bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hyperuricemia suppresses lumican, exacerbating adverse remodeling after myocardial infarction by promoting fibroblast phenotype transition
Authors: Zhuang Zehao , Liu Ao , Zhang Jinghong , Han Shuangjian , Tang Lu , Yu Tingting , Shi Yiping , Li Hui , Yang Heng , Bai Peiyuan , Tang Yanhua 
Published: October 2024

Abstract
Background
Hyperuricemia is independently associated with a poor prognosis in patients with myocardial infarction (MI). Furthermore, MI induces activation of the repair response in local fibroblasts, resulting in extracellular matrix accumulation that generates a stable fibrotic scar in the infarcted area. However, researchers have not determined whether hyperuricemia affects fibroblast activation and its involvement in postinfarction cardiac remodeling.

Objectives
We aimed to trigger hyperuricemia by administering potassium oxonate in a mouse model of MI to evaluate the role of hyperuricemia in MI pathogenesis.

Methods
Microarray datasets and single-cell sequencing data from gout patients, heart failure patients, and model mice were used to identify the underlying mechanisms responsible for the effect of hyperuricemia on MI progression. A hyperuricemia-related MI mouse model was established. Cardiac function was assessed, followed by sample collection and a uric acid assay. We conducted an enzyme-linked immunosorbent assay, histological detection, immunofluorescence, sequencing data processing, single-cell RNA-seq, and functional enrichment analysis. We then isolated and cultured cardiac fibroblasts and performed Western blotting, quantitative real-time polymerase chain reaction, and shRNA-mediated lumican knockdown assays.

Results
Hyperuricemia decreased cardiac function, increased mortality, and aggravated adverse fibrosis remodeling in mice after MI. These outcomes were closely related to reduced levels of fibroblast-derived lumican. This reduction activated the TGF-β/SMAD signaling pathway to induce aberrant myofibroblast activation and extracellular matrix deposition in the infarcted area. Furthermore, lumican supplementation or uric acid-lowering therapy with allopurinol alleviated hyperuricemia-mediated abnormal cardiac remodeling.

Conclusion
Hyperuricemia aggravates postinfarction cardiac remodeling by reducing lumican expression and promoting fibroblast phenotype transition. We highlight the clinical importance of lowering uric acid levels in hyperuricemia-related MI to prevent adverse ventricular remodeling.
Operational and organizational variation in determinants of policy implementation success: the case of policies that earmark taxes for behavioral health services
Authors: Purtle Jonathan , Stadnick Nicole A. , Mauri Amanda I. , Walker Sarah C. , Bruns Eric J. , Aarons Gregory A. 
Published: October 2024

Abstract
Background
Research on determinants of health policy implementation is limited, and conceptualizations of evidence and implementation success are evolving in the field. This study aimed to identify determinants of perceived policy implementation success and assess whether these determinants vary according to: (1) how policy implementation success is operationally defined [i.e., broadly vs. narrowly related to evidence-based practice (EBP) reach] and (2) the role of a person’s organization in policy implementation. The study focuses on policies that earmark taxes for behavioral health services.

Methods
Web-based surveys of professionals involved with earmarked tax policy implementation were conducted between 2022 and 2023 (N = 272). The primary dependent variable was a 9-item score that broadly assessed perceptions of the tax policy positively impacting multiple dimensions of outcomes. The secondary dependent variable was a single item that narrowly assessed perceptions of the tax policy increasing EBP reach. Independent variables were scores mapped to determinants in the Exploration, Preparation, Implementation, and Sustainment (EPIS) framework. Multiple linear regression estimated associations between measures of determinants and policy implementation success.

Results
Perceptions of tax attributes (innovation determinant), tax EBP implementation climate (inner-context determinant), and inter-agency collaboration in tax policy implementation (outer-context and bridging factor determinant) were significantly associated with perceptions of policy implementation success. However, the magnitude of associations varied according to how success was operationalized and by respondent organization type. For example, the magnitude of the association between tax attributes and implementation success was 42% smaller among respondents at direct service organizations than non-direct service organizations when implementation success was operationalized broadly in terms of generating positive impacts (β = 0.37 vs. β = 0.64), and 61% smaller when success was operationalized narrowly in terms of EBP reach (β = 0.23 vs. β = 0.59). Conversely, when success was operationalized narrowly as EBP reach, the magnitude of the association between EBP implementation climate and implementation success was large and significant among respondents at direct service organizations while it was not significant among respondents from non-direct service organizations (β = 0.48 vs. β=-0.06).

