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Digital health interventions (DHIs) have gained increasing attention as strategies to improve maternal health in low- and middle-income countries (LMICs). Previous reviews of DHIs have included studies from Southeast Asia (SEA) but have not examined maternal health outcomes in SEA LMICs as a distinct regional evidence base. This scoping review aimed to map maternal health outcomes of DHIs in SEA LMICs using an adapted proximal-intermediate-distal (PID) framework, describe DHI characteristics, and summarize contextual factors related to target groups and intervention settings. The review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) and the Joanna Briggs Institute guidance. PubMed, CINAHL, and Scopus were searched for English-language interventional studies evaluating DHIs that were published from January 2005 through May 2025. Google Scholar, reference lists, and the Index Medicus for the South-East Asia Region were searched as supplementary sources. Maternal health outcomes were mapped using an adapted PID framework, and all results were summarized descriptively. Twenty-five studies from 7 SEA LMICs were included. Mobile apps and SMS were the most commonly used technologies, reported in 22 (88%) studies. Fourteen (56%) studies reported maternal health outcomes across more than one PID domain. Intermediate outcomes were reported most frequently (n=23, 92%), followed by proximal knowledge outcomes (n=10, 40%) and distal biomedical and clinical outcomes (n=8, 32%). Findings related to proximal knowledge outcomes were predominantly significant, whereas intermediate and distal outcomes showed mixed results. All but one study (n=24, 96%) recruited participants through existing health care services, and most interventions were implemented in primary care settings (n=17, 68%). Maternal health outcomes were represented across all 3 PID domains, with intermediate outcomes reported most frequently and distal biomedical and clinical outcomes least frequently. Future studies should give more attention to distal biomedical and clinical outcomes, as well as underrepresented SEA LMICs.

Basal-like double-negative prostate cancer (DNPC) and triple-negative breast cancer (TNBC) are aggressive tumors with few targeted treatment options, raising the question of whether a shared, druggable cell-surface antigen can be leveraged for effective immunotherapy. Here, we integrated analyses of independent bulk and single-cell transcriptomic datasets with mechanistic and preclinical therapeutic studies to evaluate CDH3 (P-cadherin) as a candidate target in basal-like disease. CDH3 expression was consistently enriched in basal-like subtypes across prostate and breast cancer cohorts and was preferentially expressed in basal epithelial tumor compartments. Mechanistically, CDH3 expression was governed by a YAP1-WNT5A/ROR2 signaling axis, linking basal subtype gene expression to non-canonical Wnt signaling. To exploit this target, we evaluated both a CDH3-directed antibody-drug conjugate (ADC) and CDH3-specific chimeric antigen receptor (CAR)-T cells. The ADC exhibited antigen-dependent internalization and cytotoxicity in vitro and reduced metastatic tumor burden in vivo. CDH3 CAR-T cells showed antigen-specific activation and tumor cell killing in vitro and improved tumor control and survival in metastatic prostate and breast cancer xenograft models, with additional benefit when combined with PD-1 blockade (nivolumab). Together, these findings establish CDH3 as a clinically relevant and therapeutically actionable target and support CDH3-directed ADC and CAR-T strategies for aggressive, basal-like DNPC and TNBC.

The collapse of the World Trade Center (WTC) towers on September 11, 2001 resulted in an unprecedented environmental disaster that released carcinogenic particulates and chemicals. Exposure to these toxicants has been associated with increased cancer incidence among responders and community members. While female breast cancer has been characterized in this population, male breast cancer (MBC) remains underexplored. To describe the demographic, clinical, and exposure characteristics of MBC cases among community members enrolled in the WTC Environmental Health Center (WTC EHC). Eligible participants included men with primary breast cancer who met WTC exposure criteria and provided informed consent from the WTC EHC as of December 31, 2024. Demographic, exposure, tumor characteristics and molecular subtypes were analyzed descriptively. Among 1,575 WTC EHC breast cancer cases, 22 were male, with 16 consented for the analysis. The median age at diagnosis was 64 years, with a median latency of 15.4 years post-9/11. Most tumors were ductal, moderately differentiated, early stage (I-II), and Luminal A. Most patients were Non-Hispanic White and overweight or obese. Although MBC is rare, its occurrence in an environmentally exposed civilian cohort highlights potential long-term effects of WTC-related toxicants and supports continued surveillance.

The expansion of kratom's availability, popularity, and product diversity in the United States has drawn scientific and national attention. Characterizing the sociodemographic and behavioral correlates of kratom use may help public health efforts. We examined data from the National Survey of Drug Use and Health (2022-2023), to investigate lifetime prevalence and sociodemographic, mental health, and behavioral correlates of self-reported use of kratom as well as the interaction of cannabis and heroin with sex, given co-used patterns with kratom and report sex differences. A pooled prevalence estimate of lifetime kratom use among U.S. adults (18+) was 1.95%, of whom 34.84% reported past-year use and 18.39% reported past-month use. Among those with past-year use, 52.79% reported past-month use. Lifetime use was most common among White, unmarried, younger, working males and those with lower incomes, living in poverty, and participating in government assistance programs. In multivariable analysis, lifetime kratom use was associated with lifetime major depressive episodes, use of pain-relieving medications, and past-year serious psychological distress. Lifetime cannabis and heroin use were associated with elevated odds of kratom use in both sexes. However, kratom's relationship with cannabis use was over three times stronger in males, while its relationship with heroin use was approximately half as strong in males compared to females. Kratom use was correlated with specific demographic, behavioral, and sex- and substance-specific characteristics, suggesting the need for more study to examine whether certain populations may benefit from targeted screening and intervention.

