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 2026-06-17T09:09:50Z Mar Joanpere Ana Burgues-Freitas Cristina Pulido Adriana Aubert Elisabeth Torras-Gómez Maria Vieites Marta Soler-Gallart Ramon Flecha 10.1371/journal.pone.0351979 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Mar Joanpere, Ana Burgues-Freitas, Cristina Pulido, Adriana Aubert, Elisabeth Torras-Gómez, Maria Vieites, Marta Soler-Gallart, Ramon Flecha</p> Brian Mac Grory Cécile Preterre Pierre Lebranchu Stephen James Ryan Øystein Kalsnes Jørstad Morten Carstens Moe Johannes Tünnerhoff Martin S. Spitzer Carsten Grohmann Oana M. Dumitrascu Valérie Biousse Benoit Guillon Anne Hege Aamodt Sven Poli Matthew Schrag The Central Retinal ArterY OcclusioN (CRAYON) Collaborators 10.1371/journal.pone.0351934 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Brian Mac Grory, Cécile Preterre, Pierre Lebranchu, Stephen James Ryan, Øystein Kalsnes Jørstad, Morten Carstens Moe, Johannes Tünnerhoff, Martin S. Spitzer, Carsten Grohmann, Oana M. Dumitrascu, Valérie Biousse, Benoit Guillon, Anne Hege Aamodt, Sven Poli, Matthew Schrag, The Central Retinal ArterY OcclusioN (CRAYON) Collaborators </p> Tatsuya Yoshihara So Owada Harumasa Arita Akiko Nakagomi Kota Tanaka Yosuke Ono Osamu Yoshino 10.1371/journal.pone.0351855 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Tatsuya Yoshihara, So Owada, Harumasa Arita, Akiko Nakagomi, Kota Tanaka, Yosuke Ono, Osamu Yoshino</p> Background <p>To investigate the association between menstrual-related disorders and sexually transmitted infections (STI) among young women in Japan, and to examine differences according to disorder type and hormonal therapy use.</p> Methods <p>This cross-sectional study used the Japan Medical Data Center Claims Database and included women younger than 40 years who had at least one healthcare visit in 2023. Menstrual-related disorders were defined as endometriosis or dysmenorrhea based on ICD-10 codes. The prevalence of five STIs—gonorrhea, genital chlamydia infection, trichomoniasis, genital herpes, and other sexually transmitted conditions—was compared between women with and without menstrual-related disorders. Subgroup analyses were conducted for endometriosis, dysmenorrhea, and hormonal therapy (low-dose estrogen–progestin combinations or dienogest). Prevalence ratios (PR) and prevalence differences (PD) with 95% confidence intervals (CI) were estimated.</p> Results <p>Among 3,440,929 women, 257,897 (7.5%) had menstrual-related disorders. All STI were substantially more prevalent in this group than in women without menstrual-related disorders, with PRs ranging from 4.31 to 5.29. Endometriosis showed the highest prevalence, particularly for genital chlamydia infection (4.98%; PR 7.44). Dysmenorrhea was also associated with consistently elevated STI prevalence. Among women with menstrual-related disorders, STI prevalence differed only slightly according to hormonal therapy use, with differences generally within one percentage point.</p> Conclusion <p>Menstrual-related disorders were strongly associated with increased diagnosis of STI in Japanese young women. These findings highlight the importance of integrating STI screening and reproductive health education into routine gynecologic care for women with endometriosis or dysmenorrhea. The influence of healthcare-seeking behavior and diagnostic patterns should be considered when interpreting claims-based STI data.</p> Soo-Hyun Kim Yunjung Choi Hyung Jun Park Ji-Man Hong Young-Chul Choi 10.1371/journal.pone.0351854 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Soo-Hyun Kim, Yunjung Choi, Hyung Jun Park, Ji-Man Hong, Young-Chul Choi</p> Sara Grafenauer Belinda Durey Kevin Norton 10.1371/journal.pone.0351794 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Sara Grafenauer, Belinda Durey, Kevin Norton</p> Barbie and Ken dolls have been criticized over time for their overt misalignment of body shape in comparison with the average adult, and the possibility that this impacts the formative minds of children, particularly girls. Updating a previous examination of the original Barbie and Ken dolls from 1996, this study compared the body measures of the 2016 “Fashionista” range—including Curvy, Petite, Tall, and Standard Barbie models, and new Malibu Ken—with representative population data of young adult females and males using anthropometric techniques. A range of anthropometric girth measures plus height were taken from each doll, and body proportions were calculated. The rules of allometry were used to scale the dolls to a standardized adult height of 170.18 cm to determine the dimensions the dolls at this adjusted size. The dimensions were then compared to the same height-adjusted reference population norms used in the original study. The comparison revealed significant alterations in the dolls’ morphology compared with the original Barbie and Ken, with key measures of waist-to-hip and chest-to-waist ratios becoming more realistic and falling within the 95% confidence range of the population. According to z-score deviation data, Curvy Barbie fell closest to the mean for most of the scaled girth measures, while new Ken was closer to the mean for all girths except ankle. Design changes reflect a shift toward greater body diversity, with potential benefits for children’s health behaviours through the production of a broader range of more diverse, human-like dolls. Importantly, key measurements and body proportions were generally closer to the respective reference populations. Karin Törnbom Dominique Hange Eva-Lisa Petersson Irene Svenningsson 10.1371/journal.pone.0351766 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Karin Törnbom, Dominique Hange, Eva-Lisa Petersson, Irene Svenningsson</p> Background <p>Despite increasing attention to youth mental health, children and adolescents in Sweden experience fragmented, inequitable care with regional variation. Delays in diagnosis, limited preventive interventions, and poor inter-sectoral collaboration contribute to significant unmet needs. This study investigates system-level challenges and stakeholder perspectives on opportunities to enhance care pathways.</p> Methods <p>We conducted a qualitative study in the Västra Götaland region, Sweden. Fourteen purposively selected participants – including senior executives, healthcare professionals, and parents took part in semi-structured interviews. We used systematic text condensation, according to Malterud, and the four steps involved in this method for analysing the interviews.