Original research publications

Ferroptosis induced by Fenton-reaction holds great promise in triple-negative breast cancer (TNBC) therapy. However, its efficacy is severely constrained by limited endogenous hydrogen peroxide (H 2 O 2 ) substrates and poor Fenton reaction efficiency. To overcome these limitations, we propose a strategy to initiate a heterogeneous photo-Fenton-like reaction in H 2 O 2 -rich lysosomes and design a reaction engine for amplified cascade toxic oxidative radical propagation (REACTOR), which can confine the reaction to lysosomes for light triggering and accelerate it with p-benzoquinone (DMBQ). The REACTOR nanoplatform encapsulates copper-enriched Prussian blue (CuPB) and a redox-active DMBQ within thermosensitive liposomes, enabling preferential accumulation in lysosomes. Under irradiation, REACTOR triggers lipid phase transition, exposing the co-encapsulated CuPB and DMBQ to the lysosomal H 2 O 2 pool and initiating a highly efficient Fenton reaction that induces lysosomal membrane lipid peroxidation. Concurrently, ferrous ions released from lysosomal stores, together with CuPB-catalyzed quinone redox cycle, propagate oxidative damage to mitochondrial membranes, culminating in an explosive burst of lipid peroxides that efficiently triggers ferroptosis. REACTOR combined with irradiation significantly inhibits tumor growth, even achieving complete tumor regression and effectively suppressing metastasis in a TNBC-model. This light-activatable REACTOR transitions from a ready to a reactive state by mimicking the bombardier beetle's defense strategy, leveraging the lysosomal compartment to trigger, amplify, and sustain oxidative damage, offering a highly efficient and low-toxicity platform for precision cancer therapy.

BpTx-I, a novel acidic phospholipase A 2 (PLA 2 ), was purified from Bothrops pictus venom by CM Sephadex C-25 and ENrich™ SEC 70. BpTx-I was characterized as a monomer (SDS-PAGE and DLS analysis) of 13,807.8 Da (MALDI-TOF) with predominantly α-helical secondary structure (circular dichroism). From cDNA cloning, its deduced amino acid sequence revealed high homology with other Asp49-PLA 2 s. It exhibited enzymatic and edema-inducing activities, lacking myotoxic effects. Using assays of impedance-based cell growth kinetics for eight cell lines (RMF621, MCF10F, MCF7, A549, HeLa, Caco-2, ZR75-1, and MDA-MB-231), BpTx-I inhibited the proliferation of cancer cell lines compared to non-cancer cells. Functionally, it arrested cell cycle in the S phase, reduced clonogenicity, and impaired fibronectin-mediated adhesion and migration in MDA-MB-231 cells. No effects on mitochondrial ROS, ATP, Δψm, mitochondrial respiration, but an increased glycolytic capacity was observed. In silico studies suggested BpTx-I might bind to β-integrin subunits. In contrast to cancer cells, BpTx-I acted as a stromal immunomodulator in RMF621 fibroblasts, upregulating ITGAV, ITGA2, and NFKB1, which triggered the secretion of pro-inflammatory cytokines (IL-6, IL-8, and IL-1β) without altering cell proliferation. These findings highlight BpTx-I as a potential lead migrastatic compound that disrupts extracellular matrix protein-cancer cell interactions and modulates the tumor microenvironment in a mitochondrial metabolism-independent manner.

Fear of cancer recurrence is one of the most prevalent and enduring psychosocial challenges encountered by breast cancer survivors. Although this fear can prompt health-monitoring behaviors such as breast self-examination (BSE), comprehensive survivorship care models addressing these psychological dynamics remain limited. This study was aimed at determining the level of fear of cancer recurrence in women who have survived breast cancer and examining its relationship with their health beliefs and awareness regarding breast self-examination. This descriptive, cross-sectional, and correlational study was conducted between June 2024 and October 2024 with 259 breast cancer survivors registered at the radiation oncology outpatient clinic of a tertiary hospital in Türkiye. Data were collected using a Patient Information Form, the Champion Health Belief Model Scale, and the Fear of Cancer Recurrence Inventory. The study was reported in accordance with the STROBE checklist. Data were analyzed using descriptive statistics, independent samples t test, ANOVA, and linear regression analysis. The mean total score for fear of cancer recurrence among the survivors was 1.42 ± 0.82 points. A statistically significant positive correlation was identified between fear of recurrence and health belief model dimensions, particularly perceived severity and health motivation (p < 0.05). Linear regression analysis revealed that fear of cancer recurrence had a significant positive effect on the health belief model (F = 31.690, p < 0.001), explaining 11% of the total variance (R 2 = 0.110). Fear of cancer recurrence is common among breast cancer survivors and significantly influences their health beliefs and self-monitoring behaviors. While moderate fear may heighten surveillance awareness through BSE, structured psychosocial support and educational programs are essential to help survivors manage recurrence concerns adaptively within holistic nursing care.

