bluuebunny/crossref_metadata_2025_split huggingface dataset:
Older Adults’ Social Profiles and Links to Functional and Biological Aging in the United States and Mexico
Authors: Wilson Stephanie J. , Marini Christina M. 
Published: September 2023

ABSTRACT

Objective
Social stress—loneliness, isolation, and low relationship quality—increase risks of aging-related diseases. However, the ways in which they intersect to undermine healthy aging remain poorly understood. We used latent class analysis to identify groups of older adults based on their social stress in both the United States and Mexico. Thereafter, we examined their cross-sectional associations with markers of functional and biological aging.

Method
Participants in the Health and Retirement Study (HRS; N = 8316) and Mexican Health and Aging Study (MHAS; N = 15,001) reported their loneliness, isolation (i.e., living alone), and relationship quality with spouse, children, and friends. Outcomes included C-reactive protein, functional limitations, self-rated health, comorbidities, gait speed, and grip strength. Models controlled for demographics, health behaviors, and body mass index.

Results
In both countries, five classes emerged, a supported group and four with elevated social stress: a) strained, b) isolated, c) spousal ambivalence, and d) unhappily married. Compared with the others, strained participants in both samples had greater functional limitations, poorer self-rated health, and more comorbidities, as well as slower gait in HRS and weaker grip in MHAS. Generally, supported participants fared better than the other groups. In HRS, C-reactive protein levels differed between the strained group and others, but these associations were explained by health behaviors and body mass index.

Conclusions
Older adults in both countries with strained relationships fared worst in their aging-related outcomes, revealing new insights about the links between toxic social stress and unhealthy aging.
Association of Self-Reported Autonomic Symptoms With Sensor-Based Physiological Measures
Authors: Kolacz Jacek , Chen Xiwei , Nix Evan J. , Roath Olivia K. , Holmes Logan G. , Tokash Clarissa , Porges Stephen W. , Lewis Gregory F. 
Published: September 2023

ABSTRACT

Objective
Autonomic regulation of organ and tissues may give rise to disruptions of typical functions. The Body Perception Questionnaire Short Form (BPQ-SF) includes items that were developed to assess autonomic symptoms in daily life. This pair of studies aimed to establish previously unexplored psychometric properties of the BPQ-SF autonomic symptoms scale, develop normative values for clinical and research use, and assess the convergence of self-reports with sensor-based measures.

Methods
Study 1 reports exploratory and confirmatory factor analysis on BPQ-SF autonomic symptom items from a large US population-based online study (n = 2048). In study 2, BPQ-SF scores were examined for associations with heart period, respiratory sinus arrhythmia, and skin conductance during seated leg lifts in a community sample (n = 62).

Results
Study 1 results supported a two-factor supradiaphragmatic and subdiaphragmatic autonomic symptom solution (confirmatory factor analysis: root mean squared error of approximation = 0.040, Comparative Fit Index = 0.99, Tucker-Lewis Index = 0.99), although a one-factor solution also fit the data well (root mean squared error of approximation = 0.080, Comparative Fit Index = 0.99, Tucker-Lewis Index = 0.99). In study 2, heart period responses to leg lifts and rests were demonstrated at all autonomic symptom levels. However, low autonomic symptoms were associated with optimal autonomic nervous system patterns of activation and recovery to baseline levels. Moderate symptoms were associated with prolonged sympathetic activation. The highest symptom levels were associated with impaired autonomic nervous system coordination across activation and recovery.

Conclusions
Results support the utility of self-reports of autonomic symptoms in research and clinical applications, with higher symptoms likely indicating autonomic impairment.
Associations of Germline Genetic Variants With Depression and Fatigue Among Hematologic Cancer Patients Treated With Allogeneic Hematopoietic Cell Transplantation
Authors: Hoogland Aasha I. , Gonzalez Brian D. , Park Jong Y. , Small Brent J. , Sutton Steven K. , Pidala Joseph A. , Smith Kristen S. , Bower Julienne E. , Jacobsen Paul B. , Jim Heather S.L. 
Published: September 2023

ABSTRACT

Objective
Depression and fatigue are common among cancer patients and are associated with germline genetic variation. The goal of this pilot study was to examine genetic associations with depression and fatigue in the year after allogeneic hematopoietic cell transplant (HCT).

