PLOS ONE Alerts: New Articles

Effects of vitamin D supplementation on vitamin D status and physical performance in football players: A systematic review and meta-analysis

2026-11-06T14:00:00Z

by Jinfa Gu, Yu Zhang, Luhua Xiao

Background/Objectives

Low vitamin D status is frequently reported among athletes, but whether vitamin D supplementation improves physical performance in football players remains uncertain. This systematic review and meta-analysis aimed to evaluate the effects of vitamin D supplementation on serum 25-hydroxyvitamin D [25(OH)D] concentration, jump performance, sprint performance, aerobic capacity, and muscular performance in association football and futsal players.

Methods

PubMed, Embase, the Cochrane Library, Scopus, and Web of Science were searched from database inception to 31 May 2026. Controlled intervention studies comparing vitamin D supplementation with control conditions were eligible. Standardized mean differences were calculated as Hedges’ g and pooled using random-effects meta-analyses. Two reviewers independently extracted data and assessed risk of bias using RoB 2 or ROBINS-I. The certainty of evidence was assessed using GRADE. The protocol was prospectively registered in PROSPERO (CRD420261430873).

Results

Eleven reports representing nine independent studies and 312 players were included. In RCT-only primary analyses, vitamin D supplementation was associated with higher circulating 25(OH)D concentrations (g = 1.41, 95% CI 0.90 to 1.92; I² = 58.0%). Pooled effects were not statistically significant for jump performance (g = 0.21, 95% CI −0.10 to 0.53), sprint performance (g = −0.03, 95% CI −0.40 to 0.34), aerobic capacity (g = 0.00, 95% CI −0.45 to 0.45), or muscular performance (g = 0.19, 95% CI −0.14 to 0.51). The certainty of evidence was low for circulating 25(OH)D, jump performance, and muscular performance, and very low for sprint performance and aerobic capacity.

Conclusions

Vitamin D supplementation was associated with increased circulating 25(OH)D concentrations, whereas current evidence is insufficient to support a consistent improvement in physical performance. Given the low to very low certainty of evidence, these findings should be interpreted cautiously. Larger, well-designed randomized controlled trials using standardized, football-relevant performance tests are warranted.

Tranexamic acid for anemia in women of reproductive age: A systematic review of randomized trials

2026-11-06T14:00:00Z

by Sima Berendes, Katharine Ker, Hilary O. D. Critchley, Raoul Mansukhani, Ian Roberts

Objective

The global target to halve the prevalence of anemia by 2025 has not been met. New strategies are needed. This systematic review examined the effect of tranexamic acid on anemia, menstrual health and wellbeing in women of reproductive age.

Methods

We searched six databases from inception to 30 August 2025 and reference lists of seven related reviews. We included randomized trials comparing the effects of tranexamic acid with placebo or standard care on uterine bleeding. Eligible participants had normal menstrual bleeding or any type of non-pregnant abnormal uterine bleeding. Outcomes included hemoglobin concentration and anemia prevalence as the primary outcome, estimated blood loss, quality of life, thromboembolic events, and other adverse events. We conducted meta-analyses and assessed risk of bias (Cochrane risk-of-bias tool for randomized trials) and the certainty of evidence.

Results

We included 17 trials in the review and 15 in the meta-analyses. None of the trials reported adequate data on hemoglobin concentration. For the anemia outcome, only one small trial contributed data (risk ratio 0.15, 95% confidence interval 0.01 to 2.74, very low certainty). Meta-analyses of secondary outcomes showed that tranexamic acid reduced objectively measured menstrual blood loss among women with heavy menstrual bleeding (6 trials, mean difference −47.0 milliliters, 95% confidence interval −56.6 to −37.4, I² = 13%, moderate certainty) and in women with intrauterine devices (3 trials, mean difference −41.6 milliliters, 95% confidence interval −52.2 to −30.9, I² = 64%, low certainty) and improved quality of life in women with heavy menstrual bleeding (2 trials, mean difference 0.5, 95% confidence interval 0.4 to 0.7, I² = 0%, moderate certainty). The risk of nausea or vomiting was similar between groups (4 trials, risk ratio 1.0, 95% confidence interval 0.6 to 1.8, I² = 0%, moderate certainty). Certainty of evidence for other outcomes ranged from very low to low, including for thromboembolic events, with only one event reported in the control arm of one trial.

Conclusions

Tranexamic acid appears to reduce menstrual blood loss, but its impact on anemia is unclear. High-quality randomized trials of TXA for menstruating women with anemia are needed.

Artificial intelligence (AI) adoption and Chinese art teachers’ career exploration behavior: The roles of job substitution risks, job insecurity, and organizational AI readiness

2026-11-06T14:00:00Z

by Jia Li, Yun Gao

The increasing use of artificial intelligence (AI) in art education raises questions about teachers’ professional security and career development. Drawing primarily on Conservation of Resources (COR) theory and, in a complementary manner, on Career Construction Theory (CCT), this cross-sectional study examined associations among AI adoption, perceived job substitution risk, job insecurity, career exploration behavior, and organizational AI readiness. Survey data from 381 Chinese art teachers were analyzed using Mplus 7.4. AI adoption was positively associated with career exploration behavior. Statistically significant indirect associations were observed through job substitution risk, job insecurity, and their hypothesized sequential combination. Organizational AI readiness positively moderated the AI adoption–career exploration relationship: the association was stronger at higher readiness. COR theory offers a resource-threat interpretation of the indirect associations, while CCT highlights that career exploration may reflect threat-related coping, growth-oriented development, or both. The data did not separately measure these motivations or establish causal ordering. The findings provide context-specific insights into career exploration among art teachers during AI-related technological change.

Estimation of aerobic and anaerobic performance using a novel intermittent reactive agility test – An exploratory correlation study

2026-11-06T14:00:00Z

by Bettina Karsten, Richard Latzel, Michael Kölling, Thorben Hülsdünker

Separate tests are usually used to assess an athlete's ability to meet the aerobic and anaerobic demands of ball sports. These tests often compromise ecological validity by relying on linear runs and sprints rather than multidirectional reactive agility. This study investigated the correlations between a novel motor-cognitive reactive agility (RA) test and aerobic and anaerobic performance indices. Twenty-two trained participants (V˙O_2max: 56 ± 6.4 ml ∙ kg^-1 ∙ min^-1) performed a treadmill ramp test to determine maximum oxygen uptake (V˙O₂max), a running-based anaerobic sprint test (RAST) to determine peak power output (PPO), average power putput (POAV), fatigue index (FI) and anaerobic capacity (AC) and a motor-cognitive RA test on the SKILLCOURT. The RA test required participants to perform four 150 m maximal multidirectional change of directions runs with a break of 30 s. Running time, heart rate and power output were determined for all runs and correlated to V˙O_2max and anaerobic performance indicators. Running time of the 4th SKILLCOURT run was correlated to V˙O_2max (r₂₀ = −0.80, p < 0.001) and a strong relation was found between PPO determined in the RAST and SKILLCOURT test (r₂₀ = 0.72, p < 0.001). The SKILLCOURT RA test provides a promising tool for sport coaches to monitor aerobic and anaerobic performance indices, considering reactive agility. This needs to be validated in future studies.

