bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epigenomic profiling of isolated blood cell types reveals highly specific B cell smoking signatures and links to disease risk
Authors: Wang Xuting , Campbell Michelle R. , Cho Hye-Youn , Pittman Gary S. , Martos Suzanne N. , Bell Douglas A. 
Published: May 2023

Abstract
Background
Tobacco smoking alters the DNA methylation profiles of immune cells which may underpin some of the pathogenesis of smoking-associated diseases. To link smoking-driven epigenetic effects in specific immune cell types with disease risk, we isolated six leukocyte subtypes, CD14+ monocytes, CD15+ granulocytes, CD19+ B cells, CD4+ T cells, CD8+ T cells, and CD56+ natural killer cells, from whole blood of 67 healthy adult smokers and 74 nonsmokers for epigenome-wide association study (EWAS) using Illumina 450k and EPIC methylation arrays.

Results
Numbers of smoking-associated differentially methylated sites (smCpGs) at genome-wide significance (p < 1.2 × 10−7) varied widely across cell types, from 5 smCpGs in CD8+ T cells to 111 smCpGs in CD19+ B cells. We found unique smoking effects in each cell type, some of which were not apparent in whole blood. Methylation-based deconvolution to estimate B cell subtypes revealed that smokers had 7.2% (p = 0.033) less naïve B cells. Adjusting for naïve and memory B cell proportions in EWAS and RNA-seq allowed the identification of genes enriched for B cell activation-related cytokine signaling pathways, Th1/Th2 responses, and hematopoietic cancers. Integrating with large-scale public datasets, 62 smCpGs were among CpGs associated with health-relevant EWASs. Furthermore, 74 smCpGs had reproducible methylation quantitative trait loci single nucleotide polymorphisms (SNPs) that were in complete linkage disequilibrium with genome-wide association study SNPs, associating with lung function, disease risks, and other traits.

Conclusions
We observed blood cell-type-specific smCpGs, a naïve-to-memory shift among B cells, and by integrating genome-wide datasets, we identified their potential links to disease risks and health traits.
Tau accumulation in autosomal dominant Alzheimer’s disease: a longitudinal [18F]flortaucipir study
Authors: O’Connor Antoinette , Cash David M. , Poole Teresa , Markiewicz Pawel J. , Fraser Maggie R. , Malone Ian B. , Jiao Jieqing , Weston Philip S. J. , Flores Shaney , Hornbeck Russ , McDade Eric , Schöll Michael , Gordon Brian A. , Bateman Randall J. , Benzinger Tammie L. S. , Fox Nick C. 
Published: May 2023

AbstractCortical tau accumulation is a key pathological event that partly defines Alzheimer’s disease (AD) onset and is associated with cognitive decline and future disease progression. However, an improved understanding of the timing and pattern of early tau deposition in AD and how this may be tracked in vivo is needed. Data from 59 participants involved in two longitudinal cohort studies of autosomal dominant AD (ADAD) were used to investigate whether tau PET can detect and track presymptomatic change; seven participants were symptomatic, and 52 were asymptomatic but at a 50% risk of carrying a pathogenic mutation. All had baseline flortaucipir (FTP) PET, MRI and clinical assessments; 26 individuals had more than one FTP PET scan. Standardised uptake value ratios (SUVRs) in prespecified regions of interest (ROIs) were obtained using inferior cerebellar grey matter as the reference region. We compared the changes in FTP SUVRs between presymptomatic carriers, symptomatic carriers and non-carriers, adjusting for age, sex and study site. We also investigated the relationship between regional FTP SUVRs and estimated years to/from symptom onset (EYO). Compared to both non-carriers and presymptomatic carriers, FTP SUVRs were significantly higher in symptomatic carriers in all ROIs tested (p < 0.001). There were no significant regional differences between presymptomatic carriers and non-carriers in FTP SUVRs, or their rates of change (p > 0.05), although increased FTP signal uptake was seen posteriorly in some individuals around the time of expected symptom onset. When we examined the relationship of FTP SUVR with respect to EYO, the earliest significant regional difference between mutation carriers and non-carriers was detected within the precuneus prior to estimated symptom onset in some cases. This study supports preliminary studies suggesting that presymptomatic tau tracer uptake is rare in ADAD. In cases where early uptake was seen, there was often a predilection for posterior regions (the precuneus and post-cingulate) as opposed to the medial temporal lobe, highlighting the importance of examining in vivo tau uptake beyond the confines of traditional Braak staging.
Obesity and dyslipidemia are associated with partially reversible modifications to DNA hydroxymethylation of apoptosis- and senescence-related genes in swine adipose-derived mesenchymal stem/stromal cells
Authors: Glasstetter Logan M. , Oderinde Tomiwa S. , Mirchandani Mohit , Rajagopalan Kamalnath Sankaran , Barsom Samer H. , Thaler Roman , Siddiqi Sarosh , Zhu Xiang-Yang , Tang Hui , Jordan Kyra L. , Saadiq Ishran M. , van Wijnen Andre J. , Eirin Alfonso , Lerman Lilach O. 
Published: May 2023

