Original research publications

Residual invasive disease (RD) after neoadjuvant systemic therapy identifies patients with triple-negative breast cancer (TNBC) at increased but heterogeneous recurrence risk. Continued perioperative pembrolizumab may overlap with postoperative radiotherapy (RT), raising unresolved questions about treatment timing and long-term net clinical benefit. This narrative review examines the pathologic definition and distribution of RD, prognostic stratification, mechanistic evidence, and clinical studies of postoperative RT-pembrolizumab integration. Breast-only, nodal-only, and combined breast and nodal RD should be distinguished alongside residual burden. Residual cancer burden, nodal status, tumor-infiltrating lymphocytes, and circulating tumor DNA may inform prognosis or research stratification, but none is validated to predict benefit from a specific RT-pembrolizumab schedule. Longitudinal molecular monitoring and cell-free DNA fragmentomics remain investigational for postoperative treatment selection. DNA repair, hypoxia, metabolic adaptation, tumor-cell plasticity, and immune suppression provide plausible mechanisms of resistance. However, features measured in surgically removed RD cannot be assumed to persist in occult postoperative disease, and much of the supporting evidence is preclinical or derived from other treatment settings. RT may stimulate antitumor immunity while also injuring immune cells. Small nonrandomized postoperative studies support short-term feasibility of concurrent treatment, but do not establish comparative efficacy or long-term safety. Severe adverse events and treatment interruptions have occurred, and late cardiopulmonary injury, fibrosis, and reconstruction outcomes remain insufficiently characterized. Management should preserve timely, guideline-concordant RT and base pembrolizumab continuation or interruption on clinical recovery and toxicity. Prospective comparisons with clearly defined schedules, prespecified RD subgroups, biomarker analyses, and adequate follow-up are needed to establish long-term net clinical benefit.

The etiology of endometriosis (EM) remains unclear. Evidence indicates a correlation between intestinal microbial communities and immune homeostasis in the pathogenesis of EM. This investigation leverages Mendelian randomization (MR) to delineate causal links connecting gut microbiota composition, specific immune cell phenotypes, and endometriosis, aiming to identify novel therapeutic avenues. Using publicly available genetic data from genome-wide association study (GWAS) summary datasets that encompass 473 microbial taxa, 731 immunological traits, and endometriosis cases, we executed bidirectional and two-step Mendelian randomization (MR) frameworks to assess causality and quantify mediation effects, aiming to evaluate the associations between intestinal microbial communities and immune homeostasis in the pathogenesis of endometriosis (EM). Utilizing single nucleotide polymorphisms (SNPs) as instrumental variables (IVs), we ensured robustness through sensitivity assessments, specifically Cochran's Q statistic and MR-Egger regression, to mitigate concerns regarding horizontal pleiotropy and heterogeneity. Our analysis revealed that Actinobacteria exerted an influence on HLA-DR+ CD8+ T cells (total effect: -0.2736; mediated proportion: 6.45%), whereas Actinomycetales regulated DN (CD4-CD8-) NKT cell populations (total effect: -0.1961; mediated proportion: 5.77%). Furthermore, Aneurinibacillaceae demonstrated a 14.30% mediation effect operating through CD28 expression levels on resting regulatory T cells (Tregs) (total effect: 0.4053). Eisenbergiella sp900066775 displayed pleiotropic impacts on markers associated with both Tregs and B cells (total effect: -0.1447). Notably, protective correlations were identified for Actinobacteria (Odds Ratio [OR] = 0.76, 95% Confidence Interval [CI]: 0.65-0.89) and Bifidobacterium angulatum (OR = 0.88, 95% CI: 0.83-0.94). Conversely, Aneurinibacillaceae abundance was linked to elevated endometriosis susceptibility (OR = 1.50, 95% CI: 1.13-1.98). Dysbiosis within the gut microbiome fosters endometriosis development by modulating immune cell dynamics, predominantly via pathways involving Tregs and NKT cells. These results underscore the microbiota-immune axis as a promising target for intervention, warranting future clinical trials to evaluate probiotic or immunomodulatory strategies.

In 2025, we developed and published a detection test using digital droplet polymerase chain reaction (ddPCR) from cell-free DNA that indicates the presence of ovarian cancer (OC) in peripheral blood immediately before surgery with a sensitivity and specificity of 80%. By applying a new classification approach based on semidefinite programming (SDP), we were able to significantly improve the predictive power of this test, which consists of six ddPCR combinations that indicate genomic imbalances. In addition to the previously used ratio of the ddPCR combination products, we now also include the sum of the ddPCR combination products. Data from the already published 57 controls without tumor background and a positive cohort of 15 OC were expanded by 5 additional OCs. With these data, we were able to define a separating boundary plane in a multidimensional space that better distinguishes the test results. This new method allows the detection of cell-free tumor DNA from OC with high tumor burdens in the plasma with high sensitivity and specificity. Further studies using larger and independent cohorts are needed to evaluate the robustness of our approach to evaluate its potential use as a screening algorithm and to assess the diagnostic potential of minimally invasive blood-based ddPCR tests in OC.

Patients with infertility often have inadequate reproductive health literacy (RHL), while existing health education materials may be difficult to read, overly complex, and insufficiently tailored to individual needs. In recent years, large language models (LLMs) have created new opportunities to improve health education through their ability to generate and interpret medical information. However, their applicability and content quality in infertility education remain insufficiently evaluated. This study systematically evaluated the readability and content quality of LLM-generated health education materials for patients with infertility, identified model strengths and limitations, and provided evidence to support their standardized use in reproductive health. This study selected DeepSeek-R1, ChatGPT (GPT-5.2 Plus), Kimi 2.5, Qwen 3, and Gemini 3 as the study subjects. Based on the theoretical framework of RHL, this study developed a standardized question list comprising 6 dimensions and 93 items, and used unified prompts to generate health education texts in both Chinese and English. In this study, the Datayze Readability Analyzer was used to assess readability via the Flesch Reading Ease, Gunning Fog Index, and Flesch-Kincaid Grade Level (FKGL). Meanwhile, the content quality was evaluated in a double-blinded manner by reproductive medicine experts across 3 dimensions: accuracy, comprehensiveness, and humanistic care. Repeated-measures analysis of variance was used to compare performance across the LLMs, and Pearson correlation analysis was conducted to examine the associations between readability and content quality. A radar chart was used to evaluate the overall performance of each model. The 5 LLMs differed significantly in both text readability and content quality. In terms of readability, Gemini 3 and Qwen 3 performed best, with significantly higher FRE scores than the other 3 models. DeepSeek-R1 and Kimi 2.5 performed least favorably, with FKGL scores corresponding to a ninth-grade reading level. ChatGPT (GPT-5.2 Plus) showed intermediate performance. In terms of content quality, Kimi 2.5 performed best across accuracy, comprehensiveness, and humanistic care, followed by DeepSeek-R1. ChatGPT (GPT-5.2 Plus) performed least favorably. Analysis revealed significant negative correlations between readability and content comprehensiveness for texts generated by Kimi 2.5, indicating a trade-off between these 2 attributes. The composite radar chart analysis showed that Kimi 2.5 achieved the highest score (11,594.33), whereas ChatGPT (GPT-5.2 Plus) had the lowest score (5555.83). Different LLMs showed significant differences in performance in generating health education texts for patients with infertility. In some models, readability was negatively correlated with content comprehensiveness. Under the conditions of this study, Kimi 2.5 demonstrated strong overall performance. However, no model achieved the best performance across all evaluation dimensions. Future applications of LLMs in reproductive health education will require domain-specific optimization, context-specific adaptation, and systematic quality control to support more accurate, comprehensive, and patient-centered communication.

