Implementation Science (IS) is the study of methods and strategies that facilitate the uptake of evidence-based practice and research into regular use. The use of IS in graduate surgical education has not been well characterized. This scoping review aims to identify key barriers, facilitators, and best practices for integrating IS into surgical education. Embase, PubMed, Scopus, Cochrane Library, and ERIC were searched in accordance with PRISMA guidelines. Included studies utilized a validated IS strategy to implement an educational or curricular intervention for surgical residents. Qualitative analysis was used to map the IS theories, models, and frameworks used in the included studies to existing IS frameworks, as well as characterize barriers and facilitators to implementation via the Theoretical Domains Framework (TDF). Six studies were identified with surgical residents from general surgery, urology, obstetrics-gynecology, vascular surgery, and cardiothoracic surgery programs. Each study used a different approach informed by IS to successfully implement an educational intervention (e.g., quality improvement research curriculum, faculty-resident coaching program, or surgical skills simulation course). IS theories, models, and frameworks included: the Replicating Effectiveness Programs Framework, Fixsen's 6-stage Implementation Framework, Expert Recommendations for Implementing Change, RE-AIM Framework, Normalization Process Theory, and Theory of Change Methodology. Barriers to implementation included variability in resident schedules and competing demands of clinical responsibilities. Facilitators to implementation included protected didactic time, endorsement from program leadership, and incorporation into established educational programming. The studies identified in this review utilized a variety of IS theories, models, and frameworks to successfully implement new educational practices. The majority of barriers and facilitators identified fit into the "Environmental Context and Resources" and "Social Influences" domains of the TDF. Key facilitators to implementation shared across the six studies included protected didactic time, buy-in from leadership, and integration into established resident education time. IS represents a promising field for enhancing graduate surgical education.
This study aimed to describe overall survival outcomes by treatment modality among women with International Federation of Gynecology and Obstetrics stage I to IVA cervical cancer treated with external beam radiotherapy using a boost technique in Rwanda, where brachytherapy is unavailable. We conducted a retrospective cohort study of women with International Federation of Gynecology and Obstetrics stage I to IVA cervical cancer treated at the Rwanda Cancer Centre/Rwanda Military Teaching Hospital between July 2018 and April 2023. All patients were planned for pelvic external beam radiotherapy with a simultaneous integrated boost (45 Gy to the whole pelvis with a boost to 70 Gy to the primary tumor and involved nodes in 30 fractions) delivered using intensity-modulated radiotherapy. Overall survival was defined as the time from the date of pathologic diagnosis to death or last contact, and was censored at 3 years. Overall survival was estimated using Kaplan-Meier methods and compared using log-rank tests. Multi-variable Cox regression with multiple imputation for missing covariates was used to assess associations between treatment modality and overall survival. Of 591 women seen, 577 met the eligibility criteria. Most (42.7%) presented with stage III disease. Treatment allocation was as follows: no treatment (12.7%), radiotherapy alone (3.9%), concurrent chemoradiotherapy (67.5%), and induction chemotherapy followed by concurrent chemoradiotherapy (15.9%). Two-year overall survival was 13.9% for no treatment, 44.1% for radiotherapy alone, 62.2% for concurrent chemoradiotherapy, and 76.4% for induction chemotherapy plus concurrent chemoradiotherapy. In adjusted models, all active treatment modalities were associated with lower hazards of death compared with no treatment. In this cohort in which brachytherapy was unavailable, survival among women with cervical cancer was strongly determined by treatment modality. Timely delivery of concurrent chemoradiotherapy, with or without induction chemotherapy, achieved 2-year overall survival comparable to regional reports, whereas absence of treatment was associated with dismal outcomes. These findings reinforce the urgent need to invest in brachytherapy capacity in Rwanda and similar resource-constrained settings.