Methods
Blood was collected from patients and their donors before HCT. Patients completed self-report measures of depression and fatigue before HCT (T1), 90 days post-HCT (T2), and 1 year post-HCT (T3). Of the 384 genetic variants genotyped on a custom Illumina BeadChip microarray, 267 were retained for analysis based on quality control. Main effects of patient and donor variants as well as their interaction were examined using regression analyses. Significant variants were defined as those with a false discovery rate–adjusted p value of <.05.

Results
The sample consisted of 59 patient-donor pairs. Mean levels of depression and fatigue did not change significantly over time (p values of > .41). Increases in depression from T1 to T2 were associated with patient-donor interactions at rs1928040 (p = 3.0 × 10−4) and rs6311 (p = 2.0 × 10−4) in HTR2A. Increases in fatigue from T1 to T2 were associated with patient rs689021 in SORL1 (p = 6.0 × 10−5) and a patient-donor interaction at rs1885884 in HTR2A (p < 1.0 × 10−4).

Conclusions
Data suggest that variants in genes regulating the serotonergic system (HTR2A) and lipid metabolism (SORL1) are associated with changes in depression and fatigue in allogeneic HCT patients, implicating patients’ own genetic inheritance as well as that of donors. Additional studies are warranted to confirm these findings.
Therapeutic developments for valosin-containing protein mediated multisystem proteinopathy
Authors: Boock Victoria , Roy Bhaskar , Pfeffer Gerald , Kimonis Virginia 
Published: September 2023

Purpose of review
Missense mutations in valosin-containing protein (VCP) can lead to a multisystem proteinopathy 1 (MSP1) with any combination of limb-girdle distribution inclusion body myopathy (IBM) (present in about 90% of cases), Paget's disease of bone, and frontotemporal dementia (IBMPFD). VCP mutations lead to gain of function activity with widespread disarray in cellular function, with enhanced ATPase activity, increased binding with its cofactors, and reduced mitofusin levels.

Recent findings
This review highlights novel therapeutic approaches in VCP-MSP in in-vitro and in-vivo models. Furthermore, we also discuss therapies targeting mitochondrial dysfunction, autophagy, TDP-43 pathways, and gene therapies in other diseases with similar pathway involvement which can also be applicable in VCP-MSP.

Summary
Being a rare disease, it is challenging to perform large-scale randomized control trials (RCTs) in VCP-MSP. However, it is important to recognize potential therapeutic targets, and assess their safety and efficacy in preclinical models, to initiate RCTs for potential therapies in this debilitating disease.
A cross-sectional questionnaire-based landscaping of female infertility reveals genital Infections as a major contributor to reproductive tract anomalies, menstrual disorders, and infertility
Authors: Patnaik Naresh , Sarkar Uttam , Jojula Malathi , Vaddiraju Hema , Dey Ruchi Jain 
Published: September 2023

AbstractObjectivesFemale infertility is a global health concern. The association of genital infections with female infertility is neglected due to their chronic but asymptomatic nature. Lack of routine diagnosis and delay in treatment further causes intractable pathological sequalae and consequential infertility. This study aims to identify the most significant prognostic symptoms of genital infection(s) that correlate strongly with reproductive tract anomalies, menstrual disorders, and infertility.MethodsWe designed a detailed questionnaire and conducted a cross-sectional study with 100 female subjects, categorized into infertile (n1 = 62) and healthy groups (n2 = 38). The data collected was documented and statistically analyzed.ResultsThis study highlights an early onset of infertility (21-30 years). Almost 27% of the infertile subjects are symptomatic for genital infections and ∼42% exhibit menstrual irregularities. Polycystic ovarian syndrome/disease (PCOS/PCOD, ∼30%), are observed to be the most predominant disorders followed by endometrial disorders (∼10%) and tubal damage (∼8%) in infertile subjects. A multivariate correlation analysis revealed a highly significant (p≤ 0.05) and strong association (0.15 < Φ ≤ 1.0) between menstrual disorders, endometrial disorders, uterine/tubal blockage, and hormonal disruption with infection-associated symptoms, such as vaginitis, cervicitis, pelvic inflammatory disorder (PID), dyspareunia, tuberculosis (TB), urinary tract infection (UTI), sperm, and semen abnormalities.ConclusionsOur study reveals genital infections to be a significant contributor to female infertility. The questionnaire designed here offers a useful tool for self or clinical assessment and may help in timely prognosis/diagnosis of genital infections which may contribute to improved management of reproductive health and fertility.SynopsisThe study reveals impact of genital infections on female infertility and offers a comprehensive questionnaire-based tool for an early self/clinical prognosis of infection induced infertility.
Single cell sequencing data identify distinct B cell and fibroblast populations in stricturing Crohn’s disease
Authors: Humphreys David T , Lewis Amy , Pan-Castillo Belen , Berti Giulio , Mein Charles , Wozniak Eva , Gordon Hannah , Gadhok Radha , Minicozzi Annamaria , ChinAleong Joanna , Feakins Roger , Giannoulatou Eleni , James Louisa K , Stagg Andy J , Lindsay James Oliver , Silver Andrew 
Published: September 2023

