young patients at risk.HighlightsSevere gastrointestinal symptoms are associated with protracted course of Epstein-Barr virus-associated Infectious Mononucleosis (EBV-IM).Signs of immune dysregulation prior to EBV-IM can indicate an increased risk of protracted symptoms.Greater number of initial symptoms helps to identify patients developing postviral fatigue.
Compound heterozygous mutations in the kinase domain of IKKα lead to immunodeficiency and immune dysregulation
Authors: Riller Quentin , Sorin Boris , Courteille Charline , Ho-Nhat Duong , Voyer Tom Le , Debray Jean-Christophe , Stolzenberg Marie-Claude , Pellé Olivier , Becquard Thomas , Riestra María Rodrigo , Berteloot Laureline , Migaud Mélanie , Delage Laure , Jeanpierre Marie , Boussard Charlotte , Brunaud Camille , Magérus Aude , Michel Victor , Roux Camille , Picard Capucine , Masson Cécile , Bole-Feysot Christine , Cagnard Nicolas , Corneau Aurélien , Meyts Isabelle , Baud Véronique , Casanova Jean-Laurent , Fischer Alain , Dejardin Emmanuel , Puel Anne , Boulanger Cécile , Neven Bénédicte , Rieux-Laucat Frédéric 
Published: May 2024

AbstractIKKα, encoded byCHUK, is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKβ. Absence of IKKα cause fetal encasement syndrome in human, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and cause combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features. We showed that both variants were loss-of-function. Non-canonical NF-κB activation was profoundly diminished in stromal and immune cells while the canonical pathway was partially impaired. Reintroducing wild-typeCHUKrestored non-canonical NF-κB activation. The patient had neutralizing autoantibodies against type I IFN, akin to non-canonical NF-κB pathway deficiencies. Thus, this is the first case of bi-allelicCHUKmutations disrupting IKKα kinase function, broadening non-canonical NF-κB defect understanding and suggesting IKKα’s role in canonical NF-κB target gene expression in human.
Impact of Covid-19 on Bangladeshi university students mental health: ML and DL analysis
Authors: Atique Md Monir Ahammod Bin , Bappi Md Ilias , Kim Kyungbeak , Choi Kwanghoon , Ahamad Md Martuza , Reza Khondaker Masfiq 
Published: May 2024

AbstractThe Covid-19 outbreak has adversely influenced university students across the world both physically and psychologically. The psychological struggle faced by students, is effected by various factors, including disruptions to daily routines and academic activities, increased reliance on smartphones and the internet, limited social interaction, and confinement to their homes. These impediments reflect a broader issue of imbalance in cognitive health status among them during the pandemic. In Bangladesh, despite having the necessary population to study, understanding the impact of Covid-19 on the mental health status of university students has been limited. Hence, it is imperative to diagnose mental health issues and deal with the underlying reasons in order to enhance students’ psychological well-being, which leads to academic achievement. Nowadays, Artificial Intelligence (AI) based prediction models have the potential to play a crucial role in predicting mental state early. The purpose of the study is to explore the following effects of the pandemic on the mental health of Bangladeshi university students using Machine Learning (ML) and Deep Learning (DL) techniques. A reliable AI prediction system requires real-world data, that was collected by a survey through a Google form (online questionnaires) among 400 students of 16 universities, and the respondents were 253. In this paper, after data preprocessing, ten widely known ML and four DL models were developed to automatically and accurately predict mental well-being during or after the Covid-19 circumstance. According to our findings, the Random Forest (RF) algorithm and Siamese Neural Networks (SNNs) outperformed other models in terms of accuracy (86% and 75%). Additionally, Chi-Square test was conducted, which revealed the five most common and significant predictors (“Stable family income”, “Disruption of daily life”, “Own income”, “Sleep status”, and “Fear of getting infected with Covid-19”) of psychological health conditions. Overall, this work could assist university administrations, government agencies, and health specialists in taking appropriate measures to understand and maintain students’ mental health. This research also suggests proper monitoring, government support, and social awareness during and after the worldwide epidemic to keep an excellent mental health state of university students.
Safety and effects of acetylated and butyrylated high amylose maize starch in recently diagnosed youths with type 1 diabetes; a Pilot Study
Authors: Ismail Heba M , Liu Jianyun , Netherland Michael , Evans-Molina Carmella , DiMeglio Linda A 
Published: May 2024