</p> Results <p>A central theme across interviews was the requirement for a formal diagnosis before children can access mental health support, particularly in school and primary care settings. Participants described this as a major barrier that delays early intervention and leaves children and young people with complex or atypical presentations without adequate support. Primary care professionals reported increasing mental health caseloads without corresponding increases in staffing or funding, limiting preventive work. Child and adolescent psychiatry (BUP) was described as overwhelmed, with long waiting times and limited continuity of care. A care manager within primary care was proposed as a way to help families navigate fragmented services and improve collaboration, although participants emphasised that such a role would need to be part of broader structural reform.</p> Conclusions <p>Our findings highlight persistent systemic issues in mental health care for children and young people, including inequitable access, insufficient prevention, and fragmented collaboration across sectors. Strengthening primary prevention, reallocating resources to primary and school-based mental health care and implementing well-defined care coordination roles within broader restructuring may improve continuity and equity in service delivery. Comprehensive policy reform is needed to support person-centred, integrated care pathways for children and young people with mental health needs.</p> Rui Sun Zhihao Chen 10.1371/journal.pone.0351750 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Rui Sun, Zhihao Chen</p> This paper details the design and development of a discipline-specific English for Academic Purposes (EAP) syllabus for undergraduate students majoring in architecture and design related disciplines in an art school in China. Guided by the comprehensive needs analysis model established by Dudley-Evans and St. John [Developments in English for specific purposes: a multi-disciplinary approach. Cambridge University Press (1998)] and Swales [Genre analysis: English in academic and research settings. Cambridge University Press (1990)] genre theory, this study employed a university-wide questionnaire to gather data from 650 participants, including students and faculty. The needs analysis identified a critical disparity between students’ target academic aspirations—such as engaging in international collaboration, pursuing studies abroad, and understanding foreign lectures—and their present situational capabilities, particularly in listening comprehension and command of disciplinary vocabulary. In response to these findings, the proposed “Architectural Art English” syllabus is constructed around a genre-based, content and language integrated learning (CLIL) as well as task-based language teaching (TBLT) approach. It systematically incorporates seven key academic and professional genres relevant to the field: textbooks and monographs, research papers, case studies, and lecture scripts as input genres; and design statements, presentation scripts, and research abstracts as output genres. Each instructional unit is organized around a central architectural theme, utilizing authentic cases and genre analysis of move structures to make disciplinary discourse conventions explicit. The pedagogical framework emphasizes task-based learning, featuring authentic activities such as case analysis, design project presentations, and paper abstract writing to bridge the gap between language skills and disciplinary knowledge. This syllabus aims to addresses the complex interaction of learners’ target needs, subjective wants, and current proficiencies, facilitating their active participation in the global academic community of architecture and design. Imteaz Mahbub Bimal Chandra Shil Sadeed Araf Reza 10.1371/journal.pone.0351741 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Imteaz Mahbub, Bimal Chandra Shil, Sadeed Araf Reza</p> Background <p>Functional dyspepsia (FD) is a common gastrointestinal disorder with multifactorial pathogenesis. Recent evidence suggests that duodenal eosinophilia may contribute to low-grade immune activation in FD. This study evaluated the association between increased duodenal eosinophil count and functional dyspepsia.</p> Materials and methods <p>This case-control study was conducted in the Department of Gastroenterology, Sir Salimullah Medical College, Mitford Hospital, Dhaka, Bangladesh, from January to December 2022. Forty-six adult patients with functional dyspepsia diagnosed by Rome-III criteria were included as cases, while forty age- and sex-matched individuals without functional dyspepsia undergoing upper gastrointestinal endoscopy for other indications with normal endoscopic findings served as controls. Multiple biopsies were obtained from the second part of the duodenum. Formalin-fixed paraffin-embedded tissue sections were stained with hematoxylin and eosin. Eosinophils were counted manually by light microscopy in five randomly selected high- power fields (x 400 magnification), and the mean eosinophil count per high-power field (HPF) was calculated.</p> Results <p>The mean duodenal eosinophil count was significantly higher in patients with functional dyspepsia compared with controls (23.98 ± 7.98 versus 15.63 ± 5.94 eosinophils/HPF, p <0.001). Duodenal eosinophilia (≥21 Eosinophils/HPF) was present in 69.6% of patients with functional dyspepsia compared with 17.5% of controls. Increased duodenal eosinophil count was significantly associated with functional dyspepsia (odds ratio 9.74, 95% confidence interval 3.50-27.08).</p> Conclusions <p>Patients with functional dyspepsia demonstrated significantly greater duodenal eosinophil infiltration than controls, supporting the role of low-grade immune activation in its pathogenesis. Further multicenter studies with larger samples are required to clarify the clinical implications of duodenal eosinophilia in functional dyspepsia.</p> Sneha Vidyasagar Kanakamani Jeyaraman Syeda Farah Zahir Paul Varghese 10.1371/journal.pone.0351739 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Sneha Vidyasagar, Kanakamani Jeyaraman, Syeda Farah Zahir, Paul Varghese</p> Objective <p>This retrospective study evaluated calcitonin as an adjunct therapy for reducing phantom limb pain (PLP) following lower limb amputation.