Research Appraisals
Evidence-based critical appraisals of the latest medical research, systematically evaluated using Oxford CEBM methodology.
Showing 28 appraisals
JMIR formative research
Development of a User-Informed Decision Aid for Contraceptive Decision-Making Among Adolescents and Young Adults: Qualitative Study
BACKGROUND: Adolescents and young adults seeking contraceptive care face many considerations related to differences in contraceptive indications and knowledge, which are often overlooked and can lead to contraceptive nonadherence or nonuse as well as adverse health outcomes. OBJECTIVE: This study aimed to develop a digital decision aid that meets the contraceptive decisional needs of adolescents and young adults from diverse backgrounds. METHODS: We developed a web-based decision aid using a user-centered design framework and the International Patient Decision Aid Standards. The design and development process was informed by a literature review and consultations with scientific experts, health informatics specialists, clinicians experienced in adolescent reproductive health, and a diverse group of adolescent and young adult advisors. We gathered feedback on the decision aid's content and functionality from clinicians, adolescents, and young adult stakeholders during focus group interviews conducted across 2 user testing cycles. Each focus group was recorded and transcribed, and the data were analyzed using a focus group guide to identify key attributes, patterns, and perspectives among users. Two qualitative researchers used rapid qualitative analysis to explore and summarize findings across 4 key domains, which contributed to the refinement of the decision aid content and the improvement of its functionality. RESULTS: Twenty-four clinicians, adolescents, and young adult participants from diverse backgrounds shared their perspectives on the decision aid's content, relevance, design, and usability across 2 user testing cycles conducted from February 2023 to June 2024. The decision aid includes a survey, a decision algorithm that generates a summary of contraceptive method recommendations, infographics, and a health care provider summary view. The decision algorithm applies a weighted scoring system ranging from +1 or -1 to +10 or -10 for each method, reflecting the user's primary indication for seeking contraception, contraceptive use preferences, and relevant health history. CONCLUSIONS: This approach allowed us to capture rich perspectives from a diverse group of stakeholders that accounted for the unique contraceptive decision-making needs of adolescents and young adults, resulting in a functional, youth-informed decision aid prototype, MyPlanMyChoice, ready for pilot and feasibility evaluation in a clinical setting.
22 July 2026
Read appraisal →JMIR formative research
Effects of Virtual Reality on Postoperative Pain Management Following Minimally Invasive Gynecologic Surgery: Randomized Controlled Trial
BACKGROUND: Postoperative pain and anxiety remain common concerns after minimally invasive gynecologic surgery despite advances in surgical techniques and analgesic strategies. Virtual reality (VR) has been investigated as a potential nonpharmacological intervention for pain management; however, evidence in gynecologic postoperative settings is limited. OBJECTIVE: This study aims to evaluate the efficacy and safety of VR technology compared with standard postoperative analgesia for pain and anxiety management in patients undergoing minimally invasive gynecologic surgery. METHODS: This randomized controlled trial was conducted at Sun Yat-sen Memorial Hospital of Sun Yat-sen University in China. A total of 131 patients undergoing laparoscopy or combined hysteroscopy for benign gynecologic diseases were randomly assigned in a 1:1 ratio to either a VR group (n=68) or a control group (n=63). All patients received a standardized general anesthesia protocol intraoperatively. The control group received conventional analgesic therapy after surgery, and the VR group received a 20-minute VR intervention 6 hours postoperatively. The pain and anxiety levels were evaluated using a visual analog scale at 6 and 7 hours postoperatively. The primary outcome was the change in pain scores between 6 and 7 hours. Secondary outcomes included maximum pain score, anxiety score changes, length of hospital stay, hospitalization costs, and occurrence of adverse events. Analyses were performed according to the intention-to-treat principle. RESULTS: There was no statistically significant difference in the primary outcome between the VR and control groups (mean difference 0.169, 95% CI -0.271 to 0.608; P=.45). Similarly, no significant differences were observed in the maximum pain score (mean difference 0.839, 95% CI -0.101 to 1.779; P=.08), and no improvement was observed in the anxiety score (mean difference 0.042, 95% CI -0.365 to 0.449; P=.84). No significant differences were found in length of hospital stay, hospitalization costs, or incidence of adverse events, including dizziness, nausea, and vomiting (all P>.05). CONCLUSIONS: A single 20-minute VR intervention did not provide additional analgesic or anxiolytic benefit compared with standard postoperative care after minimally invasive gynecologic surgery. VR was well tolerated, and its role in postoperative recovery requires further investigation. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2400091244; https://tinyurl.com/4b92a9td.
5 July 2026
Read appraisal →Advanced drug delivery reviews
Artificial intelligence and machine learning in smart vaginal formulation development
Vaginal drug delivery in women's health remains underutilized and insufficiently studied, largely due to the complexity and dynamic nature of the vaginal microenvironment. Variations in vaginal pH, hormonal levels, and microbiota composition introduce significant biological variability, complicating formulation design and contributing to inconsistent therapeutic outcomes and poor patient adherence. Conventional vaginal formulations often fail to account for these individual differences, highlighting the need for more adaptive and predictive approaches. Emerging advances in artificial intelligence (AI) and machine learning (ML) offer promising strategies to address these challenges by enabling multi-parameter, data-driven formulation development that explicitly considers biological variability. Despite their transformative potential, the application of AI and ML in vaginal drug delivery remains limited. This review addresses this gap by examining the emerging role of AI/ML in the design, optimization, and development of next-generation vaginal formulations, including mucoadhesive, mucus-penetrating, bio-responsive, and controlled-release systems. Key factors influencing formulation performance, such as vaginal microbiota composition, are discussed, and ethical, regulatory, and technical challenges relevant to integrating AI/ML into vaginal drug delivery are also considered. Although research is in its early stages, existing studies indicate that AI and ML integration can enhance predictability, efficiency, and reproducibility in vaginal formulation development. Finally, we highlight the potential of developing personalized medicines through the integration of AI/ML and digital health monitoring devices to create patient-centered vaginal drug delivery systems, thereby advancing therapeutic outcomes and transforming women's health.
1 July 2026
Read appraisal →PloS one
Determinants of dropout from lifestyle interventions for overweight polycystic ovary syndrome: An exploratory analysis of randomized controlled trial.