Hispanic-American populations face a high and growing burden of cancer and health disparities. Financial toxicity (FT) describes the economic distress experienced by cancer patients during diagnosis/treatment; familial financial toxicity (FFT) describes the financial distress experienced by families adapting to the economic challenges of cancer. This study assesses FT/FFT among Hispanic-American breast cancer patients enrolled in the Navigator-Assisted Hypofractionation (NAVAH) Phase I clinical trial. Six patients undergoing radiation therapy were assessed using the validated Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT) instrument. The mean score of the first 11 questions was used to classify individual FT as grade 0 (absent), grade 1 (mild), grade 2 (moderate), or grade 3 (severe), with lower scores indicating greater FT. Question 12 (Q12) was evaluated separately to measure FFT, with scores ranging from 0 to 4. An exploratory linear regression analysis examined the relationship between individual FT and FFT. All patients reported mild or moderate individual FT, with Q12 scores ranging from 2 to 4. An exploratory linear regression analysis demonstrated a strong inverse association between individual COST-FACIT scores and Q12 scores (r=-0.891, P=0.01). Lower COST-FACIT scores (indicating greater individual FT) were associated with higher Q12 scores, indicating greater perceived familial financial hardship. These findings suggest a strong association between individual and familial FT among Hispanic-American breast cancer patients. Assessing familial FT may help identify the broader economic impact of cancer treatment and inform supportive interventions addressing financial hardship among patients and their families.

Increased awareness in women's health has taken place over the last 5 to 10 years, especially associated with aging, where perimenopause and menopause have been highlighted topics. This review examines how changes with age in women during perimenopause and menopause lead to estrogen-deficient skin and impaired quality of life (QOL). The topics presented include: (1) the reasons why women's health (perimenopause and menopause) is finally taking a prominent position in the public and medical mindset, (2) chronological (intrinsic) and photo (extrinsic) skin aging characteristics and skin changes by each decade of life, (3) the importance of and the changes to estrogen levels in aging women (especially with perimenopause and menopause) that lead to estrogen-deficient skin, (4) in brief, hormonal and selective estrogen receptor modulators (SERMs), including polyphenolic and isoflavonoid treatments, plus influencing lifestyle factors, and (5) using skin changes, as the "observable organ" and a reflective mirror of internal aging in women that may signal the potential decline of various unseen tissue/organ systems. This represents a different paradigm for the functional aspects in the body associated with the shifts in and loss of estrogen. Thus, skin health with aging (and the decline in and loss of estrogen) may provide nutritional and medical professionals, especially dermatologists, with a unique position to lead a discussion with patients to consider healthiness beyond dermal changes. Finally, potential treatments to assist and/or enhance women's healthspan and longevity may be part of this exchange in a collaborative examination.Graphical abstract available for this article.

We reported earlier that the occurrence of seizures in the pre-pregnancy year was the main determinant of the following pregnancy being seizure-affected. Additional risk factors were assessed in this study. The pregnancies involved first pregnancies of women with epilepsy. Two categories were compared. One category comprised 711 pregnancies in which seizures had occurred during the pre-pregnancy year and where seizures might reasonably be expected to continue to occur during the 9 months involved in any following pregnancy. The other category contained 634 pregnancies that were seizure-free in the pre-pregnancy year. Multivariate logistic regressions were fitted for 1345 subjects for seizure occurrence during pregnancy for co-variates listed to identify statistically seizure-related co-variates. Seizure-affected pregnancy rates in the 1345 pregnancies studied remained stable over the consecutive 5-year intervals from 1999 onwards, viz. 50.5%, 53.9%, 50.3%, 52.8% and 48.2%. Seizure-affected pregnancy was more likely in WWE, who had: (1) Shorter durations of pre-pregnancy freedom from seizures. (2) Focal epilepsy. (3) Not taken ASMs while pregnant. (4) Not used pre-pregnancy folate supplementation. (5) Longer durations of epilepsy. (6) Earlier age onset of epilepsy. The hazard of a seizure-affected next pregnancy was over threefold higher when the pre-pregnancy year was seizure-affected than when it had been seizure-free. The finding that a year's pre-pregnancy seizure freedom was associated with a reduced risk of seizures in the next pregnancy was expected. The magnitude of the greater than threefold higher seizure risk in the next pregnancy if seizures had occurred in the pre-pregnancy year was not. It identifies a group of women with epilepsy whose medical management during pregnancy warrants particular care.

Data on the risk factors that increase the risk of brain metastases (BM) in breast cancer is lacking. Mining the prospectively collected data of adjuvant studies for BM at first recurrence may identify a population for prevention strategies. Data collected from 7 sequential adjuvant studies conducted by the Hellenic Cooperative Oncology Group was queried for recurrence in CNS. Parameters associated with the development of BMs at first recurrence were collected. 5,318 patients were included. After a median follow-up time of 137.0 months (range, 0-334.1), the iBCFS at 120 months was 73.2% (95% CI: 72.0%-74.4%) and OS 78.3% (95% CI: 77.2%-79.4%). 106 patients (2%) developed BM at first recurrence and of those 68 (64.2%) had BM only. In cause-specific Cox models fitted on the entire cohort, triple-negative subtype (HR 3.43, 95% CI: 2.05-5.75) and four or more positive axillary nodes (HR 2.52, 1.47-4.33) were independently associated with BM at first recurrence; AJCC stage III (HR 3.41, 1.56-7.44) and hormone receptor negativity (HR 2.08, 1.37-3.15) remained independently associated in alternative parameterizations. Triple negative breast cancer patients had a higher cumulative incidence of BM (3.86%, 95% CI: 2.74-5.42, at 120 months versus 1.27%, 0.90-1.79, in luminal A/B disease; Gray's test p < 0.0001) with a steep rise in the early years after adjuvant therapy. BM patients had significantly worse survival from first recurrence than patients with extracranial first recurrence (median 8.0 versus 31.2 months; HR 2.66, 95% CI: 2.15-3.29), with HER2-positive patients having significantly longer brain metastasis-specific survival (BMSS) than other subtypes (median 13.0 versus 5.4 months; HR 0.56, 95% CI: 0.36-0.86, p = 0.007). In this large, prospectively annotated database of early breast cancer (eBC) patients, BM seem to occur rarely at first recurrence but carry a poor prognosis. HER2-positive patients with BM had a significantly better prognosis than other subtypes. These estimates describe an era in which adjuvant trastuzumab was reimbursed only from 2006 and contemporary CNS-active regimens were not available and should be read accordingly. Not applicable.