</p> Method <p>The study included 35 patients who received at least 3 days of calcitonin treatment between January 1, 2017, and December 31, 2023. We collected demographic data and pain ratings (intensity, distress, and interference with activity) before and after calcitonin treatment. Descriptive statistics and paired t-tests analysed the data, with a two-way repeated measures ANOVA used to compare outcomes between patients with and without diabetes. Raw and Standardized mean differences (Cohen’s d) are presented for each measure.</p> Results <p>The average age of participants was 57.09 years (SD = 13.66), with 40% female. Amputation types were below-knee (65.7%), above-knee (25.7%), and other (8.6%). The main causes of amputation included diabetic foot infection (25.7%), peripheral vascular disease (34.3%), trauma (25.7%), and other (14.3%). Ten participants had diabetes, and 20% had depression.Calcitonin was associated with significant reductions in pain outcomes from pre- to post-intervention (Day 0 to Day 7), with calcitonin given from day 1–3. Mean pain intensity decreased from 6.41 to 5.24 (Cohen’s d = 0.66); p = 0.02), and pain-related distress decreased from 5.85 to 4.81 (Cohen’s d = 0.71; p = 0.014). Perceived pain relief scores increased from 33.69 to 58.21, indicating greater patient-reported pain relief following treatment (Cohen’s d = 0.53; p = 0.035). No significant differences in pain intensity or distress were observed between patients with and without diabetes. Additionally, there was no significant change in the Oral Morphine Equivalent Daily Dose (p = 0.94).</p> Conclusion <p>In conclusion, calcitonin significantly reduced perceived pain intensity and pain-related distress scores while increasing perceived pain relief scores (i.e., patients’ reported degree of pain reduction), with similar effects observed in both patients with and without diabetes.</p> Jack Palmieri Frida Pilgaard Anette Agardh 10.1371/journal.pone.0351724 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Jack Palmieri, Frida Pilgaard, Anette Agardh</p> Sexual harassment persists in academic workplaces despite extensive policy frameworks. This study explored how employees at a large Swedish university perceive and articulate the organisational culture and everyday norms that shape sexual harassment. Ten focus group discussions were held with forty staff members, separated by managerial role and conducted in Swedish or English. Transcripts were analysed using qualitative content analysis to identify shared meanings, latent themes and interpretive patterns. Analysis generated one overarching theme, perceiving sexual harassment through the lens of organisational silence, power relations, and negotiated boundaries, supported by four sub-themes. Participants described boundary-setting as a collective, situational process: definitions of harassment shifted in real time, with women often seeking peer confirmation while men framed the same conduct as innocuous. Formal and informal hierarchies amplified this ambiguity: senior researchers with grant-generating prestige were deemed ‘untouchable’, and managers reported uncertainty about how to act without clear procedural guidance. Silence emerged as a strategic response to protect careers and collegial relationships, normalising borderline behaviours through humour and rationalisation. Yet employees also engaged in discrete forms of peer solidarity, staying with vulnerable colleagues after meetings, quietly redirecting collaborations, which signalled a sense of collective responsibility even in the absence of robust institutional support. These findings show that policy compliance alone cannot shift workplace culture when interpretive authority rests with peer groups and incentive structures reward silence. Universities therefore need to focus on organisational level responses that equip leaders with emotional competence and procedural clarity and support the creation of a work environment that can identify, prevent, and respond to sexual harassment. Embedding such measures can transform informal solidarity into a shared, institutionally endorsed standard of respect. The PLOS One Editors 10.1371/journal.pone.0351709 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by The PLOS One Editors </p> The PLOS One Editors 10.1371/journal.pone.0351708 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by The PLOS One Editors </p> Agatha Ribeiro Kalthof Nikolas Dresch Ferreira Caio Mateus Silva Iuri Cordeiro Valadão Iguaracy Pinheiro de Sousa Ester Riserio Matos Bertoldi Vanessa Morais Lima Lauro Thiago Turaca Ana Beatriz Ruiz Afonso Barbosa Miriam Helena Fonseca-Alaniz Jean-Paul Concordet Elida Adalgisa Neri Jose E. Krieger 10.1371/journal.pone.0351704 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Agatha Ribeiro Kalthof, Nikolas Dresch Ferreira, Caio Mateus Silva, Iuri Cordeiro Valadão, Iguaracy Pinheiro de Sousa, Ester Riserio Matos Bertoldi, Vanessa Morais Lima, Lauro Thiago Turaca, Ana Beatriz Ruiz Afonso Barbosa, Miriam Helena Fonseca-Alaniz, Jean-Paul Concordet, Elida Adalgisa Neri, Jose E. Krieger</p> Generating mature human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) remains a major obstacle to accurate disease modeling and cardiac repair. As the transcription factor Irx3 is a key determinant of ventricular conduction system fate in mice, we hypothesized that suppressing <i>IRX3</i> expression accelerates human working cardiomyocyte differentiation. Here, we demonstrate that depleting <i>IRX3</i> enhances hiPSC-CM differentiation. <i>IRX3</i>-knockout (KO) hiPSCs generated a greater number of cardiomyocytes with elevated expression of TNNI1 and CX43. Notably, <i>IRX3</i>-KO cardiomyocytes exhibited improved electrophysiological properties, more uniform mitochondrial distribution, better sarcomere organization, and enhanced intercellular connectivity. We observed that <i>IRX3</i> expression peaks during the early stages of cardiomyocyte differentiation, whereas <i>IRX3</i>-KO cardiac progenitors have increased expression of GATA4, NKX2–5, and <i>TBX5</i>, as well as enhanced cell proliferation. These integrative analyses indicate that IRX3 influences cardiomyocyte differentiation by modulating the gene regulatory networks driven by GATA4, NKX2–5, and TBX5, providing functional evidence linking gene regulatory networks to the structural and electrophysiological development of cardiomyocytes. Collectively, these findings identify IRX3 as a key regulator of early cardiac commitment and highlight the potential of IRX3 suppression to enhance the molecular and functional phenotype of hiPSC-derived cardiomyocytes. The PLOS One Editors 10.1371/journal.pone.0351703 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by The PLOS One