A disproportionality analysis of FDA adverse event reporting system (FAERS) events for filgotinib

by Yinli Shi, Shuang Guan, Sicun Wang, Muzhi Li, Yanan Yu, Jun Liu, Weibin Yang, Zhong Wang

Background

Although filgotinib, a selective Janus kinase 1 inhibitor, has been increasingly applied in the treatment of inflammatory diseases, its comprehensive safety profile remains insufficiently characterized. Using data from the FAERS database covering Q1 2014 to Q2 2024, this study attempts to analyze adverse event signals linked to filgotinib and provide guidance for the safe and sensible clinical usage of filgotinib.

Methods

From Q1 2014 to Q2 2024, information on adverse drug events (ADEs) associated with filgotinib was gathered. The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) were among the signal detection methods that were employed for analysis following data normalization.

Results

Filgotinib was shown to be the main suspected medication in ADE reports, exposing 103 preferred terms (PTs) in 17 system organ classes (SOCs). Infections, gastrointestinal disorders, and musculoskeletal and connective tissue disorders were the most commonly reported adverse effects. Additionally, atrial fibrillation, alopecia, elevated serum creatinine, blood creatinine increased, pulmonary embolism, epididymitis, respiratory failure, and osteopenia were identified as potential disproportionate reporting signals for filgotinib, although these were not listed in the official drug label. Notable significant signals included large intestine erosion (ROR 2186.05, 95%CI_(ROR): 1015.94–4703.86, PRR 2176.18, 95%CI_(PRR): 1014.64–4667.42), mesenteric arterial occlusion (ROR 1832.17, 95%CI_(ROR): 897.68–3739.48, PRR 1822.71, 95%CI_(PRR): 896.17–3707.20), repetitive strain injury (ROR 1149.27, 95%CI_(ROR): 363.16–3637.01, PRR 1147.05, 95%CI_(PRR): 363.24–3622.15), oligoarthritis (ROR 755.02, 95%CI_(ROR): 310.74–1834.54, PRR 752.59, 95%CI_(PRR): 310.60–1823.51), and periostitis (ROR 676.03, 95%CI_(ROR): 319.36–1431.06, PRR 672.98, 95%CI_(PRR): 318.97–1419.87). The subgroup analysis identified obvious sex and age-specific trends in filgotinib-related adverse reactions, emphasizing a higher risk of renal disorders in females, a preponderance of gastrointestinal events in males, and age-dependent trends involving mesenteric occlusion, increased serum creatinine, and immunoglobulin reduction.

Conclusion

While filgotinib demonstrates therapeutic efficacy, it is associated with a range of potential adverse events, underscoring the need for vigilant clinical monitoring. Particular attention should be given to gastrointestinal, cardiovascular, respiratory, and metabolic complications.

Study on the release pattern of Zn in soil of ionic rare earth mining areas under different leaching conditions

by Zhongqun Guo, Qiangqiang Liu, Feiyue Luo, Shaojun Xie, Tianhua Zhou

The acidic leachate injected during the mining process of ion-type rare earth ores can damage the environmental characteristics of the soil, thereby triggering the activation and release of associated heavy metals. Severe Zn contamination has been found in the environment of ion-type rare earth mining areas, but the activation and release of Zn in the soil during the leaching process have not been fully understood. This study investigated the activation and release patterns and mechanisms of Zn in soil under different leaching agents ((NH₄)₂SO₄, MgSO₄, Al₂(SO₄)₃) and varying concentrations of Al₂(SO₄)₃ (1%, 3%, 5%, 7%) using a simulated leaching experimental system. The results show that the activation and release patterns of Zn in the soil vary significantly under the influence of the three leaching agents. During the entire leaching cycle, the peak Zn concentration in the leachate was highest under MgSO₄ leaching, while the residual Zn content in the soil under Al₂(SO₄)₃ leaching approached the high-risk environmental threshold. The high-concentration systems (5%, 7%) of Al₂(SO₄)₃ significantly enhanced the activation and release efficiency of Zn in the soil compared to the low-concentration systems (1%, 3%) of Al₂(SO₄)₃. (NH₄)₂SO₄ mainly promotes the activation and release of Zn through ion exchange between NH₄⁺ and Zn²⁺ and the acidification effect; Al₂(SO₄)₃, on the other hand, dominates the activation and release of Zn by providing a strongly acidic environment and dissolving and damaging the mineral lattice; while MgSO₄ not only exchanges ions between Mg²⁺ and Zn²⁺, but also alters the soil colloidal structure, facilitating Zn activation and release. The promoting effects of the three leaching agents on the transformation of Zn in soil follow the order of Al₂(SO₄)₃> (NH₄)₂SO₄ > MgSO₄, with the environmental risk assessment index (RAC) being highest after Al₂(SO₄)₃ leaching, indicating the greatest potential environmental risk. Compared to the other three concentrations (1%, 5%, 7%) of Al₂(SO₄)₃, the 3% concentration of Al₂(SO₄)₃ had the most significant promoting effect on the transformation of Zn in soil. This study provides a theoretical basis for optimizing the green mining process of ion-type rare earth ores and preventing heavy metal pollution, and offers scientific support for revealing pollution mechanisms and formulating remediation and risk assessment strategies.