Aggressive vertebral hemangiomas (VHs) rarely cause fracture or epidural hemorrhage. Pregnancy- related hemodynamic changes may promote progression, whereas the role of instability is poorly defined. A 30-year-old female presented 2-week postpartum with severe mechanical thoracolumbar pain and mild right leg weakness. Imaging showed an aggressive T12 VH with >50% collapse, kyphosis, posterior epidural hemorrhagic extension, and marked canal compromise. The retrospective Spinal Instability Neoplastic Score was 15/18. After preoperative embolization, a T12 and superior L1 laminectomy/decompression was performed, and the hematoma was removed. Gross T11-L1 instability was noted intraoperatively, thus warranting simultaneous T10-L2 fusion plus open T12 cement augmentation. Postoperatively, strength normalized within 1 week, and 2 years later, she remained pain-free and neurologically intact without radiological progression or recurrence. In this postpartum case, pathological collapse and instability accompanied hemorrhagic progression of an aggressive VH. When instability is evident, simultaneous stabilization should be considered along with decompression.

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, which highlights the need for more effective and safer therapeutic strategies. Quinoline is an important nitrogen-containing heterocycle that has been widely studied for the development of anticancer agents. Its structural flexibility facilitates extensive chemical manipulation, enabling alterations for potency, selectivity, physicochemical characteristics, and target interactions. Recent research has revealed how structural changes in quinoline derivatives affect their anticancer properties and interactions with biological targets for breast cancer treatment. Selected quinoline derivatives have shown biological activity involving ERα, EGFR, HER2, or VEGFR-2, but the exact role played by these target molecules in achieving these biological activities requires further confirmation for individual compounds. According to the literature, substituents such as halogens and electron donors can affect interactions with targets, inhibitory activities on kinases, physicochemical characteristics, and antiproliferative activity. This depends on the chemical series and experimental conditions. Several quinoline-containing or quinoline-derived drugs have clinical applications in oncology, including camptothecin, lenvatinib, neratinib, bosutinib, and cabozantinib. These findings underscore the significance of quinoline as an important framework in medicinal chemistry that continues to be explored for anti-cancer drugs. Among the selected papers, structural differences correlated with variations in target affinity, kinase inhibition, antiproliferative activity in cells, and selectivity; yet the SAR trends were series-specific, model-dependent, and assaydependent. Overall, the available evidence supports the potential of quinoline derivatives as promising leads for breast cancer drug discovery, although additional validation is needed for the targets, pharmacokinetics, safety, and clinical research. These findings provide useful guidance for future medicinal chemistry optimization.

Doxorubicin efficacy in breast cancer is constrained by chemoresistance and toxicity. Hesperidin, a citrus flavonoid, exhibits anticancer and epigenetic regulatory properties. This study evaluated whether hesperidin enhances doxorubicin cytotoxicity in MCF-7 cells and characterized the associated apoptotic and Heat-Shock (HSP60, HSP90) transcripts, as well as global DNA methylation. Cytotoxicity and synergy were assessed using the MTT assay and the Chou-Talalay method (CI). Apoptosis and cell cycle were analyzed by flow cytometry. Expression of BAX, BCL2, HSP60, and HSP90 was quantified using RT-qPCR. Global DNA methylation (5-mC%) was assessed colorimetrically, alongside molecular docking simulations for HSP60 and HSP90. Combining hesperidin with doxorubicin produced synergistic cytotoxicity (CI < 1) and a dosereduction index of 1.95 for doxorubicin. The combination induced apoptosis, accompanied by upregulation of BAX, downregulation of BCL2, and modulation of HSP60/HSP90 transcript levels. Additionally, the combination attenuated doxorubicin-induced global hypermethylation. Molecular docking demonstrated favorable binding affinities of hesperidin toward both HSP60 and HSP90, particularly HSP60; however, these findings remain correlative without proving direct target engagement. The synergistic response, paired with modulated apoptotic markers and global DNA methylation, suggests that hesperidin sensitizes MCF-7 cells to doxorubicin through multi-targeted cellular and epigenetic pathways. While docking and transcriptomic shifts indicate potential chaperone involvement, these preliminary observations require further functional validation. Hesperidin enhances doxorubicin cytotoxicity in MCF-7 cells by modulating apoptosis, stressresponse transcripts, and DNA methylation. These in-vitro findings support further mechanistic and in-vivo evaluation of this combination strategy.

Maternal anxiety and depression have been associated with alterations in functional connectivity (FC) in infancy, a period in which rapid brain development and functional network organization have been linked to longer term socioemotional outcomes. Investigating maternal anxiety and depression within the same sample is important, given that they frequently co-occur and may show distinct associations with infant brain development. A longitudinal approach is key to understanding whether and how changes in maternal mental health across the perinatal period relate to infant brain development. We examined associations of subclinical prenatal and postnatal maternal depression and anxiety, measured via questionnaires at 32 weeks of gestation and 1 month postpartum, with infants' FC at 1 month of age. Task-free FC data were collected during natural sleep using High-Density Diffuse Optical Tomography (HD-DOT) in the home. No associations were observed between maternal anxiety symptoms and FC, and neither postnatal depression nor anxiety alone predicted infant FC. Lower maternal prenatal depression scores were associated with stronger FC in the infants' frontal network (n = 39). In contrast, greater increases in maternal depressive symptoms from the prenatal to postnatal periods were linked to increased frontal FC, particularly when mothers had higher prenatal depression levels (n = 28). Most symptom changes were small in magnitude and did not cross clinical thresholds, suggesting largely subclinical and transient mood shifts. We speculate that while early prenatal exposure may signal vulnerability in specific neural circuits, the subsequent increase in symptoms could trigger compensatory or accelerated development in the same networks. Replication with larger, more diverse, samples and longitudinal research is needed to determine whether these subtle early fluctuations in maternal symptoms are associated with longer-term trajectories of infant brain development beyond the perinatal window.