The 2023 update of the International Federation of Gynecology and Obstetrics (FIGO) staging system introduced significant changes in the classification of endometrial cancer by incorporating key pathological and molecular features. This study aimed to evaluate the impact of the revised FIGO 2023 staging system on stage distribution and adjuvant treatment decisions in patients undergoing surgical management of this malignancy. This retrospective study included 220 patients who underwent surgical staging for endometrial cancer between January 2018 and December 2025. All patients were initially staged using the FIGO 2009 classification. Cases were subsequently reclassified according to the FIGO 2023 staging criteria, using the algorithm proposed for settings in which routine molecular classification is unavailable. The McNemar test was used to compare stage categories between the two staging systems, and the Wilcoxon signed-rank test was applied to evaluate the impact of stage migration on adjuvant treatment recommendations. Stage migration occurred in 12.7% of patients (28/220) following the application of the FIGO 2023 criteria, predominantly due to upstaging. The most common factor associated with stage reclassification was substantial lymphovascular space invasion (LVSI). The proportion of patients managed with observation alone significantly decreased from 44.5% to 32.7% (p<0.001), while the use of pelvic radiotherapy increased from 19.1% to 28.2% (p=0.004). Similarly, the proportion of patients receiving combined chemoradiotherapy significantly increased from 11.8% to 17.3% (p=0.012). The implementation of the FIGO 2023 staging system has resulted in clinically meaningful stage migration and significantly impacted adjuvant treatment strategies. In particular, the recognition of substantial LVSI as a defining feature of stage IIC disease has led to more intensive adjuvant therapy in a subset of patients previously categorized as low risk. Uluslararası Jinekoloji ve Obstetrik Federasyonu (FIGO) evreleme sisteminin 2023 güncellemesi, endometriyum kanserinin sınıflandırılmasında temel patolojik ve moleküler özellikleri içerecek şekilde önemli değişiklikler getirmiştir. Bu çalışmanın amacı, revize edilen FIGO 2023 evreleme sisteminin cerrahi tedavi uygulanan endometriyum kanseri hastalarında evre dağılımı ve adjuvan tedavi kararları üzerindeki etkisini değerlendirmektir. Bu retrospektif çalışmaya Ocak 2018 ile Aralık 2025 tarihleri arasında endometriyum kanseri nedeniyle cerrahi evreleme uygulanan hastalar dahil edilmiştir (n=220). Tüm hastalar başlangıçta FIGO 2009 sınıflamasına göre evrelendirilmiştir. Bu çalışmanın amacı doğrultusunda olgular daha sonra, rutin moleküler sınıflandırmanın yapılamadığı durumlar için önerilen algoritma kullanılarak FIGO 2023 evreleme kriterlerine göre yeniden sınıflandırılmıştır. İki evreleme sistemi arasındaki evre kategorilerini karşılaştırmak için McNemar testi, evre değişiminin adjuvan tedavi önerileri üzerindeki etkisini değerlendirmek için ise Wilcoxon işaretli sıralar testi kullanılmıştır. FIGO 2023 kriterlerinin uygulanması sonrasında hastaların %12,7’sinde (28/220) evre değişimi saptanmış olup bu değişim çoğunlukla evre yükselmesi şeklinde gerçekleşmiştir. Evre yeniden sınıflandırmasına yol açan en sık faktör substantif lenfovasküler alan invazyonu (LVSI) olmuştur. Yalnızca gözlem ile takip edilen hasta oranı %44,5’ten %32,7’ye düşerken (p<0.001), pelvik radyoterapi uygulanan hasta oranı %19,1’den %28,2’ye yükselmiştir (p=0.004). Benzer şekilde kombine kemoradyoterapi uygulanan hasta oranı da %11,8’den %17,3’e artmıştır (p=0.012). FIGO 2023 evreleme sisteminin uygulanması klinik olarak anlamlı evre değişimine yol açmış ve adjuvan tedavi stratejileri üzerinde önemli bir etki oluşturmuştur. Özellikle substantif LVSI evre IIC hastalığın tanımlayıcı bir özelliği olarak kabul edilmesi, daha önce düşük riskli olarak değerlendirilen bazı hastalarda daha yoğun adjuvan tedavi uygulanmasına neden olmuştur.
Does the degree of extravillous trophoblast (EVT) invasion influence decidual tissue architecture and immune cell distribution in first-trimester decidua? Areas of pronounced morphological changes have been identified at sites of strong EVT invasion in the decidua basalis-defined as 'remodeling lesions'-and are associated with a substantially reshaped immune cell landscape. During early human placental development, EVTs invade the decidua to facilitate placental attachment and nutrient supply to the fetus. EVT-driven decidual tissue restructuring and vascular adaptation are essential for establishing a functional fetal-maternal interface, to which the decidual microenvironment is thought to contribute substantially. However, the precise impact of the degree of EVT invasion on decidual architecture and immune cell distribution remains poorly understood, underscoring the need to elucidate how varying EVT abundances shape the morphological and cellular landscape of the decidual microenvironment. First-trimester decidual tissue (n = 23, gestational age Weeks 7-9) was analyzed from women undergoing elective terminations of pregnancy between 2011 and 2023. Additionally, hematoxylin and eosin-stained sections from archival specimens (n = 11), obtained from three different sources, were included in the study. Matched first-trimester decidua basalis and decidua parietalis samples from the same donors were analyzed through a comprehensive approach combining