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20 pages, 8601 KB  
Article
Altered Lipolytic Protein Expression in Tumor-Associated Adipose Tissue Correlates with Aggressive Breast Cancer Features
by Priscila Pagnotta, Tomás González-Garello, Cecilia Lotufo, María Luján Crosbie, Natalia Santiso, Anabela Ursino, Celeste Frascarolli, Alicia Amato, Rubén Dreszman, Camila Ramos Quintana, Juan Carlos Calvo and Judith Toneatto
Cancers 2026, 18(18), 3001; https://doi.org/10.3390/cancers18183001 - 16 Sep 2026
Viewed by 82
Abstract
Background: Adipose tissue (AT) has emerged as a metabolically active component of the breast tumor microenvironment that contributes to breast cancer (BC) progression. Adipocytes release adipokines and lipids that influence tumor growth; however, the specific lipolytic proteins involved in these interactions remain poorly [...] Read more.
Background: Adipose tissue (AT) has emerged as a metabolically active component of the breast tumor microenvironment that contributes to breast cancer (BC) progression. Adipocytes release adipokines and lipids that influence tumor growth; however, the specific lipolytic proteins involved in these interactions remain poorly characterized. Methods: In this study, we analyzed the expression of perilipin 1, adipose triglyceride lipase (ATGL), and hormone-sensitive lipase (HSL) by Western blot and immunofluorescence in adipose tissue explants from BC patients and healthy donors, evaluating their associations with clinicopathological features related to BC prognosis. Results: We found that perilipin 1 expression was increased in AT from patients with aggressive tumor characteristics, including advanced stage, premenopausal status, and obesity. In contrast, ATGL and HSL levels were reduced in specific patient subgroups, particularly in obese and postmenopausal patients and in tumor-adjacent AT from invasive lobular carcinoma. Conclusions: Together, these findings indicate that the expression of proteins involved in the regulation of lipolysis is influenced by both tumor proximity and clinicopathological characteristics, suggesting alterations in the molecular machinery governing lipid droplet regulation and lipid mobilization within tumor-associated AT. The observed associations identify perilipin 1, ATGL, and HSL as potential candidate markers of tumor-associated AT alterations and provide further insight into tumor–adipocyte interactions in BC. Despite the exploratory nature of this study, the observed associations provide a basis for further investigation into their potential biological and clinical relevance in BC. Full article
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19 pages, 12067 KB  
Review
Chronic Endometritis and Endometrial Polyps in Female Infertility: Etiological Mechanisms, Diagnostic Insights, and Prognostic Implications
by Zofia Maria Kiestrzyn, Tatiana Antczak, Jakub Dyś, Maciej Wilczak and Karolina Chmaj-Wierzchowska
J. Clin. Med. 2026, 15(18), 7045; https://doi.org/10.3390/jcm15187045 - 11 Sep 2026
Viewed by 128
Abstract
Background/Objectives: Endometrial polyps (EPs) are common benign intrauterine lesions associated with abnormal uterine bleeding, infertility, recurrent implantation failure, and recurrent pregnancy loss. Although traditionally considered hormone-dependent lesions, increasing evidence suggests that chronic endometritis (CE) may contribute to their development and recurrence. This review [...] Read more.
Background/Objectives: Endometrial polyps (EPs) are common benign intrauterine lesions associated with abnormal uterine bleeding, infertility, recurrent implantation failure, and recurrent pregnancy loss. Although traditionally considered hormone-dependent lesions, increasing evidence suggests that chronic endometritis (CE) may contribute to their development and recurrence. This review summarizes current evidence regarding the relationship between CE and EPs, focusing on pathophysiological mechanisms, diagnostic approaches, and clinical implications. Methods: This narrative review was conducted according to the Scale for the Assessment of Narrative Review Articles (SANRA). A literature search was performed using PubMed/MEDLINE, Scopus, and Google Scholar to identify original studies, systematic reviews, meta-analyses, and consensus statements addressing CE, EPs, infertility, endometrial microbiota, and polyp recurrence. Results: Current evidence demonstrates a consistent association between CE and EPs, with approximately half of premenopausal women with EPs showing histological evidence of CE. Chronic inflammation may promote polyp formation through immune activation, inflammatory cytokine signaling, abnormal angiogenesis, extracellular matrix remodeling, dysregulated apoptosis, and alterations in the endometrial microbiome. CE has also been identified as an independent predictor of EP recurrence after hysteroscopic polypectomy and may impair endometrial receptivity. Histopathological examination with CD138 immunohistochemistry remains the diagnostic reference standard. Conclusions: Emerging evidence supports an inflammatory component in the pathogenesis of endometrial polyps and suggests that CE may represent a potentially modifiable risk factor for recurrence and reproductive failure. Incorporating assessment of CE into the evaluation of selected women with recurrent polyps or infertility may improve individualized management. However, prospective studies are needed before routine screening and treatment can be universally recommended. Full article
(This article belongs to the Section Obstetrics & Gynecology)
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21 pages, 1142 KB  
Article
Urinary Concentrations of Non-Nutritive Sweeteners and Breast Cancer: A Case-Cohort Analysis of the Moli-sani Study
by Marialaura Bonaccio, Augusto Di Castelnuovo, Simona Costanzo, Claudia F. Martinez, Emilia Ruggiero, Teresa Panzera, Simona Esposito, Amalia De Curtis, Sara Magnacca, Jacopo Troisi, Chiara Cerletti, Maria Benedetta Donati, Giovanni de Gaetano and Licia Iacoviello
Nutrients 2026, 18(18), 2958; https://doi.org/10.3390/nu18182958 - 9 Sep 2026
Viewed by 296
Abstract
Background: Non-nutritive sweeteners (NNS) are chemical substances developed by the food industry to reduce sugar and calories while preserving sweetness. Epidemiological studies have indicated a potential increased risk of certain cancers, including breast cancer (BC), associated with NNS consumption. However, the evidence has [...] Read more.