Metabolomic characteristics of aerobic and resistance exercise modes

by Junjie Kuang, Jie Ju, Xin Xu

Aerobic and resistance exercises are the two most common modes of physical activity. They may cause some functional changes such as elevation of VO2max and muscle mass. However, descriptions of changes in complex molecular network induced by exercise are often insufficiently comprehensive, limiting the exploration of some new indicators. We utilized a metabolomics analysis method based on Liquid chromatography-mass spectrometry (LC-MS) to investigate the metabolic characteristics of 10 healthy male college students at two time points before and after a single session of aerobic and resistance exercise. The analysis was conducted at both the metabolite and metabolic pathway levels. Notably, the concentrations of several amino acids including aspartic acid, glutamic acid, histidine and tryptophan exhibited significant changes following both modes of exercise. These findings offer a more comprehensive understanding of the molecular effects of acute exercise on the human body, contributing to evaluating post-exercise physiological states and screening for relevant metabolite indicators. Future research could employ multi-omics approaches to validate these results and explore the long-term impact of exercise on human metabolic profiles, linking specific metabolic pathways to functional outcomes.

Identification and validation of palmitoylation-related signature genes based on machine learning for prostate cancer

by Qijun Wo, Jiafeng Shou, Jun Shi, Lei Shi, YunKai Yang, Yifan Wang, Liping Xie

Prostate cancer (PCa) remains a leading cause of cancer-related mortality in men, with challenges in diagnosis and treatment due to tumor heterogeneity. This study identifies palmitoylation-related signature genes as potential diagnostic and therapeutic targets. Integrating GEO datasets, six differentially expressed genes (DEGs) linked to palmitoylation were identified. Machine learning algorithms (LASSO, RF, SVM) selected three core genes: TRPM4, LAMB3, and APOE. A diagnostic model based on these genes achieved an AUC of 0.929, demonstrating robust accuracy in distinguishing PCa from normal tissues. Functional analysis revealed roles in lipid metabolism and immune modulation, with ssGSEA highlighting correlations between key genes and immune cell infiltration. Experimental validation showed that LAMB3 overexpression suppressed PCa cell proliferation, migration, and invasion, while knockdown enhanced these processes. Molecular docking identified diethylstilbestrol as a potential therapeutic agent targeting LAMB3 and APOE. These findings emphasize the clinical relevance of palmitoylation-related genes in PCa diagnosis and therapy, offering novel biomarkers and insights for personalized treatment strategies.

Interventions to enhance medication therapy safety in older patients with cognitive impairment--protocol of a systematic review with public involvement

Introduction

Cognitive impairment is considered a challenge in medication management for both the affected patient as well as their caregiver. Numerous studies have investigated interventions aiming to improve medication therapy safety in this population; however, there is insufficient knowledge on interventions which support patients and caregivers effectively. The aim of this systematic review is to (1) identify interventions to improve medication therapy safety in older patients with cognitive impairment, and (2) to evaluate their effectiveness.

Methods and analysis

We will conduct a systematic review of literature with participatory elements of public involvement in every step of the process. Five literature databases (PubMed, CENTRAL, Embase, PsycINFO and CINAHL) will be screened to identify interventions to improve medication therapy safety in older (≥65 years of age) adults with cognitive impairment. To support methodology and evidence synthesis, we will conduct expert panel discussions as well as focus group discussions of caregivers and healthcare professionals. Study selection, data extraction and bias assessment will be conducted independently by two reviewers. For data synthesis, studies will be organised by setting (eg, community setting, hospital setting, nursing home setting).

