PLOS https://journals.plos.org/plosone/ customercare@plos.org https://journals.plos.org/plosone/feed/atom All PLOS articles are Open Access. https://journals.plos.org/plosone/resource/img/favicon.ico https://journals.plos.org/plosone/resource/img/favicon.ico 2026-11-12T00:19:42Z Juan Carlos Gómez de la Torre Pretell Miguel Hueda-Zavaleta Luis Alvarado Ríos German Valenzuela-Rodríguez Alberto Martin La Rosa Thales Polis 10.1371/journal.pone.0362811 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Juan Carlos Gómez de la Torre Pretell, Miguel Hueda-Zavaleta, Luis Alvarado Ríos, German Valenzuela-Rodríguez, Alberto Martin La Rosa, Thales Polis</p> Weiqiang Fei Feng Yang Yongbang Zhu YiNa Le Shan Wang Danxia Sun XiaoXu Zhang 10.1371/journal.pone.0362761 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Weiqiang Fei, Feng Yang, Yongbang Zhu, YiNa Le, Shan Wang, Danxia Sun, XiaoXu Zhang</p> Most patients undergoing percutaneous coronary intervention (PCI) are diagnosed with coronary heart disease (CHD). The triglyceride glucose‑body mass index (TyG‑BMI) has been reported to be associated with CHD. This study aimed to investigate the association between TyG‑BMI and the risk of repeat PCI among post‑PCI patients, with additional exploratory stratification analyses according to glucose‑metabolism status. Data for this study were derived from resident health‑record follow‑up records of Yipeng Community Health Service Center, covering January 2015 to January 2025. Logistic regression models and restricted cubic spline (RCS) were used to evaluate the association between TyG‑BMI and the risk of repeat PCI among post‑PCI patients, with exploratory stratification by glucose‑metabolism status. Logistic regression and restricted cubic spline analyses showed no significant linear or nonlinear association between TyG‑BMI and repeat PCI (<i>OR</i>=0.999,<i>95%CI</i>:0.994 ~ 1.003, <i>P</i> = 0.534; nonlinear <i>χ</i>² = 0.91, df = 3, <i>P</i> = 0.8223). Stratified analyses by glucose metabolism status also revealed no significant correlation in any stratum(<i>P ></i> 0.05). No independent association between TyG‑BMI and repeat PCI was identified in post‑PCI patients, even within different glucose‑metabolism strata. Relevant findings require further verification in larger prospective cohorts. Saida Heshmati Jaymes Paolo Rombaoa Courtney M. Allred Alexander P. Christensen Stacey N. Doan 10.1371/journal.pone.0362751 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Saida Heshmati, Jaymes Paolo Rombaoa, Courtney M. Allred, Alexander P. Christensen, Stacey N. Doan</p> Family emotional processes play a central role in adolescent well-being, yet most research relies on dyadic or static approaches that do not capture the dynamic, system-level nature of family emotional life. In a sample of adolescents (ages 12–17), mothers, and fathers (<i>N</i> = 120; 2,365 assessments), constituting 40 family triads, we used ecological momentary assessment and a dynamic network approach to estimate how emotions fluctuate over time and co-vary across family members within each system. Emotional synchrony—defined as the extent to which family members’ affective states change together—was modeled at both overall (between-family) and momentary (within-family) levels. Results indicated that families exhibited greater synchrony in positive affect than negative affect, alongside substantial heterogeneity in network structures. At the person level, greater positive affect synchrony was associated with higher adolescent well-being and lower distress, whereas negative affect synchrony showed inverse patterns. At the momentary level, increases in negative affect synchrony were associated with higher concurrent well-being and lower stress. Many of these person-level associations were substantially attenuated once adolescents’ general affect levels were accounted for, whereas synchrony at the between-family level continued to predict adolescents’ momentary well-being beyond their concurrent affect. These findings highlight emotional synchrony as a dynamic property of family systems and underscore the importance of modeling family processes across multiple timescales. Teklehaimanot Gereziher Haile Negasi Asres Dawit Gebregziabher Birhane Fissahaye Yemane Leake Girmay Teklay Haftu Berhe Gebru 10.1371/journal.pone.0362748 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Teklehaimanot Gereziher Haile, Negasi Asres, Dawit Gebregziabher, Birhane Fissahaye, Yemane Leake, Girmay Teklay, Haftu Berhe Gebru</p> Introduction <p>Intimate partner violence is a major global public health concern and a serious human rights violation, involving physical, sexual, and psychological abuse within intimate relationships. Worldwide, about one in three women experiences intimate partner violence during their lifetime. Accordingly, this study aims to estimate the overall prevalence and identify the key predictors of intimate partner violence in Ethiopia.</p> Methods <p>A comprehensive systematic search was carried out in PubMed, Web of Science, Google Scholar, and African Journals Online to identify relevant systematic reviews and meta-analyses on the prevalence and predictors of intimate partner violence against women in Ethiopia. The methodological quality of the included studies was assessed using the AMSTAR-2. A random-effects meta-analysis was conducted using STATA version 18 to generate pooled estimates.