Editors </p> The PLOS One Editors 10.1371/journal.pone.0351696 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by The PLOS One Editors </p> Wen Lin Qiong-zhi Shi Xiang-ru Liao Yuan Zeng Xiang-yang Xie Gang-jian Ji Yin-ke Li 10.1371/journal.pone.0351679 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Wen Lin, Qiong-zhi Shi, Xiang-ru Liao, Yuan Zeng, Xiang-yang Xie, Gang-jian Ji, Yin-ke Li</p> Burn wound infections are frequently complicated by biofilm-forming and multidrug-resistant pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), posing major therapeutic challenges. Antimicrobial peptides (AMPs) such as PL-5 (peceleganan) exhibit broad-spectrum activity but are limited by instability, poor biofilm penetration, and reduced efficacy in complex wound environments. Here, a red-light-responsive, porphyrin-phospholipid (PoP)-containing cationic liposomal system for PL-5, aiming to enhance its antibacterial and antibiofilm performance was developed. Optimized liposomes achieved high encapsulation efficiency (~73%), uniform nanoscale size (~50 nm), narrow polydispersity, and positive surface charge. They demonstrated good storage stability and controlled peptide release under red-light irradiation (635 nm). <i>In vitro</i>, red-light activation significantly enhanced antimicrobial activity against MRSA and methicillin-susceptible <i>S. aureus</i> (MSSA), reducing minimum inhibitory concentration (MIC) values fourfold and accelerating bactericidal kinetics compared with free PL-5 and non-irradiated liposomes. Additionally, red-light-activated liposomes markedly inhibited biofilm formation. These results indicate that light-responsive liposomal delivery enables spatiotemporally controlled release of PL-5, significantly potentiating its antibacterial and antibiofilm efficacy. This approach offers a promising localized treatment strategy for biofilm-associated burn wound infections and a foundation for future translational studies. Jing-le Zhuge Xi-yong Li Yong-le Wang Juan-fen Ma 10.1371/journal.pone.0351666 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Jing-le Zhuge, Xi-yong Li, Yong-le Wang, Juan-fen Ma</p> Objective <p>This study aimed to comprehensively analyze differentially expressed genes (DEGs) in chondrocytes from patients with knee osteoarthritis (OA) by integrating multiple machine learning algorithms and bioinformatics techniques, to unravel the underlying molecular mechanisms associated with OA chondrocytes, and to provide novel insights for the innovation of clinical therapeutic strategies.</p> Methods <p>We downloaded the GSE117999, GSE114007, GSE169077, GSE246425, and GSE178557 datasets from the public Gene Expression Omnibus (GEO) database as the training set, while GSE57218 served as an independent validation set. To ensure data consistency and comparability, the training set was normalized, and the ComBat algorithm was applied to eliminate batch effects, yielding a merged gene expression dataset. Subsequent differential expression analysis was performed to identify genes with significant changes under disease conditions, followed by enrichment analysis. To more accurately identify genes closely linked to disease characteristics, we independently analyzed the merged dataset using three machine learning algorithms: Lasso regression, random forest, and support vector machine (SVM). The intersection of results from these three methods was used to construct a robust list of disease-related feature genes. These prominent feature genes were validated in the training set and further externally confirmed using the GSE57218 dataset. Additionally, the CIBERSORT algorithm was employed to quantify immune cell infiltration in the normalized gene expression data, selecting infiltration results with high reliability (P < 0.05). Focusing on the target genes, we clarified the strength and significance of their associations with immune cell infiltration levels, comprehensively revealing differences in immune cell infiltration profiles between groups and the potential associations with target genes.</p> Results <p><i>DDIT3</i> and <i>PFKFB3</i> were significantly downregulated in OA patients. <i>DDIT3</i> was specifically associated with lipid metabolism, apoptosis, and inflammatory genes (e.g., <i>TNFRSF12A</i>), whereas <i>PFKFB3</i> was linked to phospholipid synthesis and cell cycle genes (e.g., <i>CHKA</i>). Both genes were associated with core OA-related pathways, including PI3K-Akt and AGE-RAGE. Immune infiltration analysis revealed that <i>DDIT3</i> was positively correlated with pro-inflammatory mast cells and M1 macrophages, while <i>PFKFB3</i> was negatively correlated with activated dendritic cells. Collectively, these two genes were associated with immune cell infiltration patterns. The competing endogenous RNA (ceRNA) network analysis indicated that <i>DDIT3</i> was associated with axes such as <i>LINC00689-miR-769-5p</i>, and <i>PFKFB3</i> was associated with complex networks like <i>GAS6-AS1-miR-146a-5p.</i></p> Conclusion <p><i>DDIT3 and PFKFB3 are key candidate genes associated with the pathological progression of OA. Their downregulation is correlated with inflammatory and metabolic disturbances in chondrocytes, supporting their potential use as diagnostic biomarkers and therapeutic targets for OA.</i></p> Sevilay Gülesen Victoria Most Clara T. Schoeder Jens Meiler 10.1371/journal.pone.0351662 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Sevilay Gülesen, Victoria Most, Clara T. Schoeder, Jens Meiler</p> Viruses such as coronaviruses or filoviruses use their surface glycoproteins (GPs) to attach to the host cell, triggering the fusion of the viral membrane with the endosome membrane. Epitopes on the viral GP are major targets for antibody-mediated recognition and neutralization. During the fusion process, the GP undergoes conformational changes triggered by fluctuations in environmental pH. Structural states are typically classified into three distinct conformations: prefusion, intermediate, and postfusion. These conformations serve as essential templates for prediction of conformational epitopes and structure-based vaccine design. Despite their importance, many viral GP structures remain absent from the Protein Data Bank (PDB). Fortunately, recent breakthroughs in computational structure prediction have greatly enhanced the accuracy and accessibility of protein modeling. In this study, we utilized AlphaFold2-Multimer (AF2-M), version 2.3, to predict various GP structural conformations and observed that the overall