Ethics and dissemination

The responsible Ethics Committee of the Medical Faculty of Heidelberg granted approval for the public involvement strategies in this project (S-562/2024). Results will be presented by publication in an academic journal and at scientific conferences.

PROSPERO registration number

CRD42024623352.

ceRNA regulatory network and immune-neurodegenerative mechanisms of peripheral CD4+ T cells in parkinson’s disease

by Lijun Guo, Qiong Li, Jingyi Li, Feng Yang

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by dopaminergic neuron loss and neuroinflammation, with emerging roles of peripheral immune dysregulation in disease progression. This study aimed to investigate the regulatory network of CD4 + T cells in PD through multi-omics integrative analysis. Transcriptomic and miRNA datasets from peripheral blood mononuclear cells (PBMCs) of 20 PD patients and 17 healthy controls were analyzed (GSE22491, GSE100054, GSE16658). Differential expression analysis identified 287 mRNAs and 73 miRNAs (|log₂(fold change)| ≥ 0.5, false discovery rate CD4 and SEMA6A. A competing endogenous RNA (ceRNA) network was constructed, comprising 38 lncRNAs, three miRNAs (miR-155-5p, miR-27a-3p, miR-27b-3p), and their target mRNAs CD4 and SEMA6A. Four lncRNAs (including XIST, NORAD, and INE1) were identified to functionally regulate CD4. Immune cell infiltration analysis revealed increased proportions of naïve CD4 + T cells and activated dendritic cells in PD patients. CD4 expression positively correlated with γδ T cells (r = 0.48, p = 0.032) and activated NK cells (r = 0.45, p = 0.048). Gene set enrichment analysis associated CD4 with neurodegenerative pathways (e.g., Parkinson’s disease: normalized enrichment score = 1.57, p = 0.002) and oxidative phosphorylation (normalized enrichment score = 1.89, p = 7.4 × 10 ⁻ ⁶). These findings highlight a peripheral CD4 + T cell-centric ceRNA network that modulates immune-metabolic crosstalk and neuroinflammation in PD. This study provides novel insights into immune-driven neurodegeneration and suggests potential therapeutic targets for PD through metabolic-immune reprogramming.

Global, regional, and national burden of endometriosis among women of reproductive age, 1990–2021: Insights from the global burden of disease study 2021

by Jun Zhang, Mengduan Pang, Ling Li, Chuanjia Guo

Background

Endometriosis is a common gynecological disorder among women of reproductive age worldwide. This study aims to examine global patterns of endometriosis disease burden among reproductive-aged women and to evaluate its correlation with socioeconomic development indices.

Methods

This study conducted a comprehensive analysis of endometriosis disease burden using epidemiological parameters from the Global Burden of Disease (GBD) 2021 database, including incidence rates, prevalence rates, Disability-Adjusted Life Years (DALYs), and corresponding age-standardized rates. Through stratified analyses at global, regional, and national levels, we systematically evaluated the disease burden patterns among reproductive-aged women and performed correlation analysis with socioeconomic development indices.

Results

We found that the highest incidence of endometriosis among women of reproductive age globally occurs in the 20–24 age group, with an incidence rate of 399.49 per 100,000 in 1990 and 304.31 per 100,000 in 2021. The results show that the global disease burden of endometriosis is mainly influenced by population size, followed by epidemiological changes. Compared to countries with a medium Social Development Index (SDI), the disease burden of endometriosis in low and high SDI regions fluctuated significantly from 1990 to 2021. In most countries with SDI values between 0.2 and 0.6, the burden of endometriosis showed a gradual decline.

Conclusion

Endometriosis remains a significant public health issue for women of reproductive age globally. Although the global disease burden of endometriosis among women of reproductive age showed a slight decline from 1990 to 2021, the disease burden continues to fluctuate in certain regions and countries. In light of the differences in the disease burden of endometriosis across regions and countries, regionalized disease management strategies are expected to be developed in the future.

TNFAIP3 alleviates cerebral ischemia-reperfusion injury by inhibiting M1 microglia polarization via deubiquitination of RACK1

by Wenya Bai, Shixuan Liu, Guilin Zhou, Xuelian Li, Huan Jiang, Jianlin Shao, Junchao Zhu

Background

Microglia polarization plays a crucial role in the progression of cerebral ischemia-reperfusion injury (CIRI), but the mechanisms remain largely undefined. The preset study aimed to investigate the mechanism of microglia polarization following CIRI.