OBJECTIVE: This exploratory analysis of a randomized controlled trial aimed to identify baseline predictors of dropout in overweight women with polycystic ovary syndrome (PCOS) participating in a lifestyle intervention program. METHODS: An exploratory analysis was conducted using data from a randomized controlled trial involving overweight or insulin-resistant women with PCOS aged 18-45. All participants received cyclic progestin, metformin, and a structured lifestyle intervention. Dropout was defined as proactive withdrawal, missing two consecutive visits, or loss of contact for more than six months. Univariate and adjusted multivariable logistic regression models were used to identify factors associated with dropout. RESULTS: Among the participants, 61.06% (n = 69) dropped out within one year. No significant differences were observed in baseline demographic, clinical, biochemical, psychological, or dietary characteristics between completers and dropouts. However, baseline physical activity level (PAL), objectively measured using an accelerometer, was identified as the strongest predictor of dropout. Each 0.3-unit increase in PAL was associated with a 29.6% reduction in the likelihood of dropout. CONCLUSION: Baseline PAL is strongly associated with the risk of dropout. Screening for PAL in women with PCOS is recommended, and those with lower PAL should receive personalized support in addition to lifestyle interventions to improve adherence and promote weight loss.
28 June 2026
Read appraisal →Journal of robotic surgery
Emerging robotic platforms in gynecologic surgery: a systematic review.
Robotic innovation in gynecologic surgery has expanded beyond established multiport ecosystems toward single-port, modular multi-arm, transvaginal, AI-enabled, and teleoperated platforms. However, available evidence remains fragmented and unsuitable for quantitative synthesis. This systematic review evaluated emerging robotic platforms in gynecologic surgery, focusing on procedure types, outcomes, costs, and learning curves. The review was prospectively registered in PROSPERO (CRD420261360389). Eligible studies included clinical studies evaluating emerging robotic platforms in gynecologic surgery. PubMed, Scopus, and Web of Science were searched on 4 April 2026. After duplicate removal, 408 records were screened, 160 full texts assessed, and 92 studies included. Data extraction and risk of bias assessment were performed independently in duplicate. The 92 studies covered 13 platforms and were mainly retrospective single-center studies. Evidence was most extensive for da Vinci SP and HUGO RAS, with more limited but informative data for Senhance, Versius, hinotori, and KANGDUO. Evidence for other systems consisted mainly of first-in-human, pilot, or feasibility studies. Hysterectomy and sacrocolpopexy were the most frequently reported procedures. Overall, perioperative outcomes and short-term safety appeared favorable, despite limited follow-up and heterogeneous outcome definitions. Cost data were mainly available for Senhance and KANGDUO. Learning-curve evidence was strongest for da Vinci SP and HUGO RAS. Risk-of-bias was predominantly moderate. Emerging robotic platforms have demonstrated broad technical feasibility and generally acceptable short-term perioperative safety in selected gynecologic procedures, but current evidence is heterogeneous, observational, and methodologically limited. Rigorous prospective studies, standardized economic analyses, longer follow-up, and learning-curve evaluations are needed before comparative conclusions can be drawn.
23 June 2026
Read appraisal →Journal of robotic surgery
Robot-assisted peritoneal flap vaginoplasty in gender-affirming genital reconstruction: a systematic review and single-arm meta-analysis
Robot-assisted peritoneal flap vaginoplasty has emerged as an evolving reconstructive option in gender-affirming genital surgery. This systematic review and single-arm meta-analysis aimed to synthesize the available evidence regarding its perioperative, functional canal, and postoperative safety outcomes. This study was conducted according to PRISMA guidelines and prospectively registered in PROSPERO. PubMed, Cochrane Library, Embase, and Web of Science were searched from database inception to May 2026. Eligible studies included transfeminine or gender-diverse individuals undergoing robot-assisted peritoneal flap-based vaginoplasty with extractable clinical outcomes. Continuous outcomes were synthesized as weighted mean estimates with 95% confidence intervals (CIs), and overall postoperative complications were pooled using Stata version 18.0. Heterogeneity was assessed using the I² statistic, and leave-one-out sensitivity analyses were performed. Ten studies involving 974 patients were included. The pooled mean operative time was 305.37 min (95% CI 244.62, 366.12), and the pooled length of hospital stay was 5.80 days (95% CI 4.72, 6.87). At the last available follow-up, pooled neovaginal depth was 13.41 cm (95% CI 12.86, 13.96), and pooled neovaginal width was 3.61 cm (95% CI 3.55, 3.67). The pooled overall postoperative complication rate was approximately 30.1%. Sensitivity analyses suggested that the pooled estimates were not driven by any single study. Robot-assisted peritoneal flap vaginoplasty appears feasible and may achieve neovaginal dimensions broadly comparable to those reported for other full-depth vaginoplasty approaches. However, predominantly retrospective single-arm evidence precludes conclusions regarding superiority and highlights the need for standardized prospective studies with longer follow-up and patient-reported outcomes.
20 June 2026
Read appraisal →Sexual health
A systematic review of barriers to cervical cancer screening among Thai women based on the social ecological model: a multi-level analysis of local evidence
BACKGROUND: Cervical cancer is a significant public health issue in Thailand. Despite the implementation of a national screening program, its coverage remains suboptimal. This study aims to systematically review local Thai evidence and comprehensively analyze the multi-level barriers affecting women's participation in cervical cancer screening using the social ecological model (SEM). METHODS: Systematic searches were conducted in PubMed, Scopus, CINAHL and ThaiJO databases from inception to 2025. Literature was screened according to pre-defined inclusion and exclusion criteria, resulting in the inclusion of 11 studies. The Newcastle-Ottawa scale and a mixed-methods assessment tool were used for rigorous quality appraisal. Thematic synthesis was used to categorize screening barriers into five levels: individual, interpersonal, community, health system and public policy. RESULTS: The key obstacles identified include: at the individual level, lack of knowledge, fear, shame and insufficient risk perception; at the interpersonal level, the influence of family and social norms; at the community level, cultural, religious and regional factors; at the health system level, poor service accessibility and system inefficiencies; and at the public policy level, incomplete health insurance coverage and insufficient awareness campaigns. Many of these obstacles show distinct characteristics of Thai society and culture. CONCLUSION: Barriers to cervical cancer screening among Thai women constitute a complex, multi-level system. Future intervention strategies must move beyond single-level health education, and should develop cross-level, culturally-appropriate, comprehensive measures. These include promoting HPV self-sampling, conducting community empowerment education, optimizing the health service system and strengthening policy support to systematically increase screening participation.