Pharmacological cGAS-STING pathway inhibition on neuroinflammation in animal models of traumatic brain injury: A systematic review and meta-analysis protocol

2026-11-06T14:00:00Z

by Myriam Lamamri, Stéphanie Sigaut, Hélène Cwerman-Thibault, Valérie Faivre, Juliette Van Steenwinckel, Vincent Degos, Pierre Gressens, Alice Jacquens

Background

Traumatic brain injury (TBI) is a major cause of mortality and long-term neurological disability worldwide. Secondary injury mechanisms, particularly neuroinflammation, play a key role in determining neurological outcomes after the initial trauma. The cyclic GMP-AMP synthase stimulator of interferon genes (cGAS-STING) pathway has recently been identified as a mediator of innate immune activation following brain injury. Activation of this pathway promotes microglial activation and the release of pro-inflammatory cytokines, contributing to neuronal damage and impaired recovery. Pharmacological inhibition of the cGAS-STING signaling pathway has therefore emerged as a promising neuroprotective strategy in experimental TBI models. However, the available preclinical evidence has not yet been systematically synthesized.

Methods

A systematic literature search was performed across MEDLINE, EMBASE and Web of Science without language or publication date restrictions. Titles and abstracts were screened independently by two reviewers, followed by independent full-text eligibility assessment. Data extraction was initiated subsequently and will be completed independently by two reviewers. Eligible studies will include in vivo animal models of TBI investigating direct or indirect pharmacological inhibition of the cGAS-STING pathway administered after injury, compared with vehicle-treated or untreated controls. The primary outcome will be quantitative measures of microglial activation within the first 72 hours post-injury, preferentially assessed using Iba1-positive cell density or percentage-stained area. Secondary outcomes will include astrocytic reactivity, cytokine expression (TNF-α, IL-1β, IL-6), lesion volume and neurological functional recovery. Risk of bias will be assessed using the SYRCLE tool. When appropriate, pooled effect sizes will be calculated using random-effects meta-analysis. Heterogeneity, publication bias and certainty of evidence will also be evaluated.

Discussion

This systematic review and meta-analysis will help clarify the magnitude and consistency of therapeutic effects and inform the translational potential of this strategy while identifying methodological limitations that may guide future experimental and clinical research.

Systematic review registration

PROSPERO CRD420261367166.

Adaptive–based cascaded PI–PID controller for load frequency regulation with real time verification

2026-11-06T14:00:00Z

by Abdullah M. Alharbi, Mohamed A. Awad, Mahmoud A. Attia, S.F. Mekhamer, Ahmed H. EL-Ebiary

In order to address Load Frequency Control (LFC) problems in single-area and interconnected two-area power systems, this work proposes a cascaded control scheme that combines PI–PID control with the Set-Membership Affine Projection Algorithm (SMAPA). The proposed approach is evaluated under various practical operating conditions, including step load disturbances, random load variations, wind power fluctuations, and parameter uncertainty. In addition, frequency-domain stability analysis is performed to further assess the robustness of the proposed controller, while real-time validation is conducted for the two-area system to demonstrate its practical effectiveness. The proposed controller is compared with conventional PI controllers tuned using five optimization methods for the single-area system. For the two-area system, its performance is benchmarked against PID controllers designed using three optimization methods and the recently reported SPPI-based approach. The simulation results show that the proposed controller achieves lower overshoot and faster settling time in both configurations. These improvements are attributed to the integration of real-time adaptive parameter updating provided by SMAPA with the favorable dynamic characteristics of the PI–PID control structure. The results demonstrate that the proposed cascaded SMAPA-based PI–PID controller provides robust frequency regulation under different operating conditions and offers promising potential for practical interconnected power system applications.

Aligning entity of knowledge graph based on graph convolutional network with maximum translated similarity

2026-11-06T14:00:00Z

by Jianhui Zhou, Yun Gao, Xiangbing Zhao, Yanping Guo, Xulong Zhang

Entity alignment is a pivotal technology for integrating heterogeneous knowledge graphs, yet most embedding-based alignment methods destroy the inherent structural embedding information of knowledge graphs when unifying cross-graph embedding spaces, resulting in limited alignment accuracy and stability. To tackle this issue, this paper proposes a novel model for entity alignment tasks, which named as Graph Convolutional Network with Maximum Translated Similarity (GCN-MTS). GCN-MTS innovatively leverages a maximum translated similarity mechanism to optimize the adjacency matrix, degree matrix and loss function. This core design effectively maintains the original relative embedding structure of cross-graph entities during embedding space unification, which is the key improvement over existing approaches. Comprehensive experiments on 3 pairs of real-world knowledge graph dataset demonstrate the superior performance of GCN-MTS against advanced baseline methods. It achieves average performance gains of 5%–15% in Hits@1 and 4%–16% in Hits@10. Ablation results confirm that the optimized module brings a nearly 22% improvement in alignment metrics compared with the vanilla GCN. Furthermore, GCN-MTS presents excellent robustness and stability across different seed alignment quantities and seed combinations.

HIV/AIDS knowledge and stigmatizing attitudes among adult residents of the United Arab Emirates: A cross-sectional study

2026-11-06T14:00:00Z

by Hiba Jawdat Barqawi, Kamel A. Samara, Abdul Rahman Sheiko, Mohamed Alhariri, Moustafa Saber Mashal, Amal Abu Helwa, Eman Abu-Gharbieh

Background

HIV-related stigma remains a significant barrier to prevention and treatment efforts in the Middle East and North Africa (MENA) region. This study assessed HIV knowledge and stigmatizing attitudes among United Arab Emirates (UAE) residents.

Methods

A cross-sectional survey was conducted across the UAE between January and March 2025. A total of 1,211 eligible adult residents were recruited through convenience sampling. Demographic analyses included all 1,211 participants, while HIV knowledge and stigma analyses included 1,171 participants with analyzable outcome data. The questionnaire assessed demographics, HIV transmission knowledge, and stigmatizing attitudes using the Stigmatizing Attitudes Towards People Living with HIV/AIDS Scale (SAT-PLWHA-S). Data were analyzed using descriptive statistics, bivariate analyses, and multiple linear regression.

Results

Among the 1,211 participants included in the study, 1,171 contributed analyzable data to the HIV knowledge and stigma analyses. While 96.4% had heard of HIV/AIDS and demonstrated moderately high transmission knowledge (mean score: 75.5%), significant misconceptions persisted, particularly regarding condom effectiveness (60.5% overestimated risk). Strong stigmatizing attitudes emerged, especially regarding criminalization of transmission (79.6% support) and moralistic views. Higher knowledge correlated with less stigma (r = 0.347, p < 0.001), though nationality, language preference, and knowing someone with HIV were stronger predictors. Only 6.2% knew someone with HIV.

