Integrating sequence-based GWAS and comparative genomic analysis reveals conservation and species-specificity of putative functional variants influencing tail length and tail abnormalities in pigs and sheep

by Xuying Zhang, Johanna Mainzer, Isabella Giambra, Tong Yin, Petra Engel, Hannah Hümmelchen, Henrik Wagner, Axel Wehrend, Christiane Egerer, Katharina Gerhards, Gerald Reiner, Sven König

Long tails trigger tail biting in pigs and increase the risk of flystrike infections in sheep. Tail docking has been a common management practice in both species for decades, but increasingly conflicts with legal animal welfare guidelines. Sustainable solutions require breeding strategies targeting shorter tails. In consequence, the aims were to conduct whole-genome sequencing (WGS)-based genome-wide association studies (GWAS) and comparative genomic analyses (CGA) to explore functional elements influencing tail traits. Phenotypically divergent experimental populations of pigs and sheep were established through unified selection and mating experiments. Tail traits included tail length (TL) measured at birth, and tail abnormalities (TA) assessed radiographically at 14 weeks of age. WGS-based GWAS identified a significant locus on SSC18 in pigs and suggestive loci for TL in both species, which, together with previously reported loci for TA, were further analyzed by CGA. The genomic windows of the significant locus on SSC18 in pigs and the TL GWAS locus on OAR4 in sheep were found to be conserved, harboring six common genes with predicted functional variants. These variants were jointly associated with TL (P_lm ) in both species in linear regression models adjusted for sex, age of the dam, body length, and body weight. In other GWAS locus windows (±1 Mb), species-specific TL candidate genes were identified in sheep (HOXB13, MUC5B, EPB41L3, MTCL1, PIEZO2, MPPE1, and LOXHD1) and in pigs (KNL1, DISP2, SPRED1, TGFB2, and HAND1), each harboring associated putative functional variants. For TA, sheep-specific candidates (PGM2, LRRC66, CRACD, LOC105601916, and SH2D4B) and pig-specific candidates (MYOT, TMCO6, and PCDHAC2) were revealed using logistic regression models (P_glm ). GO analyses of candidate genes predicted shared biological processes between sheep and pigs, whereas pathway analyses indicated that common carbohydrate metabolism pathways, along with species-specific immune and inflammatory signaling, and pig-specific TGF-β signaling and endochondral ossification, may contribute to tail length variation and abnormalities. These findings provided deeper insights into the genetic basis of differential embryonic tail morphogenesis and perinatal tail development across species.

COVID-19 knowledge, attitudes, and practices among people vulnerable to HIV in Uganda: A cross-sectional cohort analysis

by Job Kasule, Julius L. Tonzel, Natalie Burns, Tyler Hamby, Roger Ying, Grace Mirembe, Immaculate Nakabuye, Hannah Kibuuka, Margaret Yacovone, Betty Mwesigwa, Trevor A. Crowell, for the Multinational Observational Cohort of HIV and other Infections (MOCHI) Study Group

Background

People with behavioral vulnerability to HIV face barriers to healthcare engagement that may impede uptake of non-pharmaceutical and other interventions to prevent COVID-19. Understanding COVID-19 knowledge, attitudes, and practices in this population can inform disease prevention efforts during future pandemics.

Materials and methods

From October 2022 to September 2024, we enrolled participants aged 14–55 years without HIV who endorsed recent sexually transmitted infection, injection drug use, transactional sex, condomless sex, and/or anal sex with male partners. At enrollment, we collected socio-behavioral data, including assessments of COVID-19 knowledge, attitudes, and practices. Robust Poisson regression with purposeful variable selection was used to estimate prevalence ratios with 95% confidence intervals for factors associated with COVID-19 preventive practices.

Results

Among 418 participants, 228 (56.9%) were female, the median age was 21 years (interquartile range 19−24), and 362 (84.9%) reported sex work. Knowledge about SARS-CoV-2 transmission routes was high (95.4%) but lower for the consequences of genetic variants (48.5%−69.7%) and possibility for asymptomatic infection or transmission (66.7%−80.8%). Handwashing was practiced by 90.8% of participants in the preceding month, whereas mask-wearing (76.5%), avoiding symptomatic people (73.7%), and any history of COVID-19 vaccination (46.9%) were less prevalent. Males were more likely to report avoiding symptomatic people (adjusted prevalence ratio 1.16 [95% confidence interval 1.03–1.31]) and COVID-19 vaccination (1.30 [1.05–1.60]). Enrollment during the BQ.1/BQ.1.1 Omicron wave was associated with less mask-wearing (0.81 [0.67–0.99]) but more vaccination (1.59 [1.29–1.95]).