Endometriosis affects approximately 10% of women of reproductive age with a mean diagnostic delay of 7-10 years. Image-guided procedures show increasingly promising results as minimally invasive alternatives to excision. Structured overview of image-guided minimally invasive treatment options for endometriosis with focus on percutaneous cryoablation. Percutaneous cryoablation demonstrates the strongest evidence for extraperitoneal and intramuscular lesions and represents a valid minimally invasive alternative to excision. Three institutional cases illustrate technique and outcomes. Ethanol sclerotherapy is established for ovarian endometriomas. High-intensity focused ultrasound (HIFU) shows promising results for abdominal wall disease; radiofrequency ablation (RFA) and microwave ablation are investigational. Interventional radiology offers a growing therapeutic spectrum. Prospective randomized trials are needed for guideline integration. HINTERGRUND: Die Endometriose betrifft schätzungsweise 10 % aller Frauen im reproduktiven Alter und ist durch eine diagnostische Verzögerung von durchschnittlich 7–10 Jahren gekennzeichnet. Bildgesteuerte Verfahren zeigen zunehmend vielversprechende Ergebnisse als minimal-invasive Alternative zur chirurgischen Exzision. ZIEL: Strukturierter Überblick über bildgesteuerte minimal-invasive Therapieverfahren bei Endometriose mit Fokus auf die perkutane Kryoablation. Die perkutane Kryoablation zeigt die stärkste Evidenz für extraperitoneale und intramuskuläre Endometrioseherde und stellt eine valide minimal-invasive Alternative zur Exzision dar. Drei eigene Fälle illustrieren Technik und Ergebnisse. Die Ethanol-Sklerosierung ist eine etablierte Option für ovarielle Endometriome. Hochintensiver fokussierter Ultraschall (HIFU) zeigt vielversprechende Resultate bei Bauchdeckenherden; Radiofrequenzablation (RFA) und Mikrowellenablation kommen in frühen Untersuchungsphasen zum Einsatz. Die interventionelle Radiologie bietet ein wachsendes Therapiespektrum. Prospektive randomisierte Studien sind für die Leitlinienintegration erforderlich.

Menopause is associated with hormonal, structural, and functional changes affecting the vulvovaginal tissues, pelvic floor, and urinary tract. Weight loss may further alter soft-tissue volume and body composition, although effects on pelvic floor function remain incompletely understood. The aim of this study was to review menopause-associated vulvovaginal and pelvic floor changes and discuss implications for dermatologic evaluation, weight loss, symptom management, and procedural counseling. A narrative review of literature addressing menopause, pelvic floor dysfunction, weight loss, glucagon-like peptide-1 receptor agonists, pelvic floor rehabilitation, and emerging vulvovaginal therapies was performed. Menopause-associated tissue remodeling may contribute to genitourinary syndrome of menopause, urinary symptoms, sexual dysfunction, and pelvic floor disorders. Weight loss may improve obesity-associated urinary incontinence but can also reduce lean mass and external soft-tissue volume. Evidence regarding glucagon-like peptide-1 therapies and pelvic floor function remains limited. Pelvic floor physical therapy is an established treatment, whereas high-intensity focused electromagnetic therapy shows preliminary evidence of benefit. Dermatologists should recognize functional symptoms, provide evidence-based counseling, and coordinate care with gynecology, urogynecology, urology, and pelvic floor physical therapy while approaching emerging procedural therapies cautiously.

Acquired elastotic hemangioma is an uncommon benign cutaneous vascular proliferation first described in 2002 that typically presents as a solitary erythematous plaque arising on chronically sun-exposed skin. Histologically, it is characterized by a superficial, band-like, horizontally oriented capillary proliferation associated with marked solar elastosis. In contrast, vulvar elastosis develops in an anatomical site protected from ultraviolet radiation and has been linked to aging, hormonal changes, and inflammatory or reparative processes.In this article, we report the lesion of a 67-year-old woman with vulvar lichen sclerosus who presented with a palpable 1-cm nodule involving the left labium majus. Her medical history was notable for an undifferentiated ovarian carcinoma diagnosed 19 years earlier, treated with chemotherapy and currently in remission. Histopathological examination revealed superficial features of lichen sclerosus and, within the underlying dermis, a nodular accumulation of thick, irregular elastic fibers intermingled with numerous mature blood vessels lacking endothelial atypia.In conclusion, a prominent vascular component may represent a feature of nodular vulvar elastosis and should not necessarily be interpreted as evidence of a primary vascular neoplasm.