Conclusions

Despite adequate basic knowledge, significant HIV-related stigma persists in the UAE, driven by cultural and moral perspectives. Comprehensive interventions combining education, contact-based strategies, and policy reform are needed to reduce stigma and improve HIV prevention outcomes.

Harrowing experiences of vagina fistula victims in the Kpandai District of Ghana: A qualitative study

2026-11-06T14:00:00Z

by Eric Elorm Ahorsu, Joshua Adeti, Ernest Kemevor Selasie, Mohammed Ibn Shamsudeen, Cynthia Akos Okumasi, Benjamin Amedume, Justice Wiston Amstrong Jonathan

Background

Vaginal fistula (VF), particularly vesicovaginal fistula (VVF), remains a significant reproductive health challenge in many low-resource settings, including the Kpandai District of Ghana. Despite its profound physical and psychosocial impact, the lived experiences of affected women in rural districts remain under-documented.

Aim

This study explored the lived experiences of women diagnosed with vesicovaginal fistula in the Kpandai District of Ghana, focusing on their physical, emotional, and social challenges, as well as coping strategies.

Methods

A qualitative descriptive study was conducted using in-depth interviews with ten women with clinically confirmed VVF. Participants were initially identified through a district health facility and subsequently recruited using a combination of purposive and snowball sampling techniques. Interviews were audio-recorded, transcribed verbatim, and analysed thematically.

Results

Prolonged and obstructed labour—often occurring at home—emerged as the primary reported cause of VVF. Cultural beliefs, gender-based decision-making dynamics, limited access to healthcare, and financial constraints were key barriers to timely medical intervention. Consequences included persistent urinary incontinence, social stigma, emotional trauma, marital dissolution (reported by eight participants), loss of livelihood, and social isolation. Coping strategies included frequent washing, use of absorbent materials, and reliance on perfumes or herbal remedies.

Conclusions

Vesicovaginal fistula remains a devastating yet largely preventable condition in rural Ghana. The findings highlight the need to strengthen maternal health services, improve timely referral systems, and integrate psychosocial support within community-based care frameworks.

Epidemiological surveillance of bacterial pathogens in cultured European sea bass (Dicentrarchus labrax) along the Aegean coast of Türkiye

2026-11-06T14:00:00Z

by Pınar Çelik, Vyron Georgalas, İhsan Çelik

Intensive aquaculture of European sea bass (Dicentrarchus labrax) along the Aegean coast of Türkiye faces continuous production challenges from infectious diseases, yet comprehensive multi-year baseline data remain limited. This study presents a multi-year retrospective surveillance program (2020–2025) monitoring bacterial pathogens associated with 748 distinct cage-level disease outbreaks in fish across 19 discrete offshore commercial sea farms. To maintain industry confidentiality, diagnostic data from these separate facilities were fully aggregated and evaluated across three broad macro-regional surveillance zones. A total of 5,235 fish displaying clinical signs underwent diagnostic necropsy. Presumptive bacterial identification was conducted using phenotypic profiling through the API 20E system, and organ touch-imprint cytology. Six distinct bacterial species were isolated from positive clinical individuals, recovering a total of 2,490 isolates. Across the recorded outbreak events, etiological agents were ranked as primary drivers as follows: Photobacterium damselae subsp. piscicida (48.80%; N = 365), Tenacibaculum maritimum (35.83%; N = 268), Vibrio (Listonella) anguillarum (9.49%; N = 71), V. harveyi (3.74%; N = 28), V. ordalii (1.20%; N = 9), and V. alginolyticus (0.94%; N = 7). This hierarchy directly mirrored the overall bacterial isolation frequency, where P. damselae subsp. piscicida showed the highest relative distribution rate (46.18%; n = 1,150), followed by T. maritimum (34.10%; n = 849). Significantly lower isolation rates were recorded for V. (Listonella) anguillarum (11.41%; n = 284), V. harveyi (5.26%; n = 131), V. ordalii (1.77%; n = 44), and V. alginolyticus (1.29%; n = 32). Descriptive tracking of the purified laboratory isolates revealed localized variations in diagnostic recovery frequencies among the three sectors, while establishing a highly stable baseline dominated by P. damselae subsp. piscicida and T. maritimum across the Eastern Aegean Turkish mariculture network.

Source apportionment and non-carcinogenic health risk assessment of selected heavy metals in the Turag river area of Gazipur District, Bangladesh

2026-11-06T14:00:00Z

by Juned Hussain Chowdhury, Md Jamil Hossain, Ryadul Alam, Ifteker Uddin Sakib, Wahida Ahmed, Naimur Rahman Sarker, Sangita Chakroborty, Md Mushfiqur Rahman Porosh, Md Shakhaoat Hossain, Badhan Saha, Mohammad Moniruzzaman, Ayesha Ahmed

Introduction

Rapid industrialization in Bangladesh, especially in Gazipur District, has raised concern over heavy metal contamination of soil and water and the associated health risks to nearby residents. This study compared the concentration, spatial distribution, probable sources, and non-carcinogenic health risk of five heavy metals (Hg, Ni, Mn, Zn, and Co) in soil and water in the Turag River areas in Gazipur District.

Methods

Soil and water samples were collected from 18 sites in the Turag River (including both industrial and non-industrial zones) and analyzed for five heavy metal concentrations (Hg, Ni, Mn, Zn, and Co) using inductively coupled plasma-mass spectrometry (ICP-MS). Statistical analyses included principal component analysis (PCA), hierarchical cluster analysis (HCA), and Pearson correlation analysis, while non-carcinogenic human health risks were evaluated using the USEPA-based chronic daily intake (CDI), hazard quotient (HQ), and hazard index (HI) models for both adults and children.

Results

Mean soil metal concentrations followed the order Mn > Zn > Ni > Co > Hg in both zones, with markedly higher and more spatially concentrated Ni and Zn levels in the industrial zone near the Turag River areas. Spatial mapping, PCA, HCA, and correlation analyses consistently suggested a common anthropogenic influence on soil and water contamination in the industrial zone, with the strongest spatial concentrations observed near its northern boundary, compared with patterns consistent with multiple diffuse influences in the non-industrial zone. The modeled soil CDI values were generally higher for children than adults. Soil-based screening estimates indicated potential non-carcinogenic concern for children, including an Ni HQ of 1.66 in the industrial zone and cumulative hazard index values above the screening benchmark of 1 for children in both the industrial (HI = 2.32) and non-industrial (HI = 1.31) zones, while all modeled HQ and HI values for water remained below the screening benchmark of 1.