Cue exposure contributes to craving and reinforces alcohol misuse, potentially by altering interoceptive processing and physiological arousal. However, few studies have reported changes in physiological arousal or their neural underpinnings in response to alcohol cues. Here, we addressed these questions in 94 adult drinkers (39 females; age mean ± SD: 59.1 ± 19.1 years and range: 19-85 years) who underwent functional magnetic resonance imaging and skin conductance recording during alcohol and neutral cue exposures and completed clinical assessments including the Alcohol Use Disorder Identification Test (AUDIT; mean ± SD: 4.4 ± 5.5). Imaging data were processed with published routines and evaluated at a corrected threshold. The results showed significantly higher skin conductance response in 'alcohol>neutral' blocks (SCR Al-Ne ) in females than in males. However, SCR Al-Ne was positively correlated with participants' AUDIT scores in males but not in females. SCR Al-Ne was also positively correlated with global positive alcohol expectancy and novelty seeking scores in males but not in females. A voxel-wise two sample test of the contrast 'alcohol>neutral' did not show any clusters with significant sex differences in cue reactivity. Whole-brain regression of the same contrast on AUDIT scores identified a large cluster in the perigenual anterior cingulate cortex (pgACC), with the beta estimates showing a significant positive correlation with the SCR Al-Ne , again in males only. These sex differences were all confirmed by slope tests. Thus, males with more drinking problems showed higher arousal as well as the pgACC response to alcohol cues in association with alcohol expectancy and novelty seeking. In chain mediation modelling, the pgACC response and alcohol expectancy interlinked SCR Al-Ne and AUDIT scores in males. In contrast, we failed to observe any significant neural or psychological correlates of physiological arousal, despite higher SCR Al-Ne , in females. With the caveat of a smaller sample size for females, these findings highlight sex and individual differences in physiological responses to alcohol cues and the neural and psychological underpinnings in male adult drinkers. Whether or how physiological arousal may play a role in the pathophysiology of alcohol misuse remains to be investigated for females.

This study evaluated women's overall satisfaction with a combined oral contraceptive containing estetrol 15 mg/drospirenone 3 mg (E4/DRSP) in clinical practice. This prospective, multicentre, six-cycle, non-interventional study included women aged 18-45 years who initiated hormonal contraception (starters) or switched from another hormonal contraceptive (switchers) to E4/DRSP. Of 380 women starting E4/DRSP, 201 (52.9%) were switchers and 226 (59.5%) completed the six-cycle follow-up. In women with available follow-up data, satisfaction with E4/DRSP was high at Cycle 6 (starters 76.9% [95% CI 68.3-84.0], switchers 72.0% [95% CI 63.5-79.5]), with no significant differences between groups or over time (p > 0.05). Users reported a stable profile across well-being, mood, sexual life, premenstrual period and skin condition. Starters experienced significant improvements in breast tenderness between Cycles 3 and 6 (p = 0.024). Satisfaction with the cycle pattern improved significantly in both groups between baseline and Cycle 3, and baseline and Cycle 6 (all p < 0.05). Adherence among respondents was significantly higher for switchers (95.8%) than starters (83.3%) at Cycle 6 (p = 0.022), and approximately 80% of respondents intended to continue using E4/DRSP. Sixty-six women (17.4% [95% CI 13.6-21.2]) reported discontinuing E4/DRSP because of adverse events (AEs). The types of AEs most reported were consistent with those described in Phase 3 trials, with no new safety signals reported. Among women who completed six cycles of follow-up, E4/DRSP users reported high satisfaction, high intention to continue use, and an AE profile generally consistent with that described in Phase 3 trials.

Young age is associated with poorer outcomes and more aggressive clinicopathological features in breast cancer, but the biological underpinnings are incompletely understood. With the emergence of infiltrating immune cell tissue-based biomarkers, we aimed to investigate a relation to age by mapping of CD45, CD3, CD8, FOXP3, and CD163 positive cells. We examined a population-based cohort of women under the age of 50 years (BCY-B cohort, n = 311) in comparison to a previously reported series of patients aged 50-69 (TBC cohort, n = 282) years. The BCY-B cohort was additionally stained for two PD-L1 markers. Young age (under 50 years) was not associated with higher levels of tumor-infiltrating lymphocytes (TILs), represented by markers such as CD45 and CD3. However, younger patients presented with lower levels of FOXP3-positive TILs, both in luminal and non-luminal subgroups, and higher levels of CD163-positive tumor-associated macrophages (TAMs) in combined analyses only. CD163 showed prognostic value when analyzing all patients together and within the luminal subgroups. For non-luminal subgroups, CD3 expression was prognostic, while CD8 expression showed a trend. Notably, no age-associated difference in prognostic value was observed for any marker. Among patients within the BCY-B cohort (aged under 50 years), those below 40 years demonstrated higher PD-L1 tumor cell expression, also within the triple-negative subgroup, when compared to those aged 40-49 years. In conclusion, our study found only limited differences in tumor-infiltrating immune cells with age, with higher density of FOXP3-positive TILs in patients aged 50 years or above. Within the BCY-B cohort (age under 50), patients aged under 40 years showed higher tumor expression of PD-L1 when compared to those aged 40-49 years, suggesting age-associated differences in immune checkpoint regulation.

Personalised care, targeting therapy to individuals and minimising treatment-related risks for most ailments, is the trend in modern times. For cancers and in particular breast cancer (BC), the treatment focus has varied over the years as more knowledge about the ailment is acquired. This review summarises the individualisation of BC treatment over time along with their scientific rationale for those treatments. The manuscript also takes a peek into the near future as to the likely direction of further research and treatment in BC as research findings further evolve.