</p> Results <p>This umbrella review synthesized evidence from six systematic reviews and meta-analyses comprising 80 primary studies involving 43,785 women. The overall prevalence of intimate partner violence was 35% (95% CI: 28–42%), with substantial heterogeneity across reviews (I² = 83.48%). It also revealed a prevalence of 32% (95% CI: 26–37%) among pregnant women and 33% (95% CI: 25–40%) during the COVID-19 pandemic. The prevalence of specific forms of violence was estimated at 18% (95% CI: 14–22%) for sexual violence, 19% (95% CI: 15–23%) for physical violence, and 27% (95% CI: 23–31%) for psychological violence. Key predictors of IPV included both partners’ and women’s educational status, partner alcohol consumption, women’s decision-making power, substance use, and income loss during the COVID-19 pandemic, with all associations found to be statistically significant.</p> Conclusion <p>This umbrella review shows that intimate partner violence remains a major public health issue in Ethiopia, affecting over one-third of women. Strengthening policy implementation and expanding survivor-centered services are essential to reduce IPV and advance Sustainable Development Goal 5.</p> Trung-Duc Nguyen Gia-Bao Do Phan-Anh Le Mai-Anh T. Nghiem Linh T. Ho Thuy T. Le Hong-Nhung T. Le Tuan-Nghia Phan Hong-Loan T. Nguyen 10.1371/journal.pone.0362685 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Trung-Duc Nguyen, Gia-Bao Do, Phan-Anh Le, Mai-Anh T. Nghiem, Linh T. Ho, Thuy T. Le, Hong-Nhung T. Le, Tuan-Nghia Phan, Hong-Loan T. Nguyen</p> Fusion tags are widely employed to enhance recombinant protein expression, solubility, and purification. However, efficient tag removal is often necessary to obtain proteins in their native form. In this study, SARS-CoV-2 3C-like protease (3CLpro) was evaluated as a sequence-specific protease for fusion-tag removal using a recombinant fusion protein substrate under standard protein purification conditions. A substrate containing the canonical recognition sequence AVLQ↓SG was efficiently cleaved by 3CLpro, whereas no detectable cleavage was observed for a variant substrate harboring the sequence TVRLQ↓SG. Biochemical characterization demonstrated that 3CLpro maintained cleavage activity across a range of pH values and temperatures and in the presence of reagents commonly used for protein purification and stabilization. 3CLpro-mediated cleavage was successfully integrated into different fusion-protein processing workflows, including in-solution cleavage, on-column cleavage, and dialysis-coupled cleavage. To further evaluate the practical utility of 3CLpro, a modular expression vector (pET_RPLa) incorporating a 3CLpro cleavage site was constructed and validated using the light chain of botulinum neurotoxin serotype A (LC-BoNT/A) as a model protein. Following expression and purification, the fusion protein (6 × His-GST-AVLQSG-LC-BoNT/A) retained SNAP25-cleaving activity and was efficiently processed by 3CLpro. Together, these results support the potential use of SARS-CoV-2 3CLpro as a versatile sequence-specific protease for fusion-tag removal and recombinant protein processing. Omar Qaladi Fahda Alrasheedi Manahil Alhawsawi Raghad Alluhebi Abeer Abujalid 10.1371/journal.pone.0362675 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Omar Qaladi, Fahda Alrasheedi, Manahil Alhawsawi, Raghad Alluhebi, Abeer Abujalid</p> Background <p>Pilgrims performing Hajj are exposed to extreme heat and ultraviolet (UV) radiation, which pose distinct risks: heat contributes to dehydration and heat-related illness, whereas UV radiation causes sunburn and eye damage and increases long-term skin cancer risk. While heat illness and infectious diseases have been widely studied, awareness and use of UV-protective measures, including sunscreen and ultraviolet protection factor (UPF)-rated clothing and umbrellas, remain underexplored in this context. Understanding both pilgrim and nursing perspectives is essential for developing effective interventions.</p> Methods <p>In this qualitative descriptive study, retrospective semi-structured interviews were conducted via Zoom between 20 June and 11 July 2025, within approximately one month after the 2025 Hajj season, with 16 Saudi pilgrims and 13 registered nurses who had worked in hospitals in Makkah and Madinah during Hajj. Interviews explored awareness, attitudes, and behaviors related to UV and sun protection. Data were analyzed thematically following Braun and Clarke’s six-phase approach. Lincoln and Guba’s criteria guided trustworthiness.</p> Results <p>Five major themes were identified: (1) physical and emotional impact of sun exposure, (2) limited awareness and knowledge gaps, (3) attitudes and cultural influences on UV/UPF use, (4) barriers and challenges to sun protection, and (5) recommendations and suggestions for improvement. Notably, many participants perceived sun exposure as a spiritual challenge rather than a health risk, UPF-rated products were poorly understood, and practical barriers such as cost, availability, and cultural clothing norms limited use of protection.</p> Conclusions <p>The findings highlight critical gaps in awareness and practice regarding sun protection during Hajj. Targeted education before and during Hajj, wider availability of affordable protective items, and culturally appropriate communication strategies are needed, with messages that distinguish heat-related illness from UV-related harm.</p> Ying Lin Rong-Dong Zhang Xin-Yu Xu Huang-zhou Jiang Ren-Li Chen Jian-Zhen Shen 10.1371/journal.pone.0362674 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Ying Lin, Rong-Dong Zhang, Xin-Yu Xu, Huang-zhou Jiang, Ren-Li Chen, Jian-Zhen Shen</p> Background <p>UHRF1 has been established as a susceptibility gene in multiple cancer types; however, its functional role in the pathogenesis of adult T-cell leukemia/lymphoma (ATLL) remains poorly defined. This study aimed to investigate UHRF1 expression in ATLL and assess its clinical and biological significance.