Conclusion

These soil-based screening estimates suggest potential non-carcinogenic concern for children, particularly regarding Ni in the industrial zone, but are based on the < 0.5 mm fraction of soil collected at 15–20 cm depth and may not represent actual exposure to ground-surface soil or airborne particles. The study highlighted the need for targeted control of potential industrial sources and child-focused environmental health monitoring in industrializing peri-urban districts of Bangladesh.

Finite-time robust motion control of intelligent vehicles based on neural approximation and disturbance estimation

2026-11-06T14:00:00Z

by Lijuan Zhang

This paper addresses the inherent trade off between rapid convergence and high‑precision disturbance rejection in intelligent vehicle motion control under severe nonlinearities, parametric uncertainties, and time varying external perturbations. A composite finite‑time robust control strategy is proposed by synergistically integrating a nonsingular fast terminal sliding mode (NFTSM) surface, radial basis function neural networks (RBFNN), and a finite time disturbance observer (FTDO). The NFTSM guarantees singularity free finite time convergence of the tracking errors. The RBFNN approximates the slowly varying unknown dynamics, while the FTDO compensates online for the neural approximation residual and fast varying disturbances in a cascaded “coarse to fine” manner. Lyapunov-based Extensive co‑simulations with MATLAB/Simulink, conducted under double lane change and sinusoidal path scenarios with simultaneous road friction drops and stochastic lateral wind gusts, demonstrate that the proposed framework significantly outperforms conventional nonsingular terminal sliding mode control and disturbance observer based sliding mode control in terms of tracking accuracy, convergence speed, and chattering suppression.

Exploratory cluster analysis of noninvasive vascular measures reveals heterogeneous vascular profiles after stroke

2026-11-06T14:00:00Z

by Bria L. Bartsch, Amanda N. Engler, Sandra A. Billinger

Vascular dysfunction is prevalent after stroke and contributes to elevated cardiovascular risk; however, the extent to which vascular heterogeneity exists in this population remains unclear. This study examined whether distinct multi-domain cluster-derived vascular profiles are present in individuals with chronic stroke and whether these profiles are associated with functional performance. Vascular structure and function were assessed using flow-mediated dilation, carotid intima-media thickness, pulse wave velocity, and augmentation index, with age included in vascular clustering to account for vascular aging. Unsupervised k-means clustering was applied to identify vascular profiles. Functional performance was assessed using gait speed and predicted peak oxygen consumption (VO_2peak) derived from a submaximal exercise test. Between-cluster differences were characterized using analysis of variance. Forty-five individuals with chronic stroke (62 ± 12 years; 29 ± 30 months post-stroke) were included. Three vascular profiles were identified (cluster 1: n = 13; cluster 2: n = 11; cluster 3: n = 21), with significant differences across clusters for all vascular measures (p < 0.01). Although age increased across clusters, vascular structure and function did not change uniformly. One profile exhibited elevated arterial wave reflection despite relatively preserved endothelial function and arterial structure, whereas another demonstrated impairment in all vascular variables. Vascular profile was not associated with predicted VO_2peak (p = 0.31) or gait speed (p = 0.65). Three exploratory cluster-derived vascular profiles emerged among participants with chronic stroke, and age did not fully account for the observed vascular heterogeneity. Multi-domain cluster-derived vascular profiling revealed heterogeneous vascular profiles in individuals with chronic stroke, providing a basis for future studies to evaluate their relevance to cardiovascular risk stratification and long-term health management. NCT05936008: https://clinicaltrials.gov/study/NCT05936008

A Kampo medicine, kamishoyosan, ameliorates menstruation-associated symptoms in patients with premenstrual syndrome: An exploratory open-label, randomized controlled trial

2026-11-06T14:00:00Z

by Jun Chikumi, Eri Sato, Ai Ikebuchi, Yohei Tokita, Mitsuto Fukushige, Mayu Yamamoto, Hiroshi Sunada, Yusuke Endo, Hisashi Noma, Tasuku Harada, Fuminori Taniguchi

Premenstrual syndrome (PMS) is a psychological or physical symptom. We conducted an open-label, randomized, exploratory trial with the aim of evaluating the efficacy and safety of kamishoyosan (KSS) for PMS. KSS was administered orally during three menstrual cycles. The primary endpoint was the change in the premenstrual Menstrual Distress Questionnaire (MDQ) total score. The secondary endpoints included MDQ total and subscale scores, a daily symptom questionnaire, the Work Productivity and Activity Impairment (WPAI) Questionnaire, overall impressions, sleep status, and heart rate. A total of 50 patients were enrolled. The primary endpoint, the premenstrual MDQ total score, was significantly ameliorated after KSS treatment. Furthermore, KSS reduced MDQ scores during the menstrual cycle. Among the MDQ subscales, KSS decreased score of pain, concentration, behavioral change, and negative feelings during the premenstrual cycle. In addition, hyperthymia reduced during the menstrual cycle. The results of the daily symptom questionnaire indicated that KSS treatment alleviated irritability, easy anger, anxiety, emotional instability, abdominal distension, coldness, and stiff shoulders.The WPAI activity impairment score was lower in the KSS group, and overall impression favoured in KSS treatment.. The only adverse event related to KSS was headache in one case. These exploratory findings suggest that KSS may improve menstrual-related symptoms in PMS.

Antibiotic stewardship challenges in Madagascar’s poultry sector: informality, knowledge gaps, and market constraints

2026-11-06T14:00:00Z

by Sophie Molia, Ilo Tsimok’Haja Ramahatafandry, Michel Rakotoharinome, Christian Lienhardt, Muriel Figuié, Alexandre Hobeika, Daouda Kassié

Antibiotic resistance (ABR) is a major global public health threat, largely driven by the overuse and misuse of antibiotics. Tackling its animal health component is particularly difficult in low- and middle-income countries, where data and resources are limited. This qualitative study aims to explore antibiotic use (ABU) and its underlying drivers in poultry farms in Analamanga, Madagascar’s region with the highest poultry density. In April 2023, we conducted semi-structured interviews with 79 poultry farmers (13 backyard and 66 semi-intensive), 10 animal health professionals, and 10 agrovet shop sellers. Thematic analysis was used to examine farm characteristics, poultry health management, veterinary medicine supply and use, and interactions with poultry production stakeholders, in order to identify antibiotic stewardship challenges in Madagascar's poultry sector. Backyard and semi-intensive farmers shared several features: informality (absence of farm registration, rare cooperative membership, limited training), irregular profitability, easy access to antibiotics, recurrent antibiotic misuse (for example use in poultry viral infection treatment, first-line fluoroquinolone treatments), and limited veterinary inspection by competent authorities. However, the two farmer groups differed, as semi-intensive farmers had slightly greater knowledge of ABU and ABR than backyard farmers; they primarily consulted chick and feed suppliers for health advice and medicine purchase; and they widely perceived antibiotics as essential to maintaining poultry health and productivity. Practical roadblocks to invest in preventive measures or adopt effective antibiotic stewardship (ABS) were their narrow profit margins, limited access to credit, and weak bargaining power towards poultry product buyers. Tailored approaches such as supporting professionalization of poultry sector, building capacity of chick and feed suppliers to provide training in appropriate ABU and management of flocks, flock vaccination, deworming schedules, treatment record keeping and ABS principles may enhance antibiotic usage in the Madagascar poultry sector. Future research should build on this exploratory study, which used a convenience sample of stakeholders, by examining ABU trends and drivers in Analamanga with representative sampling and rigorous quantitative validation across Madagascar’s poultry sector.