Methods

CIRI was modeled in C57BL/6J mice through middle cerebral artery occlusion-reperfusion and in BV2 cells via oxygen and glucose deprivation/reoxygenation. Reverse transcription-quantitative PCR, western blotting, flow cytometry and fluorescence staining were used to detect the expression levels of key proteins associated with microglia polarization, as well as the expression of TNFAIP3 and RACK1. The interaction between TNFAIP3 and RACK1 was verified by co-immunoprecipitation. TNFAIP3 or RACK1 gene interference (overexpression and/or silencing) was employed to examine the role of the TNFAIP3/RACK1 axis in microglia polarization following CIRI.

Results

The results revealed that Arg-1 expression decreased, inducible nitric oxide synthase expression increased and TNFAIP3 was upregulated 24 h after CIRI. Furthermore, TNFAIP3 interacted with RACK1 to deubiquitinate and increase the expression of RACK1. These results indicate that knocking down either TNFAIP3 or RACK1 promotes microglia M1 polarization, and overexpression of RACK1 can promote microglia M2 polarization. RACK1 exerts its neuroprotective effects through NF-κB, as demonstrated by the use of NF-κB inhibitors.

Conclusion

The present findings indicate that TNFAIP3 inhibits M1 microglial polarization via deubiquitination of RACK1 after CIRI, RACK1 exerts its effects through NF-κB.

Disruption of <i>yqhG</i> attenuates virulence in <i>methicillin-resistant Staphylococcus aureus</i> by compromising membrane stability and oxidative stress resistance

by Jianhua Liao, Jun Cheng, Baoqing Liu, Yuzhi Shao, Chunyan Meng

The growing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) infections, coupled with the increasing resistance to existing antibiotics, underscores the critical need for novel therapeutic approaches to combat this pathogen. In this study, the role of yqhG, a conserved gene encoding a periplasmic protein, in MRSA virulence and stress adaptation was investigated. yqhG deletion in MRSA significantly attenuated virulence in a murine infection model, leading to reduced bacterial burden in infected organs and improved host survival. In vitro, the yqhG mutant exhibited impaired membrane integrity, reduced motility, and increased sensitivity to oxidative stress, but did not affect biofilm formation. These defects were fully restored upon genetic complementation. These findings highlight the critical role of yqhG in maintaining MRSA’s ability to withstand host-imposed stresses, suggesting that yqhG is a key determinant of MRSA pathogenesis. The study provides new insights into the stress-defense mechanisms employed by MRSA and underscores yqhG as a potential target for therapeutic strategies aimed at combating MRSA infections.

Quantitative proteomic analysis reveals key proteins involved in radiation-induced brain injury

by Jing Liu, Junshuang Wang, Shuang Lv, Hengjiao Wang, Defu Yang, Ying Zhang, Ying Li, Huiling Qu, Ying Xu, Ying Yan

Objective

Radiation-induced brain injury (RIBI) is a significant complication following radiotherapy for brain tumors, leading to neurocognitive deficits and other neurological impairments. This study aims to identify potential biomarkers and therapeutic targets for RIBI by utilizing advanced proteomic techniques to explore the molecular mechanisms underlying RIBI.

Methods

A rat model of RIBI was established and subjected to whole-brain irradiation (30 Gy). Tandem mass tagging (TMT)-based quantitative proteomics, combined with high-resolution mass spectrometry, was used to identify differentially expressed proteins (DEPs) in the brain tissues of irradiated rats. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to identify the biological processes and pathways involved. Protein-protein interaction (PPI) networks were constructed to identify key hub proteins.

Results

A total of 35 DEPs were identified, including PHLDA3, APOE and CPE. GO enrichment analysis revealed that the DEPs were mainly involved in lipid transport, cell adhesion, and metabolic processes. KEGG analysis highlighted the enrichment of pathways related to metabolism, tight junctions, and PPAR signaling. APOE was identified as a key hub protein through PPI network analysis, indicating its potential role in RIBI pathophysiology. Immunohistochemistry further validated the increased expression of PHLDA3, APOE, and CPE in the brain tissue of irradiated rats.

Conclusion

This study provides valuable insights into the molecular mechanisms of RIBI by identifying key proteins and their associated pathways. The findings suggest that these proteins, particularly APOE and PHLDA3, could serve as potential biomarkers and therapeutic targets for clinical intervention in RIBI. These results not only enhance our understanding of RIBI’s molecular pathology but also open new avenues for the development of targeted therapies to mitigate radiation-induced neurotoxicity.

