Original research publications

This work proposes a multi-stage interpretable framework for mammography-based molecular subtype-oriented risk stratification in breast cancer, focusing on visible mass lesions with segmentable tumor boundaries. The framework integrates a Boundary-Enhanced module within an attention-based U-Net architecture to improve tumor boundary delineation. Morphological and radiomics descriptors capturing shape, margin-related geometry, intensity, and texture heterogeneity are then extracted from the segmented tumor region and used for machine-learning-based subtype-oriented classification. For this task, the best-performing CatBoost model achieved an ROC AUC of 94.6% on Dataset A and 93.7% on Dataset B, used as an external test cohort for downstream subtype classification. These findings suggest that boundary-guided mammographic radiomics may provide a non-invasive adjunct for pre-biopsy risk stratification and subtype-oriented clinical assessment. However, tissue-based pathological evaluation remains the reference standard for definitive molecular subtype determination.

This qualitative study examined how senior Jewish, Muslim, and Christian religious leaders in Israel conceptualize termination of pregnancy following severe fetal anomalies. Eighteen leaders, six from each tradition, participated in semi-structured interviews analyzed thematically. All affirmed the sanctity of life but differed regarding fetal moral status, maternal harm, and permissible intervention. Jewish participants emphasized contextual halakhic reasoning and maternal priority; Muslim participants highlighted ensoulment, necessity, and harm prevention; and Christian participants stressed intrinsic fetal dignity and accompaniment. Across traditions, participants rejected framing abortion as either "mercy" or "murder," instead emphasizing tragic moral conflict, responsibility, compassion, and culturally responsive clinical dialogue.

Grade III/IV chemotherapy-induced neutropenia (CIN) is a serious complication of breast cancer chemotherapy. Existing prediction models often rely on post-chemotherapy laboratory values, limiting their utility at the point of prescribing. We aimed to develop machine learning (ML) models predicting Grade III/IV CIN using exclusively pre-chemotherapy data, and to evaluate cross-cycle stability within the same cohort. We retrospectively analysed breast cancer patients who received chemotherapy from September 2011 to January 2025. Only pre-chemotherapy variables were used as inputs. Cycle 1 records were split into training (80%) and internal validation (20%) sets. Cycles 2-8 records formed the cross-cycle test set. Nine candidate ML classifiers were evaluated. Hyperparameter tuning, Youden-index threshold optimisation, calibration, decision curve analysis, SHAP-based feature attribution, and per-cycle AUC were assessed. On the Cycle 1 validation set, the tuned Logistic L1 and Extra Trees models achieved AUCs of 0.760 (95% CI 0.703-0.812) and 0.763 (95% CI 0.707-0.815), respectively. On the pooled Cycles 2-8 cross-cycle test set, the corresponding AUCs were 0.746 (95% CI 0.727-0.764) and 0.729 (95% CI 0.709-0.748). Logistic L1 maintained an AUC above 0.70 across all cycles. SHAP attribution identified docetaxel and epirubicin as dominant predictors. Baseline neutrophil count, total bilirubin, and albumin were the leading non-drug clinical features, particularly in Logistic L1. Models trained exclusively on pre-chemotherapy data retained broadly similar discrimination when applied to subsequent cycles within the same cohort. Logistic L1 showed more consistent cross-cycle discrimination, which supports prospective, cycle-by-cycle risk stratification supporting G-CSF prophylaxis and dose-modification decisions.

Breast cancer patients often experience fatigue during treatment, which may adversely affect their health outcomes and quality of life. However, machine learning (ML) research on cancer-related fatigue (CRF) in this population remains limited. Therefore, this study aimed to assess CRF symptoms using the Cancer Fatigue Scale (CFS), identify latent classes of CRF, and apply multiple ML algorithms to identify key predictors, thereby providing a basis for developing targeted interventions. Using a cross-sectional stratified sampling approach, 1005 participants completed a self-administered questionnaire to assess CRF symptoms with the CFS. Latent profile analysis (LPA) was used to identify latent classes of CRF. Five ML algorithms were used to identify predictors of CRF. Three latent classes were identified: stable fatigue group (9.8%), low fatigue unstable group (27.4%), and high fatigue unstable group (62.9%). The area under the curve (AUC) values of the five ML models-K-nearest neighbors (KNN), Adaptive Boosting (AdaBoost), Gaussian Naive Bayes (Gaussian NB), Extreme Gradient Boosting (XGBoost), and Random Forest (RF)-ranged from 0.83 to 0.88, with XGBoost performing the best (AUC = 0.88). The final ML model identified perceived stress, depression, and self-compassion as the most important predictors of CRF. Breast cancer patients exhibit heterogeneity in fatigue symptoms during treatment. Machine learning may help identify factors associated with CRF, including perceived stress, depression, and self-compassion. For the high fatigue unstable group, interventions may target perceived stress and depression; for the low fatigue unstable group, interventions may focus on self-compassion and stress management; and for the stable fatigue group, interventions may target anxiety reduction and social support enhancement. This stratified approach may provide a practical framework for clinicians to develop individualized fatigue management plans.

Breast cancer is still a considerable public health issue worldwide. However, earlier studies reported that chemotherapeutic drugs suppress the immune system. Therefore, a combination of chemotherapeutic agents with an immunomodulator might enhance antitumor immunity through immunogenic cell death, cross-priming, and the regulation of immune checkpoint molecules. Nanotechnology-enabled drug delivery has received considerable attention in chemo-immunotherapy. A comprehensive literature review was performed using google scholar, Science Direct, the Clinical Research Database, PubMed/MEDLINE, Scopus, Web of Science, and DOAJ. The review discusses the combination of immunotherapy and nanotechnology including AI-based techniques used to identify suitable biomarkers and to enable selective drug delivery to breast cancer cells. The combinational therapy containing chemotherapeutic agents and immunomodulators has shown promising results due to their synergistic effects. The application of artificial intelligence (AI) in nanomedicine has enabled the design of nanoparticles, predict their interactions with drugs, and personalize treatment based on patients' individual tumor profiles. This advancement has marked the advent of precision medicine in oncology, which focuses on tailoring therapies to each tumor's molecular and genetic profile. Despite these encouraging developments, several challenges remain in nanotechnology for cancer therapy, including mass production, biosafety, regulatory issues, and the successful translation of laboratory findings into clinical practice.