Discussion

We observed variable COVID-19 knowledge and attitudes among Ugandan adolescents and adults with little impact on COVID-19 preventive practices. Efforts to address suboptimal uptake of disease preventive practices during this and future disease outbreaks will require more than just improving knowledge.

Association between endothelial activation and stress index and mortality in critically ill patients with atrial fibrillation: In MIMIC database: A Retrospective Cohort Study

by Peiling Zuo, Huanhuan Zhu, Chunying Sun, Xiaohan Ma, Sheng Chen, Rong Tang, Tong Wu, Ding Zhang, Xiao Tang, Wenquan Lv, Wenzhong Chen, Xiawei Wei, Encun Hou, Minsheng Wu, Minghe Jiang

Background

Evidence indicates that the Endothelial Activation and Stress Index (EASIX) is a predictor of mortality in endothelium-related conditions; however, its association with mortality risk in atrial fibrillation (AF) remains uncertain. Accordingly, this study examines the relationship between EASIX and mortality risk among patients with AF.

Methods

This retrospective analysis utilized data from the Medical Information Marketplace in Intensive Care IV (MIMIC-IV) database, which includes critically ill patients diagnosed with AF. To examine the association between EASIX scores and mortality, Kaplan–Meier survival analysis, Cox proportional hazards models, and restricted cubic spline regression were applied to evaluate the relationship between EASIX and all-cause mortality. Subgroup analyses were conducted to explore potential interactions with key patient characteristics, and sensitivity analyses were performed to further confirm the robustness of the results.

Results

A total of 3,193 patients were included in the analysis. KM survival analysis showed that elevated EASIX levels were associated with a higher risk of both in-hospital and ICU mortality. After adjusting for potential confounders, increased EASIX levels remained significantly associated with in-hospital mortality [HR, 1.09 (95% CI 1.03, 1.15), P = 0.0002] and ICU mortality [HR, 1.10 (95% CI 1.04, 1.17), P = 0.0002]. Stratified analyses revealed a significant interaction between sepsis, respiratory failure, and EASIX in relation to both in-hospital and ICU mortality. To evaluate the robustness of the findings, a sensitivity analysis was performed. After additionally adjusting for metoprolol and heparin as covariates, patients in the highest EASIX group continued to demonstrate the greatest mortality risk: the HR for in-hospital death was 2.08 (95% CI: 1.51–2.85), and the HR for ICU death was 1.83 (95% CI: 1.21–2.65).

Conclusion

Elevated EASIX levels correlate with higher mortality rates, underscoring its potential as an accessible tool for identifying high-risk patients and informing clinical decisions. However, further studies are needed to explore the underlying mechanisms and validate its applicability across diverse patient populations.

Physiological and biochemical characterization of trypsin from <i>Neocaridina denticulata sinensis</i> and its roles in ontogenesis and immune response

by Dandan Feng, Yakun Song, Zuqi Wu, Wuruo Liu, Yuting Pu, Yangcan Gao, Yuying Sun, Jiquan Zhang

Trypsin, a canonical serine protease in crustaceans, plays a crucial role in ontogeny and antibacterial defense. Whether these biological functions correlate with its catalytic characteristics remains unresolved in the freshwater shrimp Neocaridina denticulata sinensis. To address this gap, we characterized a trypsin gene from N. denticulata sinensis (NdTryp) and assessed both its biological roles and its prospective utility. NdTryp was predominantly expressed in the hepatopancreas, where it localized to storage cells (R-cells) and tubule-lining epithelial cells (ECTs). Across development, NdTryp transcripts were essentially absent during early embryogenesis but rose sharply at late stages, temporally coincident with hatching and the onset of feeding. After a challenge with Vibrio parahaemolyticus, the expression of NdTryp was induced, with the expression level significantly increased relative to the baseline expression level. RNA interference-mediated knockdown rendered shrimp more susceptible to infection and was accompanied by extensive hepatopancreatic injury, including epithelial detachment and disruption of the basement membrane. Biochemically, recombinant NdTryp (rNdTryp) displayed proteolytic activity over a broad temperature and pH span. Activity was differentially tuned by metal ions, with several divalent cations producing marked enhancement, whereas ferric iron exerted strong inhibition. Overall, our results showed that NdTryp functions as a multifunctional protease involved in both late embryonic development and innate antimicrobial defense. Furthermore, the robust stability of rNdTryp underscores its potential as an aquafeed additive and candidate for enzymatic biotransformation.

