bluuebunny/crossref_metadata_2025_split huggingface dataset:
The involvement of effector memory CD4+ T cells in mediating the impact of genus Oscillibacter gut microbiota on Alzheimer’s disease: a Mendelian randomization study
Authors: Zhang Huachang , Wang Yudong , Zhao Hui , Wang Wei , Han Fabin 
Published: August 2024

ObjectiveThis study aimed to investigate the causal relationship between gut microbiota characteristics (207 taxa and 205 pathways) and Alzheimer’s disease and determine and quantify the role of immune cells as potential mediators.MethodsGut microbiota characteristics (207 taxa and 205 pathways) were obtained from the NHGRI-EBI GWAS Catalog project, while Alzheimer’s disease data and 731 immune cell characteristics were obtained from the IEU Open GWAS project. Two-sample Mendelian randomization (MR) was conducted to determine whether gut microbiota characteristics (207 taxa and 205 pathways) were causally related to Alzheimer’s disease. Furthermore, two-step MR was employed to quantify the proportion of the effect of immune cell characteristics mediated by gut microbiota characteristics (207 taxa and 205 pathways) on Alzheimer’s disease.ResultsA total of 17 immune cell characteristics were identified as potential mediators for 13 gut microbiota influencing Alzheimer’s disease, with Effector Memory CD4+ T-cell Absolute Count accounted for 8.99% of the causal relationship between genus Oscillibacter and Alzheimer’s disease.ConclusionIn summary, our research confirms a causal relationship between gut microbiota and Alzheimer’s disease, with immune cells contributing to a significant portion of the effect. However, the full mediators of gut microbiota’s impact on Alzheimer’s disease remain unclear. Further investigation is warranted to explore additional potential risk factors acting as mediators.
Therapeutic approaches targeting seizure networks
Authors: Langbein Jenna , Boddeti Ujwal , Kreinbrink Matthew , Khan Ziam , Rampalli Ihika , Bachani Muzna , Ksendzovsky Alexander 
Published: August 2024

Epilepsy is one of the most common neurological disorders, affecting over 65 million people worldwide. Despite medical management with anti-seizure medications (ASMs), many patients fail to achieve seizure freedom, with over one-third of patients having drug-resistant epilepsy (DRE). Even with surgical management through resective surgery and/or neuromodulatory interventions, over 50% of patients continue to experience refractory seizures within a year of surgery. Over the past 2 decades, studies have increasingly suggested that treatment failure is likely driven by untreated components of a pathological seizure network, a shift in the classical understanding of epilepsy as a focal disorder. However, this shift in thinking has yet to translate to improved treatments and seizure outcomes in patients. Here, we present a narrative review discussing the process of surgical epilepsy management. We explore current surgical interventions and hypothesized mechanisms behind treatment failure, highlighting evidence of pathologic seizure networks. Finally, we conclude by discussing how the network theory may inform surgical management, guiding the identification and targeting of more appropriate surgical regions. Ultimately, we believe that adapting current surgical practices and neuromodulatory interventions towards targeting seizure networks offers new therapeutic strategies that may improve seizure outcomes in patients suffering from DRE.
The characteristics and reproducibility of motor speech functional neuroimaging in healthy controls
Authors: Kenyon Katherine H. , Boonstra Frederique , Noffs Gustavo , Morgan Angela T. , Vogel Adam P. , Kolbe Scott , Van Der Walt Anneke 
Published: August 2024

IntroductionFunctional magnetic resonance imaging (fMRI) can improve our understanding of neural processes subserving motor speech function. Yet its reproducibility remains unclear. This study aimed to evaluate the reproducibility of fMRI using a word repetition task across two time points.MethodsImaging data from 14 healthy controls were analysed using a multi-level general linear model.ResultsSignificant activation was observed during the task in the right hemispheric cerebellar lobules IV-V, right putamen, and bilateral sensorimotor cortices. Activation between timepoints was found to be moderately reproducible across time in the cerebellum but not in other brain regions.DiscussionPreliminary findings highlight the involvement of the cerebellum and connected cerebral regions during a motor speech task. More work is needed to determine the degree of reproducibility of speech fMRI before this could be used as a reliable marker of changes in brain activity.
Effect of intra-vaginal electric stimulation on bladder compliance in stress urinary incontinence patients: the involvement of autonomic tone
Authors: Lau Hui-Hsuan , Lai Cheng-Yuan , Hsieh Ming-Chun , Peng Hsien-Yu , Chou Dylan , Su Tsung-Hsien , Lee Jie-Jen , Lin Tzer-Bin 
Published: August 2024