Background: Non-nutritive sweeteners (NNS) are chemical substances developed by the food industry to reduce sugar and calories while preserving sweetness. Epidemiological studies have indicated a potential increased risk of certain cancers, including breast cancer (BC), associated with NNS consumption. However, the evidence has exclusively relied on self-reported dietary information rather than objective measurements of NNSs. We examined the association of urinary concentrations of NNS with BC risk in women from the large Moli-sani Study. Methods: Using a case-cohort design, a sample of 988 middle-aged women (mean age 55 ± 12 y) was randomly selected as a sub-cohort and compared to 272 women with incident BC (38 premenopausal and 234 postmenopausal). A total of 6 commonly used NNSs (i.e., aspartame, acesulfame, saccharin, sucralose, cyclamate, and steviol glycosides) were measured through liquid chromatography–mass spectrometry in spot urine samples (creatinine-adjusted concentrations; µg/mg) collected at baseline (2005–2010). The multivariable hazard ratios (HRs) were estimated using weighted Cox regression models for the case-cohort design, with each NNS modelled as a binary variable (i.e., presence vs. absence). The sum of these values produced a total urinary NNS score, which could range from 0 to 6, and was further categorised as low (0–1) or high (2–5). Results: The predominant NNS detected in urine was saccharin (E954), contributing to 77% of total NNSs, followed by steviol glycosides (E960;11%). In multivariable-adjusted Cox analyses, neither individual NNSs nor total NNS urinary concentrations were associated with overall BC risk (HR = 1.09; 95% CI 0.80–1.48 for high vs. low). However, the presence of sucralose (E955) was directly linked to premenopausal BC (HR = 5.90; 95% CI 1.44–24.20; p = 0.014), although this estimate was based on only 38 cases and was imprecise. Conclusions: Urinary NNS concentrations were not associated with overall BC risk. The observed association between urinary sucralose and premenopausal BC should be considered exploratory and hypothesis-generating and requires independent replication. Full article
(This article belongs to the Section Nutritional Epidemiology)
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25 pages, 2393 KB  
Article
Selection and Characterization of Vaginal Lactobacilli from Healthy Algerian Women with Potential Probiotic Properties Against Urogenital Pathogens
by Asma Mammar, Hayat Trabsa, Stefania Dentice Maidana, Ammar Ayachi, Asma Abdessemed, Leonardo Albarracin, Mariano Elean, Kamel Boubakri, Ayelen A. Baillo, Haruki Kitazawa and Julio Villena
Antibiotics 2026, 15(9), 875; https://doi.org/10.3390/antibiotics15090875 - 7 Sep 2026
Viewed by 195
Abstract
Background: The vaginal microbiota of healthy women is predominantly composed of lactic acid bacteria (LAB), particularly species from the lactobacilli group, which contribute to the maintenance of vaginal health through multiple protective mechanisms. Objectives: In the present study, vaginal LAB isolated from healthy [...] Read more.
Background: The vaginal microbiota of healthy women is predominantly composed of lactic acid bacteria (LAB), particularly species from the lactobacilli group, which contribute to the maintenance of vaginal health through multiple protective mechanisms. Objectives: In the present study, vaginal LAB isolated from healthy premenopausal Algerian women were evaluated for their probiotic potential. Methods: A total of 259 LAB isolates were initially screened for antimicrobial activity against vaginal pathogens, among which 164 strains exhibited inhibitory effects. Based on antimicrobial capacity and biofilm formation ability, 38 strains were selected for further characterization. A refined subset of 15 strains belonging to Lactiplantibacillus (Lpb.) plantarum, Limosilactobacillus (Lmb.) fermentum, and Ligilactobacillus (Lgb.) salivarius were subsequently identified according to their superior antimicrobial and probiotic-related properties. The selected strains were evaluated for several functional and safety characteristics, including antimicrobial activity, production of lactic acid and hydrogen peroxide (H2O2), biofilm formation, auto-aggregation, cell surface hydrophobicity, antibiotic susceptibility, hemolytic activity, and tolerance to acidic conditions. These studies were complemented with comparative genomics using the complete genome sequences of selected strains. Results: The isolates demonstrated significant inhibitory activity against vaginal pathogens associated with aerobic vaginitis, and vulvovaginal candidiasis. In addition, strong correlations were observed between metabolite production and antimicrobial activity. Several strains also exhibited enhanced biofilm formation, aggregation capacity, and favorable safety profiles. Among the tested isolates, Lmb. fermentum 70BJ2, Lpb. plantarum 87JG8, and Lpb.plantarum N17 emerged as particularly promising probiotic candidates due to their combined antimicrobial, metabolic, and adhesion-related properties. Conclusions: Overall, these findings demonstrate that the vaginal microbiota of healthy Algerian women represents a valuable source of potential probiotic strains and provide a strong basis for future in vivo validation and clinical application in the prevention and management of vaginal infections. Full article
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17 pages, 1405 KB  
Article
Early-Stage Evaluation of a Novel Sexual Health Care Model for Breast Cancer Survivors Undergoing Endocrine Therapy: A Case Series
by Wakako Yachi
Nurs. Rep. 2026, 16(9), 324; https://doi.org/10.3390/nursrep16090324 - 6 Sep 2026
Viewed by 190
Abstract
Background/Objectives: Women undergoing endocrine therapy after breast cancer often experience sexual-health concerns, but opportunities for individualized nursing support are limited. This case series implemented and preliminarily evaluated a novel sexual health-care model for women undergoing endocrine therapy after breast-cancer treatment. Methods: A care [...] Read more.