Preeclampsia is a multisystem hypertensive disorder of pregnancy that is defined by new-onset hypertension after 20 weeks of gestation along with proteinuria or evidence of end-organ dysfunction. Affecting 2-8% of pregnancies worldwide, preeclampsia remains a leading cause of maternal and perinatal morbidity and mortality. This disorder originates secondary to defective placentation during the first trimester, causing incomplete remodeling of the uterine spiral arteries, resulting in placental hypoperfusion, oxidative stress, and the release of anti-angiogenic factors into the maternal circulation. This pathophysiology provided researchers a rationale for the use of low-dose aspirin as a preventive strategy for preeclampsia. Early studies investigated low-dose aspirin initiated at variable gestational ages and failed to show significant reductions in the incidence of preeclampsia. However, over the years, multiple meta-analyses studying aspirin use for preeclampsia prevention revealed a consistent decrease in the incidence of preeclampsia with the use of low-dose aspirin initiated at or before 16 weeks of gestation, with the efficacy being largely dependent on the time of initiation. In 2017, a randomized controlled trial demonstrated a statistically and clinically significant reduction in the incidence of preeclampsia leading to preterm delivery with aspirin initiated before 16 weeks gestation in women identified as high risk by first-trimester algorithm-based screening. Based on the strong evidence in support of aspirin use for preeclampsia prevention, current guidelines recommend initiation of aspirin 81 mg after 12 weeks and ideally before 16 weeks for all pregnant women at increased risk for preeclampsia.

Accurate and robust survival prediction is essential for personalised breast cancer prognosis and treatment decision-making. However, existing machine learning-based survival models often lack stability under cohort heterogeneity and distribution shift, while tabular foundation models typically do not support censored time-to-event data. This study aims to develop a foundation-model-based survival framework that explicitly handles right censoring and enables stable deployment across heterogeneous cohorts without task-specific retraining. We propose TabSurv, a foundation-model-based framework for survival analysis that adapts pretrained tabular foundation models to censored time-to-event prediction. Built on TabPFN, TabSurv operates via in-context learning without gradient-based training or hyperparameter tuning. To address censoring, TabSurv introduces a two-stage, censoring-aware strategy. In the first stage, the model learns from patients with observed events and generates multiple plausible survival times for each censored patient, with all imputed times occurring after the observed censoring time. In the second stage, the model uses each imputed dataset as context and makes predictions through in-context learning. These predictions are then combined to produce the final result while accounting for uncertainty in the imputed survival times. For treatment recommendation, TabSurv fits a TabPFN regressor in context to risk scores from a random survival forest, which handles censoring, and estimates each patient's predicted risk under hypothetical treatment reassignment. TabSurv was evaluated on twelve breast cancer gene expression cohorts under in-distribution and out-of-distribution settings. It achieved competitive or superior prognostic performance compared with eight established survival models and demonstrated the highest predictive stability under cohort heterogeneity. In exploratory treatment-recommendation experiments on METABRIC, patients whose treatment matched TabSurv's recommendation showed the largest average restricted mean survival time advantage among the compared methods. TabSurv provides an efficient and stable foundation-model-based approach to censored survival analysis, supporting robust prognosis and personalised treatment recommendation in heterogeneous breast cancer cohorts.

Evidence on sex differences in cognition and dementia is inconsistent, and it is unclear whether such differences are explained by dementia risk factors. To assess (i) sex differences in cognitive decline and dementia risk, (ii) the extent to which modifiable and nonmodifiable risk factors explain these differences and (iii) whether birth cohort and apolipoprotein (APOE)-Ꜫ4 carrier status modify sex differences in cognitive decline. Data from the Whitehall II study were analysed to examine cross-sectional and longitudinal associations between sex, cognitive decline and dementia risk. Cognitive outcomes included verbal memory and verbal fluency, assessed from Phase 5 onward, with over 16 years of follow-up. Test scores were standardised using means and standard deviations from the baseline cognitive tests to generate z-scores. All-cause dementia was ascertained through linkage to three electronic health record databases. Among 5920 participants aged 44.8-68.2 years, women demonstrated better baseline performance than men in memory (adjusted mean difference = -0.2, p < 0.0001), phonemic fluency (-0.1, p = 0.001) and semantic fluency (-0.2, p < 0.0001). Men exhibited a steeper decline in semantic fluency (adjusted β = -2.6, p < 0.0001) and a nominal decline in phonemic fluency (-1.7, p = 0.007). Sex differences remained after adjustment for covariates. Dementia incidence did not differ significantly by sex. Birth cohort and APOE-Ꜫ4 carrier status did not meaningfully modify associations between sex and cognitive outcomes. Cognitive advantages observed in women in midlife did not translate into lower dementia risk. Further research incorporating biological, psychosocial and life-course factors, as well as the timing and heterogeneity of underlying disease processes, is needed to better understand sex differences in cognitive ageing and dementia.

Numerous individual studies have examined the effects of biotics on isolated health outcomes in women with polycystic ovary syndrome (PCOS). However, a comprehensive evaluation of their impact on the full metabolic panel and sex hormone profiles is lacking. Accordingly, this meta-analysis of RCTs and umbrella review attempted to form a complete picture of the overall efficacy of biotics on human metabolism and endocrine function. The PubMed, Scopus, Cochran, Web of Science, and Embase databases were used for conducting a comprehensive systematic search. Twenty RCTs were included in the meta-analysis and 11 meta-analyses were included for umbrella review. The pooled estimates of the studies evaluating the effects of biotics on anthropometric measurements indicated that biotics are associated with an improvement in weight (SMD: -1.21, 95%CI: -2.06, -0.36) and body mass index (BMI) (SMD: -0.77, 95%CI: -1.45, -0.10), waist circumference (WC) (SMD: -0.67, 95%CI: -1.18, -0.16), waist-to-hip ratio (WHR) (SMD: -0.84, 95%CI: -1.52, -0.15), glycemic control fasting plasma glucose (FPG) (SMD: -0.71, 95%CI: -1.19, -0.24), insulin (SMD: -0.64, 95%CI: -1.07, -0.21), and HOMA-IR (SMD: -0.78, 95%CI: -1.24, -0.32), total cholesterol (TC) (SMD: -0.69, 95%CI: -1.25, -0.13), low-density lipoprotein-cholesterol (LDL) (SMD: -0.71, 95%CI: -1.21, -0.20), high-density lipoprotein-cholesterol (HDL) (SMD: 0.39, 95%CI: 0.19, 0.60), triglyceride (TG) (SMD: -0.53, 95%CI: -0.95, -0.10), oxidative stress biomarkers such as malondialdehyde (MDA) (SMD: -0.96, 95%CI: -1.29, -0.63), total antioxidant capacity (TAC) (SMD: 0.59, 95% CI: 0.29, 0.89), testosterone (TT) (SMD: -1.29, 95%CI: -1.98, -0.68) level. However, umbrella review showed that biotics may contribute to an improvement in weight, BMI, WC, FPG, insulin, HOMA-IR, QUICKI, lipid profile, CRP, oxidative stress markers (MDA, TAC), TT and LH/FSH ratio too. In conclusion, this meta-analysis and umbrella review provide evidence that prebiotics, probiotics, or synbiotics may confer beneficial effects on a range of health outcomes among patients with PCOS.