Breast cancer remains a major cause of cancer-related mortality worldwide, creating a need for novel therapeutic strategies. Natural plant compounds have gained recent attention for their anticancer effects, including oleuropein from olive leaves, and punicic acid from the pomegranate fruit. In the present study, we investigated the effects of oleuropein (OL) and punicic acid (PA) on MCF-7 breast cancer cells and the role of peroxiredoxin (Prdx) antioxidants in mediating these effects. MCF-7 cells were treated with different concentrations of OL or PA for 72 h. Viable cell density was measured by MTT assay, cytotoxicity was measured by LDH release, mitochondrial ROS was measured by MitoSOX assay, and lipid peroxidation was measured by MDA assay. The effect of Prdx suppression was determined by transient siRNA transfection, followed by cell treatments and MTT assay. Treatment with OL or PA produced a concentration-dependent reduction in cell viability, increased cytotoxicity, and morphological changes consistent with cellular stress and death, with PA exhibiting greater potency at lower concentrations. Both compounds significantly increased mitochondrial superoxide production, while PA also induced lipid peroxidation. Suppression of Prdx proteins increased cellular susceptibility to OL and PA treatment, with more pronounced effects following PA exposure. OL and PA induce oxidative stress and cytotoxicity in MCF-7 cells, and peroxiredoxins play a protective role in the cellular response. This study highlights possible efficacy of these agents for treatment, and the importance of antioxidant defense systems in subsequent cancer cell survival.

Genetic testing is increasingly being offered at the time of breast cancer diagnosis to help women guide their treatment decisions. The objective of the current study was to measure decision regret 1 year after genetic testing and to evaluate the factors associated with regret. Women from across Canada were referred to receive rapid genetic testing for breast cancer predisposition genes at the time of breast cancer diagnosis (BRCA1, BRCA2, CDH1, PALB2, PTEN, STK11, TP53, ATM, and CHEK2). Questionnaires were completed prior to testing and 1-week and 1-year postgenetic testing. Decision regret was measured at one-year. Overall, 871 women participated and the mean age at diagnosis was 46.0 years (range 19-70 years), and 522 (59.9%) of the women were White. Pathogenic variants were found in 83 women (9.5%). The mean score for decision regret was 7.86 (SD 14.17), with 802 women (92.1%) having no regret and 69 participants (7.9%) having regret. Women from racialized groups were more likely to regret their decision compared to White women (13.4% vs 4.4%; p < .001). Those with a BRCA1 or BRCA2 pathogenic variant were significantly more likely to have regret compared to those with a negative result (p = .03). A minority of women who have rapid genetic testing at the time of breast cancer diagnosis later regret their decision. Women at greater risk of having decision regret included those who received a positive BRCA1 or BRCA2 genetic test, and those from racialized groups. Follow-up counseling may be warranted for those who experience decision regret.

Pregnancy and the postpartum period can present substantial psychosocial and HIV-care challenges for women living with HIV (WLWH), with potential consequences for psychological well-being, treatment engagement, and maternal and infant health. This study examined whether internalized HIV stigma mediates the relationship between depressive symptoms and antiretroviral therapy (ART) adherence among pregnant and postpartum WLWH in Ghana. Structured interviews were administered during antenatal and postnatal care visits in private settings to 176 women receiving ART at 11 public health facilities in the Greater Accra Region. Validated measures were used to assess depressive symptoms, internalized HIV stigma, and self-reported ART adherence. We tested a simple mediation model with bootstrapped confidence intervals to evaluate the indirect association between depressive symptoms and ART adherence through internalized HIV stigma, adjusting for age. Approximately one-third (35.8%) of participants reported below-average ART adherence. Greater depressive symptom severity was associated with higher internalized HIV stigma, which was associated with poorer adherence. Although depressive symptoms were not directly associated with nonadherence, a statistically significant indirect association was observed through internalized stigma, consistent with an indirect-only mediation pattern. Age was not significantly associated with either stigma or adherence. Our findings suggest that internalized HIV stigma may help explain the association between depressive symptoms and reduced ART adherence among pregnant and postpartum WLWH in Ghana. The results support consideration of integrated approaches that address both mental health and stigma within maternal HIV care. Scalable models, including group-based therapy delivered by lay health workers, may offer opportunities to support ART adherence and well-being in resource-limited settings. These findings contribute to our understanding of how psychosocial factors may shape treatment engagement among WLWH and identify potential targets for future intervention research.