Background/Objectives: Women undergoing endocrine therapy after breast cancer often experience sexual-health concerns, but opportunities for individualized nursing support are limited. This case series implemented and preliminarily evaluated a novel sexual health-care model for women undergoing endocrine therapy after breast-cancer treatment. Methods: A care model was developed from Comfort Theory, a literature review, and clinical experience and underwent content-validity review by experts, including one nurse with lived experience of breast cancer. It was implemented individually for 6 months in five premenopausal women receiving endocrine therapy after breast-conserving surgery or total mastectomy. Data included baseline characteristics, care records, final interviews, and Self-affirmation Scale scores. Nursing goal attainment and final interviews were evaluated qualitatively. Results: All nursing goals appeared to have been achieved based on provider assessment and participants’ narratives. Participants gradually expressed distress, questions, and sexual health needs related to bodily and sexual changes, developed greater understanding of treatment-related changes, identified individualized coping strategies, and showed greater self-worth and self-care. Self-affirmation scores were descriptively higher after care. Phenomenological analysis identified four constituents: having a place to discuss a body marked by breast and fertility loss; sharing with a midwife who accepted them as they were; reconnecting with their changed bodies; and discovering new meaning in life with altered fertility and bodily integrity. Conclusions: The care model may provide a safe, individualized space for women undergoing endocrine therapy after breast cancer to express concerns, understand bodily changes, and reconstruct meaning. The findings are preliminary and represent provider-assessed observations rather than evidence of effectiveness. Full article
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18 pages, 789 KB  
Article
Comparative Analysis of Cyclin E1 Expression in Uterine Leiomyosarcomas and Leiomyomas
by Aleksandar Rakić, Lazar Nejković, Dejan Oprić, Ana Đorđević, Marija Rakić, Aleksandar Jurišić and Danilo Obradović
Diseases 2026, 14(9), 324; https://doi.org/10.3390/diseases14090324 - 5 Sep 2026
Viewed by 244
Abstract
Background/Objectives: Uterine leiomyosarcoma (uLMS) shares clinical and radiological similarities with benign uterine leiomyoma (LM), while validated discriminatory markers remain scarce. We compared cyclin E1 (CCNE1) expression in uLMS and LM tissue samples. Methods: This retrospective case-control study included 61 patients (16 uLMS, 45 [...] Read more.
Background/Objectives: Uterine leiomyosarcoma (uLMS) shares clinical and radiological similarities with benign uterine leiomyoma (LM), while validated discriminatory markers remain scarce. We compared cyclin E1 (CCNE1) expression in uLMS and LM tissue samples. Methods: This retrospective case-control study included 61 patients (16 uLMS, 45 LM) treated at a single institution (2017–2023). Of 22 eligible uLMS cases, six were excluded because suitable tissue was unavailable and they had significantly higher FIGO stages than the included cases. CCNE1 immunoreactivity was assessed using an adapted Allred score in five non-overlapping high-power fields selected from regions of highest expression. Two blinded pathologists independently scored each field, and the patient-level median was used for primary analysis. Results: The median CCNE1 Allred score was 6 (IQR 5–6) in uLMS versus 2 (IQR 0–3) in LM (p < 0.001), with excellent interobserver agreement (ICC 0.94). The AUC was 0.941 (95% CI 0.875–0.990). A data-derived cut-off ≥4 yielded 93.8% sensitivity and 84.4% specificity. A conservative minimum-expression analysis yielded an AUC of 0.882. Postmenopausal status was strongly associated with uLMS but was nearly completely confounded with the diagnostic group (12/16 uLMS vs. 0/45 LM). A premenopausal-only analysis was directionally consistent but underpowered. Clinical symptoms and tumor size did not differ between the groups. Conclusions: CCNE1 immunoexpression was substantially higher in uLMS than LM, with excellent reproducibility. Diagnostic-performance estimates remain exploratory and were influenced by tumor-region sampling, menopausal imbalance, and under-representation of advanced-stage uLMS. Independent multicenter validation, particularly in premenopausal and advanced-stage disease, is required before clinical application. Full article
(This article belongs to the Section Oncology)
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18 pages, 1122 KB  
Article
Associations of General and Central Obesity with Cardiovascular Risk by Menopausal and MASLD Status
by Dong Yun Kim, Kyu-Na Lee, Kyung-Do Han and Beom Kyung Kim
Biomedicines 2026, 14(9), 1985; https://doi.org/10.3390/biomedicines14091985 - 3 Sep 2026
Viewed by 306
Abstract
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence increases during the menopausal transition, yet its interaction with obesity phenotypes in influencing cardiovascular disease (CVD) risk remains unclear. We examined how MASLD and obesity types are associated with CVD risk in pre- and postmenopausal [...] Read more.