Coordinating catalytic species, gaseous mediators, and small-molecule drugs at a tumor site remains difficult because each component follows a different activation and release process. To address this challenge, we constructed oxygen-vacancy-enriched hollow CoSn(OH)6/CuS heterostructures (CC) by alkaline etching and subsequent in situ hydrothermal deposition of CuS, and coloaded CC with tanshinone IIA (Tan-IIA) to form CCT; this formulation was then incorporated into a photothermally responsive PCL/PVP microneedle patch, denoted CCT-MN. Hollowing the CoSn(OH)6 cubes increased surface accessibility, whereas interfacial CuS growth extended near-infrared (NIR) absorption, promoted charge transfer, and strengthened photothermal conversion. Upon 808-nm exposure, a CC dispersion reached approximately 54 °C, afforded a photothermal conversion efficiency of 20.8%, and retained its heating performance during repeated irradiation cycles. The vacancy-rich heterostructure promoted singlet-oxygen production; under acidic conditions, Cu2+ sites catalyzed Fenton-like hydroxyl-radical formation, while protonation of sulfide species supplied H2S. The optimized patch possessed intact and mechanically robust needles, penetrated a skin-mimicking hydrogel, dissolved faster under laser heating, and promoted simultaneous H2S generation and Tan-IIA release in response to acidity and NIR irradiation. In 4T1 cells, the laser-activated CCT formulation increased ROS and H2S levels, disrupted lysosomes, collapsed the mitochondrial membrane potential, and caused extensive cell death. In tumor-bearing mice, CCT-MN irradiation increased the tumor-surface temperature from 38.5 to 56.5 °C and achieved the greatest tumor suppression among the tested regimens, without detectable weight loss or histological injury to major organs. These findings establish a locally implanted heterostructure microneedle system that synchronizes photothermal, photodynamic, chemodynamic, gas, and Tan-IIA-assisted antitumor actions.

Resistance to therapeutic interventions contributes to poor long-term cancer patient outcomes. Adaptation to therapy, a common mechanism of drug resistance involving drug-induced activation of pro-survival oncogenic processes, poses a challenge for the implementation of effective precision therapies. Here, we addressed this challenge using the TargetScore network modeling method to nominate combination therapies that block adaptive responses in breast cancer. TargetScore identified therapeutically actionable adaptive responses as drug-induced concurrent changes in phospho-proteins connected within a signaling network. To study how apoptotic stress rewires cancer cells and uncover therapeutically actionable oncogenic dependencies, breast cancer cells were perturbed with inhibitors of anti-apoptotic mediators, particularly MCL1. TargetScore and phosphoproteomics analyses revealed the short-term (i.e., days) stress and long-term (i.e., months) acquired drug resistance to inhibitors of anti-apoptotic mediators. TargetScore predicted concurrent activation of growth and DNA repair pathways as cells evolved to resist apoptotic targeting. Validation of the predictions demonstrated strong responses to PARP1/2 and SHP2 inhibitor combination in vitro and in vivo. In genetically engineered mouse models, PARP1/2 and SHP2 co-targeting led to near-complete tumor eradication and durable responses with significant survival benefit, laying the groundwork for clinical evaluation. Functional proteomics and perturbation biology analyses proposed a mechanism of response to PARP1/2 and SHP2 co-targeting associated with molecular markers of DNA damage response, replication stress, and cell cycle arrest. This study demonstrates that TargetScore may advance precision oncology by matching drug combinations to molecular signatures and dependencies revealed under therapeutic stress.

No clear sex difference in depressive symptoms has been observed among people with multiple sclerosis (MS), unlike for the general population in which females have higher depression rates. MS, however, is heterogeneous. The authors evaluated whether the influence of sex on depressive symptoms in MS varies across age, disease-related variables, or testing year. Data were gathered from 1,731 adults with MS assessed at a neuropsychiatry clinic between 2006 and 2025 and stratified by age (18-45, 46-55, and ≥56 years), disease duration (0-4, 5-9, and ≥10 years), Expanded Disability Status Scale (EDSS) scores (0.0-1.0, 1.5-2.5, and ≥3.0), illness subtype (primary progressive, secondary progressive, and relapsing remitting), and testing year (2006-2015, 2016-2020, and 2021-2025). Depressive symptoms were measured with the Hospital Anxiety and Depression Scale depression subscale (HADS-D). Analyses of covariance, controlled for education, were conducted to test for a sex difference in HADS-D scores and whether the influence of sex varied according to stratified subgroups. The mean±SD participant age was 43.5±11.0 years; 73% were women; and the median EDSS score was 2.0 (interquartile range 1.5-3.5). HADS-D scores did not significantly differ between men (mean=7.2±4.2) and women (mean=6.9±4.0). In analyses controlled for education, the effect of sex on HADS-D scores did not significantly differ by age (η 2 p =0.001), disease duration (η 2 p =0.003), EDSS score (η 2 p <0.001), illness subtype (η 2 p =0.003), or testing year (η 2 p =0.001). Across various disease-related characteristics and cross-sectional periods, depressive symptoms did not significantly differ between men and women with MS.

Abnormal uterine bleeding affects 15-20 % of women of reproductive age and is a common indication for surgery. The aim of this study was to describe the extent of surgical intervention and the choice of surgical procedure among premenopausal women with this condition and to identify factors associated with hysterectomy. Women aged ≤ 55 years who had contact with Sørlandet Hospital between 1. January 2011 and 31 December 2021 due to benign abnormal uterine bleeding (ICD-10 diagnosis codes N92.0-N92.6) were identified. Following data extraction from electronic patient records using a structured query language, the data were analysed using descriptive statistics. Of 4947 women with abnormal uterine bleeding, 2278 (46 %) underwent surgery. Of these, 1830 (80 %) had one procedure, 415 (18 %) had two and 33 (1 %) had three. Thermal endometrial ablation was the most common initial procedure (902 of 2278, 40 %), while hysterectomy was performed on 649 women (28 %). Fibroids, pain and anaemia were associated with hysterectomy, but age was not. Over an 11-year period, almost half of the patients with benign abnormal uterine bleeding underwent surgery. More than a quarter of these had a hysterectomy. Our findings suggest that the overall symptom burden, in addition to the amount of menstrual blood loss, is associated with the likelihood of undergoing hysterectomy.