Abstract
Background
Obesity dysregulates key biological processes underlying the functional homeostasis, fate decisions, and reparative potential of mesenchymal stem/stromal cells (MSCs). Mechanisms directing obesity-induced phenotypic alterations in MSCs remain unclear, but emerging drivers include dynamic modification of epigenetic marks, like 5-hydroxymethylcytosine (5hmC). We hypothesized that obesity and cardiovascular risk factors induce functionally relevant, locus-specific changes in 5hmC of swine adipose-derived MSCs and evaluated their reversibility using an epigenetic modulator, vitamin-C.

Methods
Female domestic pigs were fed a 16-week Lean or Obese diet (n = 6 each). MSCs were harvested from subcutaneous adipose tissue, and 5hmC profiles were examined through hydroxymethylated DNA immunoprecipitation sequencing (hMeDIP-seq) followed by an integrative (hMeDIP and mRNA sequencing) gene set enrichment analysis. For clinical context, we compared 5hmC profiles of adipose tissue-derived human MSCs harvested from patients with obesity and healthy controls.

Results
hMeDIP-seq revealed 467 hyper- (fold change ≥ 1.4; p-value ≤ 0.05) and 591 hypo- (fold change ≤ 0.7; p-value ≤ 0.05) hydroxymethylated loci in swine Obese- versus Lean-MSCs. Integrative hMeDIP-seq/mRNA-seq analysis identified overlapping dysregulated gene sets and discrete differentially hydroxymethylated loci with functions related to apoptosis, cell proliferation, and senescence. These 5hmC changes were associated with increased senescence in cultured MSCs (p16/CDKN2A immunoreactivity, senescence-associated β-galactosidase [SA-β-Gal] staining), were partly reversed in swine Obese-MSCs treated with vitamin-C, and shared common pathways with 5hmC changes in human Obese-MSCs.

Conclusions
Obesity and dyslipidemia are associated with dysregulated DNA hydroxymethylation of apoptosis- and senescence-related genes in swine and human MSCs, potentially affecting cell vitality and regenerative functions. Vitamin-C may mediate reprogramming of this altered epigenomic landscape, providing a potential strategy to improve the success of autologous MSC transplantation in obese patients.
Managing the integration of teaching resources for college physical education using intelligent edge-cloud computing
Authors: Wang Chang , Wang Di 
Published: May 2023