frequency of predictions in the postfusion conformation is low. Therefore, we hypothesized that adapting the AF2-M protocol is necessary to enrich for specific conformations, thereby enabling the prediction of both pre- and postfusion conformations. AF2-M requires only the input sequence and internally generates multiple sequence alignments (MSAs) and optional templates before applying its pretrained model weights. We tested the use of template data to enrich pre- or postfusion conformations and demonstrated that our approach significantly increases the prediction frequency of class I fusion protein structures in both conformations, with the template dataset playing a crucial role in guiding modeling towards the intended state. Furthermore, we showed that the lack of correlation between pLDDT and TM-scores suggests that low pLDDT values may obscure the presence of valid alternative conformations. Abdulmujeeb Opeyemi Muhammad-Olodo Laura Asher 10.1371/journal.pone.0351659 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Abdulmujeeb Opeyemi Muhammad-Olodo, Laura Asher</p> Introduction <p>Human papillomavirus (HPV) vaccine prevents over 90% of cervical cancers. In October 2023, Nigeria launched a free HPV vaccination campaign targeting girls aged 9–14 years. Despite removing cost barriers, misinformation about fertility impacts and population control contributed to variable uptake across states. Understanding caregiver decision-making is crucial for improving coverage. This study aimed to explore factors influencing caregivers’ HPV vaccination decisions during Nigeria’s 2023 campaign in Ilorin East Local Government Area, Kwara State.</p> Methods <p>A qualitative study using focus group discussions (FGDs) was conducted using purposive and snowball sampling. We recruited 41 caregivers (mean age 47 years; 71% female) of eligible girls from urban and rural communities. Five FGDs were conducted: four with vaccine acceptors (n = 35) and one with decliners (n = 6). Discussions were conducted in Yoruba, audio-recorded, transcribed verbatim, and analysed using Braun and Clarke’s reflexive thematic analysis. Ethical approval was obtained from two institutional review boards.</p> Results <p>Four themes emerged from the analysis. Trust operated at multiple levels: institutional (government programmes), interpersonal (healthcare worker competence), and community (religious/traditional leader endorsement). Historical medical mistrust, intensified by COVID-19 experiences, may have manifested as fertility and population control fears. Personal cancer experiences strongly motivated acceptance, whilst concerns about childhood sexuality influenced timing preferences. Despite free provision, barriers included geographic inequities (remote Fulani-Hausa communities were excluded), language barriers (no Hausa translators), school-based delivery gaps, and indirect costs (transport, time). Caregivers recommended house-to-house campaigns, multilingual services, traditional leader engagement, and permanent vaccination centres.</p> Conclusion <p>Free vaccine provision is necessary but not sufficient to ensure uptake. Successful HPV vaccination requires rebuilding trust through community engagement, addressing historical medical exploitation concerns, and ensuring equitable access. Integrating these findings into Nigeria’s National Programme on Immunisation could improve coverage from current estimates of 54% to targeted 90%, protecting more girls from cervical cancer whilst respecting community values.</p> Ying Fei Ming-Yi Gao Nan Qiao Jia Hu Ling He Jiao-Li Zhou Ning-Ning Zheng Ting-Ting Liu 10.1371/journal.pone.0351574 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Ying Fei, Ming-Yi Gao, Nan Qiao, Jia Hu, Ling He, Jiao-Li Zhou, Ning-Ning Zheng, Ting-Ting Liu</p> Background <p>The effect of fecal microbiota transplantation (FMT) in treating irritable bowel syndrome (IBS) may be attributed to the modulation of CD8 + T cells. This study aims to identify FMT-mediated key genes to explore the underlying mechanism.</p> Methods <p>Transcriptomic datasets GSE138297 (colonic biopsies from 8 IBS patients pre- and post-FMT) and GSE134649 (single-cell data from 3 healthy colon tissues) were obtained from GEO during December 2023–December 2024. Key genes were identified by intersecting differentially expressed genes (DEGs) and the most relevant co-expression module derived from weighted correlation network analysis. Functional enrichment, gene set enrichment analysis, immune infiltration profiling via TIMER 2.0, single-cell annotation using PanglaoDB and Seurat, and drug–gene interaction screening from DrugBank were conducted to decipher the regulatory mechanisms.</p> Results <p>Ten key genes were identified through integration of DEGs and the MEgreen module. Functional analyses revealed significant involvement in the positive regulation of CD8 + T cells activation. Immune infiltration assessment demonstrated a marked increase in CD8 + T cells abundance post-FMT. Single-cell data indicated predominant expression of LILRB1, P2RY13, CLEC10A, and CLEC12A in dendritic cells, and LILRB1, PIPOX, and CLEC11A were annotated within CD8 + T cells clusters in healthy colonic tissue. Nine (database-derived and speculative) drugs targeting seven key genes were identified, most implicated in the management of IBS symptoms or immunomodulation.</p> Conclusion <p>An association between key gene regulation and CD8 + T cell-related immunoregulation is correlated with the therapeutic effect of FMT in IBS.</p> Gunnhild Helmsdal Marnar Fríðheim Kristiansen Eyðbjørg Klemmentsen Gaard Barbara Joensen Eysturoy Pál Weihe Eina Hansen Eliasen Maria Skaalum Petersen 10.1371/journal.pone.0351564 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Gunnhild Helmsdal, Marnar Fríðheim Kristiansen, Eyðbjørg Klemmentsen Gaard, Barbara Joensen Eysturoy, Pál Weihe, Eina Hansen Eliasen, Maria Skaalum Petersen</p> Background <p>Six years since the emergence of SARS-CoV-2, the newer variants of the virus continue to have long-term health effects.</p> Objectives <p>The aim of the study was to investigate persistent symptoms, cognitive impairment, and clinical and paraclinical predictors of long COVID in individuals infected during the Omicron wave.</p> Methods <p>We conducted a clinical case-control study including participants with persistent symptoms up to 13 months after confirmed SARS-CoV-2 Omicron infection (long COVID or LC group) and antibody-verified never-infected controls (NI group).