Cohort discovery using electronic health records (EHR) supports research recruitment and pragmatic clinical trials; however, the validity of EHR-derived cohorts depends on whether patient characteristics recorded in EHR are representative of the target population. While methods exist for assessing internal validity, no published methods address continuous outcomes when EHR and reference population data partially overlap at the individual level. We present a novel statistical approach for assessing EHR data cohort fitness when partially overlapping data are available from an EHR and a registry. For continuous outcomes, we derived an explicit test accommodating unequal variances and correlation between paired records. For binary outcomes, we recommend generalized linear mixed models with a binomial distribution and logit link. We demonstrate the new approach using maternal health data from the OneFlorida+ Data Trust (n = 37,200) and Florida birth certificate records (n = 210,910) from 2021. OneFlorida+ EHR had higher rates of Black race identification, residence in areas of higher social deprivation, and pre-existing diabetes or hypertension, while showing lower probabilities of gestational complications. Maternal age, height, and cesarean delivery rates were not meaningfully different between data sources. Observed differences may reflect the academic health center composition of OneFlorida+ partner sites; however, substantially higher missingness in OneFlorida+ EHR than birth certificate records for race, ethnicity, and location of residence suggests that data capture differences play a role. This replicable statistical method provides researchers with quantitative tools to assess cohort fitness and is applicable to other clinical research networks where EHR and registry data overlap.

Tumor-resident intracellular bacteria (TRIB) are prevalent within triple-negative breast cancer (TNBC). As integral components of the tumor pathological microenvironment, TRIB accelerate TNBC development by regulating cell proliferation, metabolism and immunosuppression. They also enhance the resistance of circulating tumor cells to mechanical stress through cytoskeletal rearrangement, boosting tumor metastasis and hindering clinical therapy. This work develops an advanced TRIB-targeted therapeutic strategy to block TNBC progression by eliminating tumor cells and intracellular bacteria, remodeling tumor immunity and suppressing metastatic colonization. We fabricate cancer cell membrane-modified narrow-bandgap FeSe 2 nanosheets for enhanced ultrasound-triggered reactive oxygen species production and image-guided precise treatment. Such nanoplatforms utilize endogenous H 2 O 2 and GSH to amplify chemodynamic effects, induce severe oxidative stress and ferroptosis in tumor cells. Combined damage-associated and pathogen-associated molecular patterns efficiently activate dendritic cells and initiate robust antigen-specific T-cell immune responses. This study provides an alternative and promising strategy for the treatment of clinically metastatic breast cancer through intratumoral microbiota intervention.

Hypertensive disorders of pregnancy (HDP) are major contributors to maternal morbidity, mortality, and long-term cardiovascular risk. Perceived experiences of racial discrimination (EORD) have been associated with adverse cardiovascular outcomes. This study investigates the association between EORD and incident HDP among Black and White women. The Coronary Artery Risk Development in Young Adults study is a prospective cohort of 5,115 Black and White adults aged 18 to 30 years at baseline (1985-1986), followed for over 30 years. EORD was analyzed as a continuous proportion, a three-category variable (no discrimination, overall proportion < 33%, and 33% or greater), and dichotomously (none vs. ever). HDP was self-reported in pregnancies lasting at least 23 weeks. Logistic regression assessed the association between EORD and HDP among 1,184 parous women, adjusting for age, race, education, income, cardiovascular risk factors, and parity. At baseline, the mean age was 24.1 years; 48.1% were Black, 72.3% were nulliparous, and 19.7% had an income less than $16,000. Overall, 60.6% reported EORD (86.0% of Black and 37.1% of White women). Those reporting EORD were more likely to be Black, unmarried, have higher BMI, and have had one birth at baseline (p < 0.001). EORD was associated with increased odds of HDP (OR: 1.73 [1.20-2.48]) among both Black and White women. EORD < 33% (OR: 1.75 [1.20-2.55]) and 33% or greater (OR: 1.65 [1.04-2.64]) were significantly associated with HDP. EORD, regardless of race, is significantly associated with increased odds of HDP. The disproportionate burden among Black women highlights the need for targeted interventions.

To evaluate whether race affects how the healthcare team communicates with the patient, from the woman's perspective. A cross-sectional study used the postoperative module of the BREAST-Q questionnaire to assess patients' perceptions of communication with the healthcare team. The questionnaire was applied to perioperative women after being diagnosed with breast cancer. The final sample consisted of 98 patients. The main outcome was the questionnaire score. Variables included self-reported skin color, professional type, and others. We used proper tests to compare the variables, and linear regressions to test independent variables. Of the 98 women analyzed, 54 self-identified as White (55.1%) and 44 as Black (44.9%). 58.1% of Black women responded that if they had a different skin color, their treatment would have differed, compared with 29.6% of the White women (p = 0.005). Regarding communication with breast surgeon staff, self-declared race, income, and work location negatively influenced the score. However, communication with nursing staff was only negatively affected by self-declared race and income. Moreover, only self-declared race influenced communication with support staff. In the multiple regression analyses, self-declared race was the only factor that, in isolation, negatively influenced communication between woman and staff. Satisfaction scores were most similar when communicating with the support team and least similar when relating to the breast surgeon. Self-reported race was the main factor associated with perceived poorer patient-staff communication during the diagnosis and initial treatment of breast cancer. Structural inequalities in communication should be addressed.