Menopause is increasingly recognised as a significant stage of the female reproductive cycle; however, the experiences of women from Global Majority backgrounds (GMB) remain underrepresented within menopause research. To address this gap, this systematic literature review explored how women from Global Majority backgrounds living in Western countries perceive and experience menopause, and how cultural, social and structural factors shape these experiences. Multiple databases were searched in November 2025 for qualitative studies, or mixed-method studies with extractable qualitative findings. Eligible studies were appraised using the CASP qualitative checklist, and findings were synthesised using thematic synthesis. Fifteen studies conducted in US, Canada and Australia, involving women from East and Southeast Asian, South Asian, African American, Hispanic/Latina and Aboriginal backgrounds were included. Six interrelated themes were identified: menopause as a culturally constructed concept; as an embodied and identity-disrupting experience; the influence of social and gendered expectations; cultural and intersectional variation; coping strategies and healthcare navigation; and menopause as a potentially transformative life stage. Experiences were shaped by interactions among cultural beliefs, migration histories, family and community expectations, language barriers, socioeconomic circumstances and healthcare encounters. While some women described stigma, loss and disruption, others experienced greater freedom, resilience and personal transformation. These findings support the need for culturally responsive, intersectional menopause care that avoids cultural assumptions, attends to women's own understandings and treatment preferences, and strengthens clinicians' cultural awareness. Further research should include underrepresented groups and examine whether culturally adapted resources improve healthcare access, experiences and outcomes.

Perimenopause is increasingly recognized as a critical biological transition that extends beyond reproductive aging to influence multiple organ systems. Accelerated bone loss during the menopausal transition is supported by robust epidemiological, mechanistic and imaging evidence, whereas evidence for concurrent changes in muscle health and particularly neurocognitive function is more heterogeneous. Subjective cognitive complaints, including reduced concentration, forgetfulness and 'brain fog', are commonly reported, but objectively measured cognitive changes are generally modest and less consistent. Endocrine, inflammatory and mitochondrial pathways provide biological plausibility for interactions among bone, muscle and brain; however, direct evidence demonstrating an integrated relationship among these systems specifically during perimenopause remains limited. This narrative review critically synthesizes current evidence and proposes the bone-brain-muscle axis as an integrative conceptual framework. The model is presented as a biologically plausible clinical framework rather than a validated mechanistic pathway. Recognizing perimenopause as a potential neuro-musculoskeletal window may support earlier identification of multidimensional risk and individualized strategies to preserve physical function, cognitive health and healthy aging. Perimenopause is often viewed simply as the time before menopause, but it is increasingly recognized as an important stage of healthy aging. During this transition, changing hormone levels affect not only reproductive health but also the skeleton, muscles and brain. Many women experience bone loss, changes in muscle function, memory difficulties, problems concentrating and the commonly described ‘brain fog’. Although these changes are often considered separately, hormonal changes, low-grade inflammation, alterations in energy metabolism and reduced physical activity may affect more than one of these systems. These potential shared influences provide the basis for considering bone, muscle and brain health together, although their direct interrelationship during perimenopause has not yet been established.This review summarizes current evidence on how perimenopause affects bone, muscle and brain health. The strongest evidence concerns accelerated bone loss, while evidence for concurrent changes in muscle health and particularly cognitive function during perimenopause is more variable. Importantly, common cognitive symptoms during perimenopause are usually mild and should not be interpreted as early dementia.We propose the bone–brain–muscle axis as a practical framework that integrates these apparently separate changes into a single clinical perspective. Recognizing these interconnected changes may help clinicians identify women at increased risk earlier and implement lifestyle measures, menopausal hormone therapy when appropriate, and other individualized interventions to preserve function, independence and healthy aging.

To effectively support women presenting with symptoms of menopause, it is crucial for doctors to be adequately prepared through their undergraduate education. This study explored the coverage of menopause in undergraduate teaching materials, and students' perceptions of their understanding of this topic. A mixed-methods case study design was used to explore menopause teaching at the University of Dundee's (UoD) MBChB course. A two-stage content analysis identified menopause teaching within the 'Reproduction and Sexual Health' (RSH) teaching block. Data on students' knowledge of menopause and their views on the teaching they had received were gathered through a questionnaire and semi-structured interviews. Quantitative and qualitative data included the content of teaching materials, perceptions of teaching, and learning about menopause. Teaching about menopause was identified in five sessions of RSH block teaching. Teaching was predominantly lecture-based, and included discussion of the symptoms of menopause and possible treatments. All students reported a lack of confidence in both their knowledge of menopause and their ability to effectively consult a patient presenting with symptoms of menopause. Students expressed their wish for opportunities to reinforce and apply their learning. Existing methods for teaching menopause may not be the most effective. Recommendations for improving student confidence include incorporating menopause teaching content into multiple teaching blocks and providing opportunities for students to apply their learning through case discussions or workshops.