Substantial uncertainty exists regarding how healthcare system factors, especially care setting types, affect the uptake and implementation of gestational diabetes or diabetes in pregnancy screening in practice. Evidence suggests that the care environment may influence diagnostic processes. To assess the effectiveness of maternity and non-maternity healthcare settings for the diagnosis of gestational diabetes mellitus or diabetes in pregnancy. We searched CENTRAL, MEDLINE, Embase, and Cumulative Index to Nursing and Allied Health Literature (CINAHL) for randomised controlled trials (RCTs) up to April 2026, and for controlled non-randomised studies of interventions (NRSIs) up to December 2025. We also searched CENTRAL to identify ongoing trials. We included RCTs and planned to include cluster-RCTs and NRSIs, but we did not find any. Eligible participants were pregnant women being screened for gestational diabetes mellitus (GDM) or diabetes in pregnancy. We defined maternity healthcare settings as those specialising in care for pregnant, birthing, and postpartum individuals, with appropriate screening protocols, and non-maternity healthcare settings as general medical environments lacking a focus on pregnancy and women's care. We considered any screening format (e.g. risk-factor-based screening) and any diagnostic test (e.g. one- and two-step oral glucose tolerance tests (OGTT)). Critical health service outcomes were compliance with screening and follow-up guidelines, diagnosis of gestational diabetes or diabetes in pregnancy, maternal emergency department visits during pregnancy, maternal antenatal hospitalisation, length of maternal hospitalisation, length of neonatal hospitalisation, and care accessibility. Critical maternal outcomes included hypertensive disorders, maternal death, intensive care admissions, hyperglycaemia requiring pharmacological treatment, infections, and postpartum glucose intolerance, including progression to diabetes, within 15 years after birth. Critical child-related outcomes encompassed perinatal death, neonatal intensive care admissions, preterm birth, neonatal hypoglycaemia, large-for-gestational-age, shoulder dystocia, and birth trauma. Further critical and important outcomes not included in the summary of findings tables can be found in the full text. We used the Cochrane RoB 2 tool to assess bias in the RCTs. We had planned to use ROBINS-I version 2 to assess bias in the NRSIs if we had identified any. We used standard Cochrane methodology. We planned to synthesise results for each outcome using meta-analysis where possible (inverse-variance or Mantel-Haenszel approaches; fixed-effect model). We used GRADE to assess the certainty of the evidence for each outcome. We included one RCT with 781 participants: 390 were randomised to screening in a maternity healthcare setting and 391 were randomised to screening in a non-maternity healthcare setting. Except for screening compliance, trialists evaluated all outcomes using a per-protocol analysis instead of by original randomised groups. This approach created substantial disparities in sample sizes between settings and largely nullified the methodological protections typically provided by a randomised design. The trial evaluated screening for GDM only. We did not identify any ongoing studies or studies awaiting classification. Health service outcomes Screening in a maternity healthcare setting may increase compliance with screening and follow-up guidelines (risk ratio (RR) 1.69, 95% confidence interval (CI) 1.53 to 1.87; 781 participants) and may improve care accessibility, assessed as time to access antenatal diabetes care, measured in days (mean difference (MD) -4.70, 95% CI -6.03 to -3.37; 690 participants), both with low-certainty evidence. We are very uncertain about the effect of screening in a maternity healthcare setting versus a non-maternity healthcare setting on diagnosis of gestational diabetes or diabetes in pregnancy (RR 1.10, 95% CI 0.60 to 2.01; 690 participants; very low-certainty evidence) and length of neonatal hospitalisation (MD 0.04, 95% CI -0.57 to 0.65; 690 participants; very low-certainty evidence). No direct evidence was available on screening for diabetes in pregnancy as distinct from GDM. No data were reported on maternal emergency department visits, maternal antenatal hospitalisation, length of maternal hospitalisations, and costs. Maternal outcomes We are very uncertain about the effect of screening in a maternity healthcare setting versus a non-maternity healthcare setting on pre-eclampsia (RR 1.24, 95% CI 0.56 to 2.75; 690 participants; very low-certainty evidence). The following outcomes were not reported: eclampsia, HELLP syndrome, maternal death, admission to intensive care, hyperglycaemia requiring pharmacological treatment, infections, and postpartum glucose intolerance. Child-related outcomes We are very uncertain about the effect of screening in a maternity healthcare setting versus a non-maternity healthcare setting on: stillbirth or foetal death (RR 0.91, 95% CI 0.08 to 9.93), admission to neonatal intensive care (RR 1.01, 95% CI 0.59 to 1.71), preterm birth (RR 1.06, 95% CI 0.41 to 2.71), neonatal hypoglycaemia (RR 0.91, 95% CI 0.23 to 3.59), large-for-gestational-age (RR 0.73, 95% CI 0.51 to 1.04), shoulder dystocia (RR 0.15, 95% CI 0.01 to 3.70), and birth trauma (RR 0.91, 95% CI 0.08 to 9.93), all with 690 participants each and very low-certainty evidence. An effect estimate for neonatal death was not estimable (maternity setting: 0/475; non-maternity setting: 0/215). There is insufficient evidence to determine whether screening for gestational diabetes or diabetes in pregnancy in maternity healthcare settings compared with non-maternity healthcare settings improves health service, maternal, or child-related outcomes. Low-certainty evidence from a single study indicates that screening in maternity healthcare settings may result in a reduction in time to access antenatal diabetes care and may increase compliance. The effects on other outcomes remain unknown. Conducting studies using intention-to-treat analyses could bridge existing research gaps, enhancing effect estimates and certainty. This Cochrane review was funded by the World Health Organization (WHO) and the UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). Protocol available via PROSPERO: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251108692.