Combined effect of triglyceride-glucose index and glucose disposal rate on cardio-cerebrovascular disease

by Hongfei Yang, Chao Sun, Ya Li, You Zhou, Rui Wang, Yingxue Li

Objective

The triglyceride-glucose index and estimated glucose disposal rate serve as notable surrogate markers of insulin resistance, demonstrating established links to cardio-cerebrovascular disease. However, their combined prognostic value in predicting cardio-cerebrovascular disease outcomes remains unexplored. The current investigation examined the interaction between the TyG (triglyceride–glucose index) index and eGDR (estimated glucose disposal rate) concerning the danger of cardiovascular disease within a clinical population.

Methods

This investigation employed data sourced from the China Health and Retirement Longitudinal Study (CHARLS). The median TyG index and eGDR scores were used to stratify the participants into 4 categories: low TyG/high eGDR, high TyG/high eGDR, low TyG/low eGDR, and high TyG/low eGDR. Clinical characteristics across groups were systematically compared. Cox proportional hazards regression models evaluated the distinct and interconnected associations of the TyG index and eGDR with the risk of cardio-cerebrovascular disease, with multiplicative and additive interaction effects subsequently assessed through formal interaction analysis.

Results

The final study cohort comprised 7,330 participants, with 1,336 individuals (18.2%) developing cardio-cerebrovascular disease during the 9-year follow-up. Stratification using median thresholds (TyG: 8.59; eGDR: 10.55 mg/kg/min) yielded four groups: low TyG/high eGDR (n = 2,991), high TyG/high eGDR (n = 1,375), low TyG/low eGDR (n = 1,372), and high TyG/low eGDR (n = 2,292). Multivariable-adjusted Cox regression analyses revealed markedly increased risks of cardio-cerebrovascular disease among the various exposure groups when contrasted with the low TyG/high eGDR reference: high TyG/high eGDR (HR: 1.31, 95%CI: 1.10–1.57, ppp Conclusion

The TyG index and eGDR demonstrate independent associations with cardio-cerebrovascular disease risk, while their combined assessment reveals synergistic predictive capacity. Combined assessment of the two allows for further accurate stratification of the population based on insulin resistance and improved prediction of cardio-cerebrovascular disease.

IL-22 inhibits ferroptosis and attenuates ischemia-reperfusion-induced acute kidney injury: Association with activation of the P62-Keap1-Nrf2 signaling pathway

by Lin Zhang, Feng Luo, Yalin Chai, Lijie Sun, Xuan Wang, Le Yin, Congjuan Luo

Acute kidney injury (AKI) remains a major clinical challenge due to its high morbidity and mortality, with ischemia-reperfusion injury (IRI) as one of its primary causes. Severe IRI-associated AKI (IRI-AKI) can progress to irreversible renal failure, yet no effective therapies are currently available. Ferroptosis, an iron-dependent regulated cell death, has recently been implicated in the pathogenesis of IRI-AKI. Moreover, IL-22 may alleviate AKI by modulating the ferroptosis process through regulation of the P62-Keap1-Nrf2 signaling axis. In this study, we examined the protective role of the immune cytokine interleukin-22 (IL-22) in IRI-AKI and its mechanistic association with ferroptosis. Using a murine IRI model and an HK-2 cell hypoxia/reoxygenation system, we systematically assessed the impact of IL-22 treatment. IL-22 administration significantly enhanced renal function, reduced histological injury, and limited both reactive oxygen species accumulation and ferroptotic cell death. Further mechanistic studies demonstrated that IL-22 suppresses ferroptosis in vitro through an Nrf2-dependent mechanism and is associated with activation of the P62-Keap1-Nrf2 signaling pathway. These findings offer experimental evidence supporting IL-22 as a potential therapy for IRI-AKI and highlight ferroptosis modulation as a promising therapeutic strategy.