AbstractWe used human full thickness Crohn’s disease (CD) small bowel resection specimens and single cell RNA sequencing to identify potential therapeutic targets for stricturing (S)CD. Using an unbiased approach, 16 cell lineages were assigned within 14,539 sequenced cells from patient-matched SCD and non-stricturing (NSCD) preparations. SCD and NSCD contained identical cell types. Amongst immune cells, B cells and plasma cells were selectively increased in SCD samples. B cell subsets suggested formation of tertiary lymphoid tissue in SCD and compared with NSCD there was an increase in IgG, and a decrease in IgA plasma cells, consistent with their potential role in CD fibrosis. Two Lumican-positive fibroblast subtypes were identified and subclassified based on expression of selectively enriched genes as fibroblast clusters (C)12 and C9. Cells within these clusters expressed the profibrotic genesDecorin(C12) andJUN(C9). C9 cells expressedACTA2; ECM genesCOL4A1, COL4A2, COL15A1, COL6A3, COL18A1andADAMDEC1;LAMB1andGREM1. GO and KEGG Biological terms showed extracellular matrix, stricture organisation and regulation ofWNTpathway genes are associated with the C12 and C9 gene sets. Trajectory and differential gene analysis of C12 and C9 identified four sub-clusters. Intra sub-cluster gene analysis detected co-regulated gene modules that aligned along predicted pseudotime trajectories and identifiedCXCL14andADAMDEC1as key module markers. Our findings support further investigation of fibroblast heterogeneity and interactions with local and circulating immune cells at earlier time points in fibrosis progression. Breaking these interactions by targeting one or other population may improve therapeutic management for SCD.
Obesity Prediction in Young Adults from the Jerusalem Perinatal Study: Contribution of Polygenic Risk and Early Life Exposures
Authors: Hochner Hagit , Butterman Rachely , Margaliot Ido , Friedlander Yechiel , Linial Michal 
Published: September 2023

AbstractWe assessed whether adding early life exposures to a model based on polygenic risk score (PRS) improves prediction of obesity risk. We used a birth cohort with data at birth and BMI and waist circumference (WC) measured at age 32. The PRS was composed of SNPs identified in GWAS for BMI. Linear and logistic models were used to explore associations with obesity-related phenotypes. Improvement in prediction was assessed using measures of model discrimination (AUC), and net reclassification improvement (NRI). One SD change in PRS was associated with a significant increase in BMI and WC. These associations were slightly attenuated (13.7%-14.2%) with the addition of early life exposures to the model. Also, higher maternal pre-pregnancy BMI was associated with increase in offspring BMI and WC (p<0.001). For prediction obesity (BMI ≥ 30), the addition of early life exposures to the PRS model significantly increase the AUC from 0.69 to 0.73. At an obesity risk threshold of 15%, the addition of early life exposures to the PRS model provided a significant improvement in reclassification of obesity (NRI, 0.147; 95% CI 0.068-0.225). We conclude that inclusion of early life exposures to a model based on PRS improves obesity risk prediction in an Israeli population-sample.
Phonological Processing is Below Expectations and Linked to Word-Finding Difficulty in Multiple Sclerosis
Authors: Sumowski James F. , Dvorak Emily , Levy Sarah , Anderson Jordyn R. 
Published: September 2023

