Symptom overreporting is often considered to be moderated by external incentives, such as financial or legal advantages, although other factors may also play a role. Preliminary studies have suggested a connection between symptom overreporting and alexithymia, that is, trait-like difficulties in recognizing and describing internal sensations. This study aimed to further clarify the relationships among external gain expectations, alexithymia, and symptom overreporting. Specifically, we examined whether alexithymia is related to overreporting in patients without self-reported external gain expectations. Using a cross-sectional design, patients referred for psychological assessments in a hospital setting completed a questionnaire about external gain expectations (e.g., regarding work, housing, legal issues). We differentiated between those with self-reports of external gain expectations (n = 73) and those without (n = 84). Both subsamples were administered the Toronto Alexithymia Scale-20 (TAS-20), the Structured Inventory of Malingered Symptomatology (SIMS), and the Minnesota Multiphasic Personality Inventory-2 Restructured Form (MMPI-2-RF). Across the full sample, alexithymia showed a positive and statistically significant association with symptom overreporting on the SIMS and the Infrequent somatic responses scale (Fs) of the MMPI-2-RF: r = 0.44 and r = 0.31, respectively. These positive associations were also evident in the subgroup without self-reported external gain expectations (i.e., r = 0.35, 95% CI [0.14, 0.52] and r = 0.35, 95% CI [0.15, 0.53], respectively). Regression analysis indicated that self-reported external gain expectations did not account for the relationship between symptom overreporting and alexithymia. These findings suggest that alexithymia is associated with symptom overreporting independently of self-reported external gain expectations. More broadly, the results raise the possibility that alexithymic traits may compromise the accuracy of symptom reporting itself. If so, this has implications not only for the interpretation of symptom validity tests, but also for the broader use of self-report measures in clinical assessment.
Clinical decision support systems (CDSS) have emerged as a vital means to boost decision-making capabilities of clinicians, but still exhibit low clinical adoption rates. Systematically exploring the evolution, status, topic trends and variations of CDSS is expected to guide the development of next-generation CDSS. This study investigated scientific publications pertaining to CDSS over a 30-year period. Publications about primary topic (clinical decision support system) and 24 sub-topics grouped into application purposes, technical features and medical resources in PubMed and IEEE from 1 January 1995 to 31 December 2024 were collected. A total of 34,100 publications across 4315 journals were identified, where the number of publications belonged to Q1, Q2, Q3, and Q4 journals was 9721, 5074, 2667 and 1328 respectively, and 15,310 publications were not indexed by Journal Citation Reports in the publication year. This study found that data processing techniques from 2007 to 2024 profoundly steered CDSS toward data centric paradigms, whereas its clinical applications were significantly neglected from thereon. Uncannily, with the rising attention to "knowledge graph", its two important knowledge resources, "medical knowledge" and "clinical guidelines", have simultaneously declined in attention. Similarly, although interpretability has gradually gained visibility, focus on clinical reasoning/thinking/decision (RTD) theory has paradoxically declined. Concerning data processing techniques has significantly upwardly diverged with declined focus on medical related concerning. Such a focus shift has reduced contemporary CDSS to a technical showcase of data manipulation, a trend that should be reversed to enhance subsequent clinical utility.
Gene therapy offers unique therapeutic potential for treating rare genetic disorders such as DEE37, a severe Developmental and Epileptic Encephalopathy caused by biallelic loss-of-function mutations in the Ferric Chelate Reductase 1 Like (FRRS1L) gene, presenting with seizures, developmental delay, dyskinesia, ataxia and progressive, eventually debilitating cognitive and motor impairments. There is currently no treatment for DEE37. FRRS1L encodes an auxiliary subunit essential for the tetrameric assembly of α-amino-3 hydroxy-5-methyl-4 isoxazolepropionic acid receptors (AMPARs) and their recruitment to synaptic membranes. FRRS1L is expressed brain-wide, with high levels in the cerebellum. Here, we developed an adeno-associated virus 9 (AAV9) gene replacement vector expressing human FRRS1L driven by the JeT promoter. Administering the virus intrathecally in two doses (5 × 1010 and 3 × 1011 vg) to Frrs1l-knockout mice, we evaluated safety and efficacy in multiple phenotypic traits shared with affected patients. We obtained robust, near-normal, FRRS1L expression in the cerebellum and low levels of expression elsewhere in the brain, which were associated with corresponding levels of increased synaptic AMPAR abundance. Importantly, our phenotypic assessments revealed dose-dependent improvement trends, or rescue, across multiple brain structural, electrocorticographic, and behavioral domains. Our results indicate that cerebrospinal fluid-directed virally mediated FRRS1L gene replacement partially restores synaptic AMPAR and ameliorates disease-relevant phenotypes, supporting gene therapy as a promising therapeutic strategy for children suffering from this catastrophic, FRRS1L-related, 37th form of DEE.