Electronic patient-reported outcomes (ePROs) can support patient-centered oncology care, but in early breast cancer, it is unclear whether real-time ePRO-triggered triage adds benefit beyond lower-intensity app-based support and scheduled ePRO collection. We tested whether adding weekly ePRO screening, rule-based triage, and care-team escalation to app-based support improves health-related quality of life (HRQoL) during systemic therapy for early breast cancer. ENABLE was a multicenter, open-label, parallel-group randomized controlled trial at 2 German university hospitals. Adults with early (stage I-III) breast cancer initiating systemic therapy were randomized 1:1 to reactive patient-reported outcome assessment (RPA) or control. Both arms received the ENABLE app with educational and organizational support and scheduled HRQoL assessments at 6 fixed time points; only RPA received weekly EuroQol Visual Analogue Scale screening (trigger: score <50 or ≥10-point decline) followed by symptom assessment, digital triage, and care-team alerts. Patient-Reported Outcomes Measurement Information System-29 was analyzed as an 8-measure HRQoL end-point family (7 domains plus pain intensity); no single domain, composite score, or binary global success rule was prespecified. Group-by-visit mixed-effects models were fitted with Benjamini-Hochberg false-discovery-rate adjustment. The recruitment period was March 22, 2021, to September 8, 2023. Of 605 randomized patients, 487 entered the modified intention-to-treat analysis (RPA: n=242; control: n=245). End-of-treatment between-group differences (RPA minus control, T -score points, 95% CI, and adjusted P ) were: fatigue -3.90 (95% CI -5.77 to -2.03; P =.004), social participation +2.84 (95% CI 1.18 to 4.49; P =.01), anxiety -2.10 (95% CI -3.65 to -0.55; P =.049), depression -1.95 (95% CI -3.25 to -0.65; P =.10), sleep disturbance -1.82 (95% CI -3.43 to -0.20; P =.051), pain interference -1.44 (95% CI -3.38 to 0.49; P =.18), physical function +1.33 (95% CI -0.22 to 2.88; P =.18), and pain intensity -0.26 (95% CI -0.73 to 0.21; P =.32; 0-10 scale). All T -score differences were below the 5-point minimally important difference (MID). Exploratory time-to-deterioration analyses favored RPA for fatigue (hazard ratio [HR] 0.69, 95% CI 0.54-0.89), social participation (HR 0.76, 95% CI 0.59-0.97), and depression (HR 0.66, 95% CI 0.44-0.98). Of 209 monitored RPA patients, 160 (76.6%; 95% CI 70.4-81.8) triggered at least 1 alert. No intervention-related harms were identified. ENABLE tests real-time, rule-based ePRO triage with care-team escalation against an active digital comparator rather than usual care, isolating the response pathway itself; it extends this design from metastatic disease into early breast cancer and escalates to the care team rather than to the patient alone. Benefits were domain-specific and sub-MID, in anxiety, fatigue, and social participation, tempering the expectation of a global HRQoL effect. For practice, symptom-triggered triage is a supportive-care workflow tool worth embedding where alerts reach a team that acts and documents, not a stand-alone remedy for treatment-related morbidity.

Human Papillomavirus (HPV) infections are among the leading causes of cervical cancers globally. The World Health Organization has established global targets aimed at reducing the spread of HPV and its associated disease burden. To date, the detection of HPV infections relies primarily on genomic assays targeting viral DNA or mRNA, which, although highly sensitive, require time-consuming PCR protocols performed by trained personnel. In addition, these approaches may be challenged in biological matrices, such as saliva, where viral concentrations are low (e.g., head-neck HPV cancer) or early stage infections. Therefore, alternative strategies enabling rapid, sensitive, and direct detection of viral biomarkers are highly desirable. In this study, we present the Single-Molecule-with-a-Large-Surface (SiMoLS) technology for the detection of the HPV-16 L1 capsid protein in both model and clinically relevant samples added with HPV-16 L1. The SiMoLS platform exploits a biofunctionalized gate electrode integrated within an electrolyte-gated organic field effect transistor, enabling label-free detection at the single- or few-molecules level. By targeting HPV-16 L1, a structural protein abundantly expressed during productive infection, the platform provides direct evidence of viral presence without the need for nucleic acid amplification. The device demonstrates high sensitivity and selectivity across a broad concentration range, extending down to 10 -20 M with a confidence level of 99%, while PCA shows a well-defined clustering pattern that separates positive from negative swab real samples in an unsupervised manner. The SiMoLS platform (i) offers rapid analysis with ultrahigh sensitivity, (ii) it is compatible with low sample volumes, supporting its application in point-of-care (POC) settings due to its scalability and ease of use, and (iii) represents a promising tool for the early and decentralized HPV highly sensitive yet reliable screening, particularly in scenarios where conventional methods face limitations.