ABSTRACTBackgroundWord-finding difficulty is prevalent but poorly understood in persons with relapsing-remitting multiple sclerosis (RRMS).ObjectiveInvestigate our hypothesis that phonological processing ability is below expectations and related to word-finding difficulty in patients with RRMS.MethodData were analyzed from patients with RRMS (n=50) on patient-reported word-finding difficulty (PW-WFD) and objective performance on WIAT-4 Phonemic Proficiency (PP; analysis of phonemes within words), Word-Reading (WR, proxy of premorbid literacy and verbal ability), and Sentence Repetition (SR; auditory processing of word-level information).ResultsPerformance (mean [95% CI]) was reliably lower than normative expectations for PP (− 0.41[-0.69, -0.13]) but not for WR (0.02[-0.21, 0.25]) or SR (0.08[-0.15, 0.31]. Within-subjects performance was worse on PP than both WR (t[49]=4.00, p<0.001, d=0.47) and SR (t[49]=3.76, p<0.001, d=0.54). Worse PR-WFD was specifically related to lower PP (F2,47=6.24, p=0.004, η2=0.21); worse PP performance at PR-WFD Often (n=13; -1.16[-1.49, -0.83]) than Sometimes (n=17; -0.14[-0.68, 0.41]) or Rarely (n=20; -0.16[-0.58, 0.27]. PR-WFD was unrelated to WR or SR (Ps>0.25).ConclusionPhonological processing was below expectations and specifically linked to word-finding difficulty in RRMS. Findings are consistent with early disease-related cortical changes within the posterior superior temporal / supramarginal region. Results inform our developing model of MS-related word-finding difficulty.
Characterizing the phenotypic and genetic structure of psychopathology in UK Biobank
Authors: Williams Camille M. , Peyre Hugo , Wolfram Tobias , Lee Younga H. , Ge Tian , Smoller Jordan W. , Mallard Travis T. , Ramus Franck 
Published: September 2023

AbstractMental conditions exhibit a higher-order transdiagnostic factor structure which helps to explain the widespread comorbidity observed in psychopathology. However, the phenotypic and genetic structures of psychopathology may differ, raising questions about the validity and utility of these factors. Here, we study the phenotypic and genetic factor structures of ten psychiatric conditions using UK Biobank and public genomic data. Although the factor structure of psychopathology was generally genetically and phenotypically consistent, conditions related to externalizing (e.g., alcohol use disorder) and compulsivity (e.g., eating disorders) exhibited cross-level disparities in their relationships with other conditions, plausibly due to environmental influences. Domain-level factors, especially thought disorder and internalizing factors, were more informative than a general psychopathology factor in genome-wide association and polygenic index analyses. Collectively, our findings enhance the understanding of comorbidity and shared etiology, highlight the intricate interplay between genes and environment, and offer guidance for psychiatric research using polygenic indices.
Assessing the Economic Burden of Alcohol Use in India Compared to Excise Taxes on Alcohol Sales
Authors: Zadey Siddhesh 
Published: September 2023

AbstractBackgroundAlcohol use is among the topmost public health risk factors. There is a dearth of evidence on the broader impact of alcohol use on society, especially, for lower-middle-income countries like India. We retrospectively studied the economic burden of alcohol use and compared it with revenue from excise taxes on alcohol sales for India and its states in 2019.MethodsFor estimating the overall alcohol-attributable disease burden, disability-adjusted life-years or DALYs for India and its 30 states were extracted for all causes, all age groups, and both sexes with alcohol use as a risk factor from the Global Burden of Disease 2019 Study. Economic burden was calculated by the value of life-year (VLY) or full-income approach. National and state-level (top 10 revenue-earning states) data on excise taxes on alcohol sales were acquired from the Reserve Bank of India. Net losses were assessed by subtracting the revenue from the economic burden. All values are in Indian rupees (INR). Sensitivity analysis was conducted using different discount rates (0%, 3%, and 7%) for VLY values while uncertainty was propagated using 95% uncertainty intervals (UIs) for DALYs.ResultsThe economic burden of alcohol use in India was 6.2 (95% UI: 4.8, 7.8) trillion INR in 2019. State-level burden varied from 7.3 (4.7, 10.4) billion INR in Mizoram to 1.1 (0.8, 1.4) trillion INR in Maharashtra. Nationally, revenue was 1.8 trillion INR depicting a net loss of 4.4 (3.1, 6.0) trillion. Net loss was largest in Maharashtra and smallest in Telangana. Sensitivity analyses confirmed that all ten states depicted losses in the case of a 3% discount rate, while five and seven states showed losses at 0% and 7% discount rates.ConclusionThese are novel subnational estimates depicting annual net losses due to alcohol use in India with direct policy implications to disincentivize alcohol sales and raise taxes to an adequate level.HighlightsThe annual economic burden of alcohol use in India runs over six trillion rupees.Economic burden exceeds revenue from excise taxes noting net loss.Economic burden varies across states with Maharashtra having the largest burden.All of the top ten revenue-earning states depict net losses in primary analysis.
Long-term longitudinal analysis of 4,187 participants reveals new insights into determinants of incident clonal hematopoiesis
Authors: Uddin Md Mesbah , Saadatagah Seyedmohammad , Niroula Abhishek , Yu Bing , Hornsby Whitney , Ganesh Shriienidhie , Lannery Kim , Shuermans Art , Honigberg Michael C. , Bick Alexander G. , Libby Peter , Ebert Benjamin L. , Ballantyne Christie M. , Natarajan Pradeep 
Published: September 2023