16 June 2026
Read appraisal →Medicine
Effects of oxycodone and sufentanil on the quality of recovery after laparoscopic total hysterectomy: A randomized controlled trial
BACKGROUND: To compare the effects of oxycodone and sufentanil on the quality of recovery after laparoscopic total hysterectomy. METHODS: Ninety patients scheduled for laparoscopic total hysterectomy between January and December 2023 were randomly divided into 2 groups: oxycodone group (Group O) and sufentanil group (Group S), with 45 patients in each group. The primary outcome measure was postoperative recovery status recorded using the Quality of Recovery-40 questionnaire. RESULTS: At 24 hours postoperatively, the Quality of Recovery-40 scores of group O and group S were comparable (170 [156-179], 160 [146-178], P = .111). There were no statistically significant differences between the 2 groups in terms of visual analogue scale pain scores at any postoperative time points, postoperative cumulative sufentanil consumption, length of hospital stay, patient satisfaction, and incidence of postoperative nausea and vomiting, and incidence of postoperative dizziness (P > .05). CONCLUSIONS: Oxycodone and sufentanil provide comparable postoperative recovery after total laparoscopic hysterectomy.
1 June 2026
Read appraisal →JMIR formative research
Real-World Implementation of EndoConnect in Brazilian Primary Care: Formative Study of Usability, Engagement, and Equity in Digital Endometriosis Care
BACKGROUND: Endometriosis is a chronic gynecological condition affecting approximately 10% of women of reproductive age worldwide and is associated with chronic pelvic pain, infertility, and reduced quality of life. In Brazil's Unified Health System (Sistema Único de Saúde [SUS]), diagnostic delays frequently range from 7 to 10 years and disproportionately affect socially vulnerable populations, including rural, low-income, Black, and Indigenous women. Digital health interventions have been proposed as scalable solutions; however, most available applications are developed in high-income settings and do not align with the structural and operational realities of low- and middle-income countries (LMICs). OBJECTIVE: This study aimed to evaluate feasibility, usability, acceptability, and user engagement associated with the real-world implementation of EndoConnect Alpha in primary health care settings, and to explore preliminary patterns of change in symptom burden, knowledge, and care navigation. METHODS: A single-arm, prospective, formative implementation study was conducted in 10 primary health care units in Ceará, Brazil. A convenience sample of 60 participants, including women with suspected or confirmed endometriosis and primary care professionals, used the platform over an 8-week period under real-world conditions. Usability (assessed using the System Usability Scale), acceptability (assessed using the Technology Acceptance Model), engagement metrics, and exploratory outcomes were assessed. All analyses were exploratory, with no control group and no causal inference. RESULTS: High usability and acceptability were observed, with strong user engagement, including a 79% completion rate of educational modules and consistent platform use. Observed decreases in pelvic pain and anxiety were identified, alongside increases in disease-related knowledge, self-reported therapy adherence, and reported gynecological referrals. A positive association between usability and acceptability was also observed. These findings should be interpreted as exploratory signals given the study design. Descriptive subgroup analyses suggested more pronounced trends among rural participants and those with a lower education level. CONCLUSIONS: The real-world implementation of EndoConnect Alpha demonstrated high feasibility, usability, and acceptability within a public primary care setting in a middle-income country. Observed trends suggest potential benefits, particularly among underserved populations; however, causal inference cannot be established. These findings support further controlled evaluation and highlight the relevance of equity-oriented digital health strategies tailored to LMIC contexts.
30 May 2026
Read appraisal →Clinical and experimental dermatology
A systematic review of the barriers to diagnosis of vulval lichen sclerosus in primary care
BACKGROUND: Vulval lichen sclerosus (VLS) is a chronic, inflammatory genital skin condition causing itch, pain, anatomical changes and increased risk of vulval cancer. Diagnostic delay and misdiagnosis are common. Once diagnosed, VLS can be effectively treated using very strong topical corticosteroids. Most women with symptoms of VLS first present to primary care in the UK. OBJECTIVES: To identify patient and professional perspectives on barriers to diagnosis of VLS in primary care through systematic review and thematic synthesis of the literature. METHODS: Separate literature searches of seven databases relevant to patient and professional perspectives were conducted. Two reviewers screened titles and abstracts, with one performing a full text review. Data extracted were coded 'line by line', codes were organized into descriptive themes and subsequently developed into analytical themes. RESULTS: We identified 2468 references; a total of 56 studies met inclusion criteria. Six analytical themes were developed: (i) a medically challenging diagnosis; (ii) cultural and social taboos; (iii) education and knowledge gaps; (iv) feelings and attitudes; (v) inadequate health systems; and (vi) challenges in female genital examination. CONCLUSIONS: This review highlights obstacles for women in achieving a diagnosis of VLS. Education and knowledge gaps were reported by clinicians and patients. Clinicians lack knowledge of vulval skin disease and patients lack knowledge of vulval anatomy. Targeted, comprehensive education for clinicians could expedite diagnosis. Dismissive clinician attitudes compound patient feelings of anxiety and embarrassment, reinforcing taboos and stigma. Acknowledgement of embarrassment and stigma validates feelings, improving patient interactions. Future research priorities should include the development of a diagnostic tool and implementation of a complex intervention to expedite diagnosis.
27 May 2026
Read appraisal →International journal of yoga therapy
Systematic Review on the Effect of Yoga Nidra on Menstrual Disorders Among Adult Women
Menstrual disorders including amenorrhea, premenstrual syndrome, and dysmenorrhea significantly disrupt the normal menstrual cycle and negatively impact quality of life. Yoga nidra, a guided meditation technique, has been explored for its potential therapeutic benefits in menstrual health, although comprehensive evidence remains limited. The present systematic review aimed to assess the effect of yoga nidra on menstrual disorders by analyzing existing research and synthesizing findings. The review followed PRISMA guidelines and involved searches in PubMed/MEDLINE, Cochrane Library, Science Direct, and Google Scholar using keywords related to yoga nidra and menstrual disorders. Studies were selected based on predefined inclusion criteria. A total of seven randomized controlled trials were included. The findings indicated improvements across four key areas of women's health: (1) psychological well-being, (2) hormonal balance, (3) hematological profile, and (4) physiological parameters. These results suggest that yoga nidra may be an effective complementary therapy for managing menstrual disorders because of its noninvasive and low-cost nature. However, further high-quality randomized controlled trials are necessary to confirm its efficacy.