High-dimensional phenotyping reveals novel macrophage-like and hybrid subsets within murine splenic conventional dendritic cells

by Chunqing Yang, Qingjie Xue, Yu Feng, Wenjun Ding, Ying Lu, Qinqin Wang

Conventional dendritic cells (cDCs) are pivotal antigen-presenting cells (APCs) with critical roles in immune regulation, yet their subset classification remains ambiguous due to phenotypic overlap with macrophages and monocytes, particularly in the spleen. This study employed multi-parametric flow cytometry and clodronate liposome (CL) depletion to systematically re-evaluate splenic CD11c^highMHCII^high cDCs in C57BL/6 mice. We identified three novel subsets: (1) a tissue-resident T-cell zone macrophage (TZM)-like population (F4/80^inter-lowCX3CR1⁺MERTK⁺) constituting 0.59% of cDC2s with >10-fold CL-depletion resistance (p high APC subset (CCR2 ⁻ Ly6C⁻) accounting for 2.7% of cDC2s with CL-sensitivity; (3) unconventional CD4⁺CD8α⁺ hybrids present in 2.57% of cDC2 and some cDC1s. These findings demonstrate unprecedented cDC plasticity driven by microenvironmental signals, revising conventional classification frameworks and proposing new targets for DC-based immunotherapies in autoimmunity and cancer. Our phenotypic mapping provides a foundational framework for future functional investigations into these novel subsets.

Machine learning and network pharmacology identify keloid biomarkers (AMPH, TNFRSF9) and therapeutic targets (IL6, HAS2) for aloe-derived quercetin

by Congli Jia, Fu Yang, Yingchun Li

Objective

This study aimed to identify diagnostic biomarkers for keloid and explore potential therapeutic agents from traditional Chinese medicine (TCM) by integrating network pharmacology approaches. Specifically, we sought to uncover key molecular targets for Aloe vera and validate their roles in keloid pathogenesis.

Methods

We integrated keloid transcriptome datasets (GSE218007 and GSE237752) by merging GEO data, and identifying differentially expressed genes (DEGs). Functional enrichment analysis (GO, GSEA) and machine learning approaches were applied to select diagnostic biomarkers. Candidate genes were validated via Receiver Operating Characteristic (ROC) curves in training and independent cohorts (GSE44270). PPI networks and Cytohubba algorithms identified hub genes, while TCMSP-screened compounds from Aloe vera were docked with targets using molecular docking.

Results

91 Identified DEGs enriched in fibrosis-related pathways. Machine learning prioritized two diagnostic biomarkers: AMPH and TNFRSF9 (AUC > 0.85 in training/testing). PPI analysis revealed IL6 as a hub gene. Aloe vera-derived quercetin targeted HAS2 and IL6 (both P  Conclusion

AMPH and TNFRSF9 are promising diagnostic biomarkers for keloid, while quercetin from Aloe vera targets HAS2 and IL6, offering therapeutic potential. The dual role of IL6 underscores its centrality in keloid pathogenesis, connecting bioinformatics predictions with TCM pharmacology. This study provides a foundation for clinical prediction and targeted treatment strategies.

Mobile phone MIMO antenna array miniaturization-based low SAR research in the combined EMF

by Wen-Qi Hou, Yu-Xin Li, Ming-Fei Luo, Wen-Ying Zhou, Mai Lu

Due to the diversification of media functions of mobile phones, users can make calls and access the internet simultaneously, which has significantly increased the usage time of mobile phones. The exposure dose of the users in the combined electromagnetic fields (EMF) should be further quantified to better evaluate the public exposure safety. Different from most conventional EMF safety studies that only focus on a single frequency, this work not only discusses the mobile phone simultaneously operated in fourth-generation (4G) and fifth-generation (5G) mobile communications radiation impact on users, but also verifies that the miniaturized mobile phone multiple-input multiple-output (MIMO) antenna array can significantly reduce the specific absorption rate (SAR) absorbed by users. In this article, a miniaturized mobile phone MIMO antenna array is employed as the radiation source, and multi-pose human models are established to simulate the practical utilization of a smartphone. A systematic analysis of the SAR absorbed by the human model is conducted in both single and combined EMF scenarios. The results indicate that the peak SAR in various tissues under multi-frequency exposure is 1.02 to 15.85 times higher than that under single-frequency exposure.

A non-invasive urinary diagnostic signature for diabetic kidney disease revealed by machine learning and single-cell analysis

by Yonggang Chen, Jintai Luo, Yingying Zheng, Xiaomei Jiang, Zixiang Yang, Xiaobing Liu

Background

Diabetic kidney disease (DKD) poses a significant health burden with inadequate diagnostic sensitivity. This study develops non-invasive biomarkers by integrating urinary and renal single-cell sequencing with machine learning.

Methods

This study analyzed DKD single-cell and bulk transcriptomic data from public repositories. We established a computational pipeline to distinguish kidney-originating cells in urinary sediments, enabling the identification of injury-associated gene signatures. These signatures were refined using machine learning to develop a diagnostic model, which was validated in independent cohorts. The biomarkers were further verified in DKD renal tissues at single-cell resolution and across multiple nephropathies. Functional and spatial analyses confirmed biological relevance using transcriptomic and histological validation.