CST1 has been experimentally linked to estrogen receptor alpha (ERalpha) signaling in breast cancer, but clinical-tissue and public-cohort evidence remains incompletely integrated. We investigated whether CST1 is enriched in ERalpha-positive tumors and whether its expression is associated with luminal and tumor-microenvironmental features. CST1 immunohistochemistry (IHC) was analyzed in 179 unique breast cancers after exclusion of duplicate pathology identifiers, including 135 ERalpha-positive cases across four prespecified ERalpha-percentage strata and 44 mutually exclusive ERalpha-negative, triple-negative, or HER2-overexpression controls. External validation used TCGA-BRCA, METABRIC, and CPTAC-BRCA. TCGA data were analyzed for differential expression, coexpression, pathway enrichment, and curated module scores. CST1 positivity was more frequent in ERalpha-positive tumors than in controls (101/135, 74.8% vs 11/44, 25.0%; odds ratio 8.91, 95% CI 4.06-19.54), and CST1 H-score was higher in the ERalpha-positive group. Public cohorts confirmed higher CST1 mRNA in ER-positive tumors and significant PAM50 subtype differences. Institutional IHC showed moderate separation of ERalpha-positive status (AUC 0.789), whereas transcriptomic AUCs were modest in TCGA-BRCA (0.596), METABRIC (0.562), and CPTAC-BRCA (0.693). In TCGA-BRCA, CST1-high tumors showed ECM/CAF-related coexpression, pathway-enrichment, and module-score patterns. In CPTAC-BRCA, CST1 correlated with ESTIMATE and xCell-derived stromal-enrichment scores. Because ER status, PAM50 subtype, and tumor purity may confound relationships between CST1 expression and stromal estimates, these exploratory bulk-tissue associations should be interpreted in the context of tumor subtype and tissue composition. CST1 expression is enriched in ERalpha-positive breast cancer at the protein level and is reproducibly associated with ER/luminal features across public cohorts. Exploratory computational analyses further associate CST1 with ECM/CAF-related transcriptomic and stromal-enrichment features. However, potential confounding by ER status, PAM50 subtype, and tumor purity, together with the absence of spatial or functional validation, precludes independent or causal interpretation of the stromal associations.

The human epidermal growth factor receptor 2 (HER2) is overexpressed in 15-30% of breast cancer cases, plays a significant role in pathogenesis, and has been used as a diagnostic indicator and therapeutic target. Herein, a bioconjugatable porphyrin chelator is described, bearing a water-solubilizing swallowtail motif that projects above and below the plane of the macrocycle. This porphyrin, in various quantities, was reacted in stochastic fashion with the lysine side chains of the anti-HER2 antibody trastuzumab to afford a series of porphyrin-trastuzumab ( PorTraz ) products with conjugation ratios of 2.3, 3.5, 4.1, and 5.2. Radiolabeling of the conjugates with 64 Cu in HEPES buffer (pH 7.2) at 37 °C afforded a molar activity of up to 20 μCi/μg (110 MBq/nmol). Binding was specific to the HER2 receptor, and uptake was observed for each conjugate. In mice bearing HER2+ BT-474 xenografts, PET imaging studies showed significantly higher tumor uptake, with a tumor standardized uptake value (SUV) of 0.95 ± 0.08 versus 0.38 ± 0.12 in the HER2- MDA-MB-468 xenograft control group at 24 h post-injection. PorTraz conjugates showed tumor SUV results of 1.25 ± 0.31 for n = 2.3 porphyrin chelators per antibody and 0.59 ± 0.20 for n = 5.2 porphyrin chelators per antibody. In summary, a series of porphyrin-trastuzumab conjugates were synthesized and labeled with 64 Cu, displayed high binding to HER2+ cells, and illustrated uptake in mouse tumor xenografts observable by PET/CT imaging.