Breast cancer (BC) represents the most prevalent malignant tumor among women globally, with its pronounced heterogeneity presenting significant challenges for precision diagnosis and treatment. Aberrant lipid metabolism, particularly the ratio of low-density lipoprotein to high-density lipoprotein (LHR), has garnered considerable interest in relation to BC development and progression. Nevertheless, the association between LHR and clinicopathological characteristics remains inadequately explored. To address this gap, the present retrospective study analyzed 583 BC patients who underwent surgical treatment at Qilu Hospital of Shandong University. Preoperative blood lipid profiles and clinicopathological data were systematically collected to investigate the association between LHR and critical features, including molecular subtypes. The findings indicated that LHR levels were significantly elevated in patients aged 46 years or older, postmenopausal women, and individuals with a body mass index of 25 kg/m2 or higher. Subgroup analyses incorporating age, menopausal status, and BMI suggested potential interactions between these clinical factors and LHR. Although univariate analysis demonstrated an association between LHR and certain clinicopathological features, multivariate logistic regression analysis revealed that menopausal status, rather than LHR, was the sole independent predictor of ER-positive and PR-positive status. Therefore, LHR should not be considered an independent predictive biomarker for receptor status. In conclusion, although the LHR demonstrates statistically significant associations with certain clinicopathological characteristics, its modest effect sizes and discriminative ability close to chance indicate limited clinical utility as an independent biomarker. These preliminary findings highlight the need for future research focused on identifying reliable metabolic signatures. Such studies should consider utilizing multi-marker panels instead of relying exclusively on individual lipid metrics for risk stratification in breast cancer.

Maternal immunization is a critical public health strategy, yet psychological and sociodemographic factors may influence uptake. We examined vaccination decision-making among 225 pregnant women attending an obstetrics and gynecology clinic in Türkiye using the 5 C model. Only 3.1% reported preconception vaccination counseling, and 54.2% received vaccination during pregnancy; all vaccinated participants received tetanus-diphtheria vaccination, with some receiving additional vaccines. In multivariable analysis, receipt of vaccination information was independently associated with higher odds of vaccination, while Calculation showed a nonlinear association with vaccination status. We interpret these results as supporting attention to informational and psychological factors in maternal vaccination counseling.

Objective - Triple-negative breast cancer (TNBC) requires new targeted therapies with low toxicity. This study aimed to enhance therapeutic efficacy of Simarouba glauca DC also called Laxmitaru (LX), limited by poor solubility, by developing novel nanoformulation to overcome these pharmaceutical barriers. Significance - This work addresses need for effective TNBC treatments by combining a natural product with nanotechnology. Approach offers biocompatible strategy to significantly improve anticancer action of LX, potentially providing targeted alternative to conventional therapies. Methods - LX encapsulated within chitosan-carrageenan nanoparticles (LX-CC-NPs), formulation characterized for particle size, zeta potential, and physical state. Its anticancer efficacy was evaluated against HCC-70 TNBC cells using MTT assays, also comparing it to free LX and on MCF-10A. Results - Successful encapsulation yielded nanocarriers with increased size of 355.8 nm and positive surface charge of +33.25 mV, transitioned to an amorphous state, favouring drug release. In vitro, LX-CC-NPs exhibited cytotoxicity against HCC-70 cells (IC 50 = 74.60 µg/mL; 82.50% inhibition at 200 µg/mL) and demonstrated biocompatibility towards MCF-10A cells, confirming a favourable therapeutic window. Conclusions - Nanoencapsulation effectively overcomes physicochemical limitations of LX, profoundly enhancing its anticancer potency and selectivity against TNBC cells. This work presents promising biocompatible nanomedicine for targeted TNBC therapy.

Breast Cancer-Related Lymphedema (BCRL) is a common complication after breast cancer treatment, leading to chronic arm swelling and reduced quality of life. Early detection remains challenging due to limitations in current assessment methods and a shortage of expert clinicians. Point-of-care ultrasound (POCUS) imaging offers a cost-effective, non-invasive tool for BCRL evaluation; however, the visual disparity between affected and unaffected arms can be subtle. To address this, we introduce a multimodal dataset containing B-mode images, radio-frequency (RF) data, perometry-based arm volume measurements, the number of dissected lymph nodes, the time elapsed since surgery, and body mass index (BMI) from 57 subjects. Additionally, the dataset includes an assessment of the severity of BCRL by an expert clinician (A.T.). We also propose a deep learning-based framework for automated BCRL diagnosis using multimodal data. Our method first employs a Siamese-based architecture to extract and compare features from bilateral arm images, addressing subject-specific variability. We further improve the method by incorporating clinical tabular data and investigating the effect of multimodal fusion and supervised contrastive learning on the model's performance. To our knowledge, this is the first automated deep learning approach for BCRL diagnosis. Using three-fold cross-validation, the proposed Multimodal model achieved an AUC of 91.0%, an accuracy of 87.0%, and an F1 score of 83.5%. It outperformed the two other variants, Unimodal-A and Unimodal-B, in BCRL classification across most metrics. The source code and trained model will be released at http://code.sonography.ai.

Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, accounting for approximately 7-10% of all congenital cardiac malformations. Although early surgical repair has transformed its natural history in high-income settings, with contemporary long-term survival exceeding 90%, uncorrected TOF continues to be encountered in pregnancy, particularly in women from resource-limited regions or those with previously undiagnosed disease. The physiological adaptations of pregnancy, including reduction in systemic vascular resistance, plasma volume expansion, and a 30-50% rise in cardiac output, are poorly tolerated in the presence of a non-restrictive ventricular septal defect and fixed right ventricular outflow tract obstruction, leading to progressive cyanosis, right ventricular strain, and uteroplacental hypoperfusion. Current European Society of Cardiology (ESC) guidance classifies unrepaired cyanotic heart disease without Eisenmenger syndrome as mWHO 2.0 class III, while Eisenmenger syndrome is classified as mWHO 2.0 class IV. Contemporary data from the ESC EORP Registry of Pregnancy and Cardiac Disease (ROPAC) report maternal mortality of 0.7% and heart failure in 8.7% of pregnancies with uncorrected congenital heart disease, with markedly worse outcomes in cyanotic subsets. This narrative review synthesizes the pathophysiology, risk stratification, obstetric management, intrapartum anesthetic considerations, comparative outcomes of uncorrected versus corrected disease, and key evidence gaps that continue to constrain care for this population, providing a physiology-driven framework for the pregnancy heart team.

Vietnam bears a substantial burden of small-for-gestational-age (SGA) births, contributing to neonatal mortality, stunting, and long-term developmental impairment. In Southeast Asia, practical nutritional screening tools that predict objectively defined neonatal growth outcomes are poorly evaluated. We aimed to compare the predictive validity of the International Federation of Gynecology and Obstetrics (FIGO) Nutrition Checklist, pre-pregnancy body mass index, and mid-upper arm circumference (MUAC) for SGA birth outcomes in pregnant Vietnamese women and to identify the FIGO checklist items most strongly associated with distinct SGA phenotypes. In this hospital-based cross-sectional study with prospective ascertainment of neonatal outcomes, 818 mother-newborn pairs were enrolled at a national tertiary obstetric center in Hanoi, Vietnam, between June and December 2024. FIGO score (0-9), pre-pregnancy body mass index, and MUAC were assessed at the antenatal birth registration visit (mean gestational age 36.1 weeks). SGA-weight and SGA-length were classified independently as birth weight or birth length below the sex- and gestational-age-specific 10th percentile using INTERGROWTH-21st Newborn Size Standards. Predictive performance was evaluated using area under the receiver operating characteristic curve (AUC) with DeLong pairwise comparisons, and multivariable logistic regression with bootstrap confidence intervals (1000 resamples). SGA-weight occurred in 81 neonates (9.9%) and SGA-length in 39 (4.8%). The FIGO score demonstrated a significantly higher AUC than MUAC for SGA-length (0.706 [95% confidence interval (CI) 0.627-0.785] vs. 0.564 [95% CI 0.465-0.662]; ΔAUC +0.142 [+0.023 to +0.261]; P = 0.028); no significant pairwise differences were observed for SGA-weight. FIGO at-risk status (score <5) was independently associated with SGA-weight (adjusted odds ratio 3.46 [95% CI 1.17-10.24]; P = 0.025) and SGA-length (adjusted odds ratio 4.03 [95% CI 1.03-15.84]; P = 0.046). Pre-pregnancy underweight was also independently associated with both outcomes. Fish intake and folate supplementation showed SGA-length-specific associations, whereas fruit/vegetable intake and reduced packaged snack consumption were associated with both SGA phenotypes. The FIGO Nutrition Checklist demonstrated superior predictive validity over MUAC for impaired fetal linear growth and provided independent risk identification beyond anthropometric indicators alone. Its item-level specificity for SGA-length implicates chronic micronutrient inadequacy in fetal linear growth restriction in this population. Integration of the FIGO Nutrition Checklist into routine antenatal care is supported by this evidence and should be prioritized in Southeast Asian obstetric settings, with cultural adaptation needed for populations with low whole-grain consumption.

PARP inhibitors are now used as adjuvant targeted therapy for BRCA1-mutated breast cancer. Although prescribed to young women of reproductive age, their effects on fertility remain unknown, particularly when combined with highly gonadotoxic chemotherapy. This study therefore examined whether olaparib potentiates cyclophosphamide-induced gonadotoxicity in human ovarian tissue. Cryopreserved ovarian tissue from young (< 35 years) patients with breast cancer, with (n = 4) or without (n = 4) BRCA1 pathogenic variants, was exposed to anticancer drugs using two models: (i) a 3-days in vitro culture with 4-hydroperoxycyclophosphamide (10 µM) and/or olaparib (20 µM), and (ii) xenotransplantation in mice followed by one cyclophosphamide injection (75 mg/kg) and two weeks of daily oral olaparib (100 mg/kg). Across both models and regardless of BRCA1 status, the proportion of primordial follicles remained unchanged following exposure to the drugs. However, in vivo, follicle density significantly reduced with cyclophosphamide compared to controls in BRCA1-mutated xenografts. Olaparib did not exacerbate cyclophosphamide-induced follicle loss. 4HC induced DNA fragmentation and double-strand breaks in vitro in both groups, while olaparib alone caused minimal damage and did not appear to potentiate the effects of 4HC. In BRCA1-mutated xenografts, combined treatment resulted in a modest but significant reduction in RAD51 rates compared with controls, while 53BP1 expression tended to rise after cyclophosphamide alone or combined with olaparib, without reaching significance. Our findings suggest that olaparib does not exacerbate cyclophosphamide-induced gonadotoxicity, providing valuable information for reassuring patients regarding its reproductive safety.

BRCA1 and BRCA2 pathogenic variant carriers have a high lifetime risk of breast cancer. Risk-reducing bilateral mastectomy, the most established prevention method, is utilised by fewer than half BRCA1/2 carriers, despite being widely recommended by international guidelines. Currently available risk-reducing medications are limited to endocrine therapies that have limited evidence and minimal uptake. There is a pressing need for alternative strategies for carriers who wish to take action against their cancer risk, while balancing other health interests, including fertility. In this review, we explore the wide landscape of risk-reducing medications and methods that have been investigated specifically for BRCA1/2 carriers, with a focus on understanding the cells-of-origin, key determinants of tumor initiation, and signaling pathways implicated in BRCA1/2-related breast cancer, as well examining some of the practical challenges in translating this research into clinical trials.