Acute pancreatitis (AP) is a life-threatening disorder with no specific anti-inflammatory treatments available. 12-lipoxygenase (ALOX12) acts as a key regulator of inflammation and pyroptosis during AP progression. In this study, we established an LPS-induced inflammatory model in AR42J cells and confirmed that ALOX12 strongly aggravates AP-associated inflammation and pyroptosis. The ALOX12-targeted compound MH-04 was identified via virtual screening, with an IC₅₀ value of 0.72 μM. We further synthesized eight novel PROTAC molecules using linker-free PROTAC technology. Among these candidates, MH-06 was found to specifically target and effectively degrade ALOX12 protein. Mechanistic assays revealed that MH-06 dose-dependently decreases reactive oxygen species (ROS) production, restores mitochondrial function, inhibits the MAPK signaling pathway and modulates macrophage polarization, thereby lowering the release of pro-inflammatory cytokines. In the cerulein-induced AP mouse model, MH-06 exerted remarkable therapeutic and preventive effects. Collectively, this work offers new perspectives and promising chemical entities for the development of targeted therapies against AP. Given its favorable pharmacological profiles, MH-06 merits further detailed investigation.
Hepatocellular carcinoma (HCC) is characterized by lipid metabolic reprogramming. Valproic acid (VPA), a widely used antiepileptic drug known to modulate lipid homeostasis, has shown potential anti-HCC activity; however, its impact on lipid remodeling and the underlying mechanism remains unclear. We employed an integrated approach combining lipidomics, network pharmacology, molecular docking, and molecular dynamics simulations to investigate this. In HepG2 tumor-bearing mice, VPA dose-dependently inhibited tumor growth. Lipidomics identified 210 and 98 differential lipids in the 250 mg/kg and 500 mg/kg groups, respectively, primarily enriched in glycerophospholipid and choline metabolism, with 17 overlapping species in both groups. Target screening revealed 127 lipid metabolism-related targets of VPA in HCC, including 10 core targets such as PLA2G10, LCAT, and PON1. Docking and dynamics simulations confirmed stable VPA-LCAT binding, supported by functional evidence of elevated PC/LPC ratio and reduced cholesterol esterification. These findings demonstrate that VPA significantly remodels the lipid metabolic microenvironment in HCC, and these multifaceted changes offer new insights into its anti-HCC mechanisms.
The aging population, particularly women, faces complex biopsychosocial health and social challenges, necessitating whole-person approaches and innovative research methods to better understand health and well-being to guide effective interventions. The objective of this pilot comparative cross-sectional study was to examine whole-person health and resilience of older adult women ages 65 and older in the United States and Türkiye. Data were collected from adult women in the United States (n=25) and Türkiye (n=25) between March and August 2024. Whole-person health was evaluated using the MyStrengths+MyHealth application, and resilience was measured using the 14-item Resilience Scale. Data were analyzed using descriptive and inferential statistics to examine between-group differences. The average age for the US participants was 78 (SD=6.2), and the average age for the Turkish participants was 68 (SD=2.8). There were significant differences in average self-reported strengths (P<0.001), challenges (P<.001), and needs (P<.001) between US and Turkish participants. US participants had a higher mean Resilience score [88.0 (SD=5.3)] versus Turkish participants [74.9 (SD=14.7)] (P<.001). The study revealed that both groups had above-average resilience and had both common strengths and differences in health challenges and needs. These findings highlight the importance of prioritizing a whole-person health approach when developing strengths-based interventions to address the complex and diverse needs of older women.