Autophagy and ferroptosis are evolutionarily conserved stress-response pathways that critically regulate tumor progression and therapeutic responsiveness. In breast cancer, the autophagy initiator Beclin-1 acts as a haploinsufficient tumor suppressor, whereas susceptibility to ferroptosis is largely governed by the GPX4-SLC7A11-TFRC redox axis. Therapeutic strategies capable of coordinately modulating these pathways remain largely unexplored. This study aimed to identify novel redox-active anticancer agents by designing and synthesizing a focused library of oxopyrrolidine-tethered N-acylhydrazone derivatives PCH (01-17). The lead compound, PCH-03, was investigated to elucidate its ability to induce ROS-dependent JNK3 signaling and coordinate autophagy-ferroptosis crosstalk in breast cancer cells through integrated computational and experimental analyses. Computational investigations, including molecular docking, molecular dynamics simulations, and frontier molecular orbital (FMO) and molecular electrostatic potential (MESP) analyses, were performed to evaluate the structural compatibility of PCH-03 with the conserved JNK kinase domain and its electronic properties. Biological activity was assessed in four human breast cancer cell lines (MCF-7, SK-BR-3, BT-474, and MDA-MB-231) and normal breast epithelial MCF-10A cells using MTT assays, mitochondrial membrane potential analysis, intracellular ROS measurement, immunocytochemical analysis of LC3 and GPX4, MDC staining, flow cytometry, and intracellular Fe 2+ quantification. Western blotting, together with chloroquine-mediated autophagic flux analysis and p62/SQSTM1 evaluation, was used to characterize autophagy, while ferroptosis involvement was validated using ferrostatin-1 (Fer-1). Pharmacological inhibition with SP600125 was employed to investigate the contribution of JNK3 signaling. PCH-03 inhibited the viability of breast cancer cells with IC 50 values of 35.24 μM in MCF-7, 35.46 μM in SK-BR-3, 50.81 μM in BT-474, and 35.71 μM in MDA-MB-231 cells, whereas a higher IC 50 value of 141.85 μM was observed in normal breast epithelial MCF-10A cells, indicating preferential cytotoxicity toward breast cancer cells. PCH-03 induced intracellular ROS accumulation, mitochondrial membrane depolarization, and oxidative stress, accompanied by activation of JNK phosphorylation. The compound increased Atg7, Beclin-1 and phosphorylated Beclin-1 (p-Beclin-1), and LC3-II expression, and chloroquine-mediated flux assays together with p62/SQSTM1 analysis confirmed activation of functional autophagic flux. Concurrently, PCH-03 suppressed GPX4 and SLC7A11, increased TFRC expression, and promoted intracellular Fe 2+ accumulation, consistent with ferroptosis induction. SP600125 significantly attenuated autophagy-associated signaling and partially restored GPX4 expression, supporting the involvement of JNK3 signaling in mediating autophagy-ferroptosis crosstalk, whereas ferrostatin-1 partially rescued cell viability, reduced iron accumulation, and attenuated JNK3 phosphorylation, indicating that ferroptosis functionally contributes to PCH-03-induced cell death alongside JNK3 pathway activation. PCH-03 is a novel oxopyrrolidine-N-acylhydrazone derivative that exerts antibreast cancer activity by disrupting redox homeostasis and promoting coordinated autophagy and ferroptosis with the contribution of ROS-dependent JNK signaling. Although additional genetic validation is warranted to define isoform-specific JNK regulation, these findings identify PCH-03 as a promising lead scaffold for developing anticancer therapeutics that coordinately modulate autophagy and ferroptosis to potentially overcome therapeutic resistance in breast cancer.

Activity restriction and bedrest are frequently prescribed in pregnancy with the goal of preventing preterm birth, despite evidence that these practices are ineffective and harmful. While these practices persist, the American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) guidelines recommend against the routine use of activity restriction. Understanding clinicians' perspectives related to guideline-informed activity recommendations is essential to inform deimplementation strategies. This study aims to identify barriers and facilitators of deimplementation of activity restriction in pregnancy from the perspective of prenatal care clinicians, using the Consolidated Framework for Implementation Research 2.0 (CFIR) in a qualitative approach. We conducted a qualitative study using semi-structured individual interviews with prenatal care clinicians ( n = 14) at sites within or affiliated with a large urban academic medical center between November 2024 and September 2025. Participants included obstetrician-gynecologists, a maternal-fetal medicine physician, a family medicine physician, nurses, a certified nurse midwife, and office staff from both academic and community practice settings. Interviews were coded and analyzed using NVivo software. Emergent themes were mapped to CFIR domains and constructs. Clinicians universally endorsed the benefits of physical activity in pregnancy but demonstrated significant knowledge gaps regarding current evidence and professional society guidelines. No clinicians recognized the inverse relationship between physical activity and preterm birth. Many followed outdated guidance, citing contraindications to exercise that have been removed from current ACOG recommendations. Key barriers to deimplementation included a perceived lack of evidence, patient anxiety, social media misinformation, cultural expectations around rest during pregnancy, and fear of rare adverse outcomes. Trust in ACOG and SMFM as credible sources and system-level infrastructure such as consensus meetings and standardized recommendations were described as facilitating decision support. In this exploratory, single-institution study, deimplementation of activity restriction in pregnancy was less constrained by clinician opposition to physical activity and more by knowledge gaps, patient expectations, and fear of rare adverse outcomes. Strategies that leverage existing clinician trust in professional society guidelines and address condition-specific uncertainty may facilitate practice change.

Breast cancer progression reflects coupled immune and metabolic reprogramming, but biomarkers that capture this interplay and provide additional prognostic information beyond routine clinicopathological assessment remain limited. We developed an 11-gene immune-metabolic risk Score in TCGA-BRCA (n = 1099) by integrating C7 immune signatures and KEGG metabolic pathways through Cox and LASSO-Cox modeling. The fixed model was applied without retraining to three public cohorts and an independent institutional cohort of 146 patients from Harbin Medical University Cancer Hospital. The score consistently stratified overall survival across independent cohorts and provided additional prognostic information beyond conventional clinicopathological variables. Integrative analyses showed that high-risk tumors were characterized by enhanced cell-cycle and metabolic activation, reduced lymphocyte-associated immune features, and monocytic-lineage enrichment. At single-cell resolution, high-score cancer-associated fibroblasts exhibited enhanced extracellular-matrix remodeling, inflammatory iCAF activity, and TGF-β-associated immunosuppressive programs. In an exploratory pembrolizumab-containing cohort, lower pretreatment scores were associated with pathological complete response and immune-active transcriptional programs; however, these findings do not establish the score as a predictive biomarker for immunotherapy benefit. The 11-gene immune-metabolic risk Score provides complementary prognostic stratification beyond conventional clinical variables and characterizes a stromal-remodeled immune-metabolic state associated with adverse breast cancer outcomes.