spatial transcriptomics, histomorphological characterization, and quantitative image analysis. Decidua sections were (i) categorized according to the degree of invasion, (ii) subjected to spatial transcriptomics, including integration with a previously published single-cell RNA-seq dataset, and (iii) quantitatively assessed on the protein level for selected immune cell populations with immunostaining and semi-automated image analysis. The study was complemented by (iv) an observer-based histological evaluation and (v) comprehensive staining series of consecutive decidua sections. Analyses revealed a characteristic tissue restructuring of the decidua and distinct spatial patterns of immune cell abundance in relation to the degree of EVT invasion. In strongly invaded decidual areas, we identified regions with pronounced morphological changes-defined as 'remodeling lesions'. These remodeling lesions typically displayed compromised tissue integrity, eroded blood vessels, extravasal erythrocytes, fibrin deposits, and a distinct gene expression profile, reflecting coagulation, fibrinolysis, and tissue restructuring. While we observed a decline in local immune cell populations-specifically T cells, macrophages, and decidual natural killer cells-with increasing EVT density, neutrophils were almost exclusively located within or in close proximity to remodeling lesions, indicating a substantially reshaped immune landscape. Spatial transcriptomics data are available in the Gene Expression Omnibus repository under accession number GSE301306. Studies using first-trimester placental tissues from elective terminations are inherently limited by surgical disruption of the intact (in toto) anatomical architecture of the tissue and the unknown pregnancy outcome. Spatial transcriptomics was performed on a limited number of tissue sections, and histological tissue sections represent just a snapshot, highlighting the limitations of such tissue-based analyses. While blood leakage into the stromal tissue compartment has typically been documented for pathological conditions-such as large atherosclerotic plaques and tumors-we report such a scenario under physiological conditions for the early invaded decidua. We propose that strong EVT invasion induces remodeling lesions in the decidua basalis and also shapes the surrounding immune cell landscape. We further suggest that the occurrence of these remodeling lesions contributes to the establishment of a stable yet flexible basal plate and is thus necessary for a reliable connection between mother and placenta/fetus. It can be speculated that inadequate decidual tissue restructuring and vascular adaptation lead to pregnancy pathologies and complications such as placental abruption. G.M. was supported by the Austrian Science Fund (FWF): PAT9611123. M.G. was supported by the Austrian Science Fund (FWF): 10.55776/P35118 and 10.55776/I6907. This project has received funding from the European Union's Horizon Europe research and innovation programme under the Marie Skłodowska-Curie grant agreement No 101169308 (funding supported M.G.). M.G., G.M., and J.F. were supported by the Medical University of Graz through the PhD program MolMed. J.F. and G.M. were supported by the COMET center acib: Next Generation Bioproduction (Project #98.311 and #95.802) is funded by BMIMI, BMWET, SFG, Standortagentur Tirol, Government of Lower Austria and Vienna Business Agency in the framework of COMET-Competence Centers for Excellent Technologies. The COMET-Funding Program is managed by the Austrian Research Promotion Agency FFG. The authors declare that they have no conflicts of interest related to this work.
To compare the anatomical and functional outcomes of unilateral versus bilateral high uterosacral ligament suspension performed following vNOTES hysterectomy for apical pelvic organ prolapse. Prospective observational cohort study. Department of Obstetrics and Gynecology, Gazi Yaşargil Training and Research Hospital, Diyarbakır, Türkiye. A total of 160 women aged ≥40 years with symptomatic uterine prolapse undergoing hysterectomy followed by uterosacral ligament suspension. Patients were divided according to surgical technique into unilateral (n = 70) and bilateral (n=90) high uterosacral ligament suspension performed after vNOTES hysterectomy. The primary outcome was short-term objective anatomical success at 12 months, defined as apical support with point C ≤-1 cm according to the POP-Q system. Both techniques resulted in significant improvement in POP-Q parameters. Apical support improved markedly in both groups with no significant difference between unilateral and bilateral suspension (p=0.88). Perioperative outcomes, including operative time, hemoglobin decrease, hospital stay, and postoperative pain, were comparable. Patient-reported outcomes (POPDI-6, CRADI-8, UDI-6, and PISQ-12) also improved substantially in both groups. Postoperative complications were uncommon (7.1% vs 8.9%). Both unilateral and bilateral uterosacral ligament suspension following vNOTES hysterectomy provide effective anatomical and functional improvement in apical pelvic organ prolapse. Unilateral suspension yields outcomes comparable to bilateral suspension and may simplify the surgical procedure. At 12 months, unilateral suspension showed outcomes comparable to bilateral suspension; however, longer follow-up is needed before drawing firm conclusions about its role as an alternative approach.