Extreme temperature events driven by climate variability are increasingly threatening biodiversity and ecosystem functioning. Intertidal ecosystems are particularly exposed to heatwaves, and face mass mortalities, local extinctions, and range contractions among keystone species, with cascading effects on biodiversity, carbon sequestration, coastal defences, and fisheries. Symbiotic interactions play a crucial role in shaping host resistance to environmental stress, particularly thermal stress intensified by climate change. This study evaluated the potential thermal buffering effects of shell corrosion by symbiotic endoliths on the Pacific oyster (Magallana gigas) under heat stress. Laboratory and field experiments revealed significantly higher survival rates in corroded oysters, with a significant thermal buffer as high as 9.5 °C in natural settings. Spectrophotometric analyses further showed that endolithic corrosion alters shell optical properties (pale in colour - lightness, chromatic axes and reflectance), linking shell colour shifts directly to enhanced thermal buffering. While similar patterns have been previously observed in mussels, the thermal buffer effect in oysters is substantially higher, highlighting species-specific differences in the magnitude of symbiont-mediated thermal resistance. These findings contribute to a broader framework for understanding how host-symbiont interactions modulate thermal resistance across diverse marine calcifiers, highlighting the adaptive potential of shell corrosion in enhancing resistance to rising temperatures.
Click chemistry is a highly reliable and straightforward method for bioconjugation. It exhibits high selectivity and biocompatibility, rendering biorthogonal tagging and regenerative medicine. Its transformative applications in targeted therapy, drug delivery, molecular imaging, and nanotechnology are paving the way for groundbreaking advancements in chemistry and biology. In this review, we discuss the detailed application of Copper-catalysed azide-alkyne cycloaddition (CuAAC), with limited examples of SPAAC, IEDDA, SuFEX, SeNEx and PFEx including recent advances in bioconjugation through the application of bioorthognal methods using click chemistry, focusing on the synthesis of privileged bioconjugates during 2020-2025. Thus, this review highlights the significance of click chemistry as a powerful method for bioconjugation, providing a valuable resource for the scientific community on click chemistry and its applications in biomedical sciences.
Colorectal cancer (CRC) is usually diagnosed when therapeutic options are limited, highlighting the need for novel molecular targeted therapies. MicroRNAs, as important regulators in cancer-related pathways, may provide therapeutic targets through their gene networks; however, the role of the miR-625-5p network in CRC remains unclear. Therefore, this study aimed to identify potential therapeutic targets in CRC through miR-625-5p-regulated network analysis. miR-625 expression in TCGA samples was analyzed to assess its potential role in CRC development/progression. miR-625-5p targets were integrated from multiple resources to construct a protein-protein interaction network (PPIN) and identify clusters and key hub genes using Cytoscape. Key hub genes underwent enrichment analysis using DAVID and CancerHallmarks, followed by validation in independent CRC datasets from GEO and TCGA. Validated Key hub genes were further analyzed using TNMplot and Kaplan-Meier survival analysis to assess their expression patterns and prognostic significance, respectively. Druggability of the prognostic final hub gene was assessed using the Open Targets Platform. miR-625 was significantly downregulated in CRC, particularly in advanced stages (p-value < 0.05). PPIN analysis of 755 target genes identified 24 key hub genes and four functional clusters. Enrichment analysis of key hub genes showed involvement in regulation of apoptotic processes, programmed cell death, and cancer-related pathways. Five candidate genes were validated in GEO and TCGA datasets; three were confirmed in TNMplot, and only HSP90AB1 was associated with poorer disease-free survival (p-value < 0.05) and exhibited druggable potential in CRC. HSP90AB1 is a candidate therapeutic target in CRC.
This study focuses on characterizing the voices that are amplified through peer reviewed publication and how they relate to one another. This study aims to 1) identify patterns of author collaboration and representation, 2) assess how this varies among different journals, 3) examine the relationship between author collaboration and quantitative publication. This is a bibliometric analysis using descriptive statistics and network analysis, examining all publications in four influential emergency medicine journals from January 2015 through December 2024. Authors and journals were assessed on quantity of publications, patterns of co-authorship, and network characteristics of individual and aggregate journals. There is a sharp right-skew of authorship - most authors have only a single article published in ten years. The most prolific authors in emergency medicine demonstrate significantly more publications than their peers. Journals show a propensity to publish multiple articles from a small number of authors, but there is variation among journals as to how many unique authors appeared during the timeframe studied. There was a gender disparity identified among the top authors, most of whom were men. Bibliometric analysis is able to demonstrate academic influence while also casting light on the role of journals in peer-reviewed publication patterns. Publication is a vital component of academic success and tangible evidence of professional influence. How authors collaborate and journals select manuscripts is impactful, and unfortunately this study demonstrates inequity among the most visible authors in the most impactful journals.