24 May 2026
Read appraisal →Reproduction & fertility
Patient characteristics and lifestyle determinants of quality of life among women with endometriosis: a systematic review
ABSTRACT: Endometriosis is a chronic inflammatory disease presenting with debilitating symptoms strongly impacting patients' quality of life (QoL). Assessing QoL is crucial for understanding the full patient experience beyond clinical symptoms. This narrative systematic review specifically aimed to identify and describe non-pharmacological and non-surgical factors associated with QoL in women with endometriosis as reported in the literature. Following PRISMA guidelines, we systematically searched PubMed, MEDLINE, Web of Science, and Embase up to January 15, 2025, for case-control, cohort, randomized controlled trials, and cross-sectional studies. This study was registered in PROSPERO (registration number: CRD42023438457) Eligible studies assessed socio-demographic characteristics, lifestyle factors, symptoms, comorbidities, or coping strategies in relation to QoL among women with endometriosis. Twenty-one studies with a low risk of bias were included. A better QoL was related to favorable socioeconomic profiles (n = 3), high care satisfaction (n = 2), partner involvement (n = 1), healthier lifestyle habits (n = 1), and the use of coping therapeutic strategies. Poor QoL was associated with poor health (n = 5), more severe symptoms (n = 5), unhealthy lifestyle habits (n = 2), and ineffective use of coping strategies (n = 2). This review highlights a broad range of non-medical determinants of QoL, underscoring that clinical measures alone fail to capture the full patient experience. By consolidating evidence across diverse study designs, it offers a comprehensive overview of modifiable factors that could inform holistic, patient-centered approaches to endometriosis care. Further prospective and interventional studies are needed to clarify causal pathways and evaluate the effectiveness of targeted strategies to improve QoL. LAY SUMMARY: Endometriosis is a chronic disease affecting around 10% of women of reproductive age, associated with pain, infertility, and significant impacts on daily life. Because clinical measures alone fail to capture the full patient experience, assessing QoL is essential to understand the real burden of the disease. This review examined non-pharmacological and non-surgical factors that may be associated with QoL, such as lifestyle habits, socioeconomic conditions, health status, and coping strategies. Across 21 studies, we found that a better QoL was linked to good healthcare access, healthy habits, and effective coping mechanisms. Conversely, severe symptoms, poor health, and unhealthy lifestyles (smoking and alcohol use) were associated with worse QoL. The findings highlight the need for a more holistic approach to endometriosis care, combining psychological support, lifestyle guidance, and improved access to quality healthcare. Future research should use standardized QoL tools and robust study designs to develop evidence-based strategies that can meaningfully enhance patient well-being.
23 May 2026
Read appraisal →JMIR infodemiology
Japanese-Language AI Agent System for Human Papillomavirus Vaccine Infoveillance and Public Communication: Development and Feasibility Evaluation
BACKGROUND: Human papillomavirus (HPV) vaccine hesitancy remains a significant public health challenge in Japan, where proactive vaccination recommendations were suspended between 2013 and 2021. The resulting information gap between medical institutions and vaccine-hesitant populations is exacerbated by misinformation on social media platforms. Traditional public health communication strategies cannot address individual queries while simultaneously monitoring population-level discourse. OBJECTIVE: This study aimed to develop and conduct a feasibility evaluation of a dual-purpose artificial intelligence agent system that delivers verified HPV vaccine information to the public through a conversational interface while generating infoveillance reports for medical institutions based on user interactions and social media discourse. METHODS: We implemented a system with 3 components: a vector database integrating 139,803 documents, including academic papers, Japanese government sources, news media, and social media posts; a retrieval-augmented generation chatbot using a ReAct agent architecture with iterative multitool orchestration across 5 specialized knowledge sources; and an automated report generation system with modules for news analysis, research synthesis, social media sentiment analysis, including stance classification and topic modeling, and user interaction pattern identification. System performance was assessed using both automated and manual evaluation protocols on a scale from 0 to 5. RESULTS: The entire system functioned as expected. For single-turn evaluation, the chatbot achieved mean scores of 4.83 (SD 0.67; 95% CI 4.71-4.93) for relevance, 4.89 (SD 0.53; 95% CI 4.79-4.97) for routing, 4.50 (SD 1.29; 95% CI 4.27-4.70) for reference quality, 4.90 (SD 0.62; 95% CI 4.78-4.99) for correctness, and 4.88 (SD 0.54; 95% CI 4.78-4.96) for professional identity, with an overall mean of 4.80. Multiturn evaluation yielded higher mean scores: 4.94 for context memory (SD 0.25; 95% CI 4.84-5.00) and an overall mean of 4.98, with topic centering and identity achieving 5.00. The report generation system achieved high scores across all sections: 4.83 for completeness (SD 0.37; 95% CI 4.73-4.94), 4.88 for correctness (SD 0.33; 95% CI 4.77-4.96), and 4.12 for helpfulness (SD 0.48; 95% CI 3.98-4.27). Reference validity achieved perfect scores (5.00) across all periods, with citation correctness averaging 4.21 (SD 0.58; 95% CI 3.96-4.46). CONCLUSIONS: This feasibility study demonstrated that an integrated artificial intelligence agent system can support both public HPV vaccine communication and social media infoveillance in a Japanese-language context. Prospective deployment with real users is needed to assess actual public health impact.