Conclusion
Determinants of perceived policy implementation success may vary according to how policy implementation success is defined and the role of a person’s organization in policy implementation. This has implications for implementation science and selecting policy implementation strategies.
Posterior tracheal diverticulum: a case report
Authors: Safarian Afsaneh , Karimi Mehdi , Deravi Niloofar , Naseri Reza , Agin Khosrow 
Published: October 2024

Abstract
Background
Tracheal diverticulum is a rare condition often linked to other malformations. This case study highlights the posterior tracheal diverticulum, covering its causes, symptoms, diagnosis, treatment, and prognosis. The report is significant due to the rarity of tracheal diverticulum and potential for misdiagnosis, which can result in complications such as respiratory infections. The case offers novel insights into the presentation and management of tracheal diverticulum, helping to guide future diagnosis and treatment.

Case presentation
A 73-year-old Iranian man with a history of cardiac surgery 15 years ago was admitted to the Loghman Hakim Hospital in Tehran, Iran, for retrosternal chest pain, shoulder radiation, and a persistent cough lasting 4 months. The patient underwent cardiac tests and a lung computed tomography scan, which showed a 16 × 18 mm air-filled outpouching connected to the trachea’s right posterolateral side, leading to a diagnosis of tracheal diverticulum. The patient was treated with bronchodilators and antibiotics.

Conclusions
Tracheal diverticulum is typically asymptomatic but can present with respiratory difficulties, dysphagia, and hoarseness. Diagnosis relies on imaging, and treatment ranges from conservative management to surgical intervention, particularly in symptomatic cases or those with complications. Recognizing tracheal diverticulum in surgical and anesthesia planning is crucial to prevent severe risks such as airway obstruction or trauma. This case report highlights the importance of early detection and personalized management, potentially improving patient outcomes and guiding clinical decision-making in similar cases.
Preregistered test of whether a virtual nose reduces cybersickness
Authors: Yip Sai Ho , Ng Adrian K. T. , Lau Henry Y. K. , Saunders Jeffrey A. 
Published: October 2024

AbstractRecent findings suggest that adding a visual depiction of a nose to virtual reality displays (virtual nose) can reduce motion sickness. If so, this would be a simple intervention that could improve the experience of a variety of VR applications. However, only one peer-reviewed study has reported a benefit from a virtual nose, and the effect was observed in a single low-powered experiment. To further test the effectiveness of a virtual nose for mitigating motion sickness in VR, we performed a preregistered experiment with higher power and better control. Subjects were presented with simulated movement in a virtual environment using a head-mounted display, and the resulting motion sickness was measured using the Fast Motion Sickness Scale (FMS) and the Simulator Sickness Questionnaire (SSQ). Conditions with and without a virtual nose were tested in separate sessions on different days, and the mean habituation effects were removed analytically. Awareness of the manipulation was assessed with a funnel debriefing procedure. The sample size (n = 32) was chosen to have over 90% power to detect the estimated effect size based on previous data (dz = 0.6). We found no significant difference between motion sickness in conditions with and without the virtual nose. The estimated effect size was close to zero, dz = − 0.02, with a 95% credible interval [− 0.37, 0.33]. Results from a Bayesian analysis imply that any benefit from a virtual nose is unlikely to be more than a 26% reduction in FMS scores, and any cost is unlikely to be more than a 23% increase. Our results do not support the hypothesis that a virtual nose is a general and effective way to relieve motion sickness in virtual reality.
Diagnostic and prognostic value of heparin-binding protein in pediatric community-acquired pneumonia
Authors: Mohamed Samah Abdelghany , Elmeazawy Rehab , Sharaby Radwa El , Razik Ahmed Abdel 
Published: October 2024

Abstract
Background
Community-acquired pneumonia (CAP) and its associated complications pose a noteworthy public health apprehension in the pediatric population, leading to considerable morbidity and mortality. The objective of this study was to assess the diagnostic and prognostic value of heparin-binding protein (HBP) as a promising biomarker in children hospitalized with CAP.

Methods
This prospective, single-center study included 50 children admitted to the Pediatric Pulmonology Unit between April 2023 and January 2024 with a diagnosis of CAP, as well as age-matched 50 healthy children as a control group. Demographic, clinical, and laboratory data were recorded. The measurement of serum HBP was conducted upon admission utilizing the enzyme-linked immunosorbent assay technique.