Introduction of contraceptive implants as a family planning strategy in Honduras and Chiapas: Results from the Salud Mesoamerica Initiative (SMI)

2026-11-06T14:00:00Z

by Adrián Santoro, Natalia Basualdo, Federico Rolón, Lucía Bartolomeu, Camila Volij, Matt Simon, Brittany Hagedorn, Diego Ríos-Zertuche, Santiago Esteban, Adolfo Rubinstein

Expanding access to a broad range of contraceptive methods is critical for reducing unintended pregnancies and improving reproductive health. This study evaluates the introduction of subdermal contraceptive implants in the selected areas of Honduras and Chiapas, Mexico, in the context of the Salud Mesoamérica Initiative, a results-based financing program focused on disadvantaged populations. Data were obtained from household surveys conducted between 2012 and 2022 among women aged 15–49 years in selected intervention and comparison municipalities in Chiapas, Mexico, and Honduras, using a two-stage sampling design. Indicators included contraceptive prevalence rates, reasons for method switching, and adoption by sociodemographic characteristics. Findings show a substantial increase in implant use in both settings over time. In the selected areas of Honduras, implant uptake increased gradually, reaching 7.9% in the 2022 SMI household survey, while in the selected areas of Chiapas use rose to 7.2%. Younger women aged 20–29 years and those with full literacy exhibited the highest adoption rates. In the selected areas of Chiapas and Honduras, implants most often replaced non-modern and short-acting hormonal methods, suggesting successful integration into the existing method mix. Variations in adoption across sociodemographic subgroups highlight persistent inequities. The results underscore the potential of subdermal implants to expand access to long-acting reversible contraception in resource-limited settings. To sustain and enhance this progress, strategies must address sociocultural and structural barriers, ensuring equitable access across all population groups and mitigating service disruptions. These findings may inform future strategies to expand informed contraceptive choice in similar resource-limited settings; their effects on reproductive health outcomes require further evaluation.

A psychological perspective on peer tutoring in EFL collaborative writing in Chinese higher education contexts

2026-11-06T14:00:00Z

by Zefu Huang, Nalini Arumugam

In Chinese higher learning institutions, students learning English as a foreign language (EFL) often demonstrate low writing self-efficacy (WSE) and poor writing competence. The present study examined the associations between the integration of peer tutoring with collaborative writing and students’ WSE and writing outcomes from a psychological perspective. A quasi-experiment was implemented for 11 weeks for 100 Chinese university students studying EFL. Changes in WSE were examined, and writing competence was assessed using tests. The results showed a notable rise in students’ WSE after the instructional intervention. The multiple linear regression analysis indicated that gains in WSE were positively associated with the writing outcome after controlling for pretest writing competence and group membership, explaining 20.2% of the total variance. These results suggest that peer-supported collaborative writing was associated with higher EFL writing competence alongside increased WSE. These findings align with theoretical justifications based on peer scaffolding and the Zone of Proximal Development, although these processes were not directly measured in the present study. These findings imply that incorporating peer tutoring into collaborative writing might be associated with the development of WSE and improved writing competence among EFL students at Chinese universities. Increased WSE appeared to be a significant, albeit partial, predictor of writing competence, highlighting the potential relevance of WSE development in peer-supported collaborative writing contexts.

Whose morning, whose evening? Temporal asymmetries in intermedia agenda-setting between X and online news in Türkiye

2026-11-06T14:00:00Z

by Mehmet Ceylan, Ramazan Yılmaz, Rumeysa Erdoğan Bodur

This study examines whether temporal ordering between X and online news varies across first-level issue and second-level attribute agendas in Türkiye’s polarized media environment. The analysis draws on 448,664 X posts and 10,357 articles from 19 mainstream online news outlets collected during the 31-day period preceding and including the 31 March 2024 Istanbul local election. Using 12-hour AM/PM windows, we conducted 122 cross-lagged panel analyses—62 same-day AM → PM and 60 overnight PM→next-day AM panels across the two agenda levels—comparing issue- and attribute-indicator frequency profiles. First-level issue agendas were strongly synchronized, with correlations often approaching or exceeding r = .90, whereas second-level attribute relationships were weaker and less consistent. At the first level, morning online news issue salience more often preceded later X issue salience within same-day transitions, whereas evening X issue salience more often preceded the following morning’s online news issue salience across overnight transitions. Most first-level cross-lagged correlations exceeded their Rozelle–Campbell (RCb) baselines, while second-level coefficients did so less consistently. These findings indicate that agenda leadership in a hybrid media system is temporally contingent and level-specific rather than static. The observed patterns represent temporally ordered associations and should not be interpreted as evidence of direct causal influence.

Editorial Note: Early Growth Response Gene-2 (Egr-2) Regulates the Development of B and T Cells

2026-11-06T14:00:00Z

by The PLOS One Editors

Retraction: Barriers to access to care in the implementation of telemedicine in public hospitals in Southern Ethiopia: A phenomenological qualitative study

2026-11-06T14:00:00Z

by The PLOS One Editors

Protocol for investigating the association between Helicobacter pylori exposure, antigen-specific serological responses, and resistant versus non-resistant hypertension in a South African cohort

2026-11-06T14:00:00Z

by Mathilda C. Mennen, Michael Z. Zulu, Koketso C. Mabatha, Richard Baguma, Sango Skelem, Nandipha N. Mbundwini, Olukayode O. Aremu, Marguerite Adriaanse, Daphne van Dijk, Preyanka Pillay, Sam Africa, Erika Jones, Mashiko Setshedi, Adrian Brink, Wendy A. Burgers, Ntobeko A. B. Ntusi

Background

Hypertension is a leading contributor to cardiovascular morbidity and mortality, with poor control in low- and middle-income countries. Helicobacter pylori (H. pylori) has been associated with hypertension through inflammatory, endothelial, metabolic and immune pathways, but data from sub-Saharan Africa, particularly in resistant hypertension, are limited.