Background/Objectives: Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence increases during the menopausal transition, yet its interaction with obesity phenotypes in influencing cardiovascular disease (CVD) risk remains unclear. We examined how MASLD and obesity types are associated with CVD risk in pre- and postmenopausal women. Methods: This nationwide cohort analyzed 1,959,367 Korean women aged ≥40 years (848,672 premenopausal, 1,110,695 postmenopausal) followed for a median of 12.3 years. MASLD was defined by the fatty liver index plus ≥1 cardiometabolic risk factor and alcohol intake <20 g/day. General obesity was defined as body mass index ≥25 kg/m2 and central obesity as waist circumference ≥85 cm. Results: During follow-up, 106,792 women (5.45%) developed CVD. MASLD was associated with higher CVD risk regardless of menopausal status, though the association was numerically smaller in postmenopausal women. Among women without MASLD, general obesity was associated with risk before menopause (adjusted hazard ratio [aHR] 1.10, 95% confidence interval [CI] 1.04–1.17; central obesity, aHR 1.06, 95% CI 0.96–1.18), whereas after menopause central obesity was associated with risk (aHR 1.08, 95% CI 1.05–1.10). In postmenopausal women with MASLD, the estimate for general obesity was inverse (aHR 0.95) while central obesity remained positively associated (aHR 1.05); in an exploratory sensitivity analysis using an anthropometry-free metabolic proxy (the triglyceride–glucose index), the inverse estimate was not reproduced (aHR 1.06). Conclusions: MASLD was associated with elevated CVD risk across menopausal stages. Associations with obesity phenotype varied by menopausal status: general obesity was associated with risk in premenopausal women without MASLD, whereas after menopause the association was more consistent for central obesity. These are observational contrasts between groups that also differ substantially in age and should not be interpreted causally. They may nonetheless inform prevention tailored to menopausal stage, MASLD status, and obesity phenotype. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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21 pages, 647 KB  
Review
Skeletal Health in Premenopausal Women with Type 1 Diabetes: A Scoping Review
by Eugenia Vlachou, Anastasia Ntikoudi, Dimitra Anna Owens, Despoina Rizikou, Afroditi Tsalkitzi, Eleni Evangelou and Athanasios N. Tsartsalis
Diabetology 2026, 7(9), 168; https://doi.org/10.3390/diabetology7090168 - 1 Sep 2026
Viewed by 258
Abstract
Background: Type 1 diabetes (T1D) is increasingly recognized as a condition associated with impaired skeletal health and increased fracture risk. Although osteoporosis is usually considered more clinically relevant after menopause, diabetes-related skeletal alterations may begin earlier in life. This scoping review aimed to [...] Read more.
Background: Type 1 diabetes (T1D) is increasingly recognized as a condition associated with impaired skeletal health and increased fracture risk. Although osteoporosis is usually considered more clinically relevant after menopause, diabetes-related skeletal alterations may begin earlier in life. This scoping review aimed to map the available evidence on bone-health outcomes in premenopausal women with T1D. Methods: A scoping review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). PubMed/MEDLINE, Scopus, Web of Science, CINAHL and the Cochrane Library were searched, supplemented by Google Scholar and manual screening of reference lists. Eligible studies examined bone mineral density (BMD), fracture history or fracture risk, bone turnover markers, quantitative ultrasound parameters, bone microarchitecture, or other skeletal outcomes in premenopausal women or women with T1D. Results: Seven studies met the eligibility criteria. The included studies were mainly observational and varied in sample size, age range, diabetes duration, skeletal sites assessed, and bone-assessment methods. Most studies reported lower BMD or less favorable skeletal parameters in premenopausal women with T1D compared with women without diabetes, particularly at peripheral or hip-related skeletal sites. Quantitative ultrasound studies suggested impaired peripheral skeletal properties, while one MRI-based study identified trabecular microarchitectural deficits. Several studies also reported altered bone turnover markers and associations between poorer glycemic control, adverse health behaviors or diabetes-related complications, and poorer bone outcomes. Fracture data were limited and were based on previous or self-reported fractures. Potential determinants of skeletal health were variably reported across studies, with more consistent consideration of body mass index and selected lifestyle or reproductive factors than of autoimmune, nutritional, medication-related, and detailed reproductive variables. Conclusions: Available evidence indicates that premenopausal women with T1D may exhibit early alterations in skeletal health, including differences in BMD, peripheral bone measures, bone turnover, and microarchitecture. These findings highlight the potential importance of considering bone health before the menopausal transition. However, prospective data on fragility fractures remain limited, and further longitudinal studies incorporating detailed reproductive, metabolic, and clinical factors are needed to clarify the long-term skeletal implications and inform future risk-assessment strategies. Full article
(This article belongs to the Special Issue Bone Metabolism and Skeletal Health in Diabetes)
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19 pages, 413 KB  
Article
Feasibility of Targeted Case-Finding of Polyendocrine Metabolic Ovarian Syndrome in the Workplace: A Pilot Cohort Study
by Nicola Magnavita
Int. J. Environ. Res. Public Health 2026, 23(9), 1138; https://doi.org/10.3390/ijerph23091138 - 31 Aug 2026
Viewed by 194
Abstract
Polyendocrine metabolic ovarian syndrome (PMOS) is the most common endocrine disorder in working women. Workplace screening could contribute to the early diagnosis and treatment of this chronic condition. Fertile women who participated in a 2022 health food promotion campaign and had suspected eating [...] Read more.