22 May 2026
Read appraisal →PloS one
Distinct endometrial protein profiles in spontaneous and stimulated cycles in women with poor ovarian response: A prospective case-crossover clinical trial
The window of implantation is a critical period for embryo implantation. Ovarian stimulation can disrupt endometrial receptivity, potentially through altered gene expression and downstream protein profiles. However, the impact on the endometrial proteome remains underexplored. Identifying biomarkers of endometrial receptivity may provide an opportunity to develop targeted interventions aimed at improving implantation outcomes. This prospective, case-crossover, open-label study was conducted at the Department of Human Reproduction, Division of Obstetrics and Gynecology, University Medical Centre Ljubljana, Slovenia, from September 2023 to June 2024. The study included 15 women aged <43 years with primary infertility and poor ovarian response. Endometrial samples were collected using a pipelle biopsy during the window of implantation in spontaneous and stimulated cycles and analyzed using protein microarrays targeting 1,466 proteins. Differential protein abundance was assessed using a multi-factorial linear model, including patient-specific effects as an additional factor to account for the paired case-crossover design. Effect sizes are reported as log2-fold changes with corresponding 95% confidence intervals. Differential abundance was defined a priori as |log2FC| > 0.5 with FDR-adjusted p-value < 0.05. Comparison of endometrial samples from spontaneous and stimulated cycles revealed 114 antibodies with differential abundance. Key proteins were associated with immune response (IL-8, proteins S100-A8 and S100-A9, CAMP) and extracellular matrix remodeling (MMP-9). Exploratory KEGG pathway mapping suggested involvement of immune and inflammatory pathways, including cytokine-cytokine receptor interaction and IL-17 signaling. Cluster analysis demonstrated distinct proteomic patterns, with all stimulated-cycle samples showing alterations and a subset of stimulated-cycle samples (40%) exhibiting more pronounced changes. The findings indicate that ovarian stimulation is associated with measurable alterations in the endometrial proteomic profile during the window of implantation. These changes may be relevant to biological pathways involved in endometrial receptivity and implantation. Further studies in larger cohorts are needed to validate the identified candidate markers and determine their clinical relevance for implantation outcomes. Trial registration: ClinicalTrials.gov NCT06804174.
22 May 2026
Read appraisal →Apoptosis : an international journal on programmed cell death
Single-cell profiling and machine learning identify cuproptosis-related fibroblast subpopulations and fibrogenesis modulator AEBP1 in endometriosis
Endometriosis is characterized by progressive fibrosis and limited therapeutic options. Cuproptosis, a copper-dependent form of regulated cell death, has been implicated in multiple pathological conditions, but its relevance to fibroblast-mediated fibrotic progression in endometriosis remains unclear. Single-cell RNA sequencing data from normal, eutopic, and ectopic endometrial tissues were analyzed to assess cuproptosis-related gene (CRG) activity and fibroblast heterogeneity. Pseudotime analysis, cell-cell communication analysis and high-dimensional weighted gene co-expression network analysis were performed to identify disease-associated fibroblast states and candidate fibrosis-related genes. Machine learning approaches were applied to prioritize candidate hub genes. Functional validation was conducted in endometrial stromal cells, and a mouse model of endometriosis was used to assess the effects of tetrathiomolybdate (TTM), a copper chelator. Elevated CRG activity was enriched in a distinct fibroblast subpopulation with profibrotic transcriptional features. Network and machine learning analyses consistently prioritized AEBP1 as a candidate fibroblast-associated hub gene linked to cuproptosis-related signatures. In vitro, CuCl2 plus elesclomol treatment was associated with increased AEBP1 and fibrosis-related marker expression, accompanied by changes in β-catenin pathway-related proteins, whereas FDX1 or AEBP1 knockdown attenuated these effects. In vivo, TTM treatment reduced lesion burden, fibrotic marker expression and collagen deposition in ectopic lesions. Cuproptosis-related molecular alterations are associated with fibroblast activation and fibrotic progression in endometriosis. Targeting copper metabolism may have therapeutic potential in limiting lesion fibrosis.
19 May 2026
Read appraisal →African journal of reproductive health
Evaluation of the effects of probiotic supplementation on the ecology and inflammatory factors of female vaginal flora: a systematic review and meta-analysis
This meta-analysis systematically evaluated the effects of probiotic supplementation on vaginal microbiota and inflammatory factors in women. PubMed, Embase, Web of Science, CNKI, and Wanfang were searched from inception to January 2026 for randomized and controlled studies. Outcomes included vaginal pH, Nugent score, and inflammatory cytokines (IL-4, IL-6, IL-10, TNF-α). Fifteen studies were included. Compared with controls, probiotics did not significantly reduce IL-4, IL-6, IL-10, or TNFα levels, nor did they significantly improve Nugent score. However, probiotic supplementation significantly reduced vaginal pH (OR = 0.36, 95% CI: 0.15-0.89; P = 0.03), indicating improved maintenance of a weakly acidic vaginal environment. Sensitivity analyses showed generally stable results, although heterogeneity remained substantial for several outcomes. Overall, probiotics appear effective in modulating vaginal acid-base balance but show limited evidence for improving inflammatory cytokine profiles or restoring vaginal microbiota structure. Current data are insufficient to support routine probiotic use for optimizing vaginal microbiota and inflammatory status. Further high-quality, well-designed randomized controlled trials are required to clarify their clinical benefits. Cette méta-analyse a évalué de manière systématique les effets de la supplémentation en probiotiques sur le microbiote vaginal et les facteurs inflammatoires chez les femmes. Les bases de données PubMed, Embase, Web of Science, CNKI et Wanfang ont été consultées depuis leur création jusqu’en janvier 2026 afin d’identifier des études randomisées et contrôlées. Les critères de jugement comprenaient le pH vaginal, le score de Nugent et les cytokines inflammatoires (IL-4, IL-6, IL-10, TNF-α). Quinze études ont été incluses. Comparativement aux groupes témoins, les probiotiques n’ont pas réduit significativement les concentrations d’IL4, IL-6, IL-10 ou TNF-α, ni amélioré significativement le score de Nugent. En revanche, la supplémentation en probiotiques a significativement réduit le pH vaginal (OR = 0,36 ; IC à 95 % : 0,15–0,89 ; P = 0,03), indiquant un meilleur maintien d’un environnement vaginal faiblement acide. Les analyses de sensibilité ont montré des résultats globalement stables, bien qu’une hétérogénéité substantielle persiste pour plusieurs critères. Dans l’ensemble, les probiotiques semblent efficaces pour moduler l’équilibre acido-basique vaginal, mais les preuves restent limitées quant à leur capacité à améliorer les profils cytokiniques inflammatoires ou à restaurer la structure du microbiote vaginal. Les données actuelles sont insuffisantes pour recommander l’utilisation systématique des probiotiques dans l’optimisation du microbiote vaginal et du statut inflammatoire. Des essais contrôlés randomisés de haute qualité sont nécessaires pour confirmer leurs bénéfices cliniques.