Methods

This cross-sectional observational study will enrol 200 adults aged ≥18 at a tertiary academic hospital in Cape Town, South Africa: 80 with resistant hypertension, 80 with non-resistant hypertension and 40 with normotension. Participants will undergo standardised clinical assessment, blood pressure measurement, and collection of blood, urine and saliva. H. pylori exposure will be assessed using the Pylori DuoTect® point-of-care assay, which detects antibodies to CagA and FliD. Laboratory analyses will include lipid profile, inflammatory and nitric oxide-related markers, homocysteine, insulin indices, complete blood count, ghrelin, multiplex cytokine profiling and flow cytometric immunophenotyping. PAXgene® blood RNA samples will be retained for future exploratory analyses. Saliva will undergo exploratory H. pylori antigen testing using CerTest® kits, which are validated for stool rather than saliva. Saliva analysis will be exploratory, and results will not define the primary H. pylori exposure variable. Remaining saliva will be kept for potential future oral microbiome analyses not defined in this protocol. Multivariable logistic regression will evaluate associations between H. pylori exposure and hypertension phenotype, adjusting for demographic, lifestyle, and clinical covariates.

Discussion

To our knowledge, this will be the first African study to integrate point-of-care H. pylori serology with detailed clinical, inflammatory, metabolic, and immunological profiling across resistant hypertension, non-resistant hypertension and normotension. Findings may clarify biological pathways linking H. pylori exposure to blood pressure dysregulation and inform future mechanistic and interventional studies.

Visual outcomes and headache in intracranial hypertension following cerebral venous sinus thrombosis: A retrospective cohort study

2026-11-06T14:00:00Z

by Theresia Knoche, Ivo Grueninger, Charlotte Pietrock, Zohreh Jami, Leon Alexander Danyel

Intracranial hypertension is a frequent complication of cerebral venous sinus thrombosis (CVT), posing a risk for permanent visual impairment. However, long-term visual outcomes have not been systematically assessed using objective neuro-ophthalmic measures. We retrospectively evaluated consecutive adults presenting to a single-center tertiary intracranial hypertension clinic between 2019 and 2025 with intracranial hypertension following CVT. Visual outcomes were assessed using best-corrected visual acuity, automated perimetry, and optical coherence tomography measuring global peripapillary retinal nerve fiber layer thickness. Headache phenotype and medication overuse were documented. Nineteen patients (11 female; mean age 33.4 ± 12.1 years) were included, with a mean follow-up of 3.4 ± 2.4 years after diagnosis of CVT-related intracranial hypertension. The transverse sinus was involved in 78.9% of cases, and complete or near-complete recanalization was achieved in 68.4%. Although visual acuity remained normal in most patients (84.2%), 26.3% had severe visual field loss and 15.8% showed retinal nerve fiber layer thinning. Headache persisted in 94.7%, most commonly as tension-type headache (63.2%), and 26.3% fulfilled criteria for medication overuse headache. Despite generally preserved visual acuity, substantial visual field deficits and persistent headache were common in CVT-related intracranial hypertension. These findings support routine neuro-ophthalmic follow-up to facilitate early detection of visual deterioration in CVT-related intracranial hypertension. As this cohort was drawn from a specialized tertiary referral clinic, these findings should be interpreted as hypothesis-generating rather than representative of the broader CVT population.

E-Service quality and customer satisfaction in online shopping: Implications for sustainable digital commerce

2026-11-06T14:00:00Z

by Mohammed AL Awadh

The rapid growth of e-commerce has intensified competition among online retailers, making e-service quality increasingly important for building customer trust, satisfaction, and sustainable customer–platform relationships. This study examines the relationships among e-service quality, customer trust, customer satisfaction, and customer loyalty using a second-order Structural Equation Modeling (SEM) framework. The five SERVQUAL dimensions such as empathy, responsiveness, reliability, assurance, and tangibles were modeled as first-order constructs reflecting the higher-order construct of service quality. Data were collected through an online questionnaire from 402 respondents with prior online-shopping experience. Confirmatory Factor Analysis (CFA) and SEM were employed to assess the measurement and structural models. The measurement model demonstrated satisfactory reliability, convergent validity, discriminant validity, and overall model fit. The structural results showed that service quality significantly and positively influenced customer trust and customer satisfaction, while customer trust significantly enhanced satisfaction. Trust also partially mediated the relationship between service quality and satisfaction, indicating that e-service quality improves satisfaction both directly and through increased customer confidence. The SERVQUAL dimensions contributed positively to overall service quality, with responsiveness and assurance showing particularly strong contributions, while empathy exhibited a comparatively moderate contribution. In contrast, customer loyalty had no significant direct effect on trust or satisfaction, and its indirect effect on satisfaction through trust was also nonsignificant. These findings demonstrate that reliable, responsive, secure, and well-designed digital services are important for strengthening trust and satisfaction in competitive e-commerce environments. By identifying trust as a key mechanism linking multidimensional e-service quality with customer satisfaction, the study contributes to SERVQUAL and digital-commerce literature and provides implications for the economic and relational sustainability of e-commerce platforms through more resilient and durable customer relationships.

Clinical and epidemiological characteristics of invasive non-typhoidal Salmonella disease in Ghana

2026-11-06T14:00:00Z

by Francis Opoku Agyapong, Michael Owusu, Michael Owusu-Ansah, Sampson Twumasi-Ankrah, Kennedy Gyau Boahen, Gifty Nkrumah, Ezekiel Bonwin Ackah, Rachel Laadi Sulla, Akua Serwaa Boafo, Nathaniel Nsiah-Poku, Portia Okyere Boakye, Anthony Enimil, Yaw Adu-Sarkodie, Ellis Owusu-Dabo, Florian Marks

Background

Invasive non-typhoidal Salmonella (iNTS) disease remains a significant public health threat in sub-Saharan Africa (SSA). Although the disease is important, its clinical characteristics are not well described in literature. This study describes the clinico-epidemiological profile of iNTS disease in Ghana aiming to bridge important knowledge gaps and inform more effective management strategies.

Methods

The study spanned 8 years and utilized selected fever surveillance sites in Ghana. Patients with fever and/or history of fever for ≥ 3 consecutive days within the week prior to visit were approached and blood sample taken after consenting for investigations including blood culture. iNTS isolates were recovered using BACTEC blood culture, identified by Analytical Profile Index (API), sero-grouped using the Kauffmann–White scheme and confirmed by Illumina whole genome sequencing. Conditional logistic regression was used to assess associations between clinical and laboratory features and iNTS blood culture positivity in a 1:3 age-, sex-, and residence-matched case–control analysis.

Results

Of 271 blood-culture-derived bacterial pathogens, 15.5% (42/271) were identified as iNTS making it the second most common cause of bacteremia. iNTS disease exhibited seasonality with peak detections coinciding with the rainy seasons in Ghana. 23.7% (9/38) of iNTS isolates were multidrug-resistant (MDR), of which 5.3% (2/38) were extensively drug-resistant including resistance to ceftriaxone and ciprofloxacin. Several factors showed crude associations with iNTS disease; however, only anaemia retained its association after adjustment of other factors (aOR=2.41 p = 0.030).