</p> Methods <p>Immunohistochemistry was performed to evaluate UHRF1 protein expression in tumor tissues from 72 ATLL patients and 30 reactive lymphadenopathy controls. Univariate Cox’s proportional hazard regression model was used to screen the factors affecting OS and PFS, and multivariate Cox’s proportional hazard regression model was used to screen independent prognostic factors in ATLL. UHRF1 expression in the HuT-102 ATLL cell line and MT-4 cell line was evaluated by Western blotting and quantitative PCR, and shRNA-mediated knockdown was used to assess proliferation and apoptosis.</p> Results <p>UHRF1 protein was highly expressed in primary ATLL samples (P < 0.001, median 26.562 vs. 1.306), and the percentage of positive pixels (%Area) significantly higher than that in the control group (P < 0.001, median 9.914 vs. 0.574). Multivariate Cox regression analysis demonstrated that UHRF1 expression remained an independent prognostic predictor after adjustment for clinicopathological characteristics. For overall survival (OS): P = 0.026, HR = 2.397, 95%CI: 1.108–5.184; for progression-free survival (PFS): P = 0.042, HR = 1.959, 95%CI: 1.025–3.744. Mechanistically, UHRF1 knockdown significantly suppressed proliferation and induced apoptosis in ATLL cell lines (HuT-102 cells and MT-4 cell). Co-immunoprecipitation detected no stable interaction between UHRF1 and either AMPK or the PP2A catalytic subunit PPP2CA, and UHRF1 knockdown did not significantly alter LKB1, PPP2R4, or the p-AMPK (Thr172)/AMPK ratio; whether UHRF1 intersects with AMPK signaling remains to be determined. These findings identify UHRF1 as an independent adverse prognostic indicator in ATLL and provide preliminary biological evidence, though the underlying mechanisms require further validation in larger cohorts and in vivo models.</p> Deqiang Peng Daoguang Li Qingxia Li Chenyi Wang Xiaomin Ma 10.1371/journal.pone.0362662 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Deqiang Peng, Daoguang Li, Qingxia Li, Chenyi Wang, Xiaomin Ma</p> In flotation-based mineral processing, froth images contain important visual information that reflects the operating condition of the process and provides a basis for process monitoring and control. However, conventional machine-vision methods still encounter difficulties in extracting static froth features under conditions of bubble adhesion, overlap, weak boundaries, and uneven illumination. To address these problems, a flotation froth image analysis framework is proposed by combining a boundary-aware U-Net segmentation model with a segmentation-guided adaptive Hough transform. In the first stage, the U-Net architecture is enhanced with explicit boundary-oriented supervision to improve the separation of adherent and overlapping bubbles. In the second stage, the geometric priors derived from the segmentation results are used to constrain the Hough-based detection process, thereby improving the reliability of bubble counting and geometric feature extraction. Experimental results show that the proposed method achieves a <i>Dice</i> similarity coefficient of 96.39% and an intersection over union of 93.04%, while maintaining favorable inference efficiency. Compared with representative segmentation models, the proposed framework provides a better balance between accuracy and speed. The study demonstrates that the integration of deep boundary-aware segmentation and adaptive geometric detection is effective for static feature extraction of flotation froth images and has potential for intelligent monitoring of flotation processes. Haixing Li Chao Weng Wanying Huang Ming Xu 10.1371/journal.pone.0362621 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Haixing Li, Chao Weng, Wanying Huang, Ming Xu</p> Whole slide images (WSIs) are characterized by extremely high resolution and usually lack fine-grained annotations, making multiple instance learning (MIL) the dominant paradigm for weakly supervised WSI classification. Although existing MIL methods have achieved substantial progress in feature extraction and instance aggregation, most of them overlook the influence of confounding factors, thereby learning spurious associations that impair generalization performance. To address this issue, we develop an Instance Causal Multiple Instance Learning (ICMIL) framework for WSI classification, which aims to reduce the model’s reliance on potentially spurious instance-level associations. Specifically, unlike conventional likelihood-based strategies, the proposed method introduces a backdoor-adjustment-inspired prototype module during instance aggregation, where clustered prototypes are used as proxy contextual patterns to mitigate the influence of potential confounding cues. We conduct extensive experiments on two publicly available WSI datasets, Camelyon16 and TCGA-NSCLC. The results demonstrate that the proposed ICMIL framework achieves competitive performance and generally improves existing baselines, while also exhibiting a plug-and-play property. Yahya M. Altharan Shazarel Shamsudin Mohd Amri Lajis Sami Al-Alimi Nur Kamilah Yusuf Nayef Abdulwahab Mohammed Alduais Atef M. Ghaleb Wenbin Zhou 10.1371/journal.pone.0362612 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Yahya M. Altharan, Shazarel Shamsudin, Mohd Amri Lajis, Sami Al-Alimi, Nur Kamilah Yusuf, Nayef Abdulwahab Mohammed Alduais, Atef M. Ghaleb, Wenbin Zhou</p> Tetsuya Muto Shoichiro Kusuda Masaaki Sakamoto Shigeki Machida Shinichiro Imaizumi Tetsuju Sekiryu 10.1371/journal.pone.0362558 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Tetsuya Muto, Shoichiro Kusuda, Masaaki Sakamoto, Shigeki Machida, Shinichiro Imaizumi, Tetsuju Sekiryu</p> In this study, we aimed to identify factors for risk of chronic evolution in Vogt–Koyanagi–Harada (VKH) disease at 1 month following pulse steroid therapy. This was a retrospective clinical cohort, single center study. A total of 121 eyes from 61 treatment-naïve patients with acute VKH disease, who underwent pulse steroid therapy and had follow-up for over 12 months were