Results
Serum HBP was elevated in the CAP group in comparison to the control group (p < 0.001). Out of 50 patients, 27 (54.0%) had non-complicated pneumonia, and 23 (46.0%) had complicated pneumonia. The levels of HBP were significantly elevated in patients compared to the healthy control group and even higher in patients with complicated CAP compared to those with non-complicated CAP (p < 0.001). Analysis of the ROC curve revealed that the HBP level of ≥ 34.97 ng/ml was linked to a significantly higher AUC of 0.837 (95% CI 0.722–0.951, P < 0.001).

Conclusion
The level of HBP was observed to be notably elevated in patients as compared to the healthy control, thereby indicating its potential applicability in the early detection of CAP. Moreover, elevated HBP was an independent prognostic factor for complicated CAP in children.
Breast cancer risk among women with schizophrenia and association with duration of antipsychotic use: population-based cohort study in South Korea
Authors: Yang Ji Su , Kang Sunghyuk , Kim Kwanghyun , Tsai Alexander C. , Cho Chul-Hyun , Jung Sun Jae 
Published: October 2024

Background
Breast cancer is a major global health issue, especially among women. Previous research has indicated a possible association between psychiatric conditions, particularly schizophrenia, and an increased risk of breast cancer. However, the specific risk of breast cancer in women with schizophrenia, compared with those with other psychiatric disorders and the general population, remains controversial and needs further clarification.

Aims
To estimate the risk of breast cancer among people with schizophrenia compared with people with other psychiatric disorders and people in the general population.

Method
We utilised medical claims data of women aged 18 to 80 years in the Korean National Health Information Database from 2007 to 2018. Individuals with schizophrenia were defined as women with ICD-10 codes F20 or F25 (n = 224 612). The control groups were defined as women with other psychiatric disorders (n = 224 612) and women in the general Korean population (n = 449 224). Cases and controls were matched by index date and age, in a 1:1:2 ratio. We estimated the hazard of breast cancer using the Cox proportional hazards model, adjusting for insurance premiums and medical comorbidities. Among the people with schizophrenia, we used the landmark method to estimate the association between duration of antipsychotic medication use and the incidence of breast cancer.

Results
In multivariable Cox regression models, the hazard rate of breast cancer was 1.26 times higher in the people with schizophrenia than in the general population (95% CI: 1.20–1.32). In comparison with the psychiatric patient group, the hazard ratio was 1.17 (95% CI: 1.11–1.28). Among women with schizophrenia, the hazard of breast cancer was greater among those who took antipsychotic medications for 1 year or more compared with those who took antipsychotics for less than 6 months.

Conclusions
Women with schizophrenia have an elevated risk of breast cancer, and long-term use of antipsychotics is associated with an increased risk of breast cancer.
Large-Scale Pharmacogenomics Analysis of Patients With Cancer Within the 100,000 Genomes Project Combining Whole-Genome Sequencing and Medical Records to Inform Clinical Practice
Authors: Leong Ivone U.S. , Cabrera Claudia P. , Cipriani Valentina , Ross Paul J. , Turner Richard M. , Stuckey Alex , Sanghvi Sonali , Pasko Dorota , Moutsianas Loukas , Odhams Christopher A. , Elgar Greg S. , Chan Georgia , Giess Adam , Walker Susan , Foulger Rebecca E. , Williams Eleanor M. , Daugherty Louise C. , Rueda-Martin Antonio , Rhodes Daniel J. , Niblock Olivia , Pickard Alexandra , Marks Lauren , Leigh Sarah E.A. , Welland Matthew J. , Bleda Marta , Snow Catherine , Deans Zandra , Murugaesu Nirupa , Scott Richard H. , Barnes Michael R. , Brown Matthew A. , Rendon Augusto , Hill Sue , Sosinsky Alona , Caulfield Mark J. , McDonagh Ellen M. 
Published: October 2024

PURPOSE
As part of the 100,000 Genomes Project, we set out to assess the potential viability and clinical impact of reporting genetic variants associated with drug-induced toxicity for patients with cancer recruited for whole-genome sequencing (WGS) as part of a genomic medicine service.