Most maternal deaths in Ethiopia occur during childbirth and the immediate postpartum period, yet population-level evidence on intrapartum and immediate postpartum complications and their determinants remains limited. In particular, the roles of intimate partner violence (IPV) during pregnancy and pregnancy complications have been underexplored. To determine the prevalence and factors associated with intrapartum and immediate postpartum obstetric complications in Ethiopia. We conducted a secondary analysis of the Performance Monitoring for Action Ethiopia (PMA-E) longitudinal survey (October 2019 and September 2020) using a two-stage stratified cluster sampling design. Multilevel modified Poisson regression analysis was used to estimate adjusted prevalence ratio (aPR) with 95% confidence intervals (CIs). A total of 2558 women were included in the analysis. The prevalence of intrapartum and immediate postpartum complications was 37.6% and 31.6%, respectively. Rural residence (aPR = 1.72,95% CI: 1.34-2.20), intimate partner violence (IPV) during index pregnancy (aPR = 1.31,95% CI: 1.14-1.50), pregnancy complications (aPR = 1.78, 95% CI: 1.55-2.06), and nulliparity (aPR = 1.30, 95% CI: 1.07-1.58) were associated with intrapartum complications. Factors associated with immediate postpartum complications were complications during pregnancy (aPR = 1.65, 95% CI: 1.40-1.93) and prolonged labour (aPR = 1.34, 95%CI: 1.14-1.57). Childbirth at health facility was associated with a lower prevalence of immediate postpartum complications (aPR = 0.83, 95% CI: 0.70-0.98). Intrapartum and immediate postpartum obstetric complications are common in Ethiopia. IPV during pregnancy, pregnancy complications, and nulliparity were associated with intrapartum complications. Pregnancy complications and prolonged labour were associated with a higher prevalence of immediate postpartum complications, while health-facility childbirth was associated with a lower prevalence. Main findings : This national population-based survey revealed a high burden of intrapartum and immediate postpartum obstetric complications in Ethiopia, and several factors significantly increased the likelihood of intrapartum complications and immediate postpartum obstetric complications. Added knowledge : This study provides national-level evidence on the burden of intrapartum and immediate postpartum complications in Ethiopia using population data; an approach rarely applied in low-resource settings and extends existing literature by identifying intrapartum- and immediate postpartum-specific factors associated. Global health impact for policy and action : The high prevalence of obstetric complications underscores the urgent need for strengthened intrapartum and postpartum care in low-resource settings, and findings underscore the need for policies to integrate intimate partner violence screening and mitigation strategies into routine antenatal and intrapartum care and strengthen antenatal care to identify women with pregnancy complication symptoms and provide further care for those women.

Chronic hypertension (CHTN) increases the risk of superimposed preeclampsia, contributing to maternal and neonatal morbidity and mortality. Accurate hypertension classification is therefore essential for risk stratification, antenatal surveillance, prevention, and outcomes. The clinical impact of applying the American College of Cardiology/American Heart Association (ACC/AHA) classification, compared with the American College of Obstetricians and Gynecologists (ACOG) criteria, in pregnancy remains uncertain. To determine the impact of ACC/AHA versus ACOG hypertension classifications on the prevalence of CHTN and pregnancy outcomes. This population-based retrospective cohort study used a computerized maternity database from a tertiary hospital. All parturients with singleton gestations initiating prenatal care in the first trimester were included ( n = 136,606). CHTN was categorized according to ACOG and ACC/AHA criteria. Maternal, fetal, and neonatal outcomes were assessed. Statistical analyses were performed using R-Studio, with ANOVA and Poisson regression models evaluating associations between CHTN severity and outcomes. The prevalence of CHTN was 2.9% (4,127/137,606) by ACOG criteria and 3.9% (5,424/137,606) by ACC/AHA criteria ( p < 0.001). Under ACOG classification, both mild and severe range CHTN were independently associated with preeclampsia or eclampsia (RR 4.15, 95% CI 3.69-4.65; and RR 3.19, 95% CI 2.82-3.59, respectively). Using ACC/AHA criteria, elevated blood pressure (EBP), stage 1 CHTN (S1CHTN), and stage 2 CHTN (S2CHTN) were each independently associated with preeclampsia or eclampsia (EBP: RR 2.34, 95% CI 2.04-2.65; S1CHTN: RR 4.00, 95% CI 3.56-4.50; S2CHTN: RR 3.32, 95% CI 2.88-3.80). Mild CHTN, S1CHTN, and S2CHTN were independently associated with small-for-gestational-age neonates, while both ACOG-defined CHTN and ACC/AHA-defined EBP, S1CHTN, and S2CHTN were associated with preterm birth. Application of the ACC/AHA classification identifies a larger proportion of pregnant individuals as having CHTN. Notably, even those with elevated blood pressure had a two-fold increased risk of preeclampsia compared with the general obstetric population. These findings support the clinical relevance of the ACC/AHA classification in pregnancy and suggest that its implementation may improve identification of patients who may benefit from targeted preeclampsia prevention strategies.

Breast cancer presents a significant therapeutic challenge due to the substantial molecular and genetic diversity among its subtypes, thereby necessitating the development of refined intervention strategies. Macromolecular therapies, such as monoclonal antibodies, are often hindered by suboptimal biodistribution, restricted tumor penetration, and off-target toxicity in advanced diseases. The advent of affibody technology, which utilizes engineered ~7 kilodalton (kDa) scaffold proteins derived from Staphylococcus aureus protein A, introduces a distinct class of targeting agents designed to address several of these limitations. Affibody molecules exhibit favorable biophysical properties, including thermal stability, configurable binding affinities reaching picomolar ranges, rapid systemic clearance, compact molecular size, and modular engineering architecture that enables diverse therapeutic applications. This review explores potential affibody-based therapeutic strategies for breast cancer, with applications targeting human epidermal growth factor receptor 2 (HER2) and human epidermal growth factor receptor 3 (HER3) serving as the most extensively characterized and translationally advanced model systems. Two principal modalities are emphasized: direct receptor antagonism and targeted payload delivery. The latter includes covalent affibody-drug conjugates, cytotoxic fusion proteins, radionuclide-conjugated variants for diagnostic imaging and targeted radionuclide therapy, and affibody-functionalized nano-carriers designed to enhance delivery efficiency. Although most affibody-based therapeutics remain at the preclinical stage, clinical development is most advanced in diagnostic imaging, particularly for HER2-targeted agents that have undergone evaluation in patients. Collectively, this review summarizes the current landscape of affibody-based therapeutic approaches and highlights their translational potential in breast cancer.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with metabolic, reproductive, and psychological disturbances. Alarin, a neuropeptide of the galanin family, has been implicated in energy metabolism and insulin resistance, and experimental studies suggest a role in mood regulation. However, its association with psychiatric features in PCOS remains unclear. This study aimed to evaluate circulating alarin levels in women with PCOS and their relationship with depression, anxiety, and metabolic-hormonal parameters. This case-control study included 180 women divided into four groups: PCOS with depression, PCOS without depression, depression without PCOS, and healthy controls (45 participants each). Clinical, biochemical, and hormonal assessments were performed, including measurement of serum alarin levels. Depression and anxiety were assessed using validated Hamilton rating scales. Serum alarin levels were significantly higher in women with PCOS, irrespective of comorbid depression, compared with healthy controls and women with depression without PCOS. Women with depression alone showed alarin levels comparable to controls. Factorial analysis showed significant effects of PCOS status and depression status, with no significant PCOS × depression interaction (p=0.37). Serum alarin correlated positively with fasting insulin, HOMA-IR, and luteinizing hormone, but not with depression or anxiety severity. Multivariate analysis identified luteinizing hormone and PCOS status as independent predictors of serum alarin levels. Receiver operating characteristic analysis demonstrated excellent discriminative performance for PCOS. Circulating alarin is closely associated with the metabolic and reproductive features of PCOS rather than psychiatric symptom severity, indicating a stronger link to endocrine-metabolic dysregulation.