To conduct a systematic review and meta-analysis on the uptake value of fibroblast activation protein (FAP)-targeted PET (FAPI PET) across different histopathological and molecular breast cancer subtypes. As a secondary objective, to perform head-to-head comparisons with [ 18 F]FDG PET. This systematic review and meta-analysis was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Major medical literature databases were systematically searched to include studies in which biopsy-proven breast cancer patients were recruited, and uptake values for malignant primary tumors and/or metastatic lesions were reported. Meta-analyses were conducted in R (R Foundation for Statistical Computing, Vienna, Austria) using the meta package. Thirty-four studies met the inclusion criteria. Pooled average SUVmax in the primary malignancy was 11.74 (95%CI:9.95-13.53) on FAPI PET. In the studies in which SUVmax values were provided for both FAPI PET and [ 18 F]FDG PET, on average, the pooled SUVmax was 6.19 (95%CI:4.26-8.12) higher on FAPI PET compared to [ 18 F]FDG PET. FAPI PET showed rather consistently high uptake across all analyzed breast cancer subtypes (pooled estimates ranged from 10.27 to 19.99). Notably, in studies reporting SUVmax for IDC on both FAPI PET and [ 18 F]FDG PET, FAPI PET showed 11.33 (95%CI:8.36-14.30) higher pooled uptake. Similarly, in studies providing SUVmax for luminal A breast cancer, FAPI PET showed 7.85 (95%CI:5.45-10.25) higher uptake compared to [ 18 F]FDG PET. Our findings suggest that FAPI PET exhibits consistently high semi-quantitative values across breast cancer subtypes and can potentially enhance lesion conspicuity and detection rate, particularly in low-[ 18 F]FDG-avid malignancies.

Trastuzumab emtansine (T-DM1), an antibody-drug conjugate targeting human epidermal growth factor receptor 2 (HER2), is used for HER2-positive breast cancer. Although hepatotoxicity and thrombocytopenia are recognized adverse events of T-DM1, long-term hepatic vascular complications associated with this treatment remain poorly characterized. We report a case of porto-sinusoidal vascular disorder (PSVD) with noncirrhotic portal hypertension (NCPH) associated with prolonged T-DM1 therapy. We retrospectively reviewed the clinical course, serial laboratory data, imaging findings, endoscopic findings, and liver histopathology of a woman in her 70s with recurrent HER2-positive breast cancer who received prolonged T-DM1 therapy. After prior maintenance therapy with trastuzumab and pertuzumab, the patient received 60 cycles of T-DM1. During treatment, progressive thrombocytopenia developed. Serial computed tomography demonstrated splenomegaly, portal vein dilatation, and the development of portosystemic collateral vessels. Upper gastrointestinal endoscopy revealed newly developed esophageal varices. Laboratory evaluation excluded viral, autoimmune, and metabolic liver diseases. Liver biopsy showed focal sinusoidal dilatation and obliterative portal venopathy without cirrhotic architectural distortion, consistent with PSVD. Retrospective imaging review showed that splenomegaly had developed approximately 12 months after the initiation of T-DM1 therapy. Splenomegaly and platelet counts remained unchanged 2 years after T-DM1 discontinuation, whereas spleen stiffness increased. This case suggests that prolonged exposure to T-DM1 may cause sinusoidal endothelial injury and lead to PSVD with portal hypertension. Progressive thrombocytopenia and splenomegaly during T-DM1 therapy may represent early clinical indicators of this complication. Careful long-term monitoring for signs of portal hypertension should be considered in patients receiving prolonged T-DM1 treatment.

A study was conducted on women's attitudes towards cervical cancer early detection with regard to dispositional hope and religious health fatalism. The study used a cross-sectional design. A total of 1635 female volunteers aged 18 years and older residing in Türkiye were included in the study, yielding a response rate of 95.6%. The data was gathered from December 2024 to January 2025. The personal information form, dispositional hope scale, religious health fatalism scale, and attitude scale for early detection of cervical cancer were used to gather data online. The analysis was done using IBM SPSS Statistics. It involved analysis of descriptive statistics, correlation tests, and multiple linear regression. The participants' mean age was 28.37 ± 8.94 years; 50.3% were unaware of the Pap smear test, and 77.3% had never been screened. Correlation analysis indicated a weak positive relationship between hope and religious fatalism, whereas attitudes toward early detection were negatively related to both hope and fatalism. Furthermore, participant characteristics (such as education, income, and Pap smear awareness) showed significant differences in study variables. In multiple regression controlling for these background characteristics, both dispositional hope (β = - 0.272, p < .001) and religious health fatalism (β = - 0.053, p = .024) significantly predicted attitudes toward early detection, explaining 11.2% of the variance in attitude scores. These findings suggest that early-detection behaviors may be improved by strengthening education and awareness interventions, while also addressing psychosocial dimensions such as hope and health fatalism in counseling and prevention strategies.

Pruritic urticarial papules and plaques of pregnancy (PUPPP) is a common dermatosis of pregnancy, but its etiology remains poorly understood. This study aimed to identify whether maternal immune activation (MIA) is associated with PUPPP. We conducted a retrospective cohort study of pregnant patients using a population-based administrative cohort of all live births in California from 2016 to 2021. Patients with PUPPP were identified using ICD-10 code O26.86. MIA was defined by ICD-10 diagnoses of infection, autoimmune disease, or atopic disease during pregnancy. Poisson log-linear regression was used to estimate crude and adjusted risk ratios (RR, aRR) for associations between PUPPP and MIA. Among 2,275,929 pregnancies, there were 3286 (0.14%) patients with PUPPP. Compared with patients without PUPPP, patients with PUPPP had higher rates of gestational hypertension (6.2% vs. 4.0%, p < 0.0001) and preeclampsia (10.9% vs. 5.2%, p < 0.0001). Atopy was associated with increased risk of PUPPP (aRR 1.7, 95% confidence interval [95% CI] 1.6-1.9), as was autoimmunity (aRR 1.6, 95% CI 1.2-2.1) and maternal infection (aRR 1.6, 95% CI 1.4-1.7). Patients with PUPPP were less likely to have a pre-pregnancy body mass index (BMI) ≥ 30 kg/m 2 (21.2% vs. 25.4%, p < 0.0001) but more likely to exceed recommended gestational weight gain (64.3% vs. 52.4%, p < 0.0001). MIA during pregnancy, including atopy, autoimmunity, and infection, was independently associated with increased risk of PUPPP. These findings suggest immune dysregulation may contribute to PUPPP pathogenesis. The association with excessive gestational weight gain further supports a potential role for inflammation secondary to connective tissue injury from abdominal distension.