Caregiver burden profiles and associated factors among informal caregivers of children and adolescents with type 1 diabetes: a cross-sectional study

Objectives

To identify caregiver burden profiles among informal caregivers of children and adolescents with type 1 diabetes and explore associated factors.

Design

A multicentre cross-sectional survey was conducted.

Setting and participants

The study was conducted in three tertiary hospitals in Xinjiang, China, from January 2023 to February 2024. A total of 259 informal caregivers participated in the study, comprising 207 females (79.9%).

Primary outcome measures

The primary outcome was caregiver burden profiles derived from a latent profile analysis of the Caregiver Burden Inventory domain scores. The factors associated with different burden profiles were also examined, including caregiver competence.

Results

Informal caregivers have a mean age of 41.7±7.1 years. Three distinct caregiver burden profiles were identified: mild burden (29.7%), moderate burden (55.6%) and severe burden (14.7%). Caregivers of children and adolescents diagnosed within 1–5 years had significantly higher odds of experiencing severe burden compared with those with a disease duration of ≤1 year (OR 7.27, 95% CI 1.81 to 29.08). Higher caregiver competence in managing family and social resources (OR 0.67, 95% CI 0.49 to 0.91) and in self-emotion management (OR 0.55, 95% CI 0.38 to 0.79) were associated with lower odds of severe burden.

Conclusions

Targeted interventions are needed to support informal caregivers during the 1–5 years following their child’s diagnosis. Enhancing caregiver competence in managing family and social resources, as well as self-emotion management, can help alleviate caregiver burden.

Clinical impact of prophylactic antibiotics in kidney transplantation: A retrospective observational cohort study with historical comparison

by Sang Ah Lee, Jin-Myung Kim, Hye Eun Kwon, Youngmin Ko, Joo Hee Jung, Sung Shin, Young Hoon Kim, Sung-Han Kim, Hyunwook Kwon

Purpose

Optimal perioperative antibiotic prophylaxis in kidney transplantation remains undefined despite routine antibiotic administration to prevent infections. In this retrospective observational cohort study with historical comparison, we compared the clinical efficacy of 6 days of ampicillin/sulbactam vs. a single dose of cefazolin.

Materials and methods

We retrospectively analyzed 2322 kidney transplantation recipients at a single center, with the evaluation period spanning from 2015 through 2021. Patients were divided into 2 groups based on the perioperative antibiotic regimen received: 971 patients received ampicillin/sulbactam, and 1351 received cefazolin. This study focused on evaluating the impact of these regimens on postoperative infection incidence and the 6-month acute rejection (AR) rates.

Results

The cefazolin group exhibited a tendency toward higher urinary tract infection rates within 1 month after transplantation (3.4% vs. 2.2%, p= = 0.078). There were no significant differences in surgical site infections between the groups. The 6-month AR rates were significantly lower in the cefazolin group than in the ampicillin/sulbactam group (5.1% vs. 7.9%, p= = 0.009). Cefazolin was also confirmed to be significantly associated with reduced 6-month AR rates in the multivariable logistic regression analysis (odds ratio 0.63, 95% confidence interval [0.45-0.89], p= = 0.009).

Conclusion

In this study, we observed that a single dose of cefazolin as perioperative antibiotic prophylaxis may lead to higher rates of postoperative urinary tract infections, but it could potentially lower the incidence of acute rejection within six months.

Syndromic management of sexually transmitted infections among female sex workers in Lomé (Togo), 2023

by Oumarou I. Wone Adama, Iman Frédéric Youa, Alexandra Bitty-Anderson, Arnold Junior Sadio, Rogatien Comlan Atoun, Yao Rodion Konu, Hezouwe Tchade, Martin Kouame Tchankoni, Kokou Herbert Gounon, Kparakate Bouboune Kota-Mamah, Abissouwessim Egbare Tchade, Godonou Amivi Mawussi, Fiali Ayawa Lack, Fifonsi Adjidossi Gbeasor-Komlavi, Anoumou Claver Dagnra, Didier Koumavi Ekouevi

Introduction

In Togo, the syndromic approach is used for the diagnosis and management of sexually transmitted infections (STIs). The aim of this study was to evaluate the syndromic approach for diagnosis of STIs among female sex workers (FSW) in Lomé, Togo.