AbstractThese days, colleges and universities have accumulated many resources in teaching and scientific research due to the acceleration of education information in China. However, many teaching resources are in short supply due to a lack of standardized resource construction and the closeness of management methods. Physical education significant teaching resources in Chinese colleges and universities must be utilized. If not integrated, it would seriously restrict the development of physical education in China. However, the traditional management of physical education teaching resources tends to worsen the data management, which is easy to cause the loss of physical education teaching resources data. With the development of the Internet of Things (IoT), cloud computing, and other technologies, intelligent edge cloud computing can ensure the integrity of physical education teaching resources and improve utilization. In this paper, cloud computing is used to manage physical education teaching resources in colleges and universities, and virtualization technology is used to research physical education teaching resources. Moreover, a resource scheduling method is proposed to ensure equal load distribution across various edge resources. The proposed strategy also provides increased utilization levels for computing resources. The comparison between the sports teaching resources under cloud computing and traditional sports teaching resources found that cloud resource management's sharing degree of teaching equipment has increased by 20.6% compared with conventional resource management. The sharing degree of courses has increased by 16.5%, and the utilization rate of sports venues has increased by 27.1% compared with traditional resource management. The utilization rate of sports film and television materials increased by 30.7%. Teachers and students benefit significantly from college and university teaching resources in the context of cloud computing. It demonstrates how cloud computing may assist colleges and universities in managing and integrating their teaching resources more effectively. The management and integration of college sports resources through cloud computing can promote the mutual exchange of college resources and have practical significance for the development of college education.
Whole genome sequencing diagnostic yield for paediatric patients with suspected genetic disorders: systematic review, meta-analysis, and GRADE assessment
Authors: Nurchis Mario Cesare , Altamura Gerardo , Riccardi Maria Teresa , Radio Francesca Clementina , Chillemi Giovanni , Bertini Enrico Silvio , Garlasco Jacopo , Tartaglia Marco , Dallapiccola Bruno , Damiani Gianfranco 
Published: May 2023

AbstractBackgroundAbout 80% of the roughly 7,000 known rare diseases are single gene disorders, about 85% of which are ultra-rare, affecting less than one in one million individuals. NGS technologies, in particular whole genome sequencing (WGS) in paediatric patients suffering from severe disorders of likely genetic origin improve the diagnostic yield allowing targeted, effective care and management. The aim of this study is to perform a systematic review and meta-analysis to assess the effectiveness of WGS, with respect to whole exome sequencing (WES) and/or usual care, for the diagnosis of suspected genetic disorders among the paediatric population.MethodsA systematic review of the literature was conducted querying relevant electronic databases, including MEDLINE, EMBASE, ISI Web of Science, and Scopus from January 2010 to June 2022. A random-effect meta-analysis was run to inspect the diagnostic yield of different techniques. A network meta-analysis was also performed to directly assess the comparison between WGS and WES.ResultsOf the 4,927 initially retrieved articles, thirty-nine met the inclusion criteria. Overall results highlighted a significantly higher pooled diagnostic yield for WGS, 38.6% (95% CI: [32.6 – 45.0]), in respect to WES, 37.8% (95% CI: [32.9 – 42.9]) and usual care, 7.8% (95% CI: [4.4 – 13.2]). The meta-regression output suggested a higher diagnostic yield of the WGS compared to WES after controlling for the type of disease (monogenic vs non-monogenic), with a tendency to better diagnostic performances for Mendelian diseases. The network meta-analysis showed a higher diagnostic yield for WGS compared to WES (OR = 1.54, 95%CI: [1.11 – 2.12]).ConclusionsAlthough whole genome sequencing for the paediatric population with suspected genetic disorders provided an accurate and early genetic diagnosis in a high proportion of cases, further research is needed for evaluating costs, effectiveness, and cost-effectiveness of WGS and achieving an informed decision-making process.Trial RegistrationThis systematic review has not been registered.
Determinants of health-related quality of life among individuals with opioid use disorder, recently released from incarceration
Authors: Cadet Techna , Jalali Ali , Jeng Philip J. , Poole Sabrina , Woody George , Murphy Sean M. 
Published: May 2023

Abstract
Background\Objectives
Concomitant with low rates of pharmacotherapy for incarcerated individuals with OUD, there is a high rate of opioid overdose following re-entry into the community. Our research objective was to develop a better understanding of the factors that influence health-related quality-of-life (HRQoL) among this population during the high-risk transition period from incarceration to community. Few studies have assessed health-related quality-of-life (HRQoL) among individuals with OUD who are involved with the criminal-legal system, let alone over the period directly surrounding release from incarceration.