evaluated. Patients were categorized into SGF and non-SGF groups according to fundus outcomes at 12 months after treatment. Anterior chamber morphology was assessed using Pentacam^®, while axial length and lens thickness were measured with the IOLMaster 700. Multivariable analysis demonstrated that lower best-corrected visual acuity (BCVA) (<i>p</i> < 0.001) and increased corneal thickness (<i>p</i> = 0.016) at 1 month were significantly associated with the development of SGF. Receiver operating characteristic curve analysis determined optimal cut-off values for predicting SGF as a logarithmic BCVA greater than −0.040 and a corneal thickness exceeding 574.500 µm. The corresponding Youden index values were 0.291 for BCVA and 0.244 for corneal thickness. Elevated logarithmic BCVA values and increased corneal thickness at 1 month after treatment were identified as risk factors for the subsequent SGF development. Applying higher cut-off values for these factors may facilitate more targeted therapeutic strategies in patients with VKH disease. The PLOS One Editors 10.1371/journal.pone.0362523 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by The PLOS One Editors </p> The PLOS One Editors 10.1371/journal.pone.0362513 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by The PLOS One Editors </p> The PLOS One Editors 10.1371/journal.pone.0362511 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by The PLOS One Editors </p> Yueling Yang Qiang Wang Shu Wang Zihong Yang Thomas Dogot 10.1371/journal.pone.0362492 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Yueling Yang, Qiang Wang, Shu Wang, Zihong Yang, Thomas Dogot</p> This study investigates the spatiotemporal evolution and driving mechanisms of enterprise-led organic agriculture in Shandong Province, China. Using panel data on certified organic enterprise production bases across 16 prefecture-level cities from 2014 to 2023, we combine spatial statistical analysis, Local Moran’s I, two-way fixed-effects regression, and robustness checks. The results show that certified organic bases expanded substantially but became increasingly concentrated, forming a clear core–periphery structure centered on the Jiaodong Peninsula. Transportation infrastructure, e-commerce connectivity, and GI-protected agricultural products are positively associated with base expansion, while fiscal expenditure shows a negative association, possibly reflecting compensatory policy allocation to less-developed areas. Overall, the findings suggest that enterprise-led organic agriculture evolves through a layered “Pressure–Transformation–Support–Market” mechanism and provide evidence for promoting coordinated regional development in sustainable agriculture. Worapong Kosaruk Pichamon Ueangpaibool Nawapa Hirannithithamrong Janjeera Kaew-ek Taweepoke Angkawanish 10.1371/journal.pone.0362469 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Worapong Kosaruk, Pichamon Ueangpaibool, Nawapa Hirannithithamrong, Janjeera Kaew-ek, Taweepoke Angkawanish</p> Classification of hospitalization outcomes in wildlife hospitals may support clinical assessment and resource planning, but model performance can vary across institutions with different case profiles and care practices. This study evaluated a previously developed random forest model for classifying hospitalization outcomes in Asian elephants using temporally distinct 2025 data from three elephant hospitals in Thailand. The validation comprised temporal validation at the original development center and institutional validation at two additional hospitals. Because length of stay was included as a predictor, the model was evaluated as a hospitalization-course classification model rather than as an admission-time prognostic tool. The final validation cohort comprised 237 hospitalization episodes contributed by 215 elephants, including 17 deceased, 36 ongoing, and 184 recovered episodes. Overall accuracy was 0.793, compared with 0.776 for a recovered-only majority-class classifier. Macro-averaged balanced accuracy was 0.732, the prevalence-weighted one-vs-rest area under the receiver operating characteristic curve (AUC) was 0.854, and multiclass log loss was 0.617. Classification performance was stronger for ongoing and recovered episodes than for deceased episodes. The limited number of deceased episodes resulted in substantial uncertainty around mortality-focused performance and calibration estimates. Calibration patterns differed across outcome classes, with an overall multiclass Brier score of 0.323. In the binary deceased-versus-recovered sensitivity analysis, the AUC was 0.726 (95% confidence interval, 0.585–0.839), indicating moderate but imprecise discrimination. Overall, the model retained discriminatory information across the validation cohort, but its modest improvement over the majority-class benchmark, weaker deceased-class performance, and reliance on hospitalization-duration information warrant cautious interpretation. Further prospective evaluation is needed before routine clinical application. Jiaxin Zhang Siqing Zhang Junrong Lei 10.1371/journal.pone.0362452 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Jiaxin Zhang, Siqing Zhang, Junrong Lei</p> Sports-related intangible cultural heritage (SRICH) can support culturally grounded tourism, but its county-level alignment with tourism development remains unclear in ethnically diverse mountain regions. This study examined 71 county-level units in China’s Wuling Mountain Area in 2010, 2015, 2019, and 2024. Geographical concentration, kernel density estimation, and standard deviational ellipses traced the administrative distribution of officially recognized SRICH records. Entropy weighting, coupling coordination, relative-balance diagnosis, and Moran’s I assessed their county-level relationship with tourism