Medical doctors face occupational stressors threatening their mental health, particularly junior doctors in South Africa. There is a higher prevalence of depressive symptoms among medical doctors compared with the general population. The consequences of this to health systems and the patients doctors treat is a major public health concern. In South Africa, prevalence of depressive symptoms among community service doctors servicing public sector healthcare is largely unknown. To determine the prevalence of possible depression, and predictive factors thereof, among doctors in their community service year in South Africa. A national descriptive cross-sectional survey was distributed electronically between October and December 2022. The Patient Health Questionnaire 9 (PHQ-9) was used to screen for depression. Demographic, occupational and individual characteristics were included as potential predictive factors. A total of 217 participants were included in the analyses. Prevalence of depressive symptoms was 96.3% (standard error 0.13, 95% confidence interval 92.87 - 98.40%). Predictors of higher scores included: women, drug use, feeling neutral or disagreeing that one worked outside of normal working hours, working in KwaZulu-Natal or North West, burnout (emotional exhaustion), working in orthopaedics, obstetrics and gynaecology departments or the National Health Laboratory Service, first choice of placement, financial difficulties, and accessing mental health services. Predictors of a lower score included: perceiving sufficient resources at work, using colleagues to cope, good work-life balance, and certain departments, particularly neurosurgery. There is an extremely high prevalence of depressive symptoms among community service doctors. Supporting these doctors at an individual, organisational and structural level should be a priority for national policy-makers.
Do variants in YTH N6-methyladenosine RNA binding protein C2 (YTHDC2) cause male infertility in humans, and what is the underlying pathogenic mechanism? Biallelic pathogenic missense variants in YTHDC2 disrupt the mitotic-to-meiotic transition, causing meiotic arrest and non-obstructive azoospermia (NOA) or severe oligozoospermia in humans. YTHDC2 is a male germ cell-specifically expressed RNA helicase essential for meiotic progression. In mice, loss of Ythdc2 leads to meiotic arrest at the early prophase. However, clinical evidence linking YTHDC2 variants to human male infertility and the underlying mechanisms involved remains to be established. This study utilized a large cohort comprising 56 consanguineous families and 89 sporadic infertile men diagnosed with NOA or severe oligozoospermia. Through extensive genetic screening, we specifically identified five infertile men from three unrelated families who harbored candidate pathogenic variants in the YTHDC2 gene. The overall study design encompassed genetic screening followed by in vivo functional validation using a knock-in mouse model. Whole-exome sequencing (WES) and bioinformatic analyses were performed on the patient cohort to screen for candidate pathogenic variants. Human meiotic defects were characterized via histological analyses and immunofluorescence staining of testicular sections. To validate the pathogenicity of the identified variant, a knock-in mouse model harboring the equivalent variant found in patients was generated by CRISPR/Cas9 technology, and analyzed for spermatogenesis and meiosis using spermatocyte spreading and immunofluorescence staining, quantitative real-time PCR, and western blotting. Two homozygous missense variants in YTHDC2 were identified in four NOA patients from two unrelated consanguineous families (MT1: c.3491A>T, p. E1164V; MT2: c.2639G>A, p. R880H), and compound-heterozygous missense variants were identified in a sporadic patient with severe oligozoospermia (MT3: c.1145A>G, p. D382G; MT4: c.292A>G, p. R98G). The MT1 variant (p.E1164V) is not located in any annotated domains, the other three variants reside within known functional domains of YTHDC2 protein. The knock-in mouse model carrying the MT1 variant recapitulated the patient's phenotype, with both exhibiting meiotic prophase arrest during spermatogenesis. Mechanistically, significantly decreased levels of MEIOC and RBM46, two YTHDC2-interacting proteins required for meiotic transcriptome reprogramming, were observed in the patient's testes. Concurrently, mitotic cell cycle regulators such as CCNA2, CCND1, and WEE1 were aberrantly upregulated in the patient's testicular cells expressing meiosis markers, indicating a failure to silence the mitotic program upon meiotic entry. This study is limited by the small sample size of patients with pathogenic YTHDC2 variants. While the MT1 variant was functionally validated in vivo, the specific pathogenic mechanisms of the other variants identified require further investigation. Our findings provide direct clinical evidence establishing the pathogenicity of YTHDC2 variants in human NOA. The study reveals a conserved role for YTHDC2 in safeguarding the mitotic-to-meiotic transition by suppressing mitotic gene expression while maintaining the meiotic program. These findings expand the genetic spectrum of male infertility and suggest YTHDC2 screening as a promising approach for the genetic diagnosis of male infertility. This work was supported by the National Key Research and Developmental Program of China (2022YFA0806303 to H.Z., and 2024YFC2706801 to H.J.); the National Natural Science Foundation of China (32470898 to H.Z., W2412028 and 32330032 to Q.S., 32470915 to B.S.); the State Key Laboratory of Reproductive Medicine and Offspring Health, Nanjing Medical University (SKLRM-K202405); and the Open Research Project of Fuyang Normal University (FYKFKT24023). The authors declare no competing interests. N/A.