Results

Single-cell analysis of 2,089 urine-derived cells identified eight renal cell types, including injured proximal tubule cells (Inj-PTC) showing upregulated injury markers (HAVCR1, VCAM1) and enriched apoptotic/TGF-β pathways. A machine learning-selected biomarker panel (PDK4, RHCG, FBP1) demonstrated strong diagnostic value (area under the curve, AUC > 0.9), with consistent downregulation across multiple chronic kidney diseases. PDK4 and FBP1 were specifically suppressed in DKD renal Inj-PTC (p  Conclusions

This study identifies a three-gene biomarker panel (PDK4, RHCG, FBP1) as a promising non-invasive diagnostic tool for DKD. While demonstrating excellent diagnostic performance. It represents a tubular injury-associated gene signature that is detectable in urinary cells and shows strong association with DKD in transcriptomic datasets, presenting a promising candidate for a non-invasive diagnostic assay.

Reliability, validity, and correlates of an AI voice emotion recognition app among nurses

by Chu-Ying Huang, Wen-Pei Chang

Background

Digital tools are increasingly widespread in healthcare, particularly in the fields of emotion recognition and mental health assessment.

Objectives

This study evaluated whether an artificial intelligence (AI) voice emotion recognition (VER) app could identify nurses’ emotions and explored its associations with their background and health conditions.

Methods

The emotions of 349 clinical nurses at a medical center in northern Taiwan were analyzed using an AI VER app and several standardized psychological questionnaires. To control for potential confounding variables, demographic and health-related factors including age, gender, work experience, exercise habits, and history of physical symptoms were collected and statistically adjusted in correlation analyses. Convergent validity was tested with Pearson’s correlations, and test-retest reliability was evaluated in 30 nurses using intraclass correlation coefficients (ICCs).

Results

Significant correlations were observed between app-derived emotions and standard scales (anger: Novaco Anger Inventory-Short Form, r = .42; fear: Perceived Stress Scale, r = .41; happiness: Oxford Happiness Questionnaire, r = .45; and sadness: Beck Depression Inventory-II, r = .47; all p p = .025), peptic ulcers predicted greater fear (β = .19, p p = .041), and irregular menstrual cycles predicted lower happiness (β = −.13, p = .014) and greater sadness (β = .30, p  Conclusion

Peptic ulcers, irregular menstrual cycles, and lack of exercise were associated with negative emotions such as fear, sadness, and anger. The AI VER app could objectively detect these emotional patterns in nurses, helping to identify emotional fluctuations early and support timely mental healthcare.

Real-world optimization of tunnel lengths in tunneled peripherally inserted central catheters for cancer patients: A multi-center retrospective cohort study

by Yinyin Wu, Wei Ding, Yuying Liu, Qianhong Deng, Fengqin Tao, Hanbin Chen, Chang Chen, Meng Xiao, Bilong Feng

Background

Standardized guidelines for optimal tunnel length in tunneled peripherally inserted central catheters (PICCs) are lacking.

Objectives

The objective of this study was to evaluate the real-world impact of tunnel length on clinical outcomes.

Methods

This retrospective cohort study included 207 cancer patients who received tunneled PICCs, categorized into a control group (tunnel length > 4 cm, n = 134) and an observation group (tunnel length ≤ 4 cm, n = 73). Propensity score matching (PSM) was used to address baseline heterogeneity. Cox regression analyses were used to assess the risk of complication during a 120-day follow-up.

Results

Compared to the control group (tunnel length > 4 cm), the observation group (tunnel length ≤ 4 cm) had a significantly higher adjusted overall complication risk (HR = 2.92, 95% CI: 1.07–7.94, P = 0.036) and unplanned catheter removal rate (4.4% vs. 0.0%, P = 0.027), confirming the safety of longer tunnels despite comparable comfort levels between groups. After PSM, Cox regression analysis showed results consistent with those from the unmatched cohort. Subgroup analyses revealed a reduced risk of complications with longer tunnels in patients with BMI ≤ 25 kg/m² (HR = 0.29, 95% CI: 0.11–0.82), without hypertension (HR = 0.36, 95% CI: 0.13–1.00), without diabetes (HR = 0.38, 95% CI: 0.15–0.97), and with solid tumors (HR = 0.31, 95% CI: 0.11–0.85).