Although AI applications in women's health are increasing rapidly, few bibliometric studies have systematically examined research trends and priority topics in this field. We conducted a bibliometric analysis of research on women's health and artificial intelligence published between 2020 and 2025 to interpret the field's evolution and identify gaps within it. We analyzed 3241 articles indexed in the Web of Science database, retrieved on 13.09.2025, using VOSviewer software and co--authorship, co-occurrence, citation, and country analysis techniques. We found that publications increased over the years, the USA produced the most, and the most-cited studies focused on obstetric imaging, gestational diabetes, and infertility. The most frequently used keywords were machine learning, pregnancy, artificial intelligence, deep learning, and fertility. Researchers in this field focus on clinically prioritized problems and use algorithm-based approaches. International collaboration and multidisciplinary approaches will accelerate its development.

Exposure to heavy metals may lead to premature ovarian insufficiency. Research on the exposure to heavy metals and the age at menopause is scant. This study aimed to investigate the impact of heavy metal exposure on the age at the onset of natural menopause. Cox proportional hazards models were used to assess the risk of the onset of menopause. Logistic regressions were estimated to examine the relationship between heavy metals and early or premature menopause. Mean age at menopause was 47.3 (SD 5.5); 25.1% of women experienced either an early or a premature menopause. Hair nickel concentrations in the third and fourth quartiles of the distribution increased the risk of menopause and the odds of an early or premature menopause. High levels of chromium were marginally related to a lower risk of menopause. However, the likelihood of an early or premature menopause was 50% lower among women in the fourth quartile. Mercury concentrations show an increased risk of menopause only for the second quartile of the distribution. The odds of an early or premature menopause doubled for the second quartile. No significant relationships between hair copper, lead, manganese, and titanium concentrations and age at menopause were found.

Breast cancer risk and progression are shaped by interactions between inherited genetic susceptibility and modifiable exposures, including diet. Nutrigenetic and nutrigenomic evidence suggests that germline variants can modify biological responses to nutrients and bioactive food compounds, potentially affecting pathways central to carcinogenesis. This narrative review synthesizes evidence across three distinct but complementary domains: (i) germline genotype-diet associations, (ii) nutrient-responsive molecular pathway modulation, and (iii) nutrition-related effects in defined tumor molecular phenotypes. These domains are evaluated separately to avoid equating inherited nutrigenetic interactions with preclinical pathway effects or somatic tumor characteristics. A structured narrative literature search was conducted in PubMed, Web of Science, and Scopus for peer-reviewed English-language studies published up to 30 July 2026. Search terms combined breast cancer with nutrigenetics, nutrigenomics, gene-diet interactions, genetic variants, nutrient-responsive pathways, and the specific genes and dietary exposures covered in this review. Experimental, observational, and clinical/intervention studies were included when they directly addressed gene-diet interactions or nutrition-responsive molecular mechanisms relevant to breast cancer. The evidence was synthesized qualitatively according to study design and biological pathway. Within the germline nutrigenetic domain, the most direct human evidence involved BRCA1/2, COMT, CYP17A1, GST-family genes, MTHFR, and selected FTO variants, although formal interaction testing and replication were inconsistent. Evidence concerning TP53 and FOXO3 was predominantly mechanistic or preclinical and was therefore interpreted as nutrient-responsive pathway modulation rather than as an established germline gene-diet interaction. HER2-positive breast cancer, characterized clinically by ERBB2 amplification and/or HER2 overexpression, was considered separately as a somatic tumor phenotype and treatment-relevant signaling context rather than as an inherited nutritional genotype. Across these domains, nutrients and bioactive compounds-including folate and B vitamins, vitamin D, polyphenols, phytoestrogens, crucifer-derived isothiocyanates, fatty acids, and Mediterranean-style dietary patterns-have been associated with genomic stability, hormone signaling, oxidative stress, epigenetic regulation, and metabolic pathways, but the type and strength of evidence differ substantially across genetic, molecular, and tumor-phenotype contexts. However, clinical translation remains constrained by heterogeneous populations, variable dietary assessment and exposure definitions, limited biomarker standardization, and a paucity of adequately powered genotype-stratified dietary trials. Current evidence supports further investigation of genotype-aware and tumor-context-aware nutrition, but remains insufficient for routine genotype-based or tumor-phenotype-based dietary prescriptions. Future studies should clearly distinguish germline interaction effects from nutrient-responsive molecular mechanisms and tumor phenotypes while integrating standardized dietary exposures, validated biomarkers, and multi-omics approaches.

Accurate personalized prediction of delivery mode during the active stage improves resource allocation, reduces unnecessary interventions, and enhances patient-centered care. However, current machine learning models lack focus on active labor and effective use of labor-related data. The "black box" problem further impedes understanding, accuracy, and patient safety. Our aim was to develop a personalized model using real-time data to predict successful vaginal deliveries in the active phase and provide an explanation of the model's decision-making process STUDY DESIGN: Labor records from a tertiary hospital were searched and labeled over a 12-year period (2010-2021). Three models were trained using both "static features" (e.g demographics) and "dynamic features" (e.g cervical dilatation, efficacy, and newly derived features calculated as ratios between adjusted dynamic measures and time differences). To assess the explainability of the best-performing model, we employed SHAP (SHapley Additive exPlanations) analysis. A total of 94,386 cases in which a trial of labor was attempted were identified. Of them 70,000 admitted to the active phase of labor (6 cm dilatation). We trained three types of classifier models predicting successful vaginal delivery: Random Forest classifier, Histogram-Based Gradient Boosting classifier, and neural network model. Histogram-Based Gradient Boosting model achieved the highest scores: ROC AUC score and Precision recall AUC score was 0.87 (95% confidence interval, 0.858-0.892) and 0.52 (95% confidence interval, 0.511-0.542) respectively. Explainability of the best model was analyzed using SHAP. The features that contributed the most for the model prediction were: rate of fetal descent, cervical opening rate, maternal age and clinical fetal weight estimation. This study presents a personalized, explainable machine learning model that continuously predicts delivery mode in real time during active labor. By integrating dynamic intrapartum data with static maternal characteristics, the model provides interpretable, patient-specific risk estimates that can enhance intrapartum decision-making and optimize obstetric care.