Current precision mammography screening trials use heterogeneous risk models, risk strata, and screening intervals, with no consensus on how absolute breast cancer risk should translate into screening frequency. A standardized, risk-model-agnostic approach could improve consistency in trial design and facilitate broader clinical implementation. To develop and evaluate a risk-model-agnostic framework that maps guideline-defined absolute breast cancer risk cut points to screening intervals that can guide the design of future personalized screening strategies and translate smoothly to routine clinical practice. Screening interval and frequency derived from the absolute risk of breast cancer in US women is the main outcome. The framework yielded a gradient of estimated screening intervals that scaled with absolute risk: annual (2%-3%); annual with supplemental imaging/counseling (≥3%); biennial (1%-2%); and potentially less frequently. When compared with ongoing intervention trials, screening intervals assigned by trials varied widely and were not uniformly aligned with absolute-risk levels, underscoring the lack of standardized mapping between risk and screening intensity. A risk-model-agnostic framework based on absolute-risk cut points can provide a transparent and standardized method for specifying screening intervals in personalized mammography screening. This approach may improve consistency in future intervention trials and facilitate equitable implementation of precision screening across population settings.

Objective: Research on potentially avoidable caesarean deliveries frequently centres on births to nulliparous birthing people with a singleton, term delivery with vertex presentation (NTSV). However, caesarean deliveries in this population are heterogeneous, and little is known about how the association with caesarean delivery varies across risk indicators. We aimed to estimate absolute associations between caesarean delivery, categorised by risk indicators, and postpartum hospital encounters within 1 year among NTSV birthing people in Massachusetts. We used data from the Pregnancy and Early Life Longitudinal data system, which captures birth certificate and hospital discharge data for all births in Massachusetts from 2011 to 2019. Risk indicators were categorised into five groups: chronic/acute disease, placental complications, labour complications, fetal concerns and no documented risk. We estimated risk differences for the association of caesarean versus vaginal delivery with hospital encounters within one year postpartum according to risk indication subgroup. Hospital encounters within 30 days, 31 to 180 days and 181 to 365 days were examined. Overall, we estimated 23 (95% confidence interval [CI] 19, 27) excess cases of one-year postpartum hospital encounters per 1000 live births for caesarean deliveries compared to vaginal deliveries. Among birthing people with no documented risk, caesarean delivery was not associated with higher postpartum hospital encounter rates within one year compared to vaginal deliveries. Caesarean delivery was associated with an increased risk of hospital encounters for all other subgroups. All estimated risk differences were positive for hospital encounters within 30 days; however, across all subgroups, these associations diminished after 180 days postpartum. The association of caesarean delivery with postpartum hospital encounters varies by risk indicator and by the timing of the postpartum hospital encounter. These results suggest that caesarean deliveries among those with no documented risk are not associated with an increased risk of postpartum hospital encounter.

While minimally invasive surgery is the current surgical standard of care for excision of deep endometriosis of the bowel, there is little literature evaluating patient-reported outcome measures following a multidisciplinary, robotic approach. This study aimed to assess the functional outcomes of robotic surgery for patients undergoing resection of deep endometriosis involving the bowel. Retrospective cohort review. A single academic tertiary institution. Patients with endometriosis of the bowel undergoing multidisciplinary resection between January 1, 2018, and October 1, 2023. A survey assessing functional outcomes on a Numeric Rating Scale preoperatively and at multiple points postoperatively. Of 92 eligible patients, 41 completed a preoperative survey and at least one postoperative survey. Among these 41 patients, overall pain improved postoperatively from 5.3 ± 2.7 (Numeric Rating Scale) to a nadir of 1.6 ± 1.9 at 6 months and 2.3 ± 3.0 at 12 months (p < 0.001). Preoperative pain at ovulation (mean 4.2 Numeric Rating Scale ± 3.7), pre-period pain (4.9 ± 3.5), period pain (5.7 ± 3.6) and post-period pain (3.3 ± 3.3) all decreased to a mean of 1 at 12 months postoperatively (p < 0.001). The proportion of patients reporting pain impacting work decreased from 88% preoperatively to <40% postoperatively (p < 0.001). The proportion of patients happy with their bowel function increased from 39% preoperatively to 63.2% at 1 month, 80.0% at 6 months, and 69.2% at 12 months postoperatively (p = 0.014). Only 31.7% of patients responded to their 12-month survey, tertiary care center, low diversity in patient demographics, retrospective design. In this cohort of patients undergoing multi-disciplinary robotic excision for advanced endometriosis involving the bowel, patients reported significantly improved pain and quality of life measures. See Video Abstract.

Breast cancer metastasis remains a major cause of mortality, and epithelial-mesenchymal transition (EMT) is a key process driving tumor progression. Here, we developed perfluorohexane-loaded hollow iron oxide nanoparticles (PFH-HIONs) as a magnetothermal phase-transition platform for image-guided breast cancer therapy. PFH-HIONs were synthesized by vacuum-assisted loading of PFH into hollow iron oxide nanoparticles and characterized for morphology, size, zeta potential, magnetothermal performance, and ultrasound phase-transition behavior. Their antitumor effects were evaluated in MCF-7 cells and in a xenograft model. Ferroptosis-related changes, EMT-associated signaling, macrophage polarization, and immune-related responses were further assessed. PFH-HIONs showed a hollow nanostructure, AMF-responsive heating, and stimulus-triggered ultrasound contrast enhancement. PFH-HIONs combined with AMF reduced MCF-7 cell viability and increased apoptotic cell death. This treatment also induced ferroptosis-related changes, including GPX4 downregulation, 4-HNE and ACSL4 upregulation, and ROS accumulation. In TGF-β1-treated MCF-7 cells, PFH-HION plus AMF suppressed Smad2/3 phosphorylation, reversed EMT-associated protein and transcription factor expression, and these effects were partially attenuated by ferrostatin-1. In addition, PFH-HIONs plus AMF promoted a more pro-inflammatory macrophage phenotype, and conditioned medium from treated tumor cells induced a similar macrophage reprogramming. In vivo , PFH-HIONs plus AMF inhibited tumor growth, increased necrosis, reduced Ki67, and were associated with increased intratumoral infiltration of CD8-positive lymphocyte-like cells and elevated IFN-γ levels, with acceptable short-term biosafety. PFH-HIONs function as a magnetothermal phase-transition nanoplatform with antitumor activity associated with ferroptosis, EMT suppression, and immune-related tumor microenvironment changes, supporting further investigation for image-guided breast cancer therapy.