Brief rationale: To investigate associations between breastfeeding behaviours and maternal bone health at 10-year follow-up. Breastfeeding durations were not associated with DXA measurements. Significance of the paper: These findings add to the evidence that breastfeeding is not associated with adverse long-term maternal bone health. To investigate associations between breastfeeding behaviours and dual-energy X-ray absorptiometry (DXA) measurements of maternal bone health at 10-year follow-up. Associations with bone turnover markers (BTMs) were examined as exploratory secondary outcomes. This was an analysis of 196 women from the ROLO (Randomised cOntrol trial of a LOw glycaemic index diet in pregnancy to prevent macrosomia) longitudinal cohort study at 10-year follow-up. Data on demographics, lifestyle and breastfeeding were collected by questionnaire. DXA measurements were available for 171 participants and BTM measurements for 60. Exclusive breastfeeding duration, any breastfeeding duration and three mutually exclusive cumulative breastfeeding groups (never breastfed, breastfed for <12 months, and breastfed for ≥12 months) were each examined in relation to bone health outcomes. The mean (SD) age of participants was 42.8 (3.87) years and 97.9% were premenopausal. Ever breastfeeding rates were 70.9% (n = 139/196) and 40.3% (n = 79/196) had a cumulative breastfeeding duration of ≥12 months. Breastfeeding durations were not associated with DXA measurements at 10-year follow-up. An unadjusted difference in β-CTX-I was observed between the ≥12-month and never-breastfed groups (p = 0.038) however, given the small group size an adjusted analysis was underpowered. These findings reassure women that breastfeeding does not have a lasting negative impact on skeletal health. The exploratory BTM finding should be interpreted cautiously.

Trastuzumab-emtansine (T-DM1), an antibody drug conjugate, is approved in the adjuvant (residual disease post-neoadjuvant chemotherapy) and metastatic settings for HER2-positive breast cancer. Real-world evidence on T-DM1 biosimilar from India remains sparse. During October 2021-July 2025, 101 cases treated with T-DM1 biosimilar - UJVIRA ® , across seven oncology centers in India were retrospectively analyzed. The adjuvant cohort (n = 19), had patients with residual disease after neoadjuvant therapy and surgery, and the metastatic cohort (n = 82), comprised patients progressing on trastuzumab-chemo regimens. Primary endpoints were invasive Disease-Free Survival (iDFS) and Progression Free Survival (PFS) in the adjuvant and metastatic cohort respectively. Overall Survival (OS) and safety were secondary endpoints. In the adjuvant cohort (median follow-up 19 months), median iDFS was not reached (mean 14.6 months), with 2 events (10.5%). In the metastatic cohort (median follow-up 8 months), median PFS was 7.5 months (mean 8.3 months; 61 events, 74.4%). PFS was longer when T-DM1 was administered earlier: 28 months in first-line, 9 months in second-line, and 8 months in third- and fourth-line (p = 0.06). Median OS in the metastatic cohort was 15.5 months and 36 months with 1st line T-DM1. In 14.6% of metastatic patients, grade 3 thrombocytopenia occurred; there were no grade 3/4 events in the adjuvant cohort. UJVIRA ® demonstrated real-world clinical effectiveness and an acceptable safety profile in both adjuvant and metastatic HER2-positive breast cancer, with outcomes similar to landmark clinical trials supporting its role as a cost-effective biosimilar in India.

To characterize clinicopathologic, treatment-related, and sociodemographic factors associated with rapid versus late relapse in triple-negative breast cancer (TNBC), and to evaluate how relapse timing influences metastatic patterns and survival outcomes. Using linked Swedish population-based registers, we conducted a retrospective cohort study of women diagnosed with non-metastatic TNBC between 2007 and 2021. Patients were classified into three groups based on time to distant relapse or death: rapid relapse (rrTNBC; ≤24 months), late relapse (lrTNBC; >24 months), or event-free at last follow-up. Tumor characteristics, comorbidity, treatments, and sociodemographic variables were compared across groups. Multivariable logistic regression and survival outcomes were assessed. Sensitivity analyses restricted to healthcare regions with complete relapse data were performed. Among 8,298 patients, 15% experienced rrTNBC, 18% lrTNBC, and 67% remained event-free. rrTNBC was associated with older age, larger tumors, nodal involvement, advanced stage, and a higher frequency of visceral and multi-organ metastases. Patients with rrTNBC were less likely to receive adjuvant systemic therapy or radiotherapy and more likely to undergo mastectomy. Sociodemographic disparities were observed, with rrTNBC more frequent among patients who were single or widowed, lower educated, or had lower household income. Survival outcomes were substantially worse for rrTNBC compared with lrTNBC and event-free patients. Rapid relapse defines a particularly vulnerable TNBC population characterized by aggressive tumor biology, early dissemination, inferior survival, and sociodemographic disadvantage, while lrTNBC represents an intermediate phenotype with delayed disease progression. Distinguishing rrTNBC from lrTNBC may improve risk stratification, guide treatment decisions, and support more personalized follow-up strategies.