METHODS

Germline WGS from 76,805 participants was analyzed for pharmacogenetic (PGx) variants in four genes (
DPYD
,
NUDT15
,
TPMT
,
UGT1A1
) associated with toxicity induced by five drugs used in cancer treatment (capecitabine, fluorouracil, mercaptopurine, thioguanine, irinotecan). Linking genomic data with prescribing and hospital incidence records, a phenome-wide association study (PheWAS) was performed to identify whether phenotypes indicative of adverse drug reactions (ADRs) were enriched in drug-exposed individuals with the relevant PGx variants. In a subset of 7,081 patients with cancer,
DPYD
variants were reported back to clinicians and outcomes were collected.

RESULTS

We identified clinically relevant PGx variants across the four genes in 62.7% of participants in our cohort. Extending this to annual prescription numbers in England for the drugs affected by these PGx variants, approximately 14,540 patients per year could potentially benefit from a reduced dose or alternative drug to reduce the risk of ADRs. Validating PGx associations in a real-world data set, we found a significant association between PGx variants in
DPYD
and toxicity-related phenotypes in patients treated with capecitabine or fluorouracil. Reported
DPYD
variants were deemed informative for clinical decision making in a majority of cases.

CONCLUSION
Reporting PGx variants from germline WGS relevant to patients with cancer alongside primary findings related to their cancer can be clinically informative, informing prescribing to reduce the risk of ADRs. Extending the range of actionable variants to those found in patients of non-European ancestry is important and will extend the potential clinical impact.
Testosterone acts through the membrane protein GPRC6A to cause cardiac edema in zebrafish embryos
Authors: Zadmajid Vahid , Shahriar Shayan , Gorelick Daniel A. 
Published: October 2024

ABSTRACT
Androgens are classically thought to act through intracellular androgen receptors (AR/NR3C4), but they can also trigger non-genomic effects via membrane proteins. Although several membrane androgen receptors have been characterized in vitro, their functions in vivo remain unclear. Using a chemical-genetic screen in zebrafish, we found that GPRC6A, a G-protein-coupled receptor, mediates non-genomic androgen actions during embryonic development. Exposure to androgens (androstanedione, DHT and testosterone) caused cardiac edema or tail curvature in wild-type embryos, as well as in ar mutants, suggesting AR-independent pathways. We then mutated putative membrane androgen receptors [gprc6a, hcar1-4 and zip9 (slc39a9)] and found that only gprc6a mutants exhibited a significant reduction in cardiac edema after testosterone exposure. Additionally, co-treatment of wild-type embryos with testosterone and GPRC6A antagonists significantly suppressed the cardiac edema phenotype. Using RNA-seq and RNA rescue approaches, we found that testosterone and GPRC6A cause cardiac phenotypes by reducing Pak1 signaling. Our results indicate that testosterone induces cardiac edema in zebrafish embryos through GPRC6A, independent of nuclear androgen receptors, highlighting a previously unappreciated non-genomic androgen signaling pathway in embryonic development.
An image-based RNAi screen identifies the EGFR signaling pathway as a regulator of Imp RNP granules
Authors: Graeve Fabienne De , Debreuve Eric , Pushpalatha Kavya Vinayan , Zhang Xuchun , Rahmoun Somia , Kozlowski Djampa , Cedilnik Nicolas , Vijayakumar Jeshlee , Cassini Paul , Schaub Sebastien , Descombes Xavier , Besse Florence 
Published: October 2024

ABSTRACT
Biomolecular condensates have recently retained much attention given that they provide a fundamental mechanism of cellular organization. Among those, cytoplasmic ribonucleoprotein (RNP) granules selectively and reversibly concentrate RNA molecules and regulatory proteins, thus contributing to the spatiotemporal regulation of associated RNAs. Extensive in vitro work has unraveled the molecular and chemical bases of RNP granule assembly. The signaling pathways controlling this process in a cellular context are, however, still largely unknown. Here, we aimed at identifying regulators of cytoplasmic RNP granules characterized by the presence of the evolutionarily conserved Imp RNA-binding protein (a homolog of IGF2BP proteins). We performed a high-content image-based RNAi screen targeting all Drosophila genes encoding RNA-binding proteins, phosphatases and kinases. This led to the identification of dozens of genes regulating the number of Imp-positive RNP granules in S2R+ cells, among which were components of the MAPK pathway. Combining functional approaches, phospho-mapping and generation of phospho-variants, we further showed that EGFR signaling inhibits Imp-positive RNP granule assembly through activation of the MAPK-ERK pathway and downstream phosphorylation of Imp at the S15 residue. This work illustrates how signaling pathways can regulate cellular condensate assembly by post-translational modifications of specific components.
A Novel Low-Impact Resistance Exercise Program Increases Strength and Balance in Females Irrespective of Menopause Status
Authors: SVENSEN ERIKA , KOSCIEN CHRISTOPHER P. , ALAMDARI NIMA , WALL BENJAMIN T. , STEPHENS FRANCIS B. 
Published: October 2024

ABSTRACT

Introduction
The reduction in sex hormone production across the menopause transition is thought to accelerate age-related decline in muscle mass, strength, and stability, increasing the risk of falls and fractures. We aimed to investigate whether a novel low-impact resistance exercise program could improve strength, balance, and body composition and whether any improvement was affected by menopause status.