Methods

A cross-sectional study was carried out from September to October 2023 among FSW in Lomé (Togo). FSW aged 18 years and above were included. A gynecological examination was performed for syndromic diagnosis, and the Xpert® CT/NG were used to screen vaginal swabs for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG). The performance (predictive values) of the syndromic approach to STI diagnosis was evaluated using the Xpert® CT/NG test as the gold standard.

Results

A total of 357 FSW were recruited. The median age of FSW was 32 years (IQR: [26–40 years]) and 8.2% had attained a higher level of education. The prevalence of syndromic STI among FSW was 33.3%. Vaginal swabs were positive for CT (8.4%) and NG (8.7%), with a prevalence of bacterial STIs (CT and/or NG) of 14.3%. The syndromic approach to STI diagnosis demonstrated a positive predictive value of 24.3%.

Conclusion

The prevalence of STIs is relatively high among FSW in Lomé. According to this study, the diagnosis of STIs using the syndromic approach has limited relevance. National STI screening and management policies urgently need to be rethought, incorporating recent technological advances.

Food pricing: A study on the sales of food in Brazilian private schools

by Ariene Silva do Carmo, Paulo César Pereira de Castro Júnior, Thais Cristina Marquezine Caldeira, Daniela Silva Canella, Rafael Moreira Claro, Luiza Delazari Borges, Larissa Loures Mendes

The present study analyzed the prices of food sold in canteens of Brazilian private schools and described price-based marketing strategies, according to the NOVA food classification system. This is a mixed methods study combining a cross-sectional component and time series analysis, with data from 2,241 canteens in private elementary and secondary schools in the 26 capitals of Brazil and the Federal District, collected between June 2022 and June 2024. Price data collected for unprocessed, minimally processed, or processed foods and culinary preparations based on these foods (UMPCP), and ultra-processed foods and culinary preparations based on these foods (UpCP) sold in school canteens and from the National System of Consumer Price Indices (SNIPC), were used to create a data set containing deflated monthly prices for food and beverages sold between August 2022 and July 2024. Calculations were made for adjusted prices (R$/100 g or ml) and absolute prices (R$ per portion), and frequency of use of strategies such as combos and promotions. UMPCP showed lower adjusted price, but higher absolute price than UpCP, especially for solid foods. About 27% of the study canteens implemented pricing strategies for both food groups. Most of these strategies did not exclusively favor healthy foods, indicating that promotions and combos were used without distinction. The affordability of healthy foods is disadvantaged in school canteens when considering the price per portion, which may negatively influence students’ food choices. The findings show that current prices for food sold in most canteens discourage the purchase of healthy items, but favor the purchase of unhealthy ones. These results reinforce the importance of interventions for promoting healthy foods and making them more affordable.

The mediating role of blood metabolites in the association between myocardial infarction and cancer risk: An observational and mendelian randomization analysis

by Jia Zhu, Xiaojun Xia, Haodong Jiang, Congying Wang, Yunpeng Jin

Background

Myocardial infarction (MI) and cancer are major global public health challenges. Research indicates that they share common risk factors and that physiological changes following MI may affect cancer incidence and progression. However, evidence defining the independent relationship between these conditions is still limited.

Methods

We analyzed data from the National Health and Nutrition Examination Survey (NHANES) (2011–2018) using multivariable weighted logistic regression to examine the association between myocardial infarction (MI) and cancer. Additionally, we utilized genome-wide association study (GWAS) summary statistics and conducted Mendelian randomization (MR) to assess potential causal relationships and explore underlying mechanisms. Sensitivity analyses were performed to ensure the robustness of our findings.

Results

A total of 20,859 participants were included in our observational study using NHANES data. Multivariable weighted logistic regression revealed no direct association between MI and cancer (OR=1.161, 95% CI [0.895–1.507], P = 0.261). Interestingly, MR analysis indicated that MI occurrence was associated with a reduced incidence of cancer (OR=0.9497, 95% CI [0.9223–0.9778], P = 0.0005). Furthermore, two-stage MR results suggested this reduction might be mediated by increased blood levels of metabolites that inhibit cancer development, such as dihomo-linoleate (20:2n6) (beta = −0.0050, 95% CI [−0.0027–0.0004], P  Conclusion

Our integrative analysis suggests that myocardial infarction may be associated with a reduced cancer incidence through potential alterations in blood metabolite profiles, including dihomo-γ-linolenic acid, alpha-tocopherol, and inosine. These findings provide preliminary evidence that warrants further large-scale studies to validate the observed associations and to elucidate the underlying mechanisms.