development. SRICH coverage expanded and geographical concentration declined, while county-represented density peaks increased within a broadly stable regional configuration. Tourism development rose rapidly before 2019 and more slowly thereafter, retaining a marked core–periphery structure. Mean D increased from 0.192 to 0.403; 62.2% of this change was associated with counties entering the official inventory after 2010. Within the baseline-covered cohort, the joint levels of the two subsystems increased, whereas relative balance changed little, and SRICH-lagging counties remained predominant. All three indices showed significant positive global spatial autocorrelation, while FDR-adjusted local clusters were sparse and none remained significant in 2024. The results inform differentiated cross-provincial safeguarding and tourism planning, with greater attention to counties where the two subsystems follow different trajectories. The coupling coordination degree D is interpreted as a comparative measure of the recorded joint levels of SRICH and tourism development. The PLOS One Editors 10.1371/journal.pone.0362446 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by The PLOS One Editors </p> The PLOS One Editors 10.1371/journal.pone.0362434 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by The PLOS One Editors </p> Huseyin Celik Pinar Arpinar-Avsar 10.1371/journal.pone.0362399 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Huseyin Celik, Pinar Arpinar-Avsar</p> To ensure standardization, reliability, and maximal performance, physical performance tests are usually performed with little to no cognitive load. However, during training and competition, athletes usually perform physical actions while under the demands of a concurrent cognitive task (CT). This study examined the effect of a concurrent CT on the force-time metrics of the drop jump (DJ) and their reliability under single-task (DJ without a CT) and dual-task conditions (DJ with a CT based on simple arithmetic calculations). Thirty-five healthy young participants performed single-task and dual-task DJ trials in a randomized order. Nineteen force-time metrics covering the braking, propulsion, and landing phases of the DJ were compared between conditions using paired t-tests with Holm adjustment and Hedges’ gz, Bayesian paired t-tests, and statistical parametric mapping (SPM) of vertical ground reaction force (VGRF) waveforms. For three-trial mean scores, 17 of the 19 metrics had within-session intraclass correlation coefficients (ICCs) of 0.812–0.930 across both conditions. Under the dual-task condition, jump height (p < 0.001, gz=1.40, Bayes factor <i>BF</i>₁₀ = 1.76×10⁷) and reactive strength index (p < 0.001, gz=1.04, <i>BF</i>₁₀ = 45,943) were lower, while ground contact time was longer (p = 0.025, gz=−0.57, <i>BF</i>₁₀ = 20.57). SPM showed that VGRF was significantly lower under the dual-task condition during 29.2–34.3% (within braking) and 52.0–79.1% (within propulsion) of ground contact. In the landing phase, VGRF was significantly lower under the dual-task condition during 1.3–6.3% (initial force rise) and significantly higher during 15.5–19.6% (attenuation of the impact force). The spring-like correlation (p = 0.462, gz=0.20, <i>BF</i>₀₁ = 2.79) and the vertical time to stabilization (p = 0.462, gz=0.15, <i>BF</i>₀₁ = 3.74) showed no significant difference between conditions, with weak and moderate evidence for the absence of an effect. These findings suggest that a concurrent CT reduces force production within both the braking and propulsion phases of the DJ and alters the VGRF waveform during the subsequent landing phase in healthy young participants. Oussama Khibech Salma Kadda Yousra Hammouti Said Abadi Shehdeh Jodeh Belkheir Hammouti Allal Challioui 10.1371/journal.pone.0362385 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Oussama Khibech, Salma Kadda, Yousra Hammouti, Said Abadi, Shehdeh Jodeh, Belkheir Hammouti, Allal Challioui</p> Emerging SARS-CoV-2 variants continue to demand orally tractable, non-covalent inhibitors of the conserved main protease (M^pro). Here, chromone-phenyl-tetrazole hybrids were prioritized using a multiscale computational strategy that connects drug-likeness, binding stability, free-energy ranking, conformational behavior, and quantum-level electronic features. The series showed favorable oral drug-like profiles and low-to-moderate predicted acute toxicity. Among the stable M^pro complexes, M2 displayed the strongest computed affinity (MM/GBSA ΔG_bind = −38.8 kcal·mol ⁻ ¹), driven mainly by dispersion with limited desolvation cost, whereas M4 showed the most direct catalytic-dyad engagement through His41/Cys145-supported anchoring. DFT analysis rationalized these complementary profiles: M2 and M4 exhibited narrower HOMO-LUMO gaps (4.00 eV) and higher electronic softness, while ELF/NCI maps revealed heteroatom-centered electron reservoirs and weak intramolecular preorganization. The derived pharmacophore consists of a planar chromone π-platform bearing a carbonyl/phenolic acceptor-donor edge, a para-phenyl spacer for conjugation and hydrophobic occupancy, and a methoxy-tetrazole polar/π-rich head for Glu166/Phe140/His163 anchoring. Overall, M2 and M4 emerge as complementary lead chemotypes for experimental validation and structure-guided optimization against M^pro. Habtemu Jarso Rameto Asu Shumi Negawo Kemal Ahmed Biftu Geda Mark Spigt 10.1371/journal.pone.0362375 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Habtemu Jarso, Rameto Asu, Shumi Negawo, Kemal Ahmed, Biftu Geda, Mark Spigt</p> Background <p>Despite progress in reducing the time from HIV diagnosis to treatment initiation, achieving sustained viral suppression remains a major public health challenge among people living with HIV in Ethiopia. However, evidence on viral suppression and its predictors during the test-and-treat era remains limited.