Polyendocrine metabolic ovarian syndrome (PMOS) is the most common endocrine disorder in working women. Workplace screening could contribute to the early diagnosis and treatment of this chronic condition. Fertile women who participated in a 2022 health food promotion campaign and had suspected eating disorders, overweight/obesity, metabolic abnormalities, sleep problems, or mental health concerns were interviewed about PMOS symptoms during their in-office medical examination. Twenty-eight of the 1170 women examined had symptoms of suspected PMOS. By 2023, 21 of these diagnoses had been confirmed by specialists. The prevalence of newly diagnosed PMOS among the women of childbearing age was 2.7% (CI95% 1.7; 4.2). The confirmation rate of the clinical suspicion of PMOS was 75% (CI95% 55.1; 89.3). Female workers with newly identified PMOS had a significantly higher frequency of eating disorders than their pre-menopausal colleagues and higher body mass index values, higher glycemia, and higher cholesterol values. PMOS patients also had higher depression symptom scores than other workers of childbearing age. In conclusion, with a short interview during mandatory medical examinations, the occupational physician can make a significant contribution to the diagnosis of PMOS, thereby hopefully improving the quality of life of women and reducing damage to their health. Full article
(This article belongs to the Special Issue Promoting Health and Safety in the Workplace)
22 pages, 5820 KB  
Article
The FGF23/α-Klotho Axis in Postmenopausal Osteoporosis: Associations with Bone Mineral Density and Diagnostic Discrimination
by Mete Hakan Karalok, Naile Fevziye Misirlioglu, Oznur Dundar Akin and Hafize Uzun
J. Clin. Med. 2026, 15(17), 6716; https://doi.org/10.3390/jcm15176716 - 29 Aug 2026
Viewed by 317
Abstract
Background: Fibroblast growth factor 23 (FGF23) and α-Klotho are key regulators of mineral metabolism and bone homeostasis; however, their combined diagnostic value in postmenopausal osteoporosis remains incompletely understood. This study investigated the associations of serum FGF23, α-Klotho, and the FGF23/α-Klotho ratio with bone [...] Read more.
Background: Fibroblast growth factor 23 (FGF23) and α-Klotho are key regulators of mineral metabolism and bone homeostasis; however, their combined diagnostic value in postmenopausal osteoporosis remains incompletely understood. This study investigated the associations of serum FGF23, α-Klotho, and the FGF23/α-Klotho ratio with bone mineral density (BMD), bone turnover markers, and their diagnostic performance for postmenopausal osteoporosis. Methods: This cross-sectional study included 165 women divided into three groups: premenopausal healthy controls (n = 55), postmenopausal non-osteoporotic women (n = 55), and postmenopausal women with osteoporosis (n = 55). Serum FGF23 and α-Klotho concentrations were measured by enzyme-linked immunosorbent assay. Bone mineral density was assessed by dual-energy X-ray absorptiometry. Correlation analyses, age- and BMI-adjusted partial correlations, multivariable linear and logistic regression analyses, receiver operating characteristic (ROC) analyses, and incremental diagnostic models were performed. Diagnostic ROC and incremental model analyses were restricted to postmenopausal women (n = 110). Results: Serum FGF23 concentrations and the FGF23/α-Klotho ratio increased progressively across the study groups, whereas α-Klotho levels decreased (all p < 0.001). FGF23 was inversely correlated with lumbar spine, femoral neck, and total hip BMD and T-scores (all p < 0.001), whereas α-Klotho demonstrated positive correlations with all BMD parameters (all p < 0.001). These associations remained significant after adjustment for age and BMI. In multivariable linear regression analyses, the FGF23/α-Klotho ratio showed the strongest independent association with skeletal T-scores (standardized β = −0.379 to −0.404; all p < 0.001). Multivariable logistic regression identified lower 25-hydroxyvitamin D, higher parathyroid hormone, higher FGF23, and lower α-Klotho as independent factors associated with osteoporosis. In analyses restricted to postmenopausal women, the FGF23/α-Klotho ratio showed the highest numerical discriminative performance for osteoporosis (AUC = 0.832, 95% CI: 0.755–0.901), followed by α-Klotho (AUC = 0.793) and FGF23 (AUC = 0.697). The ratio significantly outperformed FGF23 alone (ΔAUC = 0.135, p = 0.001), whereas its performance did not differ significantly from that of α-Klotho (ΔAUC = 0.038, p = 0.270). Adding FGF23 and α-Klotho to age, BMI, and 25-hydroxyvitamin D increased the AUC from 0.743 to 0.882. Conclusions: Serum FGF23 and α-Klotho are independently associated with bone mineral density and are linked to bone turnover markers in postmenopausal women. The FGF23/α-Klotho ratio showed the highest numerical discriminative performance among the evaluated biomarkers, although its performance was not significantly different from that of α-Klotho alone. The combined assessment of FGF23 and α-Klotho provided additional discriminatory information beyond the measured clinical variables. Given the cross-sectional design and lack of external validation, these findings should be considered exploratory and require validation in prospective independent cohorts. Full article