Brachydactyly type A3 may be associated with shorter stature: An observation from a Chinese pediatric sample

by Hua-Hong Wu, Ya-Qin Zhang, Cheng-Dong Yu, Fang-Fang Chen, Jun-Ting Liu, Shao-Li Li, Xin-Nan Zong

Background

Brachydactyly type A3 (BDA3), a common finger deformity, demonstrates an inverse epidemiological relationship with population height, suggesting a potential link with individual stature. We aimed to investigate the distribution of BDA3 and its association with shorter stature in Chinese children.

Methods

From 2022 to 2023, we conducted a cross-sectional survey in 10 randomly selected schools in Beijing with children aged 3–18. We measured height on-site, obtained left hand-wrist X-rays, calculated predicted adult height (PAH) based on height and bone age, and diagnosed BDA3 deformity based on the X-ray images. And we compared the height and PAH between the BDA3 and Non-BDA3 groups by t-test or chi-square test, examined the association of BDA3 with shorter stature and shorter PAH using binary logistic regression model.

Results

A total of 5,567 children participated, with 573 diagnosed with BDA3 (a detection rate of 10.3%). Notably, girls exhibited a significantly higher detection rate than boys (14.5% vs. 6.3%). The detection rate in children  12 years(15.3% vs. 7.6%). The average height and PAH were 0.30 SD and 0.22 SD lower, and the risk of shorter stature and shorter PAH were 1.57 times and 1.47 times higher in the BDA3 group than in the Non-BDA3 group, respectively. And, children >12 years in the BDA3 group had a significantly lower PAH than those in the Non-BDA3 group (about 2.0 cm). Conclusion: Children with BDA3 are more likely to have shorter stature and shorter PAH than those with no BDA3 in Chinese children aged 3–18 years.

Stakeholders’ perspectives on barriers and enablers of chronic kidney disease care in Ethiopia: A qualitative study

by Daniel Bekele Ketema, Min Jun, Sradha Kotwal, Workagegnehu Hailu, Martin Gallagher, Rohina Joshi

Background

Chronic kidney disease (CKD) is a growing public health problem in Ethiopia. However, evidence on the health system and contextual factors influencing CKD care remains limited. This study explored the barriers and facilitators to CKD care from the perspectives of healthcare providers and other stakeholders.

Methods

A descriptive qualitative study was conducted using purposive and maximum variation sampling to recruit healthcare providers (including general practitioners, nephrologists/internists, nurse) and non-communicable disease (NCD) officers and program coordinators. Interviews were audio recorded, transcribed, and thematically analysed, underpinned by the Theoretical Domains Framework version 2.

Results

Fifteen participants (six general practitioners, five nephrologists/internists, one nurse, and three NCD program officers and coordinators) were included. About 40% of participants had over six years’ experience. Key barriers to CKD care included patient misconceptions, low patient and healthcare provider awareness, shortage of health workforce, knowledge gaps among junior healthcare providers, limited resources, high out-of-pocket costs, absence of registries for CKD, weak referral systems, inconsistent access to medicines and diagnostics, lack of structured training, and conflict-related disruptions. Facilitators included adherence to guidelines by senior staff, inclusion of CKD into national non-communicable disease strategies, and increased use of media for public health education.

Conclusions

Addressing key barriers and enhancing prioritisation of CKD by clinicians and policymakers is critical. Strengthening workforce capacity, awareness, referral systems, and integration into national strategies offers opportunities to improve CKD care.

Safety and efficacy of quick-soluble gelatin microparticles for transarterial embolization of the lower urinary tract: Preclinical study in a rabbit urinary bladder embolization model

by Sunghoon Jeon, Keunho Kim, Cheolwon Choe, Juil Choi, Gun Lee, Chung-Do Lee, Hyeon-Jeong Moon, Jun-Gyu Park, Jin-kyung Kim, Namsoon Lee, Dongwoo Chang