</p> Objective <p>This study aimed to assess the rate and predictors of viral suppression among adolescents and adults living with HIV during the test-and-treat era, January 2018 to December 2022, Shashemene City, Ethiopia.</p> Methods <p>A retrospective cohort study was conducted among 414 patients aged 15 years and older who initiated ART between January 2018 and December 2021. Patients were selected using a proportional stratified random sampling technique and followed for a maximum of two years in public health facilities in Shashemene City. Kaplan-Meier was used to estimate the median time to viral suppression, and Cox proportional hazards regression identified predictors of suppression.</p> Results <p>Of the 414 patients, 290 (70.05%; 95% CI: 65.64–74.46) achieved viral suppression by the end of the follow-up period (December 2022). The rate of viral suppression was 6.68 per 100 person-months (95%CI: 5.95–7.49), and the median time to suppression was 9.33 months (95%CI: 8.55–10.11). Rapid ART initiation was associated with twofold higher likelihood of early suppression (aHR = 2.05, 95%CI: 1.58–2.67) compared to delayed initiation. Undernourished patients had 46% lower chance of early suppression (aHR = 0.54, 95%CI: 0.36–0.81), and those who were ambulatory/bedridden at baseline had an 87% lower chance (aHR = 0.13; 95%CI: 0.07–0.27) than working patients. Not good adherence lowered suppression by 36% (aHR = 0.64; 95%CI: 0.41–0.99).</p> Conclusion and recommendation <p>The viral suppression rate was well below the UNAIDS target of 95%. Strengthening rapid ART initiation, adherence and providing nutritional support are essential to improve outcomes. Lower suppression rates among ambulatory/bedridden patients could partly reflect additional health challenges influencing treatment response.</p> Hongbo Liu Shuo Wang Wenpeng Xu 10.1371/journal.pone.0362364 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Hongbo Liu, Shuo Wang, Wenpeng Xu</p> To address the structural complexity and limited compliance of traditional rigid robotic wrists, as well as the absence of adjustable stiffness in soft wrists designed primarily for flexibility, a two-degree-of-freedom (2-DOF) pneumatic flexible wrist with controllable braking torque was developed. The wrist comprises three circumferentially arranged pneumatic actuators connected in parallel around a central pneumatic cross-hinge brake, enabling multidirectional pivoting, while the braking torque can be adjusted according to task requirements for pose stabilization. This configuration combines the high stiffness required for posture maintenance during braking with compliant actuation during motion. Theoretical models of the wrist pivot angle, pivoting direction, and braking torque were established. The pivot-angle model was empirically calibrated using the measured pivot-angle data, while the pivoting-direction and braking-torque models were validated experimentally. Mechanical performance was evaluated under constant-friction-torque and constant-pivot-angle conditions, and empirical relations were obtained by fitting the experimental data. A three-dimensional motion-capture system was also used to characterize the dynamic response under different braking conditions and excitation signals. Under the present experimental conditions, the results show that the wrist exhibits high compliance and enables continuous omnidirectional pivoting with a maximum single-axis pivot angle of 45.2°. The pneumatic cross‑hinge brake achieves multidirectional braking with continuously adjustable torque, reaching a maximum braking torque of 0.842 N·m under brake-only actuation at 0.35 MPa. During coordinated actuation–braking operation, the wrist’s overall resistance to external loads increased by a factor of 4.98 compared with its unpressurized initial state. This composite load-resisting capacity originates from the combined effects of the pneumatic actuators and the central brake. Thi Len Ho Thanh Tam Pham Eun-Ju Ko 10.1371/journal.pone.0362356 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Thi Len Ho, Thanh Tam Pham, Eun-Ju Ko</p> Inactivated influenza vaccines (IIVs) often fail to provide robust mucosal protection, necessitating the development of potent adjuvants for intranasal delivery. This study evaluated a novel adjuvant combination of Monophosphoryl lipid A (MPL), a TLR4 agonist, and alpha-Galactosyl Ceramide (α-GalCer), an NKT cell ligand, to enhance the efficacy of an intranasal inactivated A/PR8 (iPR8) influenza vaccine. <i>In vitro</i> results demonstrated that MPL+ α-GalCer increased the frequencies of CD4⁺ CD25⁺ , CD8⁺ CD25⁺ and CD4⁺ CD69⁺ T cells relative to both the vehicle control and either single adjuvant in splenocyte cultures, whereas in purified dendritic cell and macrophage cultures MPL+ α-GalCer was no more effective than MPL alone. Splenocyte supernatants showed higher elevated TNF- α, IL-2, IFN-γ, IL-4, and IL-13. This pre-activation drove robust allogeneic T-cell proliferation in a mixed lymphocyte reaction, indicating enhanced allostimulatory capacity rather than influenza-specific priming. <i>In vivo</i>, a single intranasal dose of iPR8+ MPL+ α-GalCer elicited high systemic IgG titers and was effective at inducing Th1-associated IgG2a alongside IgG1. Following an LD50-range PR8 challenge, the combined-adjuvant group showed 100% survival, which was not statistically significant and lower lung viral titers at 7 days post-infection. This group exhibited elevated post-challenge lung-associated antigen-specific IgA and a reduced viral burden, which was accompanied by lower inflammatory cell infiltration and cytokine levels. The protection of combination group was accompanied by increased frequencies of ex vivo antigen-responsive