The strengthening of steel structures with carbon fiber reinforced polymer (CFRP) composites has gained wide acceptance in civil engineering, yet interfacial bonding defects such as inclusion, delamination, and porosity can severely degrade structural performance. Conventional ultrasonic testing often suffers from noise contamination and limited feature extraction, restricting the reliability of defect identification. To address this issue, this study integrates phased array ultrasonic testing (PAUT) with encoder-assisted acquisition and advanced signal processing. Wavelet packet transform (WPT) was applied to denoise and decompose A-scan signals, from which eight statistical energy-based features were extracted to construct discriminative feature vectors. These vectors were then used to train and compare three backpropagation artificial neural network (BP-ANN) variants. The BP-ANN trained with the conjugate gradient algorithm achieved the highest overall accuracy of 95.83% among the three investigated optimization strategies. The results indicate that WPT-based feature engineering improves the discriminative capability of ultrasonic features under controlled laboratory conditions, while encoder-assisted acquisition improves the consistency of PAUT signal collection. The proposed framework provides a feasible approach for intelligent classification of interfacial defects in CFRP-steel hybrid structures and may serve as a reference for future studies involving real manufacturing defects and practical engineering scenarios.
Precise spatial positioning of cellular constituents is critical for bacterial replication, interactions, and behavior. Rod-shaped bacteria may concentrate molecules and machinery at the cell poles, often by leveraging polar scaffolding proteins to recruit other factors. These typically small proteins can self-assemble into higher-order structures that provide platforms to direct fundamental processes like chromosome segregation, division plane selection, and differentiation. Beyond fundamental cellular processes, polarity is implicated in a wide range of bacterial behaviors, including environmental sensing, intercellular interactions, and motility. In this review, we describe polarity-determining factors and their cellular functions specifically in bacterial predators and in host-associated bacteria, including plant and human pathogens. We aim to highlight pivotal roles cell polarity plays in promoting fitness vis-à-vis the host-microbe and microbe-microbe interface.
Epidermal Growth Factor Receptor (EGFR) signalling plays a key role in the progression of chronic kidney disease (CKD), as its persistent activation promotes inflammation, fibrosis, and tubular cell proliferation. Aberrant EGFR expression and overactivation have therefore been associated with renal injury and disease progression, making it a relevant biomarker and potential therapeutic target in CKD. Our goal was to repurpose known fluorescent ligands, originally developed for other targets, to study EGFR expression at the kidney cell membrane in healthy and diseased conditions, providing a potential tool for disease detection and staging. Drug repurposing leverages existing pharmacokinetic and safety data, reducing time and costs, and can transform off-target effects into new applications through structure-based and AI-driven approaches. We built a database of 47 commercially available fluorescent ligands with fully disclosed structures and screened them by molecular docking against EGFR. Two promising candidates were identified and validated through preliminary kinase inhibition assays. Their performance was then evaluated in three cell lines with different EGFR expression levels (RCC, HK-2, and EGFR-negative EA.hy926). Notably, the harmonic integration of in silico and experimental approaches proved effective in the rational repurposing of two fluorescent organic ligands as probes for the detection of EGFR overexpression in CKD.
The overexpression of dimethylarginine dimethylaminohydrolase 1 (DDAH1) and 2 (DDAH2) has been associated with several types of cancer. Specifically, DDAH1 has been shown to play a critical role in the establishment of a vascular network by tumour cells, vasculogenic mimicry (VM), in triple negative breast cancer (TNBC). In turn, VM favours TNBC progression and is associated with poor patient prognosis. DDAH1 is well characterised in its capacity to metabolise asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor. By contrast, DDAH2 is incapable of metabolising ADMA, and its ADMA-independent functions and role in TNBC are unknown. In an in vitro MDA-MB-231 TNBC cell model, CRISPR-Cas9 knockout and siRNA knockdown of either DDAH1 or DDAH2 significantly reduced VM. This effect was accompanied by a significant reduction in proliferation, migration, invasion, and Vascular endothelial growth factor A (VEGF-A) secretion. These results suggest ADMA-independent mechanisms for DDAH2 in the occurrence of VM and identify DDAH2 as a novel therapeutic target in TNBC.