ObjectiveIn addition to the well-established advantage that strengthened pelvic musculature increases urethral resistance in stress urinary incontinence (SUI) patients, intra-vaginal electrical stimulation (iVES) has been shown in preclinical studies to improve bladder capacity via the pudendal-hypogastric mechanism. This study investigated whether iVES also benefits bladder storage in SUI patients by focusing on compliance, a viscoelastic parameter critically defining the bladder’s storage function, in a clinical study. Moreover, the potential involvement of stimulation-induced neuromodulation in iVES-modified compliance was investigated by comparing the therapeutic outcomes of SUI patients treated with iVES to those who underwent a trans-obturator tape (TOT) implantation surgery, where a mid-urethral sling was implanted without electric stimulation.Patients and methodsUrodynamic and viscoelastic data were collected from 21 SUI patients treated with a regimen combining iVES and biofeedback-assisted pelvic floor muscle training (iVES-bPFMT; 20-min iVES and 20-min bPFMT sessions, twice per week, for 3 months). This regimen complied with ethical standards. Data from 21 SUI patients who received TOT implantation were retrospectively analyzed. Mean compliance (Cm), infused volume (Vinf), and threshold pressure (Pthr) from the pressure-flow/volume investigations were assessed.ResultsCompared with the pretreatment control, iVES-bPFMT consistently and significantly increased Cm (18/21; 85%, p = 0.017, N = 21) and Vinf (16/21; 76%, p = 0.046; N = 21) but decreased Pthr (16/21; 76%, p = 0.026, N = 21). In contrast, TOT implantation did not result in consistent or significant changes in Cm, Vinf, or Pthr (p = 0.744, p = 0.295, p = 0.651, respectively; all N = 21).ConclusionOur results provide viscoelastic and thermodynamic evidence supporting an additional benefit of iVES-bPFMT to bladder storage in SUI patients by modifying bladder compliance, possibly due to the potentiated hypogastric tone, which did not occur in TOT-treated SUI patients.Clinical trial registration:ClinicalTrials.gov, NCT02185235 and NCT05977231.
Association of chronotype with language and episodic memory processing in children: implications for brain structure
Authors: Yamashita Masatoshi , Shou Qiulu , Mizuno Yoshifumi 
Published: August 2024

IntroductionChronotype refers to individual preference in circadian cycles and is associated with psychiatric problems. It is mainly classified into early (those who prefer to be active in the morning and sleep and wake up early) and late (those who prefer to be active in the evening and sleep and wake up late) chronotypes. Although previous research has demonstrated associations between chronotype and cognitive function and brain structure in adults, little is known regarding these associations in children. Here, we aimed to investigate the relationship between chronotype and cognitive function in children. Moreover, based on the significant association between chronotype and specific cognitive functions, we extracted regions-of-interest (ROI) and examined the association between chronotype and ROI volumes.MethodsData from 4,493 children (mean age of 143.06 months) from the Adolescent Brain Cognitive Development Study were obtained, wherein chronotype (mid-sleep time on free days corrected for sleep debt on school days) was assessed by the Munich Chronotype Questionnaire. Subsequently, the associations between chronotype, cognitive function, and ROI volumes were evaluated using linear mixed-effects models.ResultsBehaviorally, chronotype was negatively associated with vocabulary knowledge, reading skills, and episodic memory performance. Based on these associations, the ROI analysis focused on language-related and episodic memory-related areas revealed a negative association between chronotype and left precentral gyrus and right posterior cingulate cortex volumes. Furthermore, the precentral gyrus volume was positively associated with vocabulary knowledge and reading skills, while the posterior cingulate cortex volume was positively associated with episodic memory performance.DiscussionThese results suggest that children with late chronotype have lower language comprehension and episodic memory and smaller brain volumes in the left precentral gyrus and right posterior cingulate cortex associated with these cognitive functions.
Single-cell RNA and T-cell receptor sequencing unveil mycosis fungoides heterogeneity and a possible gene signature
Authors: Srinivas Nalini , Peiffer Lukas , Horny Kai , Lei Kuan Cheok , Buus Terkild B. , Kubat Linda , Luo Meng , Yin Menghong , Spassova Ivelina , Sucker Antje , Farahpour Farnoush , Kehrmann Jan , Ugurel Selma , Livingstone Elisabeth , Gambichler Thilo , Ødum Niels , Becker Jürgen C. 
Published: August 2024

BackgroundMycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma (CTCL). Comprehensive analysis of MF cells in situ and ex vivo is complicated by the fact that is challenging to distinguish malignant from reactive T cells with certainty.MethodsTo overcome this limitation, we performed combined single-cell RNA (scRNAseq) and T-cell receptor TCR sequencing (scTCRseq) of skin lesions of cutaneous MF lesions from 12 patients. A sufficient quantity of living T cells was obtained from 9 patients, but 2 had to be excluded due to unclear diagnoses (coexisting CLL or revision to a fixed toxic drug eruption).ResultsFrom the remaining patients we established single-cell mRNA expression profiles and the corresponding TCR repertoire of 18,630 T cells. TCR clonality unequivocally identified 13,592 malignant T cells. Reactive T cells of all patients clustered together, while malignant cells of each patient formed a unique cluster expressing genes typical of naive/memory, such as CD27, CCR7 and IL7R, or cytotoxic T cells, e.g., GZMA, NKG7 and GNLY. Genes encoding classic CTCL markers were not detected in all clusters, consistent with the fact that mRNA expression does not correlate linearly with protein expression. Nevertheless, we successfully pinpointed distinctive gene signatures differentiating reactive malignant from malignant T cells: keratins (KRT81, KRT86), galectins (LGALS1, LGALS3) and S100 genes (S100A4, S100A6) being overexpressed in malignant cells.ConclusionsCombined scRNAseq and scTCRseq not only allows unambiguous identification of MF cells, but also revealed marked heterogeneity between and within patients with unexpected functional phenotypes. While the correlation between mRNA and protein abundance was limited with respect to established MF markers, we were able to identify a single-cell gene expression signature that distinguishes malignant from reactive T cells.
Indications and adverse events of teriparatide: based on FDA adverse event reporting system (FAERS)
Authors: Wen Ming-Tao , Li Jia-Cheng , Lu Bo-Wen , Shao Hua-Rong , Ling Pei-Xue , Liu Fei , Li Gang , Luo Di 
Published: August 2024

BackgroundTeriparatide is approved for osteoporosis. Post-marketing surveillance is critical given its widespread use.ObjectiveTo investigate adverse events (AEs) associated with teriparatide using the FAERS database, compare association strengths for key AEs, and explore potential applications to provide clinical reference.MethodsFAERS data from 2004 to 2023 were analyzed. Reports where teriparatide was the primary suspect drug were included. Adverse events were mapped to System Organ Classes and Preferred Terms. Disproportionality analysis using ROR, PRR, BCPNN and EBGM algorithms was conducted to detect safety signals.ResultsOut of 107,123 reports with teriparatide as the primary suspect, key AEs identified included pain in extremity (PRR: 4.54), muscle spasms (PRR: 5.11), fractures (PRR range: 17.67–552.95), and increased calcium levels (PRR: 50.73). Teriparatide exhibited a stronger association with increased calcium levels (PRR: 50.73) compared to fractures (PRR range: 17.67–552.95). Notably, only 10.86% of AE reports were submitted by physicians and another 10% by other health professionals. Subset analyses showed a higher consistency of reported AEs from health professionals compared to the general dataset. Off-label uses were noted in conditions such as arthritis (0.57%) and cancer (0.12%). For osteoporosis, main AEs were pain (18.2%), fractures (12.4%), muscle spasms (7.7%), and nausea (6.5%), while glucocorticoid-induced osteoporosis AEs included fractures (24.1%), pain (13.2%), decreased bone density (9.8%), and nausea (5.1%).ConclusionOur findings provide real-world safety data on teriparatide, revealing key AEs and their association strengths. The low proportion of reports by healthcare professionals suggests the need for cautious interpretation. Continuous vigilance and further research are imperative to guide teriparatide’s clinical use.
Comprehensive mendelian randomization reveals atrial fibrillation-breast cancer relationship and explores common druggable targets
Authors: Qi Fenglin , Yang Lunzhe , Chang Guanglei , Wang Xiangbin , Tao Guanghong , Xiao Hua 
Published: August 2024