AbstractAcetylated and butyrylated high amylose starch (HAMS-AB) is a prebiotic shown to be effective in type 1 diabetes (T1D) prevention in mouse models and is safe in adults with established T1D. HAMS-AB alters the gut microbiome profile with increased bacterial fermenters that produce short chain fatty acids (SCFAs) with anti-inflammatory and immune-modulatory effects. We performed a pilot study using a cross-over design to assess the safety and efficacy of 4 weeks of oral HAMS-AB consumption by recently diagnosed (< 2 years of diagnosis) youths with T1D. Seven individuals completed the study. The mean±SD age was 15.0±1.2 years, diabetes duration 19.5±6.3 months, 5/7 were female and 4/7 were White, all with a BMI of < 85th%. The prebiotic was safe. Following prebiotic intake, gut microbiome changes were seen, including a notable increase in the relative abundance of fermenters such as Bifidobacterium and Faecalibacterium. Treatment was also associated with changes in bacterial functional pathways associated with either improved energy metabolism (upregulation of tyrosine metabolism) or anti-inflammatory effects (reduced geraniol degradation). There were no differences in stool SCFA levels. Plasma metabolites associated with improved glycemia, such as hippurate, were significantly increased after treatment and there were positive and significant changes in the immune regulatory function of mucosal associated invariant T cells. There was a significant decrease in the area under the curve glucose but not C-peptide, as measured during a mixed meal tolerance testing, following the prebiotic consumption. In summary, the prebiotic HAMS-AB was safe in adolescents with T1D and showed promising effects on the gut microbiome composition, function and immune regulatory function.
Impact of Executive and Adaptive function on functional outcomes in adults with Maple Syrup Urine Disease
Authors: Gold Jessica I , Strong Alanna , Gold Nina B , Yudkoff Marc , Szalda Dava , Jan Sophia , Schwartz Lisa A , Ganetzky Rebecca 
Published: May 2024

AbstractPurposeSuccessful transition to adulthood requires intact executive and adaptive function. These neurocognitive domains, critical for independence, are frequently impaired in inherited metabolic disorders (IMD), though predictive clinical and biochemical factors are lacking. Standardized assessments linking neurocognitive status with functional outcomes are needed to improve prognostication and tailor support for affected emerging adults.MethodsMaple Syrup Urine Disease (MSUD), a relatively prevalent IMD, is primarily diagnosed in the first week of life through newborn screening. Despite early intervention, executive and adaptive dysfunction persist. We designed a remote, interactive battery of neurocognitive and functional assessments for adults (≥21 years) with MSUD to correlate neurocognition and long-term outcomes.ResultsAssessments completed by 28 adults with MSUD (23 diagnosed after symptom onset) show a wide range in educational attainment, employment, and residence. Executive function, and adaptive function were significantly impaired in adults with MSUD compared to controls. Executive and adaptive deficits correlated negatively with obtaining skills needed for adult-oriented healthcare or independent living. Clinical history did not predict functional outcomes, but neurocognitive assessments suggest the benefits of pre-symptomatic diagnosis.ConclusionIndependent adulthood is attainable for individuals with MSUD. Routine, targeted assessment of neurocognition may improve long-term functional outcomes in IMD.
Developing an Indicator for Age-Friendly Communities: The Japan Gerontological Evaluation Study
Authors: Fujihara Satoko , Noguchi Taiji , Ide Kazushige , Jeong Seungwon , Kondo Katsunori , Ojima Toshiyuki 
Published: May 2024