Significant clinical benefit has been demonstrated in multiple clinical trials of the humanised antibody pertuzumab in breast cancer patients overexpressing the Human Epidermal Growth Factor-2 (HER2) receptor. However, economic evaluations of pertuzumab treatment have yielded conflicting results regarding its cost-effectiveness in this patient population. The objective of this study was to assess all current economic evaluations of pertuzumab in patients with primary versus metastatic breast cancer, and to provide an overview of the cost effectiveness of pertuzumab in these settings. Using Ovid MEDLINE, EMBASE, CINAHL EBSCO and Cochrane, a systematic review was conducted of economic evaluations of pertuzumab in breast cancer patients. Studies were subdivided into those assessing pertuzumab in early breast cancer with high-risk patients and in patients with metastases. A total of 888 articles were retrieved from Ovid MEDLINE, PubMed and Embase. An additional 70 articles were gathered from CINAHL EBSCO and Cochrane. Following removal of duplicates, 570 articles were screened by title, resulting in 330 screened by abstract and a total of 72 full-text articles screened for final inclusion. A total of 5 studies assessing the cost-effectiveness of pertuzumab in the early breast cancer setting and 8 studies in the metastatic setting were included in the final analysis. pertuzumab was found to be cost-effective in the early breast cancer setting, but generally not cost-effective in the metastatic setting. Pertuzumab consistently produces high pathological complete response (pCR) rates and has a significant impact on long term patient health outcomes and survival. For patients with early breast cancer with high-risk features, the lower lifetime costs associated with pertuzumab treatment make it cost- effective. However, in patients with metastatic breast cancer, the cost associated with ongoing treatment of this costly monoclonal antibody therapy argues against the economic viability of pertuzumab.

Osteogenesis Imperfecta (OI) is a group of connective tissue disorders most often caused by quantitative or qualitative changes in type I collagen. The clinical phenotype is heterogeneous. Women's health in OI has been very sparsely investigated, and whether periods of skeletal stress throughout adulthood come with an increased risk of fractures and other complications due to OI is unknown. The present review covers the current literature on menarche, pregnancy and menopause, and periods of skeletal stress in women with OI. Over 1300 articles published between 1967 and 2026 were identified and screened for relevance. The literature suggests that the age of menarche reflects the general population. Fertility may be preserved - especially in the milder affected phenotypes. Most pregnancies are successful; however, data suggest that they may be associated with a higher risk of complications and fractures compared to the general population. Likewise, caesarean section is chosen more frequently in women with OI compared to the general population. Menopause is sparsely described, and it has not been investigated whether the consequences of and symptoms associated with menopause are different in women with OI compared to the general population. The current evidence is often limited by small study size and OI subtypes. Overall, the evidence to guide clinicians in monitoring and treatment of women's health in OI is limited, and more studies are needed. As women with OI present as a very heterogeneous group, managing pregnancy and menopause requires individualized monitoring with focus on known complications.

The largest baleen whale mortality event on record, when more than 340 sei whales ( Balaenoptera borealis ) stranded in Chilean Patagonia during the extreme 2015 El Niño, provided a unique opportunity to reconstruct multi-year individual life histories from baleen plates. Baleens of seven females and four males were sampled to examine sex-specific foraging strategies, reproductive cycles and endocrine patterns through integrated molecular, isotopic and hormonal analyses. Sex was identified using a refined DNA amplification protocol. Patterns of δ 13 C and δ 15 N revealed significant annual oscillations, enabling estimates of baleen growth rates (15.7-20.5 cm yr -1 ) and retrospective timelines of up to 3.5 years. Males exhibited broader isotopic niche widths, suggesting sex-related foraging differences. Progesterone was detected in all samples, with sustained elevations in females indicating pregnancies of 7.7-10.7 months. One female exhibited two complete pregnancies recorded in baleen, enabling estimation of a 1.3-year intercalving interval. Concurrent elevations of cortisol and corticosterone were observed during pregnancy. Conceptions and births were distributed across multiple seasons, with no clear evidence of seasonal concentration. Together, these findings provide the first baleen-based reconstruction of sei whale reproductive history and endocrine variation, establishing critical baselines for assessing population resilience and informing conservation under rapid environmental change.