16 May 2026
Read appraisal →Proceedings of the National Academy of Sciences of the United States of America
Deep-learning endomicroscope with large field-of-view and depth-of-field for real-time in vivo imaging of epithelial cancer hallmarks
In vivo microscopy (IVM) has shown great promise to improve early detection of epithelial precancer, but it suffers from fundamental trade-offs that limit the resolution, field-of-view (FOV) and depth-of-field (DOF). Here, we present PrecisionView, a compact, deep learning-enabled endomicroscope that breaks these constraints and achieves 20 mm2 FOV and 500 µm DOF with 4 µm resolution, representing approximately 5× increase in FOV and 8× larger DOF compared to conventional IVM with similar resolution. PrecisionView integrates a deep learning-optimized phase mask and real-time reconstruction, enabling rapid in vivo assessment of two key hallmarks of cancer: epithelial cell nuclear morphology and subsurface microvasculature through fluorescence and reflectance imaging. By imaging the oral cavity of healthy volunteers and cervical specimens with precancerous lesions, PrecisionView generates large-scale (1 to 3 cm2) coregistered maps of cellular and vascular structures, revealing distinct microscopic patterns associated with anatomic structures and precancerous lesions. Our results suggest the potential of this computational endomicroscope to address the unmet need for early cancer detection at the point of care.
13 May 2026
Read appraisal →Expert review of vaccines
Population-level impact of HPV vaccination: a global systematic review of ecological, cross-sectional, and cohort studies
BACKGROUND: Human papillomavirus (HPV) causes approximately 4.5% of cancers globally, with the highest burden in low- and middle-income countries (LMICs). Since their introduction in 2006, HPV vaccination programs have led to substantial declines in HPV-related outcomes, although impact varies across settings. RESEARCH DESIGN AND METHODS: We conducted a systematic review to evaluate the population-level impact of HPV vaccination on HPV infection, cervical intraepithelial neoplasia grade 2 or higher (CIN2+), genital warts, invasive cervical cancer (ICC), and oropharyngeal cancer (OPC), and examined the influence of coverage, age at initiation, and vaccine type. The review followed PRISMA 2020. RESULTS: Of 13,549 records screened, 63 were included: 9 assessed HPV infection, 24 on CIN2+, 25 on genital warts, and 7 on ICC. Greatest reductions were observed in settings with at least 70% coverage and early vaccination prior to sexual debut, typically achieved through school-based programs. Reported declines ranged from 58-100% for HPV infection, 30-88% for CIN2+, 60-90% for genital warts, and 70-88% for ICC. CONCLUSIONS: HPV vaccination offers strong protection, especially when delivered early and at high coverage within schools. Expanding access and prioritizing underserved populations are essential to achieving global cancer prevention goals. Limitations include heterogeneity across designs, outcome definitions, and follow-up.
13 May 2026
Read appraisal →Vaccine
Factors affecting human papillomavirus vaccination: A review of individual, interpersonal, and structural factors affecting vaccine uptake among adolescents.
BACKGROUND: Human papillomavirus (HPV) related cancers, particularly cervical cancer, remain a major public health challenge in low- and lower-middle-income countries (LLMICs), which bear a disproportionate share of global HPV-attributable mortality. Despite the availability of safe and effective vaccines for nearly two decades, vaccination coverage remains low in LLMICs. Several barriers ranging from health misinformation to systemic delivery challenges have hindered efforts to scale up vaccination programs in these settings. OBJECTIVES: This systematic review aims to identify and synthesize the behavioral and structural factors influencing HPV vaccine uptake among adolescents in LLMICs. Guided by a multi-level behavioral health framework, findings were categorized across: individual, interpersonal, and structural domains. METHODS: A comprehensive search of seven databases identified 639 records, of which 34 empirical studies met inclusion criteria. Eligible studies focused on HPV vaccination uptake among adolescents in World Bank-defined LLMICs and were assessed for thematic relevance. Data extraction emphasized barriers and facilitators to uptake. RESULTS: Individual-level barriers included limited awareness, misconceptions about HPV and the vaccine, and fear of side effects. Interpersonal dynamics-particularly parental consent, gendered norms, and community endorsement-shaped adolescent vaccine decision-making. Structural barriers included vaccine stock-outs, weak delivery infrastructure, and limited reach among out-of-school youth. School-based delivery models, trusted healthcare workers, and community sensitization emerged as key facilitators. CONCLUSIONS: Improving HPV vaccine coverage in LLMICs requires coordinated, multi-level interventions that simultaneously address behavioral and structural determinants. Findings highlight the critical role of community engagement, flexible delivery models, and long-term sustainability planning to ensure effective implementation. These insights have direct implications for national immunization policy, health system strengthening, and achievement of global cervical cancer elimination targets in resource-limited settings. Tailoring implementation to the contextual realities of LLMICs will be essential to advancing equity in HPV-related cancer prevention.
13 May 2026
Read appraisal →Journal of medical virology
A Triage Model for HR-HPV Positive Women Based on Methylation of Human and HPV Genes
The aim of this study is to develop a machine learning triage model for HR-HPV positive women based on methylation patterns of human and HPV genes to predict the risk of CIN2 +, and to compare its performance with traditional detection techniques. A total of 512 eligible women participated in the study, with exfoliated cervical cell specimens collected for methylation analysis of both human and HPV genes. Highly methylated gene fragments related to cervical cancer were identified through high density, high association, high MHL (Methylation Haplotype Load) screening and Logistic regression. The samples were divided into a training set and a validation set at a ratio of 7:3, and a machine learning triage model was constructed using CIN2+ as the outcome. Among 512 HR-HPV positive women, 174 (34.0%) had CIN2 +. To construct the random forest model, 10 high methylation human gene fragments were identified from a pool of 45 genes, along with HPV 16, 18, and 52 L2 genes. In the validation set, the random forest model identified 45 samples as positive (38 were true positives) and 112 samples as negative (96 were true negatives). The model achieved an AUC of 0.9, and DeLong test confirmed its performance was significantly superior (p < 0.001) to HPV 16/18 genotyping and cytology testing. The random forest model constructed based on methylation patterns of human and HPV genes demonstrated strong predictive efficacy for CIN2+ in HR-HPV positive women, and may optimize the triage method in cervical cancer screening.
5 May 2026
Read appraisal →The Cochrane database of systematic reviews
Cognitive behavioural therapeutics for insomnia symptoms in the perimenopause through to the early postmenopausal period
This is a protocol for a Cochrane Review (intervention). The objectives are as follows: Primary Objective i) To assess the effects of cognitive behavioural therapy for insomnia (CBT-I) and cognitive behavioural therapy for menopausal symptoms (CBT-M) on sleep disturbances in women in perimenopause through to the early postmenopausal period. Secondary Objectives i) To assess the effects of CBT-I and CBT-M on vasomotor symptoms in women in perimenopause through to the early postmenopausal period. ii) To assess the impact of socioeconomic status on the effectiveness of CBT-I and CBT-M, in order to determine the interventions' impact on health equality.