(This article belongs to the Section Orthopedics)
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18 pages, 2081 KB  
Article
Integrated Molecular Profiling of Endometrial Cancer: NGS Findings, MSI/MMR Status, Histopathological Features, and TCGA-Inspired Molecular Classification
by Merve Cirak-Balta, Suleyman Erdogdu, Busra Ekinci, Seda Orenay-Boyacioglu, Olcay Boyacioglu, Ibrahim Halil Erdogdu and Nil Culhaci
Biomedicines 2026, 14(9), 1880; https://doi.org/10.3390/biomedicines14091880 - 23 Aug 2026
Viewed by 277
Abstract
Background/Objectives: Endometrial cancer is a heterogeneous malignancy that displays distinct molecular features and clinical behaviors. The molecular profile of endometrial cancer and its relationship with menopausal status, histological subtype, tumor grade, mismatch repair (MMR)/microsatellite instability (MSI) status, co-mutation patterns, and TCGA molecular classification [...] Read more.
Background/Objectives: Endometrial cancer is a heterogeneous malignancy that displays distinct molecular features and clinical behaviors. The molecular profile of endometrial cancer and its relationship with menopausal status, histological subtype, tumor grade, mismatch repair (MMR)/microsatellite instability (MSI) status, co-mutation patterns, and TCGA molecular classification were investigated in the current study. Methods: A total of 81 histopathologically confirmed endometrial cancer cases were retrospectively evaluated. Molecular profiling was performed using a targeted 71-gene NGS panel together with MSI-PCR and mismatch repair (MMR) immunohistochemistry. Because the targeted panel was not designed to detect genome-wide copy-number alterations or comprehensive mutational signatures, molecular subgroup assignment was performed using a surrogate TCGA-inspired molecular classification approach based on POLE mutation status, microsatellite instability (MSI)/Mismatch Repair (MMR) findings, and TP53 alterations. Histological subtypes, tumor grades, menopausal status, and molecular alterations were compared. Results: Of the cases evaluated, 57 (70.4%) were endometrioid and 24 (29.6%) were serous carcinoma. TP53 variations were significantly higher in serous carcinomas compared to endometrioid tumors (66.7% vs. 26.3%; p = 0.001). In endometrioid carcinomas, the mean number of variants increased with advancing tumor grade (Grade 1: 4.44; Grade 2: 9.68; Grade 3: 11.42; p = 0.006). Alterations in BLM, CDC27, MLH3, and MSH3 were more frequently observed in high-grade tumors. In exploratory analyses, no significant differences were detected between the premenopausal and postmenopausal groups regarding total variant load, number of altered genes, MSI status, or the distribution of TCGA-inspired molecular subgroups; however, these comparisons were limited by the small number of premenopausal patients. The most frequent co-mutation was observed between BLM and CDC27 (55.6%). In the TCGA-inspired molecular classification, the most prevalent subgroup was NSMP-proxy (33.3%). Conclusions: Serous and endometrioid endometrial cancers display distinct molecular characteristics. In endometrioid carcinomas, the genomic alteration load increases in parallel with advancing tumor grade. TCGA-inspired molecular classification and co-mutation analyses revealed the prominent molecular heterogeneity of endometrial cancer. In exploratory analyses, no significant differences were detected between the premenopausal and postmenopausal groups regarding total variant load, number of altered genes, MSI status, or the distribution of TCGA-inspired molecular subgroups. However, these findings should be interpreted with caution because of the limited number of premenopausal patients. Given the limited number of premenopausal patients, findings related to menopausal status should be considered exploratory and require validation in larger, independent cohorts. Full article
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16 pages, 556 KB  
Article
Assessment of Dietary Soy Isoflavones Intake Among Women Aged 14 Years and Older in China: A Population-Based Cross-Sectional Study
by Qiuyan Shi, Fanglei Zhao, Feng Pan, Dechun Luan, Jianwen Li and Yuxia Ma
Nutrients 2026, 18(16), 2696; https://doi.org/10.3390/nu18162696 - 18 Aug 2026
Viewed by 387
Abstract
Objective: This study assessed dietary soy isoflavone (SIF) intake among Chinese women ≥14 years, identified determinants, and evaluated adequacy against the Specific Proposed Level (SPL) in Chinese Dietary Reference Intakes, to inform targeted guidance. Methods: Intake was estimated using a distribution [...] Read more.