Despite the effectiveness of the COVID-19 vaccine, vaccination rates vary across settings and populations, especially among people living with HIV (PLHIV). We assessed factors associated with COVID-19 vaccination among PLHIV in Mbarara, Uganda. We conducted a cross-sectional, secondary analysis of a prospective cohort study consisting of PLHIV ≥18 years old on antiretroviral therapy (ART). We collected data on COVID-19 vaccine uptake and associated factors beginning in December 2021, 9 months after the vaccine became available in Uganda. Reasons for vaccine acceptance and hesitancy were analyzed descriptively, while factors associated with vaccine uptake were assessed using Poisson models with robust standard errors. We analyzed data from 449 participants with a mean age of 46 years (SD 9) and ART duration of 10 years (SD 4). 42% were female, 96% were virally suppressed (<50 copies/mL), and 83% (95% CI = 75%-92%) reported vaccination for COVID-19. In unadjusted analyses, greater concern about COVID-19, obtaining COVID-19 information from health resources, longer ART duration in years, and continuous access to soap and water were positively and significantly correlated with vaccine uptake (p < 0.05). Among those unvaccinated (n = 77/449, 17%), fear of side effects (n = 32/77, 42%) and beliefs that vaccination increased infection risk (n = 12/77, 16%) were predominant reasons for vaccine hesitancy. We found high rates of COVID-19 vaccination among PLHIV on ART in Uganda. Among those unvaccinated, lack of confidence in the safety of the vaccine was the primary barrier to uptake. Future vaccine campaigns should emphasize vaccine safety and efficacy and actively combat misinformation to promote uptake. Clinical Trials Registration. NCT04066036.
Molecular hydrogen has been reported to exert antioxidant and anti-inflammatory effects; however, its impact on inflammation and gut microbiota under aging-associated metabolic stress remains unclear. In this study, we investigated the effects of hydrogen-rich jelly (HRJ) in senescence-accelerated mouse prone-8 (SAMP8) mice fed a high-fat/high-sucrose diet (HFHSD). HFHSD feeding induced adipose tissue inflammation, metabolic disturbances, and alterations in gut microbiota composition. Treatment with HRJ suppressed macrophage infiltration into adipose tissue, reduced inflammatory cytokine levels, and restored adiponectin levels. HRJ also partially improved glucose tolerance and metabolic parameters. Gut microbiota analysis revealed that HFHSD was associated with differences in microbial community structure based on beta diversity analysis, whereas HRJ treatment was associated with exploratory changes in specific bacterial taxa and predicted microbial functions, although these changes did not remain significant after FDR correction. These findings suggest that molecular hydrogen attenuates HFHSD-induced metabolic disturbances primarily through suppression of adipose inflammation. Although exploratory changes in gut microbial composition were observed, their biological significance remains unclear and requires further investigation.
Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is an autosomal recessive metabolic disorder resulting from biallelic pathogenic variants of the SLC25A13 gene. Because NICCD requires immediate and specific dietary management, which differs fundamentally from the treatment of idiopathic neonatal hepatitis (INH), rapid and noninvasive diagnostic tools are crucial. The aim of this study was to systematically evaluate the diagnostic accuracy of amino acid-derived metabolic ratios. This retrospective study analyzed 29 patients with genetically-confirmed NICCD who were evaluated at a single tertiary center between 2011 and 2026. To comprehensively evaluate diagnostic utility, a two-tiered receiver operating characteristic analysis was conducted comparing the NICCD cohort with both a total INH clinical cohort (n = 39) and a genetically-negative INH subgroup (n = 18). The diagnostic performance of amino acid-derived metabolic ratios was comparable to that of individual citrulline levels. The citrulline/alanine and citrulline/tryptophan ratios achieved favorable diagnostic accuracy, maintaining an area under the curve > 0.95, sensitivity > 85%, 100% specificity, and 100% positive predictive value across both control cohorts. The threonine/alanine ratio exceeded the established threonine/serine ratio. Genotype-phenotype analysis indicated that the c.852_855del variant was associated with abnormal newborn screening (p = 0.016), whereas the IVS16ins3kb variant consistently yielded normal results (p = 0.011). The citrulline/alanine, citrulline/tryptophan, and threonine/alanine ratios serve as highly accurate biomarkers that reflect and enhance the detection of the unique metabolic profile of NICCD. Integration of these indices into clinical protocols can reduce the time to diagnosis and facilitate prompt dietary and medical interventions.