Conclusion

The results show that tunnel lengths > 4 cm reduce overall complications and prolong catheter retention, supporting the implementation of standardized protocols while advocating for personalized adjustments based on BMI, comorbidities, and cancer type.

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.

Investigating risk factors of hemorrhagic fever of renal syndrome (HFRS) in Qingdao, Shandong province, China

by Ying Li, Jing Jia, Runze Lu, Liyan Dong, Lizhu Fang, Litao Sun, Zongyi Zhang, Qing Duan, Lijie Zhang, Kunzheng Lv, Huilai Ma

Background

Qingdao, a historically high-risk area for hemorrhagic fever with renal syndrome (HFRS) in China, is undergoing agricultural mechanization and urbanization. However, the specific risk factors for HFRS in this context remain unclear. This study sought to determine the risk factors for HFRS in Qingdao.

Methods

Community-based, 1:2 case-control study. Each case was matched with two healthy neighborhood controls based on biological sex, age, and the same neighborhood or village. Univariate and multivariate conditional logistic regression analyses were performed. Furthermore, stratified analyses were performed to explore risk factor heterogeneity between the peak season for Hantaan virus (HTNV) type HFRS (October-January) and other months.

Results

93 cases (73.2%, 93/127) reported from January 2022 to September 2023 and 186 controls completed this questionnaire. Farmers accounted for the highest proportion (68.8%, 64/93). In multivariate logistic regression analysis, there were three significant risk factors for HFRS: piles of firewood and/or grain in residential yards (odds ratio [OR]=3.75, 95% CI: 2.14–6.55), mite and/or flea bites (OR=1.83, 95% CI: 1.06–3.18) and contacting with rats and/or their excreta (OR=1.73, 95% CI: 1.09–2.74); three variables represented significant protective factors for HFRS: frequency of sun exposure for quilts and bedding (OR=0.41, 95% CI: 0.19–0.90), rodent control measures at home (OR=0.50, 95% CI: 0.30–0.81) and knowing the main sources of HFRS transmission (OR=0.58, 95% CI: 0.36–0.90). Stratified analysis revealed that the influence of these factors varied by season, with rodent contact and control measures being particularly salient during the HTNV peak season.

Conclusion

This study provides the first comprehensive evidence of risk and protective factors for HFRS in Qingdao, highlighting the role of rodent control, promoting comprehensive health education, environmental management, and personal protection. However, the results should be interpreted considering the study’s limitations, including a 73.2% response rate and the potential for recall bias.

GV effects of diabetes mellitus on clinical outcomes of patients with acute heart failure: A systematic review and meta-analysis

by Linna Zhao, Juanjuan Zhang, Weizhe Liu, Cheng Dai, Aiying Li

Diabetes mellitus (DM) is identified as a potential modifier of clinical outcomes in acute heart failure (AHF), yet its prognostic impact is not fully determined. This systematic review and meta-analysis aimed to assess the prognostic impact of DM on survival outcomes in AHF patients by synthesizing evidence from 26 studies involving 326,928 subjects collected from Cochrane Library, PubMed, Web of Science, and Embase databases up to 1 June 2024. Both prospective/retrospective cohort and case-control studies published since 2000 were included, with outcomes evaluated through multivariate, univariate, and binary analyses using the Newcastle-Ottawa Scale for quality assessment. Multivariate analysis indicated that DM significantly increased the risk of all-cause mortality in AHF patients (cohort studies: HR = 1.21, 95%CI (1.13, 1.29), OR=1.15, 95%CI (1.05, 1.26); case-control studies: HR = 1.39, 95%CI (1.26, 1.53), OR=1.43, 95%CI (1.10, 1.84)]. Univariate analysis confirmed this finding in case-control studies [HR = 1.30, 95%CI (1.01, 1.67)], but not in cohort studies. In both cohort [RR = 1.27, 95%CI (1.12, 1.43)] and case-control [OR=1.21, 95%CI (1.08, 1.35)] studies, DM increased the risk of all-cause mortality. AHF patients with DM had a higher risk of cardiovascular mortality [cohort studies: HR = 1.85, 95%CI (1.46, 2.33); case-control: OR=1.70, 95%CI (1.17, 2.47)]. While multivariate analysis showed no association between DM and in-hospital mortality, case-control studies indicated an increased risk [OR=1.21, 95%CI (1.03, 1.42)]. DM also increased the risk of readmission [cohort studies: HR = 1.32, 95%CI (1.14, 1.53); case-control studies: HR = 1.44, 95%CI (1.23, 1.69); binary data: OR=1.19, 95%CI (1.07, 1.31)].This updated meta-analysis demonstrates that DM imposes significant adverse effects on all-cause mortality, cardiovascular-related mortality, and readmission risk in AHF patients. However, no significant connection was found between diabetes and survival outcomes with respect to the co-endpoint of death or readmission and the endpoint of in-hospital mortality. These findings underscore the necessity for implementing targeted diabetes management within AHF care protocols to enhance clinical outcomes, an essential consideration for future practice.