Objective: This study assessed dietary soy isoflavone (SIF) intake among Chinese women ≥14 years, identified determinants, and evaluated adequacy against the Specific Proposed Level (SPL) in Chinese Dietary Reference Intakes, to inform targeted guidance. Methods: Intake was estimated using a distribution model combining 2017–2020 China National Food Consumption Survey data with SIF concentrations from food composition tables. Demographic differences and adequacy versus age-specific SPL were examined; supplemental doses were calculated for individuals below SPL. Results: Mean SIF intake was 14.77 mg/standard person-day, generally low. Significant differences (p < 0.05) were observed across most demographic subgroups except education. Higher mean intakes (mg/day) were seen in women aged ≥65 years (16.20), rural residents (16.38), light activity level (15.17), annual income > 100,000 CNY (15.51), manual laborers (16.11), and central China residents (highest, 21.01). Dried legumes and products, particularly tofu and its derivatives, contributed about 80% of total intake, with tofu-derived items accounting for 57.62–71.49%. Across all age groups, intake was significantly below the SPL, with >96% of participants failing to meet the recommendation. To reach the SPL, premenopausal women require ~40 mg/day supplemental SIF (equivalent to ~45 g soybeans/products), while perimenopausal and postmenopausal women require ~60 mg/day (~60 g soybeans/products). Conclusions: Dietary SIF intake among Chinese women ≥14 years is substantially below the SPL, a deficit that may attenuate associated health benefits. As dried beans and bean products are the dominant contributors, promoting these foods represents a feasible strategy to improve population-level SIF adequacy. Full article
(This article belongs to the Section Nutrition in Women)
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16 pages, 2833 KB  
Article
Foretell Ovary: A Blood-Based Ensemble Algorithm Integrating Tumor-Educated Platelet RNA and Routine Hematology for Non-Invasive Ovarian Cancer Screening
by Eunyong Ahn, Se Ik Kim, Sarah Kim, Hyunjung Kim, Hee-yeon Kim, Sungmin Park, Eun Ji Song, Hayoon Kwon, Kyung-Ah Hwang, Yong Sang Song, Jae-Hoon Kim and TaeJin Ahn
Cancers 2026, 18(16), 2629; https://doi.org/10.3390/cancers18162629 - 14 Aug 2026
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Abstract
Background: Ovarian cancer is the most lethal gynecologic malignancy, and CA-125 has limited early-stage sensitivity. We developed and evaluated Foretell Ovary, an ensemble machine-learning classifier that integrates tumor-educated-platelet RNA markers and routine hematologic parameters for non-invasive ovarian cancer detection, and compared it head-to-head [...] Read more.
Background: Ovarian cancer is the most lethal gynecologic malignancy, and CA-125 has limited early-stage sensitivity. We developed and evaluated Foretell Ovary, an ensemble machine-learning classifier that integrates tumor-educated-platelet RNA markers and routine hematologic parameters for non-invasive ovarian cancer detection, and compared it head-to-head with CA-125. Methods: A multi-site prospective cohort study enrolled 460 South Korean participants (67 ovarian cancer, 15 borderline ovarian tumors, 197 benign gynecological conditions, and 181 asymptomatic controls) at six clinical sites between September 2024 and March 2026. The cohort was split into training (n = 279) and independent test (n = 181) sets under a pre-specified ACTB cycle threshold ≤ 28 per-protocol rule (test n = 169). The classifier blended a random forest and two calibrated logistic-regression sub-models built on eight platelet RNA markers, 24 complete blood count parameters, and 30 marker-by-hematology combination features. Performance was assessed at a pre-frozen cutoff of 0.44 and compared against CA-125 (35 U/mL cutoff) in a matched subset (n = 100). Results: Foretell Ovary achieved an area under the receiver operating characteristic curve (AUC) of 0.923, sensitivity of 87.5% (100.0% for Stage II–IV), specificity of 89.0%, and negative predictive value of 97.7% in the test set. In the matched subset, Foretell Ovary outperformed CA-125 on every metric (AUC 0.839 vs. 0.723; sensitivity 85.0% vs. 65.0%), with the largest gap in pre-menopausal participants (+25 percentage points in sensitivity). A three-tier risk-grading scheme retained no ovarian cancer in the low-risk grade. Conclusions: Foretell Ovary offers more accurate non-invasive detection of ovarian cancer than CA-125, particularly in pre-menopausal women, offering the flexibility to be used alone or combined with CA-125. Prospective validation studies are warranted. Full article
(This article belongs to the Section Cancer Biomarkers)
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19 pages, 1472 KB  
Article
Real-World Evidence for Breast Cancer Risk Stratification: Insights from the P.I.N.K. Study
by Michela Franchini, Francesca Denoth, Stefania Pieroni, Francesco Innocenti, Giada Anastasi, Edgardo Montrucchio and Sabrina Molinaro
Cancers 2026, 18(15), 2435; https://doi.org/10.3390/cancers18152435 - 29 Jul 2026
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Abstract
Background/Objectives: Early detection of breast cancer (BC) substantially improves outcomes, with a 5-year survival rate of 99% for early-stage disease. Risk-based screening, which tailors recommendations according to individual clinical, personal, and lifestyle factors, is a promising strategy to enhance early detection. However, previous [...] Read more.