Male seahorses exhibit a remarkable reproductive mode among vertebrates, in which embryos are incubated within a specialized brood pouch of the male. To clarify the endocrine mechanisms underlying male pregnancy, we integrated multi-tissue transcriptomic sequencing with stage-dependent hormonal profiling across pregnancy stages in the lined seahorse Hippocampus erectus. Our results revealed pronounced stage-specific remodeling of both the hypothalamic-pituitary-gonadal (HPG) and hypothalamic-pituitary-interrenal (HPI) axes during male pregnancy. Within the HPG axis, brain gnrh1 and gnrh2, together with pituitary lhb and fshb, were upregulated during pregnancy, whereas genes involved in testicular steroid hormone biosynthesis showed reduced expression throughout gestation. Consistently, circulating levels of estradiol-17β and 11-ketotestosterone remained low, suggesting that reduced steroidogenic activity may be associated with endocrine adaptations during male pregnancy. In the HPI axis, the cortisol-metabolizing gene hsd11b1 was highly expressed in the brood pouch during late pregnancy, coinciding with a local cortisol peak in the pouch while circulating cortisol levels remained relatively stable. This spatially restricted pattern indicates that local cortisol signaling in the brood pouch may contribute to late-pregnancy remodeling and parturition-related processes. These findings indicate that male pregnancy in seahorses involves endocrine adjustments, including altered gonadal steroidogenesis and localized activation of cortisol signaling within the brood pouch.

Small-for-gestational age birth and infant linear growth faltering are prevalent in South Asia. The World Health Organization recommends balanced energy-protein (BEP) supplementation in pregnancy for undernourished populations, but evidence on the extension of supplementation through lactation to improve infant growth remains limited. To examine the effect of daily fortified BEP supplementation during pregnancy and lactation on infant mean length-for-age z-score (LAZ) and secondary growth outcomes at 6 months of age. MINT (Maternal Infant Nutrition Trial) was a 2x2 factorial, household randomized, unblinded efficacy trial to assess a daily fortified BEP supplement during pregnancy and/or lactation compared to no supplement on birth and infant growth outcomes in Sarlahi, Nepal. A modified intention-to-treat analysis estimated the effects of supplementation on infant growth outcomes using linear and Poisson regression models. Models without and with adjustment for birth size were used to estimate the overall effect and the effect independent of birth size, respectively. Among 1,554 mothers and 1,568 infants randomized after delivery, there was no interaction between pregnancy and lactation supplementation on the primary infant growth outcome. Neither BEP supplementation during pregnancy nor lactation had an effect on mean infant LAZ at 6 months (unadjusted mean difference for pregnancy: 0.01 [95% CI: -0.10, 0.12]; for lactation -0.02 [95% CI: -0.13, 0.09]). Significant differences were not observed for any secondary outcomes: mean weight-for-length z-scores, weight-for-age z-scores, infant weight, length, head circumference, mid-upper arm circumference or prevalence of stunting, wasting, and underweight at 6-months or for a subset of infants at 12-months. Null effects persisted after adjustment for birth size. In rural Nepal, daily fortified BEP supplementation during pregnancy or early lactation did not improve linear or ponderal growth of infants at 6- or 12-months. To reduce the burden of early infant growth faltering, alternative strategies should be considered. NCT03668977. https://clinicaltrials.gov/study/NCT03668977?term=nct03668977&rank=1.

While maternal histories of adverse childhood experiences (ACEs) have been linked to altered immune signaling during pregnancy, the specific inflammatory pathways underlying these associations remain poorly characterized. We leveraged high-dimensional proteomics to examine associations between maternal ACEs and pregnancy-associated inflammatory signaling pathways defined by the Kyoto Encyclopedia of Genes and Genomes (KEGG) and tested whether these associations were moderated by neighborhood-level social vulnerability during pregnancy. Participants included pregnant individuals enrolled in the Environmental influences on Child Health Outcomes (ECHO) Cohort (N = 770). Circulating inflammatory proteins were assayed from maternal plasma using the Olink Target 96 Inflammation panel. Protein markers were mapped to Human Genome Organisation (HUGO) Gene Nomenclature Committee gene symbols and aggregated into KEGG pathway scores using curated definitions. Linear regression models evaluated associations between continuous maternal ACE scores and each pathway score. Following correction for multiple comparisons, higher maternal ACE exposure was associated with higher activity across 12 KEGG-annotated protein pathways, including AGE-RAGE, non-alcoholic fatty liver disease, chemokine, Th17 differentiation, HIF-1, cellular senescence, Rap1, NOD-like receptor signaling, transcriptional misregulation in cancer, and infection-related pathway signaling. Domain-specific analyses identified the most consistent associations for childhood household dysfunction. Neighborhood-level social vulnerability during pregnancy did not moderate ACE-inflammation associations but was independently associated with higher KSHV infection and NOD-like receptor signaling pathway scores. Together, these findings indicate that maternal ACEs and prenatal social vulnerability are independently associated with small, but directionally consistent, differences in overlapping inflammatory and growth-related protein signals during pregnancy.

Glucocorticoids are widely used in veterinary medicine for their anti-inflammatory and immunosuppressive effects; however, their administration during pregnancy requires careful consideration because of potential effects on the dam, placenta, fetus, and neonate. Endogenous glucocorticoids are essential for fetal growth, organ maturation, and the initiation of parturition, particularly through activation of the fetal hypothalamic-pituitary-adrenal axis near term. In contrast, exogenous glucocorticoids can cross the placenta and affect fetal development in a species-, dose-, timing-, and drug-dependent manner. Prolonged treatment or inappropriate glucocorticoid administration may also affect maternal metabolism and milk production. The available evidence is frequently indirect or derived from small experimental and historical studies, limiting the formulation of firm species-specific treatment recommendations. Overall, glucocorticoid therapy in pregnant animals should be guided by a careful risk-benefit assessment. This narrative review provides an overview of glucocorticoid administration during pregnancy in domestic animals, emphasizing potential fetal effects and species-specific risks relevant to veterinary clinical practice.