Methods
Secondary longitudinal analysis of data from a clinical trial where participants were randomized 1:1 to pre-release extended-release naltrexone (XR-NTX) + referral to community XR-NTX, vs. referral only. We conducted individual, multivariable regressions of EQ-5D domains (mobility, pain/discomfort, anxiety/depression; usual activities and self-care were excluded due to insufficient variation in scores), and the overall preference/utility score. HRQoL data were subset to timepoints immediately before release (baseline) and 12 weeks post-release; treatment groups were collapsed across condition. Multiple imputation by chained equations was conducted to handle missing 3-month data in the dependent variables and covariates, ad hoc.

Results
Greater severity in the psychiatric composite score was associated with substantially lower HRQoL, across all measures, following release from incarceration. Greater severity in the medical composite score was associated with lower pain/discomfort-related HRQoL.

Conclusions
Our findings highlight the importance of ensuring individuals with OUD are linked not only to MOUD, but also treatment for their comorbid conditions upon release from incarceration.
Impact of urbanization on morbidity of hepatitis A: a national panel study in China during 2005–2018
Authors: Ming Bo-Wen , Yang Zhou , Yan Ze-Lin , Shi Chen , Xu Xiao-Han , Li Li , Ou Chun-Quan 
Published: May 2023

Abstract
Background
The effect of urbanization on the morbidity of hepatitis A remains unclear. We aimed to estimate the association between various urbanization-related indices and hepatitis A morbidity in China.

Methods
Data on the annual morbidity of hepatitis A, urbanization-related measures (i.e., gross domestic product per capita, the number of hospitalization beds per 1000 persons, illiteracy rate, tap water coverage, motor vehicles per 100 persons, population density, and the proportion of arable land), and meteorological factors in 31 provincial-level administrative divisions of Chinese mainland during 2005–2018 were collected from the National Population and Health Science Data Sharing Platform, China Statistical Yearbooks, and the China Meteorological Data Sharing Service System, respectively. Generalized linear mixed models were applied to quantify the impacts of different urbanization-related indices on the morbidity of hepatitis A in China after adjusting for covariates.

Results
A total of 537,466 hepatitis A cases were reported in China during 2005–2018. The annual morbidity had a decline of 79.4% from 5.64 cases to 1.16 cases per 100,000 people. There were obvious spatial variations with higher morbidity in western China. Nationally, gross domestic product per capita and the number of hospitalization beds per 1000 persons increased from 14,040 to 64,644 CNY and from 2.45 to 6.03 during 2005–2018, respectively. The illiteracy rate decreased from 11.0 to 4.9%. Gross domestic product per capita [relative risk (RR) = 0.96, 95% confidence interval (CI): 0.92–0.99], and the number of hospitalization beds per 1000 persons (RR = 0.79, 95% CI: 0.75–0.83) were associated with the declined morbidity of hepatitis A. By contrast, the increased morbidity of hepatitis A was linked to the illiteracy rate (RR = 1.04, 95% CI: 1.02–1.06). Similar influential factors were detected for children and adults, with greater effects witnessed for children.

Conclusions
People in the western region suffered the heaviest burden of hepatitis A in Chinese mainland. Nationally, there was a sharp decline in the morbidity of hepatitis A. The urbanization process was associated with the reduction of hepatitis A morbidity in China during 2005–2018.

Graphical Abstract
A communicative validation study on an English listening test in Korea
Authors: Zhang Ci , Xu XiaoShu , Zhang Yunfeng 
Published: May 2023