Background/Objectives: Early detection of breast cancer (BC) substantially improves outcomes, with a 5-year survival rate of 99% for early-stage disease. Risk-based screening, which tailors recommendations according to individual clinical, personal, and lifestyle factors, is a promising strategy to enhance early detection. However, previous studies have reported inconsistent evidence of association with BC risk for several modifiable lifestyle factors including premenopausal adiposity, sedentary behaviour, oral contraceptive use. To address these uncertainties, we investigated the association between clinical, personal, and modifiable lifestyle factors and BC risk in the Prevention, Imaging, Network, Knowledge (P.I.N.K.) project. P.I.N.K. generated real-world evidence by integrating clinical data with information collected through a structured questionnaire evaluating the associations between BC and clinical, personal, and lifestyle factors in 27,123 Italian women aged ≥ 40 years, who underwent integrated breast imaging diagnostics. Methods: Characteristics of women with and without BC were compared. Adjusted logistic regression, Least Absolute Shrinkage and Selection Operator (LASSO), and Random Forest models were applied to identify relevant predictors. Variables selected by at least two methods were included in a multivariate logistic regression model, with BC diagnosis as the outcome. Results: Accordingly with previous studies a consistent association was found for high breast density, late menopause, overweight, abdominal adiposity, cardiovascular-cerebrovascular and oncological comorbidities and smoking. Greater consumption of plant-based foods, lower intake of red and processed meat, and regular physical activity were associated with lower odds of BC as well. Conversely, an unexpected inverse association was assessed for menstrual irregularities, hyperlipidaemia, and oral contraceptive use. Conclusions: The integration of multiple sources of information both clinical and self-reported data collected directly from women adds to the growing evidence on the role of modifiable lifestyle factors in BC risk in supporting more targeted prevention strategies. Future prospective studies should further investigate the long-term effects of lifetime physical activity trajectories, different oral contraceptive formulations, and detailed reproductive history, including menstrual cycle characteristics and menopausal timing, to refine individualized BC risk prediction. Full article
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24 pages, 712 KB  
Article
BMI-Stratified Physiological Responses to a 12-Week Mat Pilates Intervention on Body Composition, Cardiometabolic Risk Factors, and Autonomic Function in Middle-Aged Women: An Exploratory Secondary Analysis
by Won-Sang Jung, Won-Je Kim, Eunjoo Lee, Hana An and Hun-Young Park
Metabolites 2026, 16(8), 517; https://doi.org/10.3390/metabo16080517 - 23 Jul 2026
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Abstract
Background/Objectives: Mat Pilates is widely recommended for middle-aged women, but whether baseline obesity modifies its effects remains unclear. This study compared responses to a 12-week mat Pilates programme between non-obese and obese middle-aged women across body-composition, cardiovascular, blood-metabolic, haemorheological and autonomic endpoints. [...] Read more.
Background/Objectives: Mat Pilates is widely recommended for middle-aged women, but whether baseline obesity modifies its effects remains unclear. This study compared responses to a 12-week mat Pilates programme between non-obese and obese middle-aged women across body-composition, cardiovascular, blood-metabolic, haemorheological and autonomic endpoints. Methods: In an exploratory secondary analysis of a completed, uncontrolled single-arm intervention cohort, de-identified pre- and post-intervention data from 32 premenopausal women (47.5 ± 7.6 years) were stratified by BMI into non-obese (NOG; <25 kg/m2; n = 14) and obese (OG; ≥25 kg/m2; n = 18) groups using WHO Asia-Pacific criteria. All completed identical 60 min sessions three times weekly for 12 weeks, with intensity progressed every four weeks. Outcomes were analysed with mixed-design ANOVA and Bonferroni-corrected paired t-tests. Results: Group × time interactions were significant for body weight, fat mass and percent body fat (p < 0.05). Flow-mediated dilation rose in both groups (NOG +15.6%, OG +29.7%; p < 0.05). Group × time interactions were non-significant for blood pressure, lipids and haemorheology; obesity-dependent claims are therefore restricted to the outcomes with significant interactions (body weight, fat mass, percent body fat). For the remaining outcomes, within-group changes reached significance only in the OG (total cholesterol, LDL-cholesterol, aggregation index, critical shear stress) or only in the NOG (diastolic and mean arterial pressure) but did not differ significantly between groups. Conclusions: Following the programme, endothelial function improved in both groups, whereas body-composition responses differed significantly by obesity status. Because this uncontrolled secondary analysis lacked a non-exercising control group, these associations cannot be attributed causally to mat Pilates. The apparent BMI dependence was not reproduced when adiposity was modelled continuously (baseline BMI, percent body fat or fat mass), so all between-group contrasts are hypothesis-generating. Adequately powered randomised controlled trials with a non-exercising comparator and objective monitoring of diet, non-exercise activity, sleep and menstrual-cycle phase are needed before BMI-dependent adaptations to mat Pilates can be considered established. Full article
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