28 Apr 2026
Read appraisal →Journal of ethnopharmacology
Tianjing Zelan formula improves polycystic ovary syndrome by regulating steroid biosynthesis and arachidonic acid metabolism
ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a set of symptoms related to menstrual irregularities that can cause infertility in women of reproductive age. Unfortunately, there are currently no authorized treatment medications for PCOS. The Tianjing Zelan (TJZL) formula, a herbal formulation developed from the ancient Chinese medical classic Beiji Qianjin Yaofang in Tang Dynasty, is employed in the clinical management of menstrual irregularities and amenorrhea. However, its clinical characteristics and mechanism have not been systematically evaluated. AIM OF THE STUDY: To reveal the clinical characteristics and mechanisms of TJZL in treating PCOS. MATERIALS AND METHODS: A multicenter and single-arm clinical trial, and two PCOS models were used to evaluate the effectiveness of TJZL. The chemical constituents of TJZL were analyzed by UHPLC-QTOF-MS/MS. In addition, a combination of untargeted metabolomics and transcriptomics was used to reveal the complex therapeutic mechanisms of TJZL on PCOS. Subsequently, a metabolite-gene network analysis was performed to reveal potential differentially expressed genes associated with metabolites in PCOS patients. Key targets and pathways were further validated using quantitative real-time polymerase chain reaction (qRT-PCR), Western blot and immunohistochemistry in PCOS mice. Finally, molecular docking analysis was employed to explore the potential active ingredients of TJZL. RESULTS: Clinical trials provided evidence that TJZL significantly improved the menstrual cycle, sex hormone levels, and hyperandrogenic phenotypes, and reduced insulin resistance in PCOS patients. TJZL significantly improved the fertility, estrous cycle, ovarian morphology, sex hormone levels, and oral glucose tolerance in PCOS model. Transcriptomic and metabolomics results show that TJZL has a significant regulatory effect on metabolites and gene expression profiles in pathways such as steroid synthesis, arachidonic acid metabolism, and fatty acid metabolism. Utilizing metabolite-gene association analysis, We further verified that TJZL significantly improved the expression of genes and proteins related to the ovarian steroidogenesis and arachidonic acid metabolism pathways, including CYP17A1, CYP19A1, HSD17B3 and PTGS2. Furthermore, molecular docking results showed that berberine, rosmarinic acid and glycyrrhizinic acid in TJZL had strong affinity with PTGS2 in arachidonic acid metabolism, and hesperidin, naringin and liquiritin have strong affinity with CYP19A1 in steroid synthesis. CONCLUSION: TJZL exerts beneficial therapeutic effects on PCOS in both clinical and laboratory studies. TJZL improves PCOS by regulating multiple endogenous metabolites and correcting abnormal steroid synthesis and arachidonic acid metabolism in the ovaries. Our research provides a promising therapeutic agent for PCOS patients.
25 Apr 2026
Read appraisal →The Journal of clinical endocrinology and metabolism
Pharmacological interventions to improve bone density in functional hypothalamic amenorrhea: a systematic review and network meta-analysis of randomized clinical trials
CONTEXT: Women with functional hypothalamic amenorrhea (FHA) are at high risk of poor bone health. When lifestyle measures fail to restore menses, pharmacological interventions are needed for bone health, but comparative efficacy remains unclear. OBJECTIVE: To compare the efficacy of available pharmacological interventions to improve bone mineral density (BMD), in women with FHA, employing network meta-analysis (NMA). DATA SOURCES: Medline, Embase, Emcare, Cochrane CENTRAL, ISRCTN, and ClinicalTrials.gov were searched up to 20 September 2025. STUDY SELECTION: Eligible randomized-controlled trials evaluated pharmacological interventions for lumbar spine (LS), femoral neck (FN), or total hip (TH) BMD in women with FHA. Two independent reviewers screened titles, abstracts, and texts. DATA EXTRACTION: Two reviewers independently extracted data following the Preferred Reporting Items for Systematic Reviews-network meta-analysis guidelines. Outcomes were expressed as standardized mean differences (SMDs) with 95% confidence intervals (CIs) using random-effects NMA. Evidence certainty was assessed with CINeMA. DATA SYNTHESIS & RESULTS: Thirteen randomized-controlled trials (n = 897 participant observations across all pharmacotherapy comparisons) were included (LS BMD: n = 897; FN BMD: n = 370; TH BMD: n = 750). Transdermal hormone replacement therapy (HRT) was superior to control (placebo or no intervention) for LS BMD with SMD: 0.34 (0.03, 0.64) and FN BMD with SMD: 0.57 (0.04, 1.10). Oral HRT and the combined oral contraceptive pill (COCP) showed no significant benefit for any BMD site. Teriparatide was superior to transdermal HRT and COCP for LS BMD with SMDs: 1.48 (0.38, 2.59) and 1.75 (0.66, 2.83), but not FN or TH BMD. CONCLUSIONS: Transdermal HRT and teriparatide improve LS BMD in women with FHA, with transdermal HRT also improving FN BMD. STUDY REGISTRATION: PROSPERO (CRD42024576872).
25 Apr 2026
Read appraisal →Cell host & microbe
VIBRANT: A phase 1 randomized trial of multi-strain vaginal L. crispatus live biotherapeutic products in people with bacterial vaginosis
Bacterial vaginosis (BV) is characterized by high microbial diversity. High recurrence rates following antibiotics may stem from poor recolonization by protective Lactobacillus species. This phase 1 randomized trial in the United States and South Africa evaluated two vaginally delivered live biotherapeutic products (LBPs) containing multiple Lactobacillus crispatus strains. After metronidazole treatment for BV, participants received either a placebo or 3 or 7 days of active LBPs. LBP strains were detected by metagenomics in 66.1% (47/71) of participants in the active arms in the first 5 weeks. Among those, nearly half (49%, 23/47) remained colonized at 12 weeks despite the short initial treatment course. Participants were most often colonized by one of three component strains, with no geographic differences in strain colonization observed. LBPs were safe, acceptable, and well tolerated, with no serious adverse events (AEs) reported. These results provide a foundation for the development of transformational interventions aimed at optimizing the vaginal microbiome.