Prevalence and determinants of precancerous cervical lesions among women screened for cervical cancer in Africa: A systematic review and meta-analysis

by Berihun Agegn Mengistie, Getie Mihret Aragaw, Tazeb Alemu Anteneh, Kindu Yinges Wondie, Alemneh Tadesse Kassie, Alemken Eyayu Abuhay, Wondimnew Mersha Biset, Gebrye Gizaw Mulatu, Nuhamin Tesfa Tsega

Background

Precancerous cervical lesions, or cervical intraepithelial neoplasia (CIN), represent a significant precursor to cervical cancer, posing a considerable threat to women’s health globally, particularly in developing countries. In Africa, the burden of premalignant cervical lesions is not well studied. Therefore, the main purpose of this systematic review and meta-analysis was to determine the overall prevalence of precancerous cervical lesions and identifying determinants among women who underwent cervical cancer screening in Africa.

Methods

This study followed the Preferred Reporting Item Review and Meta-analysis (PRISMA) guidelines. The protocol for this systematic review and meta-analysis was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42025645427). We carried out a systematic and comprehensive search on electronic databases such as PubMed and Hinari. In addition, Google Scholar and ScienceDirect were utilized to find relevant studies related to precancerous cervical lesions. Data from the included studies were extracted using an Excel spreadsheet and analyzed using STATA version 17. The methodological quality of the eligible studies was examined using the Joanna Briggs Institute (JBI) assessment tool. Publication bias was checked by using the funnel plot and Egger’s tests. A random-effects model using the Der Simonian Laird method was used to estimate the pooled prevalence of pre-cancerous cervical lesions in Africa. The I-squared and Cochrane Q statistics were used to assess the level of statistical heterogeneity among the included studies.

Results

A total of 112 eligible articles conducted in Africa, encompassing 212,984 study participants, were included in the quantitative meta-analysis. Thus, the pooled prevalence of pre-cancerous cervical lesions in Africa was 17.06% (95% confidence interval: 15.47%−18.68%). In this review, having no formal education (AOR = 4.07, 95% CI: 1.74, 9.53), being rural dweller(AOR = 2.38, 95% CI: 1.64, 3.46), history of STIs (AOR = 3.94, 95% CI: 2.97, 5.23), history of having multiple partners (AOR = 2.73, 95% CI: 2.28, 3.28), early initiation of coitus (AOR = 2.77, 95% CI: 2.11, 3.62), being HIV-seropositive women (AOR = 3.33, 95% CI: 2.32, 4.78), a CD4 count Conclusions

In Africa, the overall prevalence of pre-cancerous cervical lesions is high (17%). The findings of this review highlight that health professionals, health administrators, and all other concerned bodies need to work in collaboration to expand comprehensive cervical cancer screening methods in healthcare facilities for early detection and treatment of cervical lesions. In addition, increasing community awareness and health education, expanding visual inspection of the cervix with acetic acid in rural areas, offering special attention to high-risk groups (HIV-positive women), encouraging adherence to antiretroviral therapy for HIV-positive women, overcoming risky sexual behaviors and practices, and advocating early detection and treatment of precancerous cervical lesions.

Socio-ecological factors influencing dietary behaviours among adolescents and young adults in rural Eastern Uganda: A qualitative study

by Thomas Buyinza, Edward Buzigi, Joshua Kitimbo, Gabriel Ssabika, Mary Mbuliro, Julius Kiwanuka, Justine Bukenya, David Guwatudde, Rawlance Ndejjo

Introduction

Adolescents and young adults (AYAs) worldwide display poor dietary behaviors, including high consumption of sugar-sweetened beverages and insufficient intake of fruits and vegetables. These issues are more pronounced in Sub-Saharan Africa, such as rural Eastern Uganda, where 45.3% of adolescents eat low-diversity diets high in refined grains and fats. Such diets raise the risk of malnutrition and diet-related non-communicable diseases (NCDs). However, there is limited contextual evidence on the multi-level factors influencing AYAs’ dietary behaviors in rural Uganda. This study examined socio-ecological factors shaping dietary behaviors among AYAs in this setting.