</p> Results <p>A total symptom score based on a 24-item questionnaire was strongly associated with increased odds of long COVID (adjusted odds ratio (aOR) 1.21, 95% CI 1.13–1.30, p < 0.001). Sub-analysis showed particularly strong associations for fatigue, cognitive impairment, neurological symptoms, and symptoms from the cardiopulmonary and musculoskeletal systems. Both mental impairment and fatigue independently predicted long COVID (aOR 1.27, 95% CI 1.14–1.42, p < 0.001, and aOR 1.27, 95% CI 1.11–1.46, p < 0.001, respectively). Additionally, a higher number of self-reported infections during the follow-up period increased the odds of long COVID (aOR 1.57, 95% CI 1.06–2.34, p = 0.025), though this was not reflected in antibiotic use. Finally, blood analyzes showed that lower white blood cell counts were associated with increased odds of long COVID in women, but not in men, however the clinical significance of this finding remains uncertain.</p> Conclusions <p>One year after Omicron infection, a subset of people continue to experience a substantial symptom burden, particularly fatigue, cognitive impairment, and mental well-being, and a higher frequency of intercurrent infections.</p> Natsuhiro Takahashi Akihiko Fujita Yuki Azetsu Akiko Karakawa Mie Myers Masamichi Takami Masahiro Chatani 10.1371/journal.pone.0351542 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Natsuhiro Takahashi, Akihiko Fujita, Yuki Azetsu, Akiko Karakawa, Mie Myers, Masamichi Takami, Masahiro Chatani</p> Bone loss occurs in astronauts during prolonged spaceflight, thus indicating the sensitivity of skeletal homeostasis to altered gravitational environments. Previous studies have shown that microgravity affects osteoclast differentiation and bone resorption, which suggests that osteoclasts possess mechanisms to sense and respond to gravity-generated mechanical forces. For testing of the related mechanisms, hypergravity can be experimentally reproduced with use of a centrifuge. In the present study, osteoclasts derived from mouse bone marrow were subjected to hypergravity under three conditions: 30G exposure using a non-CO₂ centrifuge system, and short- or long-term exposure to 3G or 5G using an incubator-compatible centrifuge system. Cytoskeletal organization and resorptive function were assessed using TRAP (tartrate-resistant acid phosphatase) staining, F-actin visualization, and dentin pit assays. In addition, phosphoproteomic analysis was performed after short-term exposure to 5G hypergravity. Hypergravity exposure for as brief as 30 minutes compromised F-actin ring integrity, reduced fluorescence intensity, and promoted nuclear repositioning toward actin rings, whereas tubulin and vinculin localization remained unchanged, and the structural alterations corresponded to attenuated resorption pit formation. Quantitative phosphoproteomic profiling revealed coordinated hypergravity-dependent changes in phosphorylation across multiple cellular modules, including cytoskeletal organization, membrane trafficking, intracellular signaling, and nuclear regulatory pathways. Together, these results indicate that osteoclasts are sensitive to gravity-generated mechanical loading, with hypergravity rapidly modifying F-actin-associated cytoskeleton properties and reprogramming phosphorylation-dependent signaling networks, ultimately attenuating bone-resorptive activity. These findings provide mechanistic insight into how osteoclasts respond to altered gravitational loading conditions and have implications for skeletal adaptation during spaceflight and under altered mechanical loading conditions on Earth. Su-jin Kim Jinhee Kim 10.1371/journal.pone.0351506 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Su-jin Kim, Jinhee Kim</p> Background <p>Post-Acute Sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is characterized by persistent and heterogeneous symptoms that impair health-related quality of life (HRQoL). Although several studies have identified symptom subgroups in Western populations using person-centered approaches, data on Asian populations remain limited.</p> Objectives <p>In this study, we aimed to classify the symptom profiles of Korean adults with PASC using latent profile analysis (LPA) and examine the differences in HRQoL and associated factors between the identified profiles.</p> Methods <p>We conducted an online survey of 629 adults in Korea who experienced persistent symptoms ≥12 weeks after coronavirus disease (COVID-19) diagnosis. Symptom burden was assessed using the Long COVID Symptom Tool (26 items), and HRQoL was measured using the SF-36 v2®. LPA was performed to identify the symptom subgroups. One-way analysis of variance (ANOVA) and multiple linear regression were used to compare HRQoL across profiles and explore predictors.</p> Results <p>A four-class model provided the best fit: Class 1 (Low symptom, 23.3%), Class 2 (Moderate multisystem, 44.1%), Class 3 (Fatigue/post-exertional malaise dominant, 15.9%), and Class 4 (High multisystem burden, 16.7%). HRQoL differed significantly between classes (<i>p</i> < .001), with a clear gradient of decreasing scores from low to high symptom burden. The independent predictors of lower HRQoL included lower education, presence of chronic disease, poor subjective health, hospitalization during acute infection, and prolonged symptom persistence. The model explained 32.9% of the variance in HRQoL.</p> Conclusions <p>Korean adults with PASC exhibit heterogeneous symptom patterns that substantially affect their HRQoL. The identification of distinct symptom profiles supports the need for tailored interventions, including rehabilitation, cognitive training, and psychological support. Our findings provide crucial evidence for developing Korean population-specific screening tools and management guidelines for PASC.</p> Burç İhsan Gencel Melahat Çelik Güven Uğur Mercan Süleyman Çağatay Dayan Onur Geçkili 10.1371/journal.pone.0351498 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Burç İhsan Gencel, Melahat Çelik Güven, Uğur Mercan, Süleyman Çağatay Dayan, Onur Geçkili</p> Background <p>Mandibular two-implant overdentures are considered the standard of care for edentulous patients. The attachment system and the shape of the bone crest can significantly influence biomechanical behaviours. This study aimed to evaluate stress distribution in mandibular implant-supported overdentures using locator and bar attachments across various bone crest designs.