The field of engineered living materials (ELMs) aims to create self-regenerative, self-assembled, and multifunctional materials that mimic natural biomaterials. Novel ELMs can be produced by engineering biomolecules that are naturally secreted and displayed on bacterial cell surfaces. Surface-layer (S-layer) proteins are a class of proteins that form a two-dimensional paracrystalline lattice on the surface of many prokaryotes. These proteins provide a secretion, surface-anchoring, and high-density display platform that can be exploited for material formation. In this review, we discuss two strategies to engineer S-layer proteins for ELMs by looking at their state of the art, analyzing their advantages and disadvantages, and discussing their challenges and opportunities.
Five novel halophilic archaeal strains, designated DTA46T, DTA98T, HHNYT27T, N11T, and SY-15T, were isolated from diverse saline environments across various regions of China. Amplicon and metagenome analyses revealed that three amplicon reads were affiliated with strains DTA46T, HHNYT27T, and N11T while two MAGs related to strains N11T and SY-15T. The sequence similarities among these five strains and current species of the genus Halorubrum were 93.1%-99.1% and 86.0%-95.9% judged by 16S rRNA and rpoB' genes, respectively. Phylogenomic and comparative genomic analyses revealed their close affiliation with Halorubrum. The average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH), and average amino acid identity (AAI) values between these strains and existing Halorubrum species ranged from 74.9%-93.6%, 22.3%-58.3%, and 68.3%-93.7%, respectively. All are below the recommended thresholds for species delineation, which supports their classification as novel taxa. The growth characteristics of strains DTA46T, DTA98T, HHNYT27T, N11T, and SY-15T were determined as follows: temperature range 20-60 °C (optima: 35, 37-42, 37, 35, and 42 °C), NaCl concentration 1.4-5.5 M (optima: 2.6, 3.1, 3.1, 3.1, and 5.1 M), and pH range 5.5-9.5 (optima: 8.0, 8.0, 7.0, 7.5, and 7.0). Based on the polyphasic characterization integrating phenotypic, chemotaxonomic, phylogenetic, and phylogenomic evidence, strains DTA46T, DTA98T, HHNYT27T, N11T, and SY-15T are proposed to represent five novel species of the genus Halorubrum, for which the names Halorubrum marinum sp. nov., Halorubrum rarum sp. nov., Halorubrum wangae sp. nov., Halorubrum shenae sp. nov., and Halorubrum zhoui sp. nov. are designated, respectively.
To evaluate longitudinal trends in gender and regional equity in membership and governance representation within the European Society of Gynaecological Oncology and the European Network of Young Gynaecological Oncologists. We analyzed European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists membership and governance data from 2013 to 2024. Descriptive analyses were supplemented with multi-variable logistic regression models to identify predictors of female membership and European Society of Gynaecological Oncology Council representation, including European Network of Young Gynaecological Oncologists status, calendar year or Council term, and United Nations geographic region. European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists membership increased from 1588 members in 2013 to 3385 in 2024, and female members reached parity by 2024. Female membership was associated with European Network of Young Gynaecological Oncologists participation (odds ratio 1.82, 95% confidence interval 1.73 to 1.91, p <.001) and calendar year (odds ratio 1.04 per year, 95% confidence interval 1.03 to 1.05, p <.001). Compared with Western Europe, female membership was higher in Northern Europe (odds ratio 1.69, 95% confidence interval 1.55 to 1.84, p <.001) and lower in Eastern Europe (odds ratio 0.78, 95% confidence interval 0.71 to 0.85, p <.001) and non-European regions (odds ratio 0.80, 95% confidence interval 0.74 to 0.86, p <.001). Gender was not associated with Council membership (odds ratio 0.95, 95% confidence interval 0.63 to 1.42, p =.79), and no independent temporal trend was observed (odds ratio 0.91 per term, 95% confidence interval 0.81 to 1.03, p =.13). Geographic variation was evident, with lower odds of Council representation in Eastern Europe (odds ratio 0.54, 95% confidence interval 0.28 to 0.98, p =.05), while estimates for non-European regions were unstable because of sparse representation. European Society of Gynaecological Oncology and European Network of Young Gynaecological Oncologists have made substantial progress toward gender equity at the membership level, largely through early-career engagement. Governance representation appears to be influenced more by geographic and structural factors than by gender, highlighting the need for equity-focused strategies that sustain gender-balanced leadership development while addressing regional disparities.