Preeclampsia (PE) is a severe pregnancy disorder characterized by hypertension and multi-organ dysfunction. Impaired trophoblast function and defective spiral artery remodeling are considered the central pathological features of PE, leading to placental ischemia/hypoxia and a subsequent inflammatory cascade. Increasing evidence has demonstrated that pyroptosis contributes to placental dysfunction and the establishment of a pro-inflammatory microenvironment in PE; however, the mechanisms remain largely unclear. O-linked β-N-acetylglucosamine (O-GlcNAc) modification is a reversible post-translational modification (PTM) that plays critical roles in maintaining cellular homeostasis and regulating multiple forms of programmed cell death (PCD), yet its role in pyroptosis during PE has not been elucidated. In the present study, we found that O-GlcNAcylation was markedly reduced in placental tissues from patients with PE and negatively correlated with pyroptosis. In both an LPS-induced PE-like mouse model and trophoblast cells, enhancement of O-GlcNAcylation significantly suppressed pyroptosis and ameliorated PE-like phenotypes. IP-MS identified UBAP2L as a critical O-GlcNAcylated protein. Mechanistically, T446, an O-GlcNAcylation site of UBAP2L, contributed to maintaining its protein stability by preventing ubiquitin-mediated proteasomal degradation and promoted its interaction with DDX21, thereby promoting stress granule assembly. This process suppressed inflammasome activation and pyroptosis, improved trophoblast function, and ameliorated PE-like phenotypes. Collectively, our findings define an O-GlcNAcylation-UBAP2L-DDX21-stress granule-pyroptosis axis in PE and nominate O-GlcNAc signaling as a therapeutic target.

Efforts to analyze breast cancer transcriptomes at scale are hindered by cross-study technical variability. To overcome this challenge, we adapt single-cell RNA sequencing analytical strategies to harmonize 7,612 bulk breast cancer transcriptomes from 22 datasets, generating a high-resolution atlas that resolves both established and unrecognized malignant transcriptional states. This framework recapitulates intrinsic subtypes and microenvironmental programs while identifying stem-like, basal-luminal progenitor (BLP), mucinous, and neuroendocrine-differentiated (NED) subtypes with distinct clinical behaviors. The NED subtype exhibits luminal characteristics, neuroendocrine differentiation, and poor prognosis after chemo-endocrine therapy. The human epithelial growth factor receptor-2-enriched (HER2E) kinase inhibitor-sensitive (HER2E KIS ) subtype identifies patients who responded to neoadjuvant HER2-targeted kinase inhibition. Transcriptomic positioning of BLP tumors suggests bipotent or myoepithelial progenitor association, unfavorable prognosis after chemotherapy, and potential benefit from VEGF and receptor tyrosine kinase inhibitors. Together, these data indicate that this atlas refines breast cancer taxonomy, provides insight into tumor cell states and origins, and establishes a framework for patient stratification and therapeutic discovery.

To compare the ease of cervical entry after administration of vaginal misoprostol at 2 different intervals before vaginoscopic hysteroscopy. In this randomized, double-blinded study, 140 women undergoing vaginoscopic hysteroscopy were allocated into two groups: 1) short-interval: placebo tablet administered vaginally 12 hours before the procedure, followed by 200 mcg vaginal misoprostol 3 hours before, and 2) long-interval: 200 mcg vaginal misoprostol 12 hours before the procedure and a placebo tablet 3 hours before. The primary outcome was the ease of cervical entry, evaluated using a 5-point Likert scale, and the secondary outcomes included 1) time interval to cervical entry and completion of the procedure, 2) pain assessment using a visual analog scale (VAS), and 3) any adverse effects associated with the drug or procedure. All except two patients with cervical stenosis underwent vaginoscopic hysteroscopy. The proportion of patients who reported "easy" or "very-easy" cervical entry was similar in both groups (64.3% [95% confidence interval [CI], 53.1-75.5%], vs. 72.9% [95% CI, 62.4-83.3%]; P=0.275). Pain perception was lower in the long-interval group than in the short-interval group (P=0.024). However, the temporal change in the pain score was not significantly different between the groups. The side effects of misoprostol were mild, self-limiting, and similar in both groups. Vaginal misoprostol administration 12 hours before vaginoscopic hysteroscopy was associated with a similar ease of entry but a lower perception of pain using the VAS than misoprostol administration 3 hours before the procedure.

Endometriosis (EMs) is a common and challenging condition affecting women of reproductive age. Local vascularisation of ectopic lesions is a key driver of disease progression, and effective anti-angiogenic therapies remain limited. Curcumin has shown therapeutic efficacy against endometriotic lesions; however, the mechanism underlying its inhibition of angiogenesis remains unclear. A mouse EMs model was established to evaluate the in vivo effects of curcumin on ectopic lesion formation and local angiogenesis. In vitro experiments using human umbilical vein endothelial cells (HUVECs) were performed to determine the optimal inhibitory concentration of curcumin. Small extracellular vesicles (sEVs) were isolated and characterised from human peritoneal macrophages and from the THP-1 and RAW264.7 cell lines. A co-culture system was employed to assess whether curcumin regulates macrophage polarisation and thereby alters the effects of macrophage-derived sEVs on HUVEC angiogenesis. Differentially expressed miRNAs were identified by high-throughput miRNA sequencing and bioinformatic analysis, followed by functional validation of key candidates. In vivo, curcumin administration significantly reduced the size, volume, and adhesion of endometriotic lesions and suppressed local angiogenesis. In vitro, direct inhibition of HUVEC angiogenesis required 30 μM curcumin, whereas a lower concentration (10 μM) effectively modulated macrophage-derived sEVs to produce comparable anti-angiogenic effects. This treatment significantly reversed the pro-angiogenic activity of sEVs derived from EMs patients. Mechanistically, treatment with 10 μM curcumin was associated with a shift towards an M1-like macrophage phenotype and altered sEVs' activity. This change altered sEVs' cargo and subsequently inhibited HUVEC tube formation. miRNA sequencing identified miR-495-3p as a key mediator. Curcumin treatment significantly increased miR-495-3p levels in macrophage-derived sEVs. Functional assays demonstrated that inhibition of miR-495-3p partially restored HUVEC proliferation, migration, and tube formation suppressed by sEVs from curcumin-treated macrophages. While bioinformatic prediction and dual-luciferase reporter analysis identified BMI1 as a direct target and potential downstream effector of miR-495-3p. Curcumin suppresses EMs progression by regulating macrophage polarisation and modifying sEVs' miRNA expression profiles. Its anti-angiogenic effect is mediated, at least in part, by upregulation of macrophage-derived sEVs' miR-495-3p. BMI1 was a direct target and potential downstream effector of miR-495-3p. These findings provide molecular evidence for the anti-angiogenic activity of curcumin and identify the macrophage-sEV-angiogenesis axis as a potential therapeutic target for EMs.