Breast cancer ranks among the most prevalent malignant tumors in women worldwide, with lung metastasis accounting for over 90% of fatalities. Despite this high mortality, effective targeted therapies remain insufficient. Although ponatinib (PNT) shows potential for treating breast cancer lung metastasis (BCLM), its delivery requires optimization. This study aims to construct a biomimetic nanomedicine for targeted delivery of PNT, thereby efficiently treating BCLM. Ginsenoside Rg3 (Rg3) can serve as a substitute for cholesterol as a membrane support material while also acting as an adjuvant in cancer treatment. We replaced cholesterol with Rg3 to prepare PNT-Rg3-Lipo liposomes, extracted the cell membrane of M1 macrophages to coat it on the surface of PNT-Rg3-Lipo, and obtained biomimetic nano MM/PNT-Rg3-Lipo. The characterization of biomimetic nanomedicines was conducted, and the functionality of biomimetic nanomedicines was evaluated at both animal and cellular levels. The macrophage membrane-modified MM/PNT-Rg3-Lipo retains most proteins found on M1-type macrophages, including the characteristic proteins integrin α4 and β1. This macrophage membrane-modified MM/PNT-Rg3-Lipo reduces macrophage phagocytosis, while enhancing uptake by metastatic breast cancer cells. In vitro , macrophage membrane-modified MM/PNT-Rg3-Lipo exhibits a stronger cytotoxic effect on breast cancer cells compared to free PNT. In vivo , MM/PNT-Rg3-Lipo shows a lower hemolysis rate, demonstrating its safety. Macrophage membrane modification guides liposomes to lung metastatic sites, leading to localized drug release and consequential inhibition of breast cancer lung metastases. The biomimetic macrophage membrane-coated liposomes, MM/PNT-Rg3-Lipo, which we have innovatively prepared, exhibit promising therapeutic effects against breast cancer lung metastases.

As a classic traditional Chinese medicine, ginseng is widely used in cancer treatment. We found that the panaxadiol derivative 6a inhibits breast cancer cell proliferation, but its anti-metastatic effect and mechanism remain unclear. Multiple breast cancer cell lines were used to assess the in vitro antiproliferative and antimigratory activities of 6a. A lung metastasis model, small animal imaging, and pathological examination were employed for in vivo efficacy evaluation. Metabolomic analysis and experimental validation focused on key metabolites and signaling pathways. Compound 6a effectively inhibited proliferation and migration of breast cancer cells, showing stronger activity than panaxadiol and ginsenoside Rg3. Further metabolomic analysis revealed that the inhibitory effect of 6a on breast cancer cells was achieved by effectively regulating the "fatty acid degradation" pathway. Focusing on palmitoylcarnitine (PC), a key differential metabolite, we further analyzed its association with the DLL4-Notch signaling pathway. The results indicated that compound 6a interfered with cancer cell metastasis through the DLL4-Notch pathway and related metastasis signaling pathways, and further promoted the accumulation of PC. In in vitro validation, as the concentration of PC increased, it exhibited the same inhibitory effect on cancer cells as that of 6a. In conclusion, this study systematically evaluated the inhibitory effect of the ginsenoside derivative 6a on breast cancer lung metastasis. This study not only provides insights for exploring the activity of panaxadiol, but also offers evidence for the application of ginsenosides in cancer therapeutic drugs.

Triple-negative breast cancer (TNBC) is a highly aggressive malignancy with poor prognosis and limited therapeutic options, underscoring the need for new treatment approaches. Ginsenoside Rh2 (G-Rh2) has demonstrated antitumor effects across multiple cancer types; however, its effects and underlying molecular mechanisms in TNBC remain poorly understood. TNBC cell viability was measured using the CCK-8 assay.Flow cytometry was used to evaluate cell cycle distribution and cell apoptosis. Proteomic analysis was performed to identify potential downstream targets of G-Rh2. The functional roles of downstream targets were validated by western blotting, flow cytometry, and luciferase reporter assays. Molecular docking was conducted to characterize protein-ligand interactions at the atomic level. G-Rh2 markedly decreased MDA-MB-468 and BT549 cells viability in a concentration-dependent manner, with IC50 values of 31.74 μM and 49.63 μM, respectively. G-Rh2 treatment induced G0/G1 phase arrest and enhanced cell apoptosis. Mechanistically, G-Rh2 suppressed the Wnt/β-catenin signaling pathway through SMG9 downregulation. Molecular docking demonstrated a stable interaction between G-Rh2 and SMG9, with a minimum binding energy of -3.4 kcal/mol, indicating direct molecular engagement. This study demonstrates that G-Rh2 exerts potent antitumor effects in TNBC by inducing cell cycle arrest and promoting cell apoptosis. Furthermore, G-Rh2 suppresses tumor progression by targeting the SMG9-Wnt/β-catenin axis. These findings identify SMG9 as a novel mediator of G-Rh2 activity, provide mechanistic insight into its antitumor effects, and highlight SMG9 as a promising therapeutic target for TNBC.

Ductal carcinoma in situ (DCIS) is usually detected with mammography screening and assumed to be a precursor of invasive ductal cancer (IDC) of the breast. Yet, despite an approximately 10-fold increase in the rate of DCIS detection and treatment within 20 years following implementation of mammography screening in the United States, IDC incidence rates remained comparatively stable (a 1.6-fold increase during the same time period). Moreover, if we accept the assumption that DCIS is a nonobligate precursor of IDC, with estimates that up to 40% may progress to IDC, then DCIS annual incidence should be at least 2.5-fold greater than that of IDC, and at least 9-fold greater than what is now reported. Such a vast underestimation of DCIS incidence seems unlikely, as over 85% of all DCIS lesions contain microcalcifications and most should therefore be detectable with modern breast screening technology. In this special report, we discuss evidence derived from population-based registries suggesting that DCIS is not a precursor but rather a low-risk variant of invasive breast cancer, with a 3.3% risk of breast cancer death over a 20-year period. A large DCIS treatment trial with a mortality endpoint is needed to bolster support for this alternative hypothesis and potentially justify treating DCIS as a low-risk systemic disease.