BackgroundAtrial fibrillation (AF) and breast cancer pose significant risks to human health. The reasons behind the concurrent occurrence of AF and breast cancer remain unclear, leading to complex treatment approaches. Mendelian Randomization (MR) analyses aim to offer genetic evidence supporting the causation of AF and breast cancer and to investigate common druggable genes associated with both conditions.MethodsWe used two-samples of MR to sequentially explore the causal relationship between atrial fibrillation and breast cancer, and between atrial fibrillation and breast cancer therapeutic drugs, and verified the stability of the results through colocalization analysis. We utilized the Connectivity map database to infer the direction of drug effects on disease. Finally, we explored druggable genes that play a role in AF and breast cancer and performed a Phenome-wide MR analysis to analyze the potential side effects of drug targets.ResultsWe found 15 breast cancer therapeutic drugs that significantly support a causal association between AF and breast cancer through expression in blood and/or atrial appendage tissue. Among these, activation of ANXA5 by Docetaxel, inhibition of EIF5A by Fulvestrant, and inhibition of GNA12 by Tamoxifen increased the risk of AF, while inhibition of ANXA5 by Gemcitabine and Vinorebine and inhibition of PCGF6 by Paclitaxel reduced the risk of AF. Inhibition of MSH6 and SF3B1 by Cyclophosphamide, as well as inhibition of SMAD4 and PSMD2 and activation of ASAH1 and MLST8 by Doxorubicin can have bidirectional effects on AF occurrence. XBP1 can be used as a common druggable gene for AF and breast cancer, and there are no potential side effects of treatment against this target.ConclusionThis study did not find a direct disease causality between AF and breast cancer but identified 40 target genes for 15 breast cancer therapeutic drugs associated with AF, clarified the direction of action of 8 breast cancer therapeutic drugs on AF, and finally identified one common druggable target for AF and breast cancer.
Mind wandering is not always harmful in sports: the role of its content
Authors: Li Jieling , Li Chuangye , Xue Shuangpeng , He Yuxiu 
Published: August 2024

ObjectiveMind wandering (MW) among athletes during training and competition can lead to poor performance. However, MW has also been found to have positive effects. This study aims to clarify the causes of the bidirectional (negative and positive) effects of MW in the sports context, specifically focusing on whether these effects are related to the content of MW.MethodsA total of 846 Chinese athletes completed the Chinese version of the MW scales. The survey data were tested for common method biases. Subsequently, Pearson correlation analysis and structural equation modeling were performed using SPSS 25.0 and Mplus 7.0.ResultsThe frequency of MW can positively predict its bidirectional effects. MW content plays an important role in the relationships between MW frequency and its negative and positive effects, but the direction of influence varies depending on the content.ConclusionMW in sports is not always harmful, and its content plays an important role. These findings suggest that managing MW content may be a promising MW intervention method for improving performance in sports.
The effect of sexual orientation on voice acoustic properties
Authors: Holmes Luke , Rieger Gerulf , Paulmann Silke 
Published: August 2024

IntroductionPrevious research has investigated sexual orientation differences in the acoustic properties of individuals’ voices, often theorizing that homosexuals of both sexes would have voice properties mirroring those of heterosexuals of the opposite sex. Findings were mixed, but many of these studies have methodological limitations including small sample sizes, use of recited passages instead of natural speech, or grouping bisexual and homosexual participants together for analyses.MethodsTo address these shortcomings, the present study examined a wide range of acoustic properties in the natural voices of 142 men and 175 women of varying sexual orientations, with sexual orientation treated as a continuous variable throughout.ResultsHomosexual men had less breathy voices (as indicated by a lower harmonics-to-noise ratio) and, contrary to our prediction, a lower voice pitch and narrower pitch range than heterosexual men. Homosexual women had lower F4 formant frequency (vocal tract resonance or so-called overtone) in overall vowel production, and rougher voices (measured via jitter and spectral tilt) than heterosexual women. For those sexual orientation differences that were statistically significant, bisexuals were in-between heterosexuals and homosexuals. No sexual orientation differences were found in formants F1–F3, cepstral peak prominence, shimmer, or speech rate in either sex.DiscussionRecommendations for future “natural voice” investigations are outlined.
Within-child associations between sleep quality and emotional self-regulation over 6 months among preschool-aged (3- to 5-year-old) children
Authors: Godzik Cassandra M. , Carlson Delaina D. , Pashchenko Oleksandra I. , Ballarino Grace A. , Emond Jennifer A. 
Published: August 2024