AbstractBackgroundAge-friendly communities (AFCs) aim to create inclusive societies for older people. Despite the World Health Organization (WHO)’s emphasis on incorporating dementia-friendliness across all phases, including planning, implementation, monitoring, evaluation, and scale-up, there are very few community-level indicators that incorporate dementia-friendly elements.ObjectiveTo develop a community-level AFC indicator based on WHO AFC guidelines incorporating dementia-friendly elements, and examine its validity and reliability.DesignA repeated cross-sectional study using data from the 2016 and 2019 waves of the Japan Gerontological Evaluation Study.Setting and SubjectsData were collected from 61 school districts in 16 Japanese municipalities, involving 45,162 individuals aged ≥65 years in 2016, and 39,313 in 2019. The 2016 and 2019 datasets were the development and retest samples, respectively.MethodsAfter identifying 23 candidate items according to the WHO AFC guidelines and expert reviews, data were aggregated by school district. Exploratory factor analysis on the 2016 data helped derive factor structure, confirming reproducibility with the 2019 data. Internal consistency and test-retest reliability were evaluated.ResultsThe final 17-item indicator comprised three subscales:Social inclusion and dementia-friendliness(7 items, α = 0.86),Social engagement and communication(5 items, α = 0.78), andAge-friendly physical environment(5 items, α = 0.82). The structure showed adequate test-retest reliability (r = 0.71–0.79; ICC = 0.67–0.78).ConclusionsA valid and reliable 17-item community-level indicator was developed, which aligns with the WHO framework and also incorporates dementia-friendly elements. This indicator is useful for monitoring and evaluating to promote the AFC and dementia-friendly communities.
Association of daily steps with incident non-alcoholic fatty liver disease: Evidence from the UK Biobank cohort
Authors: Fulda Evelynne S. , Portas Laura , Harper Charlie , Preiss David , Bennett Derrick , Doherty Aiden 
Published: May 2024

ABSTRACTBackgroundLow physical activity (PA) has been shown to be associated with higher risk of non-alcoholic fatty liver disease (NAFLD). However, the strength and shape of this association are currently uncertain due to a reliance on self-reported PA measures. This report aims to investigate the relationship of PA with NAFLD using accelerometer-derived step count from a large prospective cohort study.MethodsThe wrist-worn accelerometer sub-study of the UK Biobank (N=∼100,000) was used to characterise median daily step count over a seven-day period. NAFLD cases were ascertained via record linkage with hospital inpatient data and death registers or by using a measure of liver fat from imaging. Cox proportional hazards models were employed to assess the association between step count and NAFLD, adjusting for age, sociodemographic, and lifestyle factors. Mediation analyses were conducted.ResultsAmong 91,031 participants (709,440 person-years of follow-up), there were 762 incident NAFLD cases. Higher step count was log-linearly and inversely associated with risk of NAFLD. A 1000 step increase (representing 10 minutes of walking) was associated with a 12% (95% CI: 10%–14%) lower hazard of NAFLD. When using imaging to identify NAFLD, a 1,000-step increase was associated with a 6% (95% CI: 6%–7%) lower risk. There was evidence for some mediation by adiposity.ConclusionPhysical activity, a modifiable risk factor, is log-linearly and inversely associated with NAFLD. This association was only partially explained by adiposity. These findings from a large cohort study may have important implications for strategies to lower NAFLD risk.
Gut Microbiome Multi-Omics and Cognitive Function in the Hispanic Community Health Study/Study of Latinos- Investigation of Neurocognitive Aging
Authors: Palacios Natalia , Gordon Scott , Wang Tao , Burk Robert , Qi Qibin , Huttenhower Curtis , Gonzalez Hector M. , Knight Robert , De Carli Charles , Daviglus Marta , Lamar Melissa , Telavera Gregory , Tarraf Wassim , Kosciolek Tomasz , Cai Jianwen , Kaplan Robert C. 
Published: May 2024

STRUCTURED ABSTRACTINTRODUCTIONWeconducted a study within the Hispanic Community Health Study/Study of Latinos- Investigation of Neurocognitive Aging (HCHS/SOL-INCA) cohort to examine the association between gut microbiome and cognitive function.METHODSWe analyzed the fecal metagenomes of 2,471 HCHS/SOL-INCA participants to, cross-sectionally, identify microbial taxonomic and functional features associated with global cognitive function. Omnibus (PERMANOVA) and feature-wise analyses (MaAsLin2) were conducted to identify microbiome-cognition associations, and specific microbial species and pathways (Kyoto Encyclopedia of Genes and Genomes (KEGG modules) associated with cognition.RESULTSEubacteriumspecies(E. siraeumandE. eligens), were associated with better cognition. Several KEGG modules, most strongly Ornithine, Serine biosynthesis and Urea Cycle, were associated with worse cognition.DISCUSSIONIn a large Hispanic/Latino cohort, we identified several microbial taxa and KEGG pathways associated with cognition.