</p> Materials and methods <p>FEA was performed on mandibular overdentures supported by two implants. Three crest configurations (flat, convex, and irregular) were modelled with either bar or locator attachments. A vertical force of 100 N was applied in three loading conditions: anterior, unilateral molar, and bilateral molar. Maximum von Mises stresses and principal stresses were assessed.</p> Results <p>Anterior loading resulted in the highest stresses across all groups, with peak values reaching 12 N/mm² in the convex and irregular models. Bilateral molar loading consistently produced the lowest and most uniform stress distributions, while unilateral loading caused intermediate stress concentrations on the working side. Uneven platforms significantly increased stress levels, particularly under unilateral bar loading. Locator attachments showed slightly reduced stresses after bilateral loading in irregular crest configurations. Stress concentrations were primarily localized at the implant neck and prosthetic connectors.</p> Conclusion <p>Stress distribution in mandibular overdentures is significantly influenced by loading direction, crest shape, and attachment mechanism. Anterior loading poses the highest biomechanical risk, while bilateral posterior loading provides optimal conditions. Vertical discrepancies in implant platforms heighten stress concentrations, underscoring the importance of careful surgical planning. Locator attachments offer limited biomechanical advantages in uneven crest scenarios, supporting their use in anatomically challenging cases.</p> Anaïs Havet Annaëlle Testud Aubane L’Hospital Guy De Gevigney Nicolas Chavanis Marie Viprey Xavier Armoiry 10.1371/journal.pone.0351466 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Anaïs Havet, Annaëlle Testud, Aubane L’Hospital, Guy De Gevigney, Nicolas Chavanis, Marie Viprey, Xavier Armoiry</p> Background <p>The PARTNER trials played a key role in the expansion of transcatheter aortic valve replacement (TAVR) for severe aortic valve stenosis (AS), shaping international practice guidelines. We assessed the evolution of AS management in France between 2010 and 2022, and the impact of PARTNER trials and European guideline updates on TAVR use. Characteristics of patients, facilities and TAVR valves, and post-procedure events were also described.</p> Methods and findings <p>We conducted a nationwide cohort study using the French Health Data System (SNDS), including patients aged 18 years or older hospitalized for AS and receiving a first TAVR or surgical aortic valve replacement (SAVR) from 2010 to 2022. ARIMA models were used to study the impact of PARTNER trials and European guideline updates on TAVR use. Among 255,453 procedures, 109,739 were TAVR (N₂₀₁₀: 1,389; N₂₀₂₂: 16,770). No significant change in the proportion of TAVR was associated with PARTNER trials or European guideline updates (p ≥ 0.125). Median age and EuroSCORE II proxy were 83.0 years and 2.2 in TAVR group and 72.0 years and 1.4 in SAVR group. Approximately 60% of the TAVR and SAVR procedures were performed in public facilities. Latest valve generations replaced progressively earlier ones, with 62.5% being balloon-expandable. Mortality decreased over time in both groups, while length of stay and intensive care unit admissions decreased only in TAVR group.</p> Conclusions <p>This 13-year nationwide overview highlights the growing uptake of TAVR in France, likely driven by clinical practice and procedural innovation rather than guidelines. Further analyses will compare efficacy and safety between TAVR and SAVR.</p> Wesley Fletcher Samiran Sinha 10.1371/journal.pone.0351429 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Wesley Fletcher, Samiran Sinha</p> The practices of identifying biomarkers and developing prognostic models using genomic data has become increasingly prevalent. Such data often features characteristics that make these practices difficult, namely high dimensionality, correlations between predictors, and sparsity. Many modern methods have been developed to address these problematic characteristics while performing feature selection and prognostic modeling, but a large-scale comparison of their performances in these tasks on diverse right-censored time to event data (aka survival time data) is much needed. We have compiled many existing methods, including some machine learning methods, several which have performed well in previous benchmarks, primarily for comparison in regards to variable selection capability, and secondarily for survival time prediction on many synthetic datasets with varying levels of sparsity, correlation between predictors, and signal strength of informative predictors. For illustration, we have also performed multiple analyses on a publicly available and widely used cancer cohort from The Cancer Genome Atlas using these methods. We evaluated the methods through extensive simulation studies in terms of the false discovery rate, F1-score, concordance index, Brier score, root mean square error, and computation time. Of the methods compared, CoxBoost and the Adaptive LASSO performed well in all metrics, and the LASSO and elastic net excelled when evaluating concordance index and F1-score. The Benjamini-Hoschberg and q-value procedures showed volatile performances in controlling the false discovery rate. Some methods’ performances were greatly affected by differences in the data characteristics. With our extensive numerical study, we have identified the best performing methods for a plethora of data characteristics using informative metrics. This will help cancer researchers in choosing the best approach for their needs when working with genomic data. Weisi Zhang Jiahao Kong Wei Zhao Juanjuan Liu 10.1371/journal.pone.0351412 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Weisi Zhang, Jiahao Kong, Wei Zhao, Juanjuan Liu</p> Rising concerns about climate change and growing consumer awareness of environmental sustainability have accelerated the adoption of cap-and-trade policies worldwide. This study investigates how different supply chain operation models influence manufacturers’ carbon reduction decisions and retailers’ green advertising strategies. Our analysis reveals that higher carbon trading prices generally stimulate greater emission reduction efforts. However, when both the carbon price and the cost of emission reduction are sufficiently high, further increases in carbon prices may instead weaken firms’ incentives to reduce emissions. We further find that increasing cost-sharing ratios alone does not necessarily improve coordination outcomes. Instead, the effectiveness of coordination depends critically on the structure of cost-sharing. The effectiveness of supply chain coordination hinges on strategic allocation of cost-sharing ratios, specifically, the <i>RC</i> model performs better when carbon reduction cost-sharing is low and advertising cost-sharing is high. When carbon reduction cost-sharing is high, the <i>MC</i> model is preferred under low advertising cost-sharing, whereas the <i>DC</i> model becomes more effective when advertising cost-sharing is high. Minsoo Yeo Mi-Jeong Lee Wanhyung Lee 10.1371/journal.pone.0351399 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Minsoo Yeo, Mi-Jeong Lee, Wanhyung Lee</p> Background <p>Cancer survivors frequently experience depression and metabolic dysfunction; however, the combined impact of these conditions remains understudied.