Patients commonly use online information when considering imaging during pregnancy or breastfeeding. Information that is difficult to read, poorly contextualised or inconsistent may contribute to anxiety, delayed investigation or unnecessary breastfeeding interruption. This study aimed to evaluate the readability, understandability, actionability and information quality of highly ranked online patient information on diagnostic imaging during pregnancy and breastfeeding. A cross-sectional Google search was performed on 30 July 2026 using 15 predefined patient-relevant search terms. The first 10 organic results for each term were screened. Duplicate occurrences were removed and 51 unique eligible resources were analysed at resource level. Readability was assessed using Flesch-Kincaid Grade Level (FKGL) as the primary metric, with Flesch Reading Ease (FRE), Simple Measure of Gobbledygook (SMOG), Coleman-Liau Index and Gunning Fog Index as supplementary measures. Understandability and actionability were assessed using the Patient Education Materials Assessment Tool for Printable Materials (PEMAT-P), and information quality using Journal of the American Medical Association (JAMA) benchmarks and DISCERN (quality of written consumer health information on treatment choices). Clinical content was reviewed descriptively using structured domains. Mean FKGL was 8.6 (standard deviation [SD] 1.3); 49/51 resources (96.1%) exceeded the recommended sixth-grade level. Mean PEMAT-P understandability and actionability scores were 78.4% and 72.3%, respectively. Mean JAMA and DISCERN scores were 2.8/4 and 60.2. Inter-rater reliability was excellent for PEMAT-P understandability, PEMAT-P actionability and DISCERN [intraclass correlation coefficient (ICC) (2,1) = 0.982-0.998]. Structured narrative review identified variable risk contextualisation and inconsistencies in contrast-media and breastfeeding advice. Highly ranked resources were generally understandable but frequently exceeded recommended reading levels, while transparency, risk contextualisation and practical clinical advice varied. Radiography services should review online patient information for reading demand, transparency, risk contextualisation and consistency of practical advice, with particular attention to maternal and foetal risk communication, contrast media and breastfeeding.

Uterine fibroids (UFs) and cervical cancer (CC) are two common gynecological tumors, the pathogenesis of which has not yet been fully elucidated, with environmental factors playing a significant role. Acetyl tributyl citrate (ATBC), a widely used plasticizer, has been proven to pose a threat to human health. Although studies have indicated that ATBC exposure may be associated with tumorigenesis, the specific roles and molecular mechanisms of ATBC in UFs and CC remain unclear. This study aims to investigate the molecular mechanisms of ATBC-related UFs and CC using network toxicology, machine learning, and multidimensional bioinformatics approaches. Network toxicology methods were used to identify the relevant targets of ATBC, UFs, and CC. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were employed to explore the potential target gene pathways of ATBC-related UFs and CC. Transcriptomics analysis, Least Absolute Shrinkage and Selection Operator, and Support Vector Machine - Recursive Feature Elimination algorithms were used to determine the core targets of ATBC-related UFs and CC, and the discrimination of core genes among them was evaluated by receiver operating characteristic curve. Immune infiltration analysis was used to analyze the relationship between the expression of core target genes and the infiltration levels of various immune cells, while molecular docking and in vitro cell experiments were used to validate the above results. We identified 12 targets related to UFs and 153 targets related to CC, of which 11 were common targets for UFs and CC, significantly enriched in the ERBB signaling pathway and oxidative stress response pathway. F10, ABCB1, MMP9, CDK2, PIK3CA, and GABRA2 were identified as the core targets of ATBC-related UFs, while CDK2 and DHFR were identified as the core targets of ATBC-related CC. Among them, CDK2 is a cross-disease hub target for UFs and CC. In UFs tissues (MMP9, GABRA2, and CDK2) and CC tissues (CDK2 and DHFR), the expression of these genes was significantly higher than that in normal tissues. These genes were significantly associated with immune cell infiltration. Molecular docking and in vitro cell experiments results confirmed the stable interactions between ATBC and these targets. This study reveals that some key targets play important roles in the relationship between ATBC and UFs and CC, providing new insights into the mechanisms of ATBC in gynecological tumors and offering potential targets for future prevention and treatment strategies.

The prognostic significance of programmed death-ligand 1 (PD-L1) in high-grade serous ovarian cancer (HGSOC) remains uncertain, because of heterogeneity in assays, scoring systems, and assessment of tumor and immune compartments across studies. We therefore evaluated its biological and prognostic relevance using a standardized pathological approach in a large, well-annotated phase III trial cohort. In this ancillary retrospective biomarker analysis of PAOLA-1/ENGOT-ov25, PD-L1 was assessed by 22C3 pharmDx immunohistochemistry on whole-slide sections from 324 International Federation of Gynecology and Obstetrics stage III-IV HGSOCs. Three predefined scoring systems commonly used in PD-L1 assessment were applied: tumor proportion score (TPS ≥1%), immune cell score (IC ≥1%), and combined positive score (CPS ≥1). Associations with homologous recombination deficiency (HRD), BRCA1/2 status, and survival were examined using multivariable Cox models adjusted for major clinicopathological factors. PD-L1 positivity was observed in 38.2% of tumors by TPS, 62.4% by IC, and 66.1% by CPS. Positivity did not significantly vary by sampling site or timing of tissue collection relative to chemotherapy. PD-L1 positivity was enriched in HRD-positive tumors (TPS: 42.3% versus 28.0%, P = 0.017; IC: 65.1% versus 52.0%, P = 0.030; CPS: 70.4% versus 53.0%, P = 0.003) and remained independently associated with improved overall survival in adjusted analyses [TPS: adjusted hazard ratio (aHR) 0.70 (95% confidence interval 0.49-1.00), P = 0.046; IC: aHR 0.68 (0.49-0.95), P = 0.025; CPS: aHR 0.70 (0.50-0.97), P = 0.037]. Associations with progression-free survival were not statistically significant after adjustment. In advanced HGSOC, standardized whole-slide PD-L1 assessment identifies an HRD-associated PD-L1-positive immune context independently associated with improved overall survival. Immune-integrated scoring approaches capture this signal more effectively than tumor-cell-restricted assessment and provide a robust framework for future ovarian cancer studies.