Preeclampsia is associated with widespread endothelial dysfunction and shares several pathophysiological mechanisms with atherosclerosis. Carotid intima-media thickness (CIMT) is a well-established marker of subclinical atherosclerosis and may reflect early maternal vascular remodeling. This study aimed to compare CIMT between pregnant women with and without preeclampsia and to evaluate the association between CIMT and preeclampsia. In this prospective observational cohort study, pregnant women with singleton pregnancies who attended the outpatient obstetrics clinic between 24 and 37 weeks of gestation and met the eligibility criteria were prospectively enrolled. Participants diagnosed with preeclampsia formed the study group, and pregnant women who were not diagnosed with preeclampsia during the evaluation phase and during pregnancy formed the control group. CIMT measurements were performed at the time of evaluation for all patients, concurrently with the clinical and laboratory assessment used for diagnosis. Demographic characteristics, routine laboratory parameters, and CIMT measurements were compared between groups. Correlation analyses and receiver operating characteristic curve analysis were performed to evaluate the association between CIMT and preeclampsia. Women with preeclampsia had significantly greater CIMT than pregnant women without preeclampsia. Maternal age, body mass index, serum uric acid, urea, and creatinine levels were significantly higher, whereas serum albumin levels were significantly lower in the preeclampsia group. CIMT demonstrated significant correlations with several biochemical parameters related to renal function and systemic vascular involvement. In multivariable logistic regression analysis, median CIMT remained independently associated with preeclampsia after adjustment for maternal age, body mass index, and gestational age at CIMT measurement (adjusted odds ratio 2.53 per 0.1 mm increase; 95% confidence interval 1.36-4.71; P = 0.003). Receiver operating characteristic analysis showed that CIMT had a moderate ability to discriminate women with and without preeclampsia (area under the curve 0.75). Women with preeclampsia exhibited significantly increased CIMT compared with pregnant women without preeclampsia. Median CIMT demonstrated moderate discriminatory performance for distinguishing women with and without established preeclampsia; however, the clinical utility of CIMT for preeclampsia screening remains to be established. Larger prospective studies are required to validate the observed association and determine the clinical utility of CIMT in preeclampsia assessment.

The study aimed to assess whether baseline fluorine-18 fluorodeoxyglucose (18F-FDG) PET/computed tomography (CT)-derived CT radiomics adds predictive value to clinicopathological biomarkers and PET metabolic assessment for pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer. This retrospective study included 104 patients with stage I-III breast cancer who underwent baseline 18F-FDG PET/CT, NAC, and surgery. Clinicopathological variables and tumor maximum standardized uptake value (SUVmax) were recorded; 107 CT radiomic features were extracted using PyRadiomics. Clinical, Metabolic, Radiomics, and Combined models were developed using L2-regularized logistic regression and evaluated by nested five-fold cross-validation. Discrimination, calibration, and decision curve analysis were assessed; 95% confidence intervals (CIs) were estimated using 1000 bootstrap resamples of pooled out-of-fold predictions. Forty-six patients (44.2%) achieved pCR. Area under the curves (AUCs) were 0.784 (95% CI: 0.686-0.875) for Clinical, 0.595 (0.470-0.704) for Metabolic, and 0.636 (0.526-0.739) for Radiomics models. The Combined model had the highest numerical AUC (0.797; 95% CI: 0.705-0.880), with accuracy 0.731, sensitivity 0.630, specificity 0.810, and F1-score 0.674. Combining CT radiomics and SUVmax with clinicopathological biomarkers yielded the highest numerical discrimination for pCR, but improvement over the Clinical model was modest. Larger multicenter external validation is needed before clinical implementation.

Outcomes of vulvar squamous cell carcinoma (vSCC) are driven by human papillomavirus (HPV) and p53 status. As tumor budding activity (TBA) and tumor-stroma ratio (TSR) are prognostic in other carcinomas, we evaluated their significance in vSCCs. Tumors diagnosed from 1990 to 2022 were identified, and clinicopathologic data, TBA, and TSR were assessed. The cohort included 172 tumors: 73 (42.5%) HPV-associated, 74 (43%) HPV-independent/p53-abnormal, and 25 (14.5%) HPV-independent/p53-wild-type. Median patient age was 69.5 (22 to 98) years. Most tumors were staged as pT1b (132, 76.7%). Lymphovascular invasion (LVI) was present in 25 (14.5%), and lymph node metastases in 24.6% (33/134) of cases with nodal evaluation. The median TBA was 2 (0-45)/1 high-power field (HPF), 4 (0-198)/5 HPF, and 5 (0-304)/10 HPF. The median TSR was 60% (10% to 90%). Seventy (40.7%) patients experienced recurrences (median: 14 mo, 2-141). Increased TBA at ≥20/10 HPF was associated with shorter recurrence-free survival (RFS) in the entire cohort (P=0.002) and HPV-independent/p53-abnormal vSCCs (P=0.003). This association persisted in the HPV-independent/p53-abnormal vSCCs after adjusting for LVI, and T and N categories of pTNM stage (P=0.012), and in the entire cohort after adjusting for tumor subtype and other covariates (P=0.01). TBA was also associated with shorter disease-specific (P=0.048) and overall (P=0.009) survival after adjusting for tumor subtype, LVI, and T and N categories. Our study suggests that high TBA is associated with shorter recurrence-free survival in vSCC, particularly the HPV-independent/p53-abnormal subgroup, as well as with shorter disease-specific and overall survival after adjusting for tumor subtype, LVI, T and N categories. The findings warrant further validation.