This study aimed to investigate the relationship between breastfeeding and precancerous cervical lesions. A case control study was conducted at a tertiary training and research hospital between September 1 and November 1, 2023. A total of 168 patients who attended the gynecology outpatient clinic and reported their breastfeeding experiences were included. Patients with abnormal cervical cytology formed the study group (n = 37), while patients with normal cytology formed the control group (n = 131). Breastfeeding duration and patterns were compared between groups. The control group had normal smear results. In the study group, 15 patients had high-grade squamous intraepithelial lesions, and 22 patients had low-grade squamous intraepithelial lesions. Human papillomavirus (HPV) was positive in 54.1% of the study group versus 9.2% of the control group. The mean breastfeeding duration was shorter in the study group (9.18 ± 3.43 months) than the control group (23.6 ± 3.35 months; p < 0.05). Most control group patients breastfed for 13-36 months (35.1%), while most study group patients breastfed for <6 months (48.6%; p < 0.05). Shorter breastfeeding (<6 months) and HPV positivity were the strongest predictors of abnormal cytology. Breastfeeding <6 months increased the risk 9.883-fold compared with >36 months, while HPV positivity increased the risk 27.612-fold. Breastfeeding and longer breastfeeding duration appear to be associated with a lower risk of cervical intraepithelial neoplasia. Given its multiple health benefits, including prevention of gynecological cancers, promoting breastfeeding through public health policies is strongly recommended. Early recognition and prevention of precancerous lesions remain essential to reducing the risk of cervical cancer.
To systematically evaluate the impact of open versus minimally invasive radical hysterectomy on survival outcomes in cervical cancer patients. Relevant literature from the past 10 years was searched in PubMed, Web of Science, and Cochrane Library databases. Clinical studies comparing open radical hysterectomy (ORH) and minimally invasive surgery (MIS) were included. Study quality was assessed using the Cochrane Risk of Bias 2.0 tool and the Newcastle-Ottawa Scale. A meta-analysis was performed to compare survival outcomes between ORH and MIS, with subgroup analysis stratified by tumor size (≤ 2 cm vs. > 2 cm). Fifteen clinical studies met the inclusion criteria. All observational studies scored ≥ 7 on the Newcastle-Ottawa Scale. Patients undergoing ORH showed significantly improved 5-year disease-free survival compared with MIS (OR = 1.70 [1.27, 2.27], P < 0.001, I² = 58%). However, no significant difference was observed in overall survival between the two surgical approaches (OR = 1.08 [0.90, 1.15], P > 0.05). Subgroup analysis showed no significant differences in overall survival between ORH and MIS, regardless of tumor size (≤ 2 cm: HR = 1.10 [0.28, 4.31], P = 0.89; >2 cm: HR = 0.82 [0.38, 1.77], P = 0.61). These findings suggest that open radical hysterectomy is associated with better disease-free survival, whereas overall survival does not differ significantly between the two approaches.
In vitro gametogenesis (IVG) has attracted growing attention as a transformative reproductive technology, despite its remaining largely at the stage of basic research. This paper analyzes how IVG is represented across academic and media discourse, with a particular focus on expectations surrounding its clinical applications and the ethical implications of such expectations. Drawing on a qualitative review of bioethical literature, selected media reports, and discussions with IVG researchers, the study identifies a shared tendency to frame IVG in terms of its potential use in human reproduction, often presuming near-term feasibility. This forward-looking framing contrasts with the current scientific reality, in which significant technical and safety challenges remain unresolved. The paper argues that this discrepancy contributes to a form of "hype," wherein speculative applications prematurely shape public understanding and ethical debate. Such hype may distort discussions on ethics and policy, amplify unrealistic expectations, and obscure the value of basic research. By clarifying the gap between scientific practice and societal perception, this study highlights the need for responsible communication and ethically grounded discourse. It concludes that fostering accurate public understanding is essential for the governance of emerging biotechnologies such as IVG.
Human papilloma virus (HPV), the most prevalent sexually transmitted infection worldwide, and in particular HPV 6 and 11, contribute to >90% of anogenital warts (AGW) cases, and high-risk HPV serotypes cause >95% of cervical cancers in South Africa (SA). The healthcare resource utilisation (HCRU) and costs related to AGW in SA remain poorly understood, in both the public and private sectors. To assess the HCRU patterns and associated treatment costs for AGW across the public and private sectors. A descriptive, questionnaire-based study was conducted, involving 50 subject matter experts (SMEs) from SA: 24 from the private sector and 26 from the public sector. The study explored resource use, treatment patterns and cost estimation based on SME responses. Findings revealed that public-sector SMEs treated a larger volume of AGW patients per month (1 - 300) than private-sector SMEs (0 - 20). Most AGW patients were female, comprising 78% in the public sector and 72% in the private sector. The occurrence of AGW was higher in the public sector, ranging between 21.4% and 34.4%, while in the private sector, the occurrence ranged from 13.1% to 23.2%. The weighted cost per patient per episode was higher for females than males in both sectors. In the private sector, costs were ZAR22 482 for females and ZAR17 812 for males, while in the public sector, costs were ZAR19 220 for females and ZAR14 271 for males. The higher costs for females were driven by invasive diagnostic procedures, including vulvar colposcopy and biopsy, and a higher frequency of medical visits (2.0 - 4.4 visits in the public sector). Recurrence rates of AGW were reported at 37.6% in the private sector and 43.9% in the public sector. The total estimated treatment cost of AGW was notably higher in the public sector for both males (ZAR93.6 - ZAR138.5 billion) and females (ZAR135.2 - ZAR207.7 billion), compared with the private sector (males: ZAR11.0 - ZAR19.4 billion; females: ZAR16.7 - ZAR28.3 billion). Female patients experienced a higher burden of diagnosis, recurrence and complications than males. AGW imposes a substantial burden on SA's healthcare system, particularly in the public sector, where female patients face significant costs and complications. The use of a quadrivalent or nonavalent HPV vaccine, rather than a bivalent vaccine, could reduce the impact of AGW and its associated healthcare demands.