AbstractThis study presents the validation process of a listening test based on a communicative language test proposed by Bachman (Fundamental considerations in language testing, 1990). It was administered to third-grade high school students by the sixteen Korean Provincial Offices of Education for Curriculum and Evaluation in September 2012 to assess their listening ability at the end of high school learning and compare it with the standard of the CSAT (College Scholastic Ability Test). The research questions were the following. First, to what extent does the test measure the listening comprehension construct? Second, what sub-skills does the test measure? Third, to what extent does the test measure communicative ability? To answer these three questions, a study was designed to examine the test’s construct validity using classical test theory (CTT). Then, an exploratory factor analysis (EFA) and a confirmatory factor analysis (CFA) were applied to find a model that would fit the score of 400 examinees to explain the correlation between six divisible sub-skills of English listening comprehension and twenty listening items. R-program is used as a tool to analyze the above data. The results show that this test is not discriminatory, as the purpose of a summative assessment is not to level students into different groups. With an acceptable measurement of the construct, this research concludes that the test does not have a clear division of listening sub-skills but, on the other hand, sufficiently measures communicative ability.
A two-stage deflection system for the extension of the energy coverage in space plasma three-dimensional measurements
Authors: Kasahara Satoshi , Tao Ryo , Yoshida Emiko , Yokota Shoichiro 
Published: May 2023

AbstractThe in situ measurement of charged particles plays a key role in understanding space plasma physics. Velocity distribution functions of ions and electrons have been acquired with electrostatic analyzers onboard spacecraft. Since conventional energy analyzers (e.g., top-hat electrostatic analyzers) have essentially a two-dimensional field of view, the solid angle coverage is achieved with the aid of spacecraft spin motion or with additional entrance deflection systems in front of the electrostatic analyzer. In the latter case, however, the full angular scan is realized only in the lower energy range (typically only up to 5–15 keV/e), due to the limitation of the electric field applied to the deflector. Here we propose a novel deflection system for extending the energy coverage up to tens of keV. This is especially useful for plasma observations in situations where the anisotropy of the energetic part (> 10 keV) of charged particles plays an essential role in plasma dynamics and hence is of significant interest.
Graphical Abstract
Neuroprotective effects of the PPARβ/δ antagonist GSK0660 in in vitro and in vivo Parkinson’s disease models
Authors: Antonosante Andrea , Castelli Vanessa , Sette Martina , Alfonsetti Margherita , Catanesi Mariano , Benedetti Elisabetta , Ardini Matteo , Cimini Annamaria , d’Angelo Michele 
Published: May 2023

Abstract
Background
The underlying mechanism of Parkinson’s disease are still unidentified, but excitotoxicity, oxidative stress, and neuroinflammation are considered key actors. Proliferator activated receptors (PPARs) are transcription factors involved in the control of numerous pathways. Specifically, PPARβ/δ is recognized as an oxidative stress sensor, and we have previously reported that it plays a detrimental role in neurodegeneration.

Methods
Basing on this concept, in this work, we tested the potential effects of a specific PPARβ/δ antagonist (GSK0660) in an in vitro model of Parkinson’s disease. Specifically, live-cell imaging, gene expression, Western blot, proteasome analyses, mitochondrial and bioenergetic studies were performed. Since we obtained promising results, we tested this antagonist in a 6-hydroxydopamine hemilesioned mouse model. In the animal model, behavioral tests, histological analysis, immunofluorescence and western blot of substantia nigra and striatum upon GSK0660 were assayed.

Results
Our findings suggested that PPARβ/δ antagonist has neuroprotective potential due to neurotrophic support, anti-apoptotic and anti-oxidative effects paralleled to an amelioration of mitochondria and proteasome activity. These findings are strongly supported also by the siRNA results demonstrating that by silencing PPARβ/δ a significative rescue of the dopaminergic neurons was obtained, thus indicating an involvement of PPARβ/δ in PD’s pathogenesis. Interestingly, in the animal model, GSK0660 treatment confirmed neuroprotective effects observed in the in vitro studies. Neuroprotective effects were highlighted by the behavioural performance and apomorphine rotation tests amelioration and the reduction of dopaminergic neuronal loss. These data were also confirmed by imaging and western blotting, indeed, the tested compound decreased astrogliosis and activated microglia, concomitant with an upregulation of neuroprotective pathways.

Conclusions
In summary, PPARβ/δ antagonist displayed neuroprotective activities against 6-hydroxydopamine detrimental effects both in vitro and in vivo models of Parkinson’s disease, suggesting that it may represent a novel therapeutic approach for this disorder.