Methods

A qualitative study guided by the socio-ecological model (SEM) was conducted in Mayuge District, Eastern Uganda. Focus group discussions (FGDs) were held with AYAs, including male and female, aged 10–14, 15–19, and 20–24 years. To have a nuanced understanding of how AYAs’ dietary behaviours are shaped, additional FGDs were conducted with parents or guardians and teachers, and key informant interviews with the district education officer, nutrition focal person, civil society staff, and food vendors. Data were analyzed in ATLAS.ti using both inductive and deductive thematic approaches: data-driven sub-themes were first identified inductively, then deductively mapped onto pre-determined themes of the SEM.

Results

Dietary behaviors were shaped by satiety, energy needs, sensory appeal, and nutrition knowledge at the individual level. Peer influence, parental control, and food’s perceived link to attractiveness acted interpersonally, while community factors included gendered cultural taboos, norms, and health worker advice. At the societal level, cultural identity, ancestral restrictions, and media exposure strongly influenced choices.

Conclusions

This study contributes novel rural-specific evidence from rural Uganda, where AYAs’ diets are uniquely constrained by satiety demands, parental dominance, cultural taboos, and seasonal scarcity; contrasting with urban contexts where convenience, autonomy, and wider food environments prevail. Multi-level interventions integrating nutrition education, family and peer engagement, cultural dialogue, and household food security support are essential for promoting healthier diets in resource-limited rural settings.

Time pressure alters takeoff but not landing biomechanics in single-leg countermovement jumps

by Ugur Yilmaz, Huseyin Celik, Pinar Arpinar-Avsar

This study examined how time pressure influences lower-limb biomechanics during single-leg maximal countermovement jumps (CMJs), with a focus on kinetic and kinematic responses during both jumping and landing phases. Participants performed single-leg CMJs under two conditions: self-paced (SP) and reaction-time (RT), the latter simulating time-constrained environments. Joint angles, ground reaction forces (vGRF), and joint moments were analyzed. Significant differences emerged between SP and RT tasks in jumping-phase kinetics and kinematics, with only kinematic differences present during landing. The RT condition led to reduced hip and knee flexion, increased peak vGRF, and shorter flight times, yet no improvement in jump height. This suggests inefficient energy transfer possibly due to reduced range of motion and increased muscle co-contraction or pretension strategies. Joint moment analysis revealed a shift from a hip-dominant strategy in SP to a knee-dominant strategy in RT. Landing in RT was characterized by reduced joint flexion and increased frontal plane loading, potentially elevating the risk of lower-limb injury. Time pressure modifies motor strategies in single-leg CMJs, promoting faster execution at the cost of performance efficiency. These findings underscore the importance of training for both explosive performance and neuromuscular control under time-constrained, sport-specific conditions.

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.

Identification of pathogenic variants for the development of ultra-long axial length in myopic children

by YanYing Zhu, XueYan Li, YueXin Chen, HaiYan Xie, YuKun Liu, XiaoChen Xu, Jing Wang

Purpose

Axial elongation is a key factor in myopia progression, yet its genetic basis remains incompletely understood. This study aims to identify pathogenic genetic variants associated with excessively elongated axial length in children.

Methods

This study included 56 children with axial lengths exceeding the normal range for their age group, and whole-exome sequencing (WES) was performed on their oral mucosal samples. Clinical evaluations included axial length measurement, refraction testing, and fundus photography to assess the degree of myopia and retinal changes. Co-segregation analysis was conducted in selected families (F#1, F#2, F#5) to validate the familial inheritance patterns of the variants.

Results

Fifteen children carried variants in genes including BBS2, OPN1LW, P4HA2, FBN1, LOXL3, FZD4, USH2A, COL2A1, and BFSP2, with five novel variants identified: BBS2 (c.700C > T), P4HA2 (c.1382C > G), FBN1 (c.7130T > C), LOXL3 (c.1580delC), and FZD4 (c.1315G > A). Notably, a rare compound heterozygous BBS2 variant (c.700C > T/c.534 + 1G > T) was found in a non-syndromic child, and the P4HA2 (c.419A > G) variant in family F#5 exhibited a phenotype distinct from previous studies.

Conclusions

This study identified five novel variants sites and discovered two cases with phenotypes distinct from previous studies, thereby expanding the genetic variant spectrum associated with myopia and providing new targets for genetic screening and intervention.