CD4⁺ and CD8⁺ T cells recovered post-challenge. Our findings suggest that the MPL+ α-GalCer combination enhances innate and adaptive immune responses, providing an effective adjuvant platform for homologous mucosal protection in a murine model. Jinian Liu Haiyan Chen Yang Cao 10.1371/journal.pone.0362349 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Jinian Liu, Haiyan Chen, Yang Cao</p> This paper examines a supply chain comprising a single new energy vehicle manufacturer (NEVM) and a single power battery supplier (PBS), considering government subsidies and R&D outcome uncertainty. An exponential function is employed to characterize R&D outcome uncertainty. The impacts of R&D subsidies and R&D capability on R&D investment, supply chain members, and their expected profits are examined. A comparative analysis of cost-sharing (CS) and revenue-sharing (RS) contracts is conducted. The findings reveal that: (1) R&D investment exhibits an inverted U-shaped relationship with R&D capability and a positive relationship with R&D subsidies. (2) Under an RS contract, the expected profits of the supply chain and its members increase with higher R&D subsidies and enhanced R&D capability. Under a CS contract, the expected profits of the PBS and the supply chain increase with higher R&D subsidies and enhanced R&D capability; however, the NEVM’s expected profit exhibits a U-shaped relationship with R&D subsidies and R&D capability. (3) Compared with centralized decision-making, neither contract achieves the centralized benchmark for the supply chain’s expected profit. However, compared with decentralized decision-making, the CS contract increases the PBS’s R&D investment and expected profit; the RS contract increases the PBS’s R&D investment and expected profit as well as the supply chain’s expected profit. Both contracts can only improve the NEVM’s expected profit under certain conditions. These findings provide valuable theoretical insights and practical implications for decision-making by NEVMs, PBSs, and government agencies. Andreas Plate Nathalie Heinz Thivjan Thiruchelvam Carla Meyer-Massetti Stephen P. Jenkinson Corinne Steinbrüchel Daniel Drewniak Stefan Neuner-Jehle Oliver Senn 10.1371/journal.pone.0362328 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Andreas Plate, Nathalie Heinz, Thivjan Thiruchelvam, Carla Meyer-Massetti, Stephen P. Jenkinson, Corinne Steinbrüchel, Daniel Drewniak, Stefan Neuner-Jehle, Oliver Senn</p> Background <p>Antibiotic-sparing strategies, such as delayed prescribing or symptomatic therapy, can reduce antibiotic use in uncomplicated urinary tract infections (UTIs), yet their implementation in primary care remains inconsistent. Within this context, non-physician medical staff within general practices and community pharmacies play increasingly important roles in patient counselling and care coordination, potentially shaping treatment expectations and treatment decisions. This study investigated how general practitioners (GPs) make treatment decisions in the management of uncomplicated UTIs in women and examined their views on the roles of non-physician medical staff and community pharmacies in supporting antibiotic-sparing management.</p> Methods <p>We conducted an exploratory qualitative interview study with GPs who regularly manage women with uncomplicated UTIs. Virtual, semi-structured interviews were conducted. Interviews were transcribed verbatim and analyzed thematically.</p> Results <p>Fifteen GPs participated; their mean age was 46.6 years, 53.3% were female, and their experience in general practice ranged from 5 to 25 years. The thematic analysis generated six themes capturing clinical, relational, practical, and interprofessional influences on UTI management. Most GPs reported prior experience with antibiotic-sparing strategies, but thresholds for antibiotic prescribing varied and were shaped by clinical factors, patient expectations, trust, and practical constraints. Practice staff already influenced UTI management, both directly through triage, testing, and counselling and indirectly through practice routines and care pathways, while GPs differed in the degree of professional autonomy they considered appropriate. Pharmacy-based care was often only partly visible to GPs, with experiences varying according to local relationships and professional roles.</p> Discussion <p>The findings suggest that antibiotic-sparing UTI management extends beyond the GP prescribing decision and is shaped across the broader care pathway. Clearer professional roles, appropriate training, and feasible communication structures may support more coordinated care and antimicrobial stewardship in primary care.</p> Shanjana Awasthi Bhupinder Singh Jun Xie 10.1371/journal.pone.0362301 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Shanjana Awasthi, Bhupinder Singh, Jun Xie</p> Activation of Toll-like receptor 4 (TLR4) and accumulation of damage-associated molecular patterns (DAMPs) are hallmarks of infection and inflammation. The SPA4 peptide (amino acid sequence: GDFRYSDGTPVNYTNWYRGE) modulates TLR4-dependent host defense against <i>Pseudomonas aeruginosa</i>. In this study, we investigated the expression of TLR4, major DAMPs, and cellularity in the lungs of <i>P. aeruginosa</i>-infected mice treated with SPA4 peptide or vehicle. The expression of TLR4 and levels of DAMPs were analyzed by immunoblotting and enzyme-linked immunosorbent assay, respectively. Cellularity was determined in hematoxylin and eosin-stained lung tissue sections by microscopy. Our results demonstrated that the expression of TLR4 and DAMPs, as well as tissue cellularity, were increased in the lungs of infected mice. While <i>P. aeruginosa</i>-induced TLR4 expression was not affected, the levels of DAMPs were reduced in mice therapeutically treated with