This scoping review explores intersecting relationships among the concepts of postpartum depression, maternal-infant (dyadic) attachment (or bonding), and breastfeeding self-efficacy within postpartum populations and how often these concept relationships are examined among predominantly historically marginalized populations (non-White, low-income, low education level). To address the ongoing public health concern of postpartum depression, we must understand its relationship with dyadic attachment and breastfeeding self-efficacy. Four studies met inclusion criteria, examining the relationships between the concepts of postpartum depression, dyadic attachment, and breastfeeding self-efficacy. Because these 4 studies had heterogeneous study designs, study measures, and study time points, the exact nature of the relationship between these 3 concepts is difficult to parse. Furthermore, only 1 study evaluated these concepts in historically marginalized populations (low-income). Future research using rigorous study design approaches is warranted. While studies found a relationship between increased breastfeeding self-efficacy and increased dyadic attachment, mixed results remain regarding the relationships between postpartum depression and dyadic attachment or breastfeeding self-efficacy. Nevertheless, dyad-focused interventions have shown the potential to improve breastfeeding self-efficacy and dyadic attachment while reducing postpartum depression. The scoping review findings suggest that these concepts collectively need more research attention, given their potential effects on improving maternal-child dyadic outcomes.

Vaginal neoplasms predominantly affect elderly and intact females. Given the close relationship of sex hormones with reproductive tract carcinogenesis, this retrospective study of 36 female dogs evaluated, by immunohistochemistry, the expression of estrogen and progesterone receptors and the cell proliferation marker Ki-67 in canine vaginal neoplasms, aiming to correlate them with malignancy and clinical variables. The results demonstrated that malignant neoplasms retained estrogen receptor expression, although immunolabeling of both hormone receptors declined with increasing animal age. Older bitches presented smaller tumor diameters at diagnosis, and significant co-expression between estrogen and progesterone receptors was also observed in tumor tissue. The Ki-67 index showed no correlation with malignancy or survival time. The higher prevalence in older females suggests an oncogenesis driven by the accumulation of estrous cycles and chronic hormone exposure.

[This retracts the article DOI: 10.7759/cureus.21781.].

Full-field digital mammography (FFDM) is the standard for breast cancer screening but has reduced sensitivity in dense breasts. Digital breast tomosynthesis (DBT) improves cancer detection compared to 2D mammography but is limited by cost and longer reading times. Artificial intelligence (AI)-enhanced mammography has demonstrated improved sensitivity compared to 2D mammography. This study compares AI-enhanced 2D mammography (DM+AI) with DBT in recalling interval breast cancers (IBCs). : A multi-reader, multi-case crossover study was conducted using the Emory BrEast Imaging Dataset, which includes paired FFDM and DBT images with biopsy-proven outcomes. Six radiologists reviewed 53 IBC and 53 screen-detected cancer (SDC) cases, with random assignment to DM+AI or DBT, followed by crossover after a washout period. Primary outcomes included recall rate of IBCs. Secondary outcomes included recall rate of SDCs, interpretation time, and subgroup analysis by breast density. : For IBCs, DM+AI and DBT demonstrated similar recall rates (41.5% vs 40.9%) and detection rates (14.8% vs 11.9%). DM+AI identified more non-invasive (31.5% vs 13.0%) and mass-forming (61.0% vs 21.8%) cancers. For SDCs, recall and detection rates were comparable across modalities. In fatty breasts, recall was higher with DM+AI (91.7% vs 50.0%), while DBT performed better in extremely dense breasts. DM+AI enabled faster interpretation, averaging 24.1 seconds less per case. : AI-enhanced 2D mammography demonstrated comparable performance to DBT with shorter interpretation times, supporting a stratified screening approach. This study is the first direct comparison of AI-enhanced mammography and digital breast tomosynthesis for IBC detection.

Single-cell sequencing and analysis have advanced our understanding of intra-tumoral heterogeneity for breast cancer lymph node metastasis. However, how alterations at multi-omics levels coordinate together in a single tumor cell to drive metastasis remains unclear. Here we performed single-cell multi-omics sequencing of paired primary tumors and metastatic lymph nodes from breast cancer patients. This enabled a comprehensive reconstruction of dynamic molecular landscapes by simultaneously profiling genome, epigenome and transcriptome in the same single tumor cell. During metastasis of patients with higher heterogeneity, clonal evolution analysis based on copy number variations at single-cell resolution showed a specific clone possessing metastatic advantages. Meanwhile, the genome-wide DNA methylation underwent stageable changes. In contrast, gene expression was specifically reprogrammed concentrated at tumor cell transition, suggesting a remodelling by organ microenvironment. By integrative multi-omics analysis, we identified genes that were dysregulated at more than one omics, and showed the importance of SLC39A6, ELP2 and RPL13 genes in breast cancer metastasis or prognosis. Our study traces the genomic, epigenomic and transcriptomic dynamics simultaneously from primary tumors to metastatic lymph nodes in the same single cell, providing new insights into breast cancer metastasis.