Conclusion

iNTS is a major cause of bloodstream infections with the highest burden in children under 5 years of age with susceptibility to the infection amplified by anaemia. The Salmonella serovars involved are increasingly becoming multidrug-resistant, including resistance to critical antibiotics.

Various aspects of upper-limb muscle strength and tennis performance: A comparative study of U12 and U14 female tennis players

2026-11-06T14:00:00Z

by Tomasz Waldziński, Aleksandra Durzyńska, Bartłomiej Niespodziński, Jan Mieszkowski, Ewa Waldzińska, Andrzej Kochanowicz

This study investigated the relationship between muscle strength and tennis performance, assessed using the International Tennis Number (ITN) on-court test, operationalized as point-based outcomes (total points and subcomponent points), in young female tennis players aged under 12 (U12) and under 14 (U14). Thirty-three players underwent a comprehensive evaluation including ITN testing, general strength tests (handgrip strength, flexed arm hang, and tennis-ball throw), isometric upper-limb muscle strength, and sense of force assessment. Results demonstrated significantly higher ITN scores and muscle strength in the U14 group, with differences largely attributable to body size and training experience. Correlation analyses revealed age-specific patterns: in U12 players, ITN scores were associated primarily with general strength measures, whereas in U14 players, they were more strongly linked to joint-specific upper-limb strength and neuromuscular characteristics. Sense of force did not differ between groups, though correlations with ITN varied depending on age and joint function. These findings suggest that, in this sample, performance in younger players was more closely associated with general strength measures, whereas in older players it was more closely associated with joint-specific upper-limb strength.

Testing the effects of nicotine concentration and nicotine source claims on oral nicotine pouch packaging engagement, self-reported perceptions and use intentions, and product trial in young adults and adults: Protocol for a randomized trial

2026-11-06T14:00:00Z

by Lauren Long, Mahmood A. Alalwan, Elsa Alvarado, Anna Kozar, Elise M. Stevens, Ce Shang, Megan E. Roberts, Elizabeth G. Klein, Abigail Shoben, Darren Mays

Background

Oral nicotine pouches (ONPs) are novel nicotine products and evidence on how features of ONP packaging affect product engagement, perceptions, use intentions, and behavior is limited.

Objectives

We outline the protocol for a randomized trial examining how nicotine concentration and nicotine source claims affect engagement with ONP packaging using psychophysiological measures, self-reported ONP perceptions and use intentions, and ONP trial (ClinicalTrials.gov: NCT06192316).

Methods

Between 2024 and 2027, we will recruit 450 participants, comprised of: 150 young adults ages 18–24 who are susceptible but do not use tobacco; 150 young adults ages 18–24 who use tobacco; and 150 adults ages 25–65 who use tobacco. Participants complete procedures at an in-person laboratory visit. During the visit, participants complete pre-exposure self-report measures and are randomized between subjects to one of nine conditions in a 3 (Nicotine Concentration: None, Low, or High) x 3 (Nicotine Source Claim: None, Tobacco Free, or Synthetic) design. Within conditions, participants view 16 ONP pack images, in random order, reflecting different ONP brands and flavors. During exposure, we collect psychophysiological measures including heart rate, skin conductance, and visual attention. After exposure, participants complete self-report measures of ONP perceptions and use intentions, and a timed behavioral task where they are presented with ONP packages corresponding to their randomized condition and brands and flavors shown in the stimuli. Participants can try one of the products, and ONP trial is the behavioral outcome of interest. However, the packages do not contain ONPs; they contain commercially available pouches with food grade ingredients. At visit conclusion, participants are de-briefed and receive their incentive for participating.

Conclusions

This project will generate evidence on the effects of nicotine concentration and source claims on ONP packaging in young adults who are not using but susceptible to tobacco, young adults using tobacco, and adults using tobacco to inform potential regulations.

Effectiveness of dose-matched immersive virtual reality-stationary cycling combined with neurological physiotherapy versus neurological physiotherapy alone in individuals with chronic stroke (CIVIS): A single-blind, randomized crossover trial protocol

2026-11-06T14:00:00Z

by Daniel Asensio-Perez, David Lucena-Anton, Jose A. Moral-Munoz

Background

Stroke is a leading cause of long-term disability worldwide and frequently results in persistent motor and functional impairments, particularly affecting gait and balance. Given the high prevalence and impact of these limitations on independence and quality of life, innovative rehabilitation strategies are needed. Immersive virtual reality combined with stationary cycling (IVR-SC) has emerged as an innovative rehabilitation approach with the potential to improve mobility and functional outcomes after stroke.

Aim

To analyze the comparative effectiveness of two dose-matched programs, one combining IVR-SC plus neurological physiotherapy (NP), versus the other consisting of NP alone, in individuals with chronic stroke.

Methods

A randomized, single-blind, crossover clinical trial will be conducted. After calculating the sample size, a minimum of 8 participants with chronic stroke (≥6 months), hemiparesis, and gait and balance impairments will be randomly assigned to one of two sequences of intervention. Each participant will receive both neurological physiotherapy and IVR-SC across two 4-week intervention periods separated by a washout period (4 weeks). Each intervention period consists of 8 sessions delivered over a 4-week period, with each session lasting 60 minutes. The primary outcome will be gait quality, assessed using Wisconsin Gait Scale (WGS), while secondary outcomes will include walking endurance, balance, motor function, and muscle tone. Clinical outcomes will be assessed at baseline and after each intervention period. Satisfaction with using the IVR-SC intervention will also be evaluated. Statistical analyses will follow an intention-to-treat approach using a linear mixed-effects model (LMM) with treatment, period, sequence, baseline, and center as fixed effects, and participant as a random effect. Statistical significance will be set at p < 0.05. An individual responder analysis will be performed to determine if participants exceeded the minimal clinically important difference (MCID) of 2.25 points on the WGS.

Discussion

This study will contribute to understanding the potential comparative effects of IVR-SC in stroke rehabilitation. Given the heterogeneity of individuals with stroke, which may limit the conclusiveness of findings in parallel-group studies, the crossover design allows each participant to serve as their own control, reducing inter-individual variability and strengthening the interpretation of the results. If effective, IVR-SC could represent a feasible and scalable option for partially replacing NP within standard neurorehabilitation, with potential for implementation in both clinical and home-based settings.

Trial registration

ClinicalTrials.gov ID: NCT07529665. Effectiveness of dose-matched rehabilitation with immersive virtual reality-stationary cycling combined with neurological physiotherapy versus neurological physiotherapy alone in individuals with chronic stroke (CIVIS): study protocol for a single-blind, randomized crossover trial. URL: https://clinicaltrials.gov/study/NCT07529665. Date of registration: 2026-04-14. Version 1.