AbstractClonal hematopoiesis (CH), characterized by blood cells predominantly originating from a single mutated hematopoietic stem cell, is linked to diverse aging-related diseases, including hematologic malignancy and atherosclerotic cardiovascular disease (ASCVD). While CH is common among older adults, the underlying factors driving its development are largely unknown. To address this, we performed whole-exome sequencing on 8,374 blood DNA samples collected from 4,187 Atherosclerosis Risk in Communities Study (ARIC) participants over a median follow-up of 21 years. During this period, 735 participants developed incident CH. We found that age at baseline, sex, and dyslipidemia significantly influence the incidence of CH, while ASCVD and other traditional risk factors for ASCVD did not exhibit such associations. Our study also revealed associations between germline genetic variants and incident CH, prioritizing genes in CH development. Our comprehensive longitudinal assessment yields novel insights into the factors contributing to incident CH in older adults.
Evaluating the Potential Blood Coagulant Activity ofCaenothus americanus Compounds: Computational Analysis using Docking, Physicochemical, and ADMET Studies
Authors: Mashkani Zahra Sadat , Yali Zahra Pahlavan , Dorgalaleh Akbar , Shams Mahmood 
Published: September 2023

AbstractCaenothus americanusis a common folk remedy for the treatment of wound bleeding. Certain compounds found in this plant have been shown to reduce clotting time. However, analyzing the effects of various compounds of a folk remedy is a time-consuming and expensive process, therefore, this study employed computational analyses using docking, physicochemical, and pharmacokinetic servers to identify potential clotting activity in C.americanus compounds. The ADMETlab, SwissADME web servers, Discovery Studio, and Autodock were used to study the proper binding to target proteins and predict the physicochemical and ADMET properties (adsorption, distribution, metabolism, excretion, and toxicity) of C. americanus compounds. Coagulation factors including activated factor (F) IIa, FVa, FVIIa, FVIIIa, FIXa, FXa, FXIa, FXIIa, and FXIIIa were chosen as target proteins. Docking studies revealed that malic acid, malonic acid, oxalic acid, and succinic acid were effective on coagulation factors, of which, malic acid had better binding to intrinsic pathway factors including FVIIa, FIIa, and FXIIIa (except FVIIIa), oxalic acid to FVIIIa, and malonic acid to FVa and FXa. Moreover, ADMET studies showed the safety profile of these compounds. In conclusion, carboxylic and alcoholic groups of malic acid, malonic acid, oxalic acid and succinic acid play a role in interaction with blood coagulation factors. Additionally, based on the ADMET characteristics and suitable pharmacokinetic potentials of these compounds, they can be introduced as blood coagulant candidates with fewer side effects in bleeding disorders. However, further studies are necessary to evaluate the precise components of theC. americanuswith the suability to bind coagulation factors.
The Quest to Identify USP8 Inhibitors for Parkinson’s Disease, a PAINful Experience
Authors: Lang Stuart , Bellany Fiona , Lin De , Barrett Denise S , Cartmill Kieran R. , Fletcher Daniel A. , Kerr Catrina , Plater Andrew , Forte Barbara , Baragaña Beatriz , Dixit Parul , Littleson Mairi M. , Wheldon Mary C. , Gray David W. , Cunningham Fraser 
Published: September 2023

AbstractPan Assay INterference compoundS (PAINS) are known to be a source of false positives in High Throughput Screening (HTS) campaigns. This has become a major problem in medicinal chemistry, often resulting in undesirable project outcomes and increased overall cost. Our recent campaign to identify inhibitors of USP8 that could be used in the treatment of Parkinson’s disease identified several PAINS that workedviaa variety of mechanisms. Herein, we discuss the process developed to identify not only the PAINS but also confirming the interference mechanism causing their activity. We found in this project that our USP8 assay was susceptible to multiple modes of interference, making it difficult to identify genuine hit molecules.Abstract Figure