SPA4 peptide (fibrinogen: 8,730 ng; fibronectin: 17,925 ng; High Mobility Group Box-1 [HMGB-1]: 11,758 ng; and hyaluronan: 34,157 ng per g lung weight) compared with vehicle-treated mice (fibrinogen: 13,178 ng; fibronectin: 22,348 ng; HMGB-1: 15,896 ng; and hyaluronan: 53,644 ng per g lung weight). Correspondingly, reduced cellularity was noted in the lungs of SPA4 peptide-treated mice. These results advance our understanding of the SPA4 peptide activity against infectious stimuli. Ye Wang Donghui Ma Jiang Li Lihong Guo 10.1371/journal.pone.0362298 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Ye Wang, Donghui Ma, Jiang Li, Lihong Guo</p> Offline reinforcement learning enables policy learning from static datasets without online exploration, making it particularly suitable for robotic control under safety and data constraints. Decision Transformer recasts offline reinforcement learning as conditional sequence modeling. Extending it to heterogeneous multi-task settings is challenging because task representations and dynamics differ, while joint training can suffer from destructive gradient interference. To address these challenges, we present HeteroGrad-DT, an integrated framework that employs task-specific tokenizers and decoupled prediction heads to retain task-native input and output dimensionality at the model interfaces while learning a shared sequence backbone. It further introduces a Gradient Flow Transformer that periodically coordinates cross-task updates using fixed-dimensional task statistics, compact summaries of shared-backbone gradients accumulated within the current synchronization interval, and an alignment-based coordination objective, rather than relying only on stepwise projection or static regularization. Experiments on the DeepMind Control Suite with up to 30 tasks show that HeteroGrad-DT improves average normalized return over representative multi-task methods. In the 30-task setting, it achieves a 32.3% relative improvement over standard training with a shared backbone and an 8.6% gain over a representative gradient-conflict mitigation baseline using the same task-aware interfaces. Ablation, mechanism, and sensitivity analyses further support complementary benefits from task-aware interfaces and gradient coordination in the evaluated settings. Svala H. Mahmood Iman H. F. Alnaqshabandy 10.1371/journal.pone.0362259 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Svala H. Mahmood, Iman H. F. Alnaqshabandy</p> Uropathogenic <i>Escherichia coli</i> (UPEC) presents a significant therapeutic challenge due to increasing multidrug resistance (MDR). While acquired resistance mechanisms are well-documented, the genetic variability of intrinsic efflux pumps like EmrD remains less characterized. This study investigated the genomic diversity and structural conservation of the EmrD transporter in ten clinical MDR isolates from the Kurdistan Region, Iraq. Isolates were screened for the <i>emrD</i> and β-lactamase genes, followed by <i>emrD</i> sequencing, phylogenetic analysis, and <i>in silico</i> protein modeling. Results confirmed the universal presence of <i>emrD</i> alongside multiple resistance genes. Phylogenetic analysis identified notable local genetic diversity, including a highly divergent lineage (DUH 11). Protein modeling mapped non-synonymous substitutions to transmembrane helices 6 and 12, regions critical for the “rocker-switch” conformational changes required for substrate translocation. These findings suggest that while EmrD is a stable component of the MDR machinery, localized genomic divergence may potentially influence efflux efficiency among clinical lineages, warranting future functional validation. Yonghoon Shin Jung-Joon Cha Ju Hyeon Kim Hyung Joon Joo Jae Hyoung Park Cheol Woong Yu Minae Park Yujin Lee Soon Jun Hong 10.1371/journal.pone.0362218 2026-11-11T14:00:00Z 2026-11-11T14:00:00Z <p>by Yonghoon Shin, Jung-Joon Cha, Ju Hyeon Kim, Hyung Joon Joo, Jae Hyoung Park, Cheol Woong Yu, Minae Park, Yujin Lee, Soon Jun Hong</p> Colchicine has been associated with reduced cardiovascular events in secondary prevention, but evidence for primary prevention is limited. We examined the association between colchicine use and cardiovascular outcomes in patients with type 2 diabetes mellitus and gout without prior coronary artery disease. From the Korean National Health Insurance Service database, we identified 48,295 patients with diabetes and gout without prior coronary artery disease between 2015 and 2019. We compared 28,964 colchicine users with 19,331 non-users by 1:1 propensity score matching, which produced 17,337 matched pairs. The primary outcome was a composite of all-cause death, nonfatal myocardial infarction, and nonfatal stroke. The primary composite outcome occurred in 12.52% of colchicine users versus 15.03% of non-users (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.66–0.75; P < 0.001). All-cause mortality was significantly reduced in colchicine users (8.01% vs. 11.07%; HR 0.58; 95% CI 0.53–0.62; P < 0.001). No significant differences were observed for myocardial infarction (HR 1.15; 95% CI 0.96–1.37; P = 0.121) or stroke (HR 0.91; 95% CI 0.81–1.01; P = 0.076). In a landmark analysis at 365 days that addressed immortal time bias, the associations with all-cause mortality (HR 0.67; 95% CI 0.62–0.73; P < 0.001) and with the composite outcome (HR 0.76; 95% CI 0.71–0.81; P < 0.001) remained significant, whereas stroke (HR 0.99; 95% CI 0.87–1.12; P = 0.823) and myocardial infarction (HR 1.15; 95% CI 0.95–1.40; P = 0.144) did not differ between the two groups. In patients with diabetes and gout without prior coronary artery disease, colchicine use was associated with lower all-cause mortality. The reduction in the composite outcome was driven by mortality rather than by myocardial infarction or stroke.