This study aimed to compare the diagnostic performance of 3-mm, 4-mm, and 5-mm trans-vaginal ultrasound endometrial thickness thresholds for detecting endometrial neoplasia and to determine the optimal clinical cutoff. In this prospective cohort study, 1170 women aged ≥50 years referred for endometrial evaluation between February 2014 and October 2020 were included, with follow-up through January 2021. All participants underwent trans-vaginal ultrasound performed by certified sonographers across 4 ultrasound units within a large academic medical center with an ethnically diverse patient population. Diagnostic accuracy measures (including sensitivity, specificity, positive predictive value, and negative predictive value) were calculated for each endometrial thickness threshold. The McNemar test was used to compare diagnostic performance across cutoffs. The main outcome was the detection of endometrial cancer or hyperplasia. Among the 1170 eligible women, 82 (7.0%) had endometrial cancer and 42 (3.6%) had hyperplasia. Analyses were limited to 975 cases with a clearly visualized endometrial stripe. Sensitivity for endometrial neoplasia detection was 100%, 97.8%, and 90.2% for the 3-, 4-, and 5-mm thresholds, respectively, while specificity was 9.5%, 16.1%, and 24.4%. Sensitivity and negative predictive value did not differ significantly between the 3- and 4-mm thresholds (p =.16 and p =.40); however, both metrics were significantly higher for the 3- and 4-mm thresholds compared with the 5-mm threshold (p =.005 and p =.01). The 4-mm cutoff demonstrated significantly higher specificity and positive predictive value compared with the 3-mm cutoff (p <.001). Both the 3-mm and 4-mm endometrial thickness thresholds provided excellent sensitivity for excluding endometrial neoplasia. The 4-mm cutoff achieved greater specificity, minimizing unnecessary invasive procedures, and may represent the optimal threshold for clinical application.
Ovarian clear cell carcinoma (OCCC) is a highly aggressive gynecological malignancy characterized by distinct clinicopathological features and resistance to chemotherapy. Despite advances in multi-omics characterization, the translational regulatory landscape of OCCC remains unexplored. Here, we performed ribosome profiling to systematically investigate translation control mechanisms in OCCC. We conducted an integrated analysis of transcriptomic and translatomic data from 22 clinical specimens. This study is the first to analyze translational dysregulation in OCCC at sub-codon resolution using translational group data resources. Integrated analysis identified novel unannotated open reading frames (ORFs) encoding functional micropeptides. Furthermore, we uncovered widespread translational dysregulation in OCCC, with experimental validation confirming the pro-tumorigenic role of translationally upregulated RBM4. This study bridges a critical gap between genomic, transcriptomic, and proteomic landscapes in OCCC, offering valuable mechanistic insights into its pathogenesis.
To evaluate the association between obstructive sleep apnea (OSA) and thromboembolic events among women with polycystic ovary syndrome (PCOS). Retrospective cohort study with propensity score matching. Multicenter electronic health record database (TriNetX US Collaborative Network). Women aged 18-45 years with a diagnosis of PCOS between 2012 and 2021. Women with PCOS were stratified according to subsequent diagnosis of OSA and matched 1:1 with PCOS patients without OSA using propensity scores. Incident pulmonary embolism (PE) and venous thromboembolism (VTE) occurring after a 1-year reference period were assessed using Cox proportional hazards models. Incident pulmonary embolism and venous thromboembolism. After propensity score matching, 20 052 women were included (10 026 per group). All analyses were conducted within this propensity score-matched cohort. PE incidence was higher among women with OSA compared with those without OSA (2.88 vs. 1.48 per 1000 person-years; absolute difference 1.40 per 1000 person-years; incidence rate ratio [IRR] 1.94, 95% CI 1.49-2.53; hazard ratio [HR] 1.95, 95% CI 1.50-2.54). VTE incidence was also increased (3.74 vs. 2.87 per 1000 person-years; absolute difference 0.87 per 1000 person-years; IRR 1.30, 95% CI 1.06-1.60; HR 1.32, 95% CI 1.07-1.61). These associations persisted across clinically relevant subgroups and increased over long-term follow-up. Among women with PCOS, comorbid OSA is associated with an increased risk of thromboembolic events, particularly pulmonary embolism. These findings support consideration of OSA screening and enhanced thromboembolic risk assessment in women with PCOS.
Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that western blot data shown in Fig. 1C on p. 1232 were strikingly similar to data in a paper that had previously been published in the journal Nature Cell Biology that was written by different authors at different research institutes. Upon performing an independent analysis of the data in this paper in the Editorial Office, it also came to light that the cellular images featured in Fig. 6B on p. 1233 had also previously appeared in another article published in the journal Science that was similarly written by different authors at different research institutes. Given that the abovementioned data had already been published before the receipt of this paper at International Journal of Molecular Medicine, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 42:1229‑1236, 2018; DOI: 10.3892/ijmm.2018.3703].
The intratumoural mycobiome is a critical constituent of the tumour microenvironment; however, its specific impact on epithelial ovarian cancer (EOC) progression and the underlying molecular mechanisms remain largely elusive. In this study, internal transcribed spacer 1 (ITS1) sequencing revealed a significant enrichment of Malassezia in EOC tissues compared with epithelial borderline ovarian tumours, with its abundance positively correlated with disease progression. Subsequent intratumoural microbiota transplantation and mono-colonisation in a murine EOC model demonstrated that Malassezia restricta substantially accelerated tumour growth and increased M2 macrophage infiltration. Furthermore, in vitro assays established that M. restricta-derived extracellular vesicles (MrEVs) play a pivotal role in inducing M2 macrophage polarisation. Mechanistically, both in vitro and in vivo data showed that MrEVs activate the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway, thereby driving M2 polarisation and tumour malignancy. Collectively, these findings identify M. restricta as a pro-tumourigenic fungus in EOC and uncover a previously unrecognised fungal-immune axis that promotes tumour progression. This study provides new insight into the oncogenic role of tumour-resident fungi and highlights the M. restricta EV-JAK2/STAT3 axis as a potential therapeutic target for immune modulation.
Fetal growth restriction (FGR) diagnosed in mid-pregnancy is associated with substantial perinatal risk. However, the prognostic significance of FGR identified at the time of the second-trimester anatomy ultrasound that subsequently resolves later in pregnancy remains incompletely understood. To evaluate the association between early FGR with subsequent growth normalization and severe neonatal morbidity (SNM), and to compare neonatal outcomes across pregnancies with persistent early FGR, resolved early FGR, and normal fetal growth. This retrospective cohort study included singleton pregnancies that underwent a routine second-trimester fetal anatomy ultrasound between 18 weeks 0 days and 23 weeks 6 days of gestation and had one or more follow-up third-trimester ultrasound examinations with fetal biometry performed at 28 weeks' gestation or later, delivering at two tertiary care hospitals in New York between January 2019 and December 2023. FGR was defined as estimated fetal weight or abdominal circumference <10th percentile. Pregnancies with FGR first diagnosed after 24 weeks' gestation were excluded. Pregnancies were categorized into three groups: no FGR, early FGR that persisted into the third trimester (persistent early FGR), and early FGR that subsequently normalized (resolved early FGR), with classification based on the last third-trimester ultrasound with fetal biometry performed prior to delivery. The primary outcome was SNM, defined as a composite of life-threatening neonatal diagnoses and procedures. Secondary outcomes included respiratory distress syndrome (RDS), neonatal intensive care unit (NICU) admission, preterm birth, need for parenteral nutrition, and need for phototherapy. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) controlling for demographic and clinical covariates. Among 20,022 pregnancies, 636 (3.2%) were diagnosed with early FGR at the mid-pregnancy anatomy ultrasound, of which 181 (28.5%) subsequently demonstrated resolution and 455 (71.5%) remained persistent. Compared with pregnancies without FGR, resolved early FGR was associated with increased odds of SNM (aOR 1.80, 95% CI 1.10-2.83), RDS (aOR 3.30, 95% CI 1.01-8.90), preterm birth (aOR 2.04, 95% CI 1.18-3.34), and need for parenteral nutrition (aOR 3.66, 95% CI 1.71-7.17). NICU admission and phototherapy did not differ significantly. Persistent early FGR was associated with increased odds of SNM and secondary outcomes. Neonatal risk followed a graded pattern across groups, with lowest risk among pregnancies without FGR, intermediate risk among those with resolved early FGR, and highest risk among those with persistent early FGR, with findings largely reflecting respiratory and prematurity-related morbidity. FGR diagnosed at the time of the second-trimester anatomy ultrasound is associated with increased neonatal morbidity even when fetal growth subsequently normalizes. Resolution of early FGR is associated with reduced but persistent risk, supporting consideration of early FGR as a marker of residual neonatal vulnerability. Further prospective studies are needed to refine risk stratification and determine whether specific management strategies modify outcomes in pregnancies complicated by early FGR with subsequent growth normalization.