Methods
Seventy healthy, moderately active pre- (PRE; 46.7 ± (SD) 3.2 yr), peri- (PERI; 52.3 ± 2.2 yr), or post- (POST; 57.0 ± 2.5 yr) menopausal females, not taking hormone replacement therapy (HRT), were randomized to continue habitual physical activity (CON; n = 25) or complete a supervised resistance exercise program 4 d·wk−1 for 12 wk (EXC; n = 45). Strength at the hip and shoulder (isokinetic dynamometer), dynamic balance (Y-balance), flexibility (sit-and-reach and back-scratch), muscle thickness (rectus femoris, vastus intermedius (VI), and medial deltoid), and lean and % body fat (dual-energy x-ray absorptiometry) were measured before and after training.

Results
Hip abduction and flexion peak torque (19% ± 48% and 20% ± 17%, respectively; P < 0.05), posterolateral and posteromedial balance (12% ± 15% and 13% ± 15%, respectively; P < 0.001), flexibility (21% ± 36%, P < 0.001), VI thickness (12% ± 19%, P = 0.032), and lean mass (2% ± 2%, P = 0.007) all increased over 12 wk in EXC, but not CON, with no difference in response between PRE, PERI, and POST. The changes in shoulder strength and body mass over 12 wk were not different between CON and EXC.

Conclusions
This is the first study to demonstrate that the decline in sex hormones and an increase in age across the menopause transition do not affect the ability of lower limb (hip) strength and balance to adapt to a low-impact resistance exercise training program in females not taking HRT.
Insights into trypanosomiasis transmission: Age, infection rates, and bloodmeal analysis of Glossina fuscipes fuscipes in N.W. Uganda
Authors: Cunningham Lucas J. , Esterhuizen Johan , Hargrove John W. , Lehane Mike , Lord Jennifer , Lingley Jessica , Mangwiro T. N. Clement , Opiyo Mercy , Tirados Iñaki , Torr Steve J. 
Published: October 2024

Background
Tsetse flies (Glossina) transmit species of Trypanosoma which cause human African trypanosomiasis (HAT) and animal African trypanosomiasis (AAT). Understanding the epidemiology of this disease and controlling the vector rationally requires analysis of the abundance, age structure, infection rates and feeding patterns of tsetse populations.

Methods
We analysed a population of G. fuscipes fuscipes in the Koboko district of Uganda. Seasonal variation in the abundance of tsetse was assessed from the numbers of tsetse caught in pyramidal traps. The age structure of the population was assessed by dissecting female tsetse to estimate their ovarian categories. Classical and PCR-based methods were utilised to determine the presence of the three major pathogenic species of salivarian trypanosomes: T. vivax, T. congolense and T. brucei in a subset (n = 2369) of flies. Further, bloodmeal analysis was carried out using PCR to amplify and sequence a portion of the vertebrate cytb gene.

Results
The abundance and age structure of tsetse populations were relatively stable and a slight seasonal four-fold variation in abundance appeared to be correlated with rainfall. Analyses of age structure suggests a low natural daily mortality of 1.75% (1.62–1.88). Infection rates estimated were significantly greater (1.9–9.3 times) using the PCR-based method compared to the classical dissection-based method. Positive rates for T. brucei sl, T. congolense and T. vivax were 1.6% (1.32–2.24), 2.4% (1.83–3.11and 2.0% (1.46–2.63), respectively by PCR. The majority of bloodmeals were identified as cattle (39%, 30.5–47.8) and human (37%, 28.4–45.6).

Conclusion
The seasonally stable abundance, low mortality rate and high proportion of bloodmeals from humans may explain, in part, why this district has historically been a focus of sleeping sickness. Additionally, the high rates of cattle feeding indicate insecticide treated cattle may prove to be a useful vector control strategy in the area.