ObjectiveWe leveraged an observational, repeated-measures study to examine the within-child associations between sleep quality and emotional self-regulation, controlling for between-child effects.MethodsChildren aged 3–5 years and one parent each were recruited from the community in northern New England between 2019 and 2022. Parents completed online surveys at baseline and 2, 4, and 6 months post-baseline. Child sleep quality was measured with the validated Children's Sleep Habits Questionnaire modified for preschoolers; higher scores indicate worse sleep quality (range 32–96). Child emotional self-regulation was measured with the validated Child Social Behavior Questionnaire; higher scores indicate better emotional self-regulation (range 1–7). Adjusted mixed-effects linear regression was used to model the associations between nighttime sleep quality (exposure) and emotional self-regulation (outcome) measured at each of the four study time points while disaggregating the between- and within-child effects.ResultsChildren (n = 91) were largely white, non-Hispanic (88.7%), and from a higher social-economic status. Sleep quality scores averaged 38.9 (SD: 6.6) at baseline; 23.1% of children had scores &gt;41, which is considered evidence of significant sleep problems. Emotional self-regulation scores averaged 4.2 (SD: 1.0). There was a significant within-child association between sleep quality and emotional self-regulation. Specifically, a decrease in sleep quality at any one time point, relative to each child's mean sleep quality, related to worse emotional self-regulation [standardized beta, βs = −0.31; 95% CI (0.53, −0.09)]; the between-child effect was not significant. Results were consistent when limited to children with complete data at all study visits (n = 78).ConclusionsThe findings support a causal, within-child association between sleep quality and emotional self-regulation in preschool-aged children, with effects evident over 6 months.
Perceived benefits and barriers to exercise and associated factors among Zimbabwean undergraduate students: a cross-sectional study
Authors: Shava Beatrice K. , Vhudzijena Blessed , Kupenga-Maposa Tariro , Musingwini Thelma , Samudzi Tanaka , Muchemwa Sidney , Chibanda Dixon , Dambi Jermaine M. 
Published: August 2024

BackgroundDespite the well-documented benefits of regular physical activity (PA), many university students are physically inactive. Personal, socio-economic, and environmental factors predict PA engagement behaviours in university students. There is a need to understand context-specific perceived barriers and benefits to exercise engagement and physical activity levels amongst university students from low-income settings. This study primarily evaluated the barriers and facilitators to PA engagement in Zimbabwean undergraduate students. We also assessed the correlates of perceived barriers and benefits to PA engagement, risk of common mental disorders (CMDs) and health-related quality of life (HRQoL).MethodsWe used a cross-sectional study to recruit 465 university undergraduate students. The Exercise Benefits and Barriers Scale, International Physical Activity Questionnaire (IPAQ), Shona Symptoms Questionnaire (SSQ-8) and EuroQol 5 Dimension (EQ5D-5l) were used to measure barriers and facilitators, physical activity level, risk of depression and anxiety and HRQoL, respectively. Data were analysed through descriptive statistics and logistic regression.Results and conclusionMost participants were male (58.5%) with a mean age of 21.7 (SD 1.6) years. Majority of the participants were first year students (37.2%), consumed alcohol (66.5%), did not smoke (88.2%) and had a normal BMI (64.7%). The prevalence of low PA levels was 17.4%, with 33.5% of students at risk of CMDs. The most perceived benefits were in the physical performance (e.g., exercise improves my level of physical fitness) and life enhancement (e.g., exercise improves my self-concept) domains, while the most perceived barriers were lack of exercise infrastructure (e.g., exercise facilities do not have convenient schedules) and physical exertion (e.g., exercise tires me). Food insecurity (AOR 2.51: 95% CI 1.62–3.88) and the risk of CMDs (AOR 0.49: 95% CI 0.32–0.76) were associated with increased odds of experiencing barriers to exercise. Not using substances (AOR = 2.14: 95% CI 1.11–4.14) and a higher self-rated HRQoL (AOR 24.34: 95% CI 1.77–335.13) were associated with increased odds of a high perception of exercise benefits. Improving access to community and on-campus exercise facilities and campus-wide health promotional interventions is necessary to enhance PA amongst university students.