11 Apr 2026
Read appraisal →Cell host & microbe
Vaginal microbiota impacts of a Lactobacillus crispatus live biotherapeutic and predictors of colonization in randomized controlled trial
Bacterial vaginosis (BV) affects >25% of women worldwide and often recurs after standard-of-care metronidazole (MTZ) treatment. LACTIN-V, a live biotherapeutic product (LBP) containing Lactobacillus crispatus strain CTV-05, significantly reduced recurrent BV in a phase 2b clinical trial, but efficacy was incomplete. Here, we characterize microbiota and immune effects using multi-omics and define correlates of treatment success. By week 12, an L. crispatus-dominant microbiota was achieved in 30% of LBP recipients compared with 9% of placebo recipients (benefit ratio: 3.31; p < 0.005). This is primarily due to CTV-05, but native L. crispatus strains are also present and increase over time. Inflammatory cytokines decrease in both arms after MTZ but return to baseline in placebo recipients. Successful L. crispatus colonization is associated with pre-MTZ microbiota, baseline inflammatory profiles, post-MTZ bacterial load, and clinical and behavioral variables. These findings elucidate LBP microbiota effects and identify predictors of treatment success, informing improved intervention strategies to advance women's health.
11 Apr 2026
Read appraisal →Scientific reports
Effects of different inflatable heater temperature settings on early postoperative recovery after hysteroscopic surgery: a randomized clinical trial
To investigate the effect of perioperative temperature settings of an inflatable warming device on postoperative recovery quality in patients undergoing hysteroscopic myomectomy, this randomized controlled trial enrolled 258 patients receiving laryngeal mask general anesthesia at Xuzhou Central Hospital, China, between March 2022 and August 2024. Patients were allocated to perioperative temperature management with an inflatable warming device set to 38 °C (Group L, n = 129) or 43 °C (Group H, n = 129). A total of 211 patients were included in the final analysis after accounting for exclusions. At 24 h postoperatively, the QoR-40 score was significantly higher in Group H compared to Group L (P < 0.05). At baseline (T0), no significant differences in core body temperature, mean arterial pressure (MAP), or heart rate (HR) were observed between groups (P > 0.05). From T1 to T6, Group H exhibited higher and more stable core body temperature, MAP, and HR compared to Group L (P < 0.05). There were no statistically significant differences in QoR-40 scores at 48 h (P > 0.05) or in the incidence of postoperative restlessness, chills, and infection between the two groups. Compared to 38 °C, the perioperative application of a 43 °C inflatable warming device improved early postoperative recovery quality at 24 h in hysteroscopic myomectomy patients without increasing complication risks.
10 Apr 2026
Read appraisal →Cancer causes & control : CCC
A preference study for applying mHealth to improve the quality of cervical cancer screening management from a supply and demand perspective: a discrete choice experiment.
OBJECTIVES: This study aims to investigate the preferences of women of cervical cancer screening age regarding the use of mobile health (mHealth) technologies in Xinjiang. The purpose is to enhance adherence and acceptance of mHealth applications, thereby improving the quality of cervical cancer screening follow-up for women residing in rural areas of Xinjiang. METHODS: The attributes and levels were established based on a comprehensive literature review and qualitative interviews. The choice set questionnaire was developed using SAS 9.4 through D-efficiency analysis. The research site was identified using a multi-stage sampling method, and the survey was launched in December 2024. An Optimal Logit model was selected for preference analysis, utilizing Stata 17.0. RESULTS: A total of six attributes were identified through the literature review and subsequently combined with qualitative interviews. The mixed logit regression results indicated that, among the six attributes, five were statistically significant (P < 0.05): mHealth approach, frequency of receiving notifications, reminder content, screening notification time, missionary form, and mission strategy. The results demonstrated a preference for WeChat as the mHealth approach (β = 0.230, P < 0.001, 95%CI 1.214-1.500), not accepting receiving notifications everyday (β = - 0.144, P = 0.001, 95%CI 0.797-0.940), preferred reminders containing positive information (β = 0.159,P = 0.001,95%CI1.068-1.288), opted for screening notifications 1 month in advance (β = 0.208, P < 0.001, 95%CI 1.133-1.339), and preferred the image form of education for missionary form (β = 0.118, P < 0.001, 95%CI 1.102-1.322). CONCLUSION: A one-size-fits-all approach should be avoided in the design of mHealth solutions to effectively address the diverse needs of individuals with varying preferences, thereby promoting the adoption of mHealth and improving the feasibility of its application.
5 Apr 2026
Read appraisal →Archives of gynecology and obstetrics
Vaginal natural orifice transluminal endoscopic surgery versus laparoscopy for ovarian cystectomy: a prospective, open-label, randomized, non-inferiority pilot trial
PURPOSE: Vaginal natural orifice transluminal endoscopic surgery (vNOTES) is an innovative minimally invasive procedure. The study aimed to evaluate whether vNOTES achieves non-inferior results compared to conventional laparoscopy in patients undergoing ovarian cystectomy. METHODS: Participants with benign ovarian tumors were randomly assigned (1:1) to undergo laparoscopy or vNOTES. Randomization was stratified based on the size of the ovarian tumor. Patients and surgeons were aware of the allocated procedures. The primary outcome was the proportion of patients successfully treated by the allocated procedure (non-inferiority hypothesis, margin of 15%). The secondary outcomes included operative time, estimated blood loss, time for specimen retrieval, postoperative pain score, use of analgesics, time to first flatus, and perioperative complications. RESULTS: Sixty-four patients were randomly assigned to laparoscopy (n = 32) and vNOTES (n = 32) and were included in the intention-to-treat analysis. The success rates were 100% and 96.9%, respectively. Non-inferiority of vNOTES was demonstrated, as the lower limit of the one-sided 95% confidence interval for the stratified risk difference was -12.7%, which lies above the pre-specified non-inferiority margin of -15%. The vNOTES group exhibited lower pain scores, with a median difference of -1 (95% CI -1 - -1, p < 0.001). CONCLUSION: vNOTES demonstrates non-inferiority to laparoscopy for ovarian cystectomy in selected patients, with notable advantages in cosmetic outcomes and reduced postoperative pain. CLINICAL TRIAL IDENTIFICATION NUMBER: ChiCTR2300070890.
4 Apr 2026
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