</p> Aim <p>This study aimed to examine the joint associations between cancer, metabolic syndrome, and depression.</p> Methods <p>Data from the 2007–2021 Korea National Health and Nutrition Examination Survey encompassed 57,176 participants aged ≥ 19 years. Cancer diagnosis and components of metabolic syndrome (waist circumference, triglycerides, high-density lipoprotein cholesterol, blood pressure, and fasting glucose) were obtained through self-report or clinical measurement. Depression was assessed using a single-item question regarding persistent sadness or hopelessness. Multivariable logistic regression models evaluated the associations among cancer, metabolic syndrome, and depression, adjusting for sociodemographic and lifestyle factors.</p> Results <p>Among participants, 1,691 (3.0%) had cancer, 17,510 (30.7%) met criteria for metabolic syndrome, and 7,472 (13.1%) reported depression. Cancer was independently associated with increased risk of depression (odds ratio: 1.26; 95% confidence interval: 1.10–1.45). While metabolic syndrome alone was not significantly associated with depression, patients with cancer who had elevated triglycerides (≥ 150 mg/dL) or decreased high-density lipoprotein cholesterol exhibited substantially higher risk of depression (odds ratio: 1.51; 95% confidence interval: 1.17–1.95 and odds ratio: 1.32; 95% confidence interval: 1.07–1.62, respectively). The association between elevated triglycerides in cancer survivors and depression remained robust after FDR correction.</p> Conclusions <p>Specific lipid abnormalities, rather than metabolic syndrome as a whole, were significantly associated with a higher prevalence of depression among cancer survivors. These findings underscore the need for integrated screening and management that address both metabolic dysfunction and mental health in cancer survivorship care.</p> Marek Blatný Veronika Koutná Martin Jelínek Petr Květon Alexander T. Vazsonyi 10.1371/journal.pone.0351394 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Marek Blatný, Veronika Koutná, Martin Jelínek, Petr Květon, Alexander T. Vazsonyi</p> The present study sought to validate existing knowledge on inter-rater agreement on personality traits and social competencies. Based on longitudinal data, the study aimed to determine whether the agreement between student and teacher reports changes over time. The research sample consisted of a total of 296 early adolescents (181 females, 115 males, average age in the first wave of the two-year study period was 12.37 years). The personality traits and social competencies of students were rated by class teachers (N = 28, 75% females). Personality traits were measured by the Big Five Inventory and social competencies by the Social Skills Improvement System. The main findings of the study are as follows: 1) the highest agreement between student and teacher ratings of personality traits and social competencies was found for characteristics that were high in observability; 2) there was greater agreement between student and teacher ratings of social competencies for girls; 3) high temporal stability was found for personality traits and social competencies for both students and teachers; there were no substantial changes in the agreement of student and teacher ratings over time. Attention to hidden or difficult-to-assess student characteristics may prevent developmental, school, and social/interpersonal problems in adolescents. Qing Wang Fengjun Nie Fei Xia Xin Zhang Weiwei Jia Kegai Lu Xiao Sun Dong-guang Yang 10.1371/journal.pone.0351337 2026-06-16T14:00:00Z 2026-06-16T14:00:00Z <p>by Qing Wang, Fengjun Nie, Fei Xia, Xin Zhang, Weiwei Jia, Kegai Lu, Xiao Sun, Dong-guang Yang</p> In recent years, economically significant sandstone-hosted uranium mineralization has been identified in the Louzhuangzi area along the southern margin of the Junggar Basin. However, the controls on uranium enrichment and their links to depositional architecture and post-depositional fluid processes remain insufficiently constrained. This study integrates field geological investigations, drill-core lithofacies logging, and systematic sampling with petrographic and micro-analytical techniques, including optical microscopy, scanning electron microscopy (SEM), electron probe microanalysis (EPMA), and transmission electron microscopy (TEM). The objective is to elucidate the depositional characteristics, alteration processes, and uranium occurrence mechanisms of the ore-bearing sandstones within the Toutunhe Formation (J₂<i>t</i>). Results show that the upper member (J₂<i>t</i>²) represents meandering-river deposits, whereas economically significant uranium mineralization is hosted in the lower member (J₂<i>t</i>¹), characterized by braided-river sandstone units with high permeability. The sandstones of the Toutunhe Formation (J₂<i>t</i>) exhibit intense oxidation by surficial fluids, overprinted by post-mineralization hydrothermal alteration and sulfide-forming alteration associated with reducing fluids. Uranium is closely associated with pyrite, organic matter, and clay minerals. Uranium minerals are dominated by coffinite and pitchblende (~68%), with UO₂ contents of 52.89–86.07%. Minor Ti-bearing uranium phases (~16%), interpreted as possible brannerite, contain 38.01–41.46% UO₂ and 31.67–36.09% TiO₂, while nanoscale uranium minerals (~16%) show UO₂ contents of 9.15–60.28%. These results indicate that uranium mineralization was controlled by the coupling of braided-channel architecture and multi-stage fluid processes. Uranium was initially precipitated from oxidized fluids and subsequently modified and preserved by later thermal and reducing fluids, highlighting the importance of multi-fluid interactions in sandstone-hosted uranium systems.