Deep learning optimisation for cardiology: Neural Architecture Search-driven arrhythmia classification with electrocardiograms

2026-11-06T14:00:00Z

by Erik Vanegas Müller, Arese Joe-Oshodi, Abhirup Banerjee, Mauricio Villarroel

Cardiovascular disease is the leading cause of death worldwide. Sudden cardiac death (SCD) accounts for roughly 50% of all cardiac deaths. The electrocardiogram (ECG) is widely used for diagnosing cardiac disease. However, the complexity of interpretation limits the ECG’s efficacy. Modern deep learning methods can assist clinicians in diagnosis. We applied Neural Architecture Search (NAS) to identify optimal deep learning architectures for classifying cardiac arrhythmias with ECGs. We applied the Differentiable Architecture Search strategy to an AutoFormer search and trained, validated, and tested the resulting model on the PhysioNet Challenge 2021 (PC21) dataset (n = 88,253 from three continents). We optimised hyperparameters on the NAS output, exploring input patch size, class weighting, and loss function. The PC21 metric and the area under the receiver operating characteristic curve (AUROC) are the performance metrics. The NAS converged towards minimal architectural configurations (embedding dimension: 384, depth: 4, self-attention heads: 4, MLP ratio: 1) with a validation and test PC21 metric of 0.66 (PC21 winner: 0.63). The NAS-created network achieved an AUROC of 0.97 and a PC21 metric of 0.72 during testing (PC21 winner: 0.69). We tested the PC21 winner architecture (1D-convolutional neural network with attention mechanism) without the attention mechanism and with the NAS-suggested architecture of 4 self-attention heads (instead of 8). The architecture without the attention mechanism performed similarly to the one with 8 self-attention heads (AUROC: 0.90, PC21 metric: 0.69). The architecture with 4 self-attention heads scored an AUROC of 0.91 and improved the PC21 metric to 0.71. The attention mechanism visualisation for two SCD-related arrhythmias (premature ventricular contractions and prolonged QT-interval) showed more clinically relevant attention for the 4-self-attention-head architectures. We interpret architectural simplicity as driving performance in arrhythmia classification. The self-attention mechanism can autonomously abstract clinical representations, simplifying clinical deployment by eliminating the need for an explicit feature-extraction pipeline.

HIF-1α/PPAR-γ/SIRT1 axis drives astrocyte senescence and regulates endothelial function via GDNF/NRTN in diabetic retinopathy

2026-11-06T14:00:00Z

by Jing Wang, Shufen Fang, Ming Sun, Jue Wang, Yongqing Liu, Xuan Wang, Weiwei Liu, Lei Gao

Background

Diabetic retinopathy (DR) is a leading cause of blindness in working-age populations. Astrocyte senescence is highly prevalent in DR, but the underlying regulatory mechanism remains unclear. This study aims to investigate the role of the HIF-1α/PPAR-γ/SIRT1 axis in regulating retinal astrocyte senescence and endothelial function in DR.

Methods

Mouse retinal astrocytes were exposed to high glucose (30 mM) to mimic diabetic conditions. Senescence was evaluated by β-galactosidase staining. Signaling pathways were manipulated using HIF-1α inhibitor (PX-478), PPAR-γ inhibitor (T0070907), SIRT1 agonist (SRT2104), and autophagy inhibitor (3-MA). Protein and mRNA levels of key factors were detected by Western blot and RT-qPCR. Astrocytes and retinal microvascular endothelial cells were co-cultured in Transwell systems to assess paracrine regulation on endothelial migration, proliferation, and apoptosis.

Results

High glucose induced astrocyte senescence, inflammatory activation, and downregulation of GDNF and NRTN, accompanied by elevated HIF-1α and PPAR-γ, and reduced SIRT1 expression and autophagy activity. Inhibiting HIF-1α or activating SIRT1 attenuated senescence, apoptosis, and inflammation, restored autophagy, and upregulated GDNF/NRTN secretion. HIF-1α negatively regulated SIRT1 expression via PPAR-γ. Senescent astrocytes impaired endothelial function through reduced GDNF/NRTN; overexpression of GDNF or NRTN in astrocytes preserved endothelial migration and proliferation, and inhibited apoptosis.

Conclusion

HIF-1α/PPAR-γ/SIRT1 axis mediates high glucose-induced astrocyte senescence via autophagy dysfunction. Senescent astrocytes disrupt retinal endothelial homeostasis by reducing GDNF/NRTN secretion. Targeting this axis may represent a novel neurovascular protective therapeutic strategy for DR.

Efficacy of diadynamic currents versus transcutaneous electrical nerve stimulation for transcutaneous tibial nerve stimulation in subjects with overactive bladder syndrome: A double-blind randomized controlled trial

2026-11-06T14:00:00Z

by Jaya Shanker Tedla, Sneha Latha Lalaji, Ajaya Kumar Midde, Nirmala A. Papalkar, N. Bindhu Priya, Devika Rani Sangadala, Ravi Shankar Reddy, Debjani Mukherjee, Ahlam Mohammed Alamri, Abdullah Suwayyid Alzahrani, Najla Awn Alhadi

Background

In the traditional treatment of overactive bladder (OAB) with transcutaneous posterior tibial nerve stimulation (TTNS), physical therapists currently use only transcutaneous electrical nerve stimulation (TENS). However, the literature has commonly replaced TENS with diadynamic currents for various musculoskeletal pain syndromes. Moreover, no literature describes the use of diadynamic currents in the TTNS procedure. Therefore, our study aimed to determine the efficacy of diadynamic currents (DDC) versus TENS for TTNS in OAB Treatment.

Methodology

A randomized controlled trial was conducted among female patients with OAB aged 18–80 years. Subjects were randomly allocated to control and experimental groups. Participants in the control group received TTNS with TENS, and those in the experimental group underwent TTNS using DDC. Both groups received 8 TTNS sessions, two per week for 4 weeks. We measured pre- and post-intervention improvements using the International Consultation on Incontinence Questionnaire (ICIQ) for OAB and the ICIQ OAB Quality of Life (QOL). The study is registered with the Clinical Trials Registry of India under registration number CTRI/2025/12/099269.

Results

The mean age of the included sample was 59.75 years. Pre- and post-intervention ICIQ-OAB and ICIQ-OAB QOL scores showed significant improvements in disease symptoms and quality of life among patients with OAB in both the control and experimental groups. Comparison of improvements between the two groups on the ICIQ questionnaires showed no significant difference (p-values of 0.87 and 0.95). Correlations between patient-related characteristics and improvements in outcome measures were also not significant.

Conclusion

Eight sessions of TENS and DDC, combined with conventional physical therapy, including Kegel and breathing exercises, can reduce OAB symptoms and improve QOL in subjects with OAB syndrome. Diadynamic current can be used as an adjunct to conventional TENS in TTNS for treating OAB syndrome.