This study aimed to evaluate the validity and reliability of the Turkish version of the Menstrual Quality of Life (PERIOD-QOL) scale. This methodological study was conducted with 332 nurses and midwives. Validity and reliability were analyzed using item analysis, content and construct validity, exploratory and confirmatory factor analysis, Cronbach's alpha coefficient, the Spearman-Brown formula, and the test-retest method. Cronbach's alpha, Spearman-Brown reliability, and test-retest reliability coefficients were 0.86, 0.81, and 0.63, respectively. According to the emerging unidimensional structure, factor loadings of the scale items were between 0.50 and 0.80, and this structure alone explained 45.75 percent of the total variance. The results of the known groups validity method showed that the mean PERIOD-QOL total score of nurses and midwives with very little to little menstrual bleeding (38.00 ± 6.89) was higher than those with heavy menstrual bleeding (28.73 ± 8.09) and very heavy to extremely heavy menstrual bleeding (23.50 ± 10.34) (p < .05). The confirmatory factor analysis revealed perfect and good-fit indices (χ2/df = 2.95, RMSEA = 0.077, SRMR = 0.044, CFI = 0.98, IFI = 0.98, GFI = 0.95, and NFI = 0.97). The mean items of the scale ranged between 2.71 ± 1.38 and 4.27 ± 1.19. The Turkish version of the PERIOD-QOL scale is a valid and reliable tool to assess the level and perception of menstrual QOL of women.
Mutations in the tumour suppressor, TP53, are prevalent in human cancers yet their functional implications remain unclear. Through comprehensive pan-cancer database analysis, we identified H179 mutations in TP53 as significantly associated with poor disease-free survival across multiple cancer types. Functional studies in lung, ovarian, and prostate cancer cells over-expressing the p53H179R/Y mutants revealed that these mutants are not only defective in tumour-suppressive functions but also actively promote tumour progression. These mutants drive metabolic reprogramming by increasing neutral lipid levels through de novo fatty acid synthesis (p53H179R/Y) and fatty acid uptake (p53H179Y), accompanied by increased lipid droplets and APOE expression, collectively promoting enhanced invasiveness relative to p53-null cells. Our findings demonstrate that TP53 missense mutations are not functionally equivalent to TP53 loss. Notably, H179 mutations act as oncogenic drivers, and our data highlight APOE and lipid metabolism as potential therapeutic targets, underscoring the clinical relevance of precise TP53 mutation characterisation.
Decentralized clinical trials (DCTs) aim to increase trial access for underrepresented populations (URP) and ensure study outcomes, conclusions, and policy-related decisions are applicable to diverse populations. To assess trends in the percentage of accrued participants from more than 120 miles from the research site upon DCT program implementation. This descriptive quality improvement study was conducted from January 2024 to March 2025 at Mayo Clinic, a US multiregional, academic medical center (AMC) comprising 3 sites and an affiliated, community-based health care system. All individuals who consented and/or accrued to an institutional review board-approved clinical trial were included. DCTs are defined as trials with at least 1 decentralized capability beyond remote consent. DCT program development began July 2022. By January 2024, remote consent, video telehealth visits, remote phlebotomy, and device services were implemented across all sites and departments. Remote monitoring and oral medication delivery were available on a limited basis. Prospective automated program and DCT participant data collection and quarterly reporting began in January 2024. Percentage of all DCT accrued participants with a residential zip code more than 120 miles from 1 of 3 AMC sites. There were 7469 participants (median [IQR] age, 62 [51-70] years; 3594 [48.1%] female; 241 [3.2%] Asian, 391 [5.2%] Black or African American, and 6347 [85.0%] White individuals) accrued to 765 DCTs. During the study period, the percentage of DCT participants residing more than 120 miles from an AMC site ranged from 18.9% in the first quarter (Q1) of 2024 (383 of 2032 participants) to 29.6% in Q1 of 2025 (346 of 1170 participants). Of those accrued, 1147 (15.4%) were of a racial or ethnic URP, ranging from 12.5% in Q1 of 2024 (253 participants) to 17.4% in Q1 of 2025 (204 participants). There were 1554 (20.8%) participants from a rural location, ranging from 16.6% in Q1 of 2024 (338 participants) to 24.9% in Q1 of 2025 (291 participants). Additionally, by geospatial distance from an AMC site, the male-to-female ratio was nearly 50:50, and the age distribution appeared similar. In this quality improvement study of a DCT program implementation, DCT accruals trended favorably among those residing more than 120 miles from an AMC site and those of rural or URP populations. While these findings cannot be directly attributed to program implementation, they are reassuring that this strategy may address some barriers to clinical trial access. Future studies should assess the sustained effectiveness and scalability of DCT models in improving equitable trial access.