Quick-soluble gelatin microparticles (QS-GMP) are emerging embolic agents under investigation for temporary vascular occlusion, offering reduced ischemic risk compared to permanent materials. The aim of this preclinical study was to evaluate the safety and efficacy of QS-GMP for transarterial embolization in a rabbit model of urinary bladder embolization. Twelve male New Zealand White rabbits underwent bilateral umbilical artery embolization using QS-GMP. Animals were assigned to four time-points (immediately, 3, 7, and 14 days post-embolization), with comprehensive assessments including clinical observations, hematologic and serum biochemical analysis, angiography, and histopathology. The procedure was technically feasible in all animals without intraoperative complications. Temporary hematuria and a transient decrease in body weight were observed post-procedure, both of which resolved spontaneously. Complete occlusion of the cranial vesical artery and absence of bladder wall perfusion were achieved immediately after embolization, followed by full recanalization at 3 days. Angiographic imaging at 7 and 14 days revealed transient hypervascularization of the bladder wall. Histopathological analysis showed marked edema, epithelial necrosis, and inflammatory infiltration at 3 and 7 days, with full urothelial regeneration observed at 14 days. No signs of ureteral or renal injury, or adverse systemic responses were detected. These findings suggest that QS-GMP may serve as a feasible option for temporary arterial occlusion in future veterinary lower urinary tract applications, although further long-term evaluation is warranted.

Mesalamine for Colorectal Cancer Prevention Programme in Lynch syndrome (MesaCAPP): a multicentre, multinational, randomised, two-arm, double-blind, phase II clinical study with mesalamine or placebo in carriers with Lynch syndrome - a study protocol

Introduction

Lynch syndrome (LS) carriers have a 20–46% lifetime risk of colorectal cancer (CRC) due to mismatch repair gene variants. Mesalamine (5-ASA, 5-aminosalicylic acid), used safely in patients with ulcerative colitis, may reduce CRC risk in LS by decreasing microsatellite instability, a key driver of LS-related cancer. This study evaluates 5-ASA’s efficacy as a tolerable chemopreventive drug, aiming to improve long-term CRC prevention in LS.

Methods and analysis

This multicentre, multinational, randomised, double-blind, two-arm, phase II clinical study will compare the effects of a 2-year daily intake of 5-ASA (2000 mg) to placebo in LS carriers. The primary objective is to assess whether mesalamine reduces colorectal neoplasia, both benign and malignant, compared with placebo in LS carriers, as detected by colonoscopy at the end of the treatment period (24 months±1 month) and on study completion. Secondary objectives include evaluating whether 5-ASA reduces neoplasia/tumour multiplicity and progression compared with placebo at specified time points, examining variations in the effects of 5-ASA versus placebo based on cancer history, sex and age (

Ethics and dissemination

The trial is currently open for enrolment, having received ethical approval from the Regional Ethical Review Board in Stockholm and funding from the Swedish Research Council. The study protocol is the finalised V.10.0 (11 April 2024), transitioned to the European Clinical Trials Information System. LS remains underdiagnosed, which may limit recruitment. The results are of global interest and will be published in peer-reviewed journals and presented at scientific conferences.

Trial registration number

ClinicalTrials.gov: NCT04920149. EudraCT: 2019-003011-55. EU CT: 2024-514765-19-01.

Effects of exercise modalities on heart rate recovery and its association with cardiometabolic risk in adolescents with overweight or obesity

by Rubin Pooni, Silva Arslanian, Heather Edgell, Hala Tamim, SoJung Lee, Jennifer L. Kuk

Objective

Attenuated heart rate recovery (HRR) immediately after exercise is an independent predictor of cardiovascular disease and mortality in adults. We examined the effects of aerobic exercise (AE), resistance exercise (RE), and combined AE and RE on HRR, and the relationship of HRR with body composition and metabolic risk factors in adolescents with overweight or obesity.

Research design and methods

We included 147 adolescents (BMI ≥ 85^th percentile, 12–18 years) who participated in exercise intervention studies (3–6 months), and had a complete data set including VO_2peak, body composition by dual-energy X-ray absorptiometry, and cardiometabolic risk factors before and after the interventions. HRR was calculated as the difference between peak HR during the maximal treadmill test and HR at 1-, 2-, 3-, 4-, and 5-min after the cessation of the test.

Results

After interventions, a faster HRR at 2–5 min was observed following AE (17.3–25.6% change, P P P P P 2peak. Changes in HRR were not associated with the changes in % body fat or metabolic risk factors.

Conclusion

AE training is more beneficial than RE or combined AE and RE training for improving HRR in adolescents with overweight or obesity.