Improving therapeutic efficacy and antitumor immune responsiveness in BRCA1-mutant ovarian cancer remains challenging. Here, we developed a BRCA1 mutation-guided tetrahedral framework nucleic acid nanosystem, FBOA-tFNA, for coordinated intracellular delivery of the PARP inhibitor olaparib and the WEE1 inhibitor adavosertib. After folate receptor-mediated uptake, FBOA-tFNA recognizes BRCA1 mutant RNA through toehold-mediated strand displacement, enabling mutation-selective beacon activation, while drug release is independently regulated by reduction-responsive disulfide cleavage. Coordinated PARP/WEE1 inhibition amplified DNA damage, impaired G2/M checkpoint protection, and promoted tumor-cell killing in BRCA1-mutant ovarian cancer models. Resulting DNA damage-associated intracellular dsDNA signals activated STING-associated signaling, type I interferon responses, immunogenic cell death (ICD)-associated stress, dendritic-cell maturation, and CD8 + T-cell activation. Engineered patient-derived ovarian cancer organoids expressing a BRCA1 2594delC -containing transcript further supported the mutation-selective recognition and therapeutic potential of FBOA-tFNA ex vivo. In vivo, FBOA-tFNA showed tumor-associated fluorescence accumulation, BRCA1 mutant-transcript recognition-associated beacon activation, enhanced antitumor efficacy, and preliminary repeated-dose tolerability. Moreover, FBOA-tFNA enhanced antitumor immune responses and improved the response to anti-PD-1 therapy, accompanied by increased effector and memory-like T-cell populations. This programmable DNA nanoplatform provides a personalized combination strategy for coordinated DNA-damage therapy and immunomodulation in BRCA1-mutant ovarian cancer.

Many Korean women stay in postpartum care centers ( Sanhujoriwons ) for 2 weeks after childbirth, a critical period for both mothers' and fathers' transition to parenthood. Research has been conducted to improve the support and education provided to Sanhujoriwon users. However, most studies have been quantitative, failing to reflect the diverse opinions of users or provide in-depth insight into their experiences. We aimed to explore the experiences of first-time mothers and their spouses using Sanhujoriwons . The qualitative, interpretive phenomenological study employed reflexive thematic analysis. Data were collected through in-depth Zoom interviews with 10 couples who had given birth within the previous year and had stayed at a Sanhujoriwon for 2 weeks following childbirth. The results revealed 4 themes: (1) Prioritizing maternal recovery through structured support, (2) Struggling to breastfeed within the institutional environment, (3) Ambivalence toward rooming-in, and (4) Navigating emotional support within the couple. The findings underscore the need for practical education and professional support in Sanhujoriwons to promote successful breastfeeding and facilitate the transition to parenthood. Furthermore, greater emphasis should be placed on rooming-in practices and family-centered care within Sanhujoriwons .

Does intimate partner violence (IPV) before or during pregnancy increase the likelihood of unsafe infant sleep practices (surface sharing and non-supine positioning) among women with a recent live birth? The sample included 213,556 women with a recent live birth participating in the 2016 to 2022 Pregnancy Risk Assessment Monitoring System (PRAMS) from 41 U.S. jurisdictions. We analyzed PRAMS data to estimate the prevalence of physical IPV 12 months before or during pregnancy and infant sleep practices (i.e., surface sharing and supine positioning) by demographic characteristics. We calculated adjusted odds ratios (aORs) to examine associations between physical IPV and infant sleep practices. Overall, 3.2% (95% confidence interval [CI] [3.1, 3.3]) of women reported physical IPV in the 12 months before or during pregnancy. Experiences of physical IPV in the 12 months before or during pregnancy were significantly associated with an increased likelihood of reporting surface sharing in the 2 weeks before survey administration and those who had experienced physical IPV had 20% higher odds of putting their infant in a non-supine sleep position compared to those who had not experienced IPV (aOR = 1.2, 95% CI [1.1, 1.4]). Physical IPV before or during pregnancy may be an important risk factor for unsafe infant sleep practices. Attention to IPV as a potential barrier to safe infant sleep practices may be an important consideration for perinatal care and support.

Women with adverse pregnancy outcomes (APOs) have a 2- to 8-fold increased risk of future atherosclerotic cardiovascular disease (ASCVD), yet the mechanistic pathways are not well-defined. Potential vascular and inflammatory factors contributing to ASCVD are not known in women with a history of preeclampsia (PE) or spontaneous preterm delivery (sPTD). Describe the vascular and inflammatory factors of women with PE or sPTD and compare differences that may contribute to ASCVD risk. Women 18 years or older, 2-3 years postpartum, with a history of PE ( N = 19) or sPTD ( N = 13), and reference controls ( N = 19; delivery ≥ 37 weeks' gestation without APO) were enrolled. All cohorts underwent phlebotomy to measure inflammatory biomarkers and SphygmoCor testing for vascular function, including augmentation index (AIx75), central pulse pressure (CPP), and pulse wave velocity (PWV). Participants with sPTD had higher interleukin-8 concentrations of 6.6 pg/mL (interquartile range [IQR] 5.7, 8.7), compared with 4.7 pg/mL (IQR 2.2, 6.3) in controls ( p = 0.0279). Brachial systolic pressure was higher in PE (120 [standard deviation or SD 12.01]) than in sPTD (110.9 [SD 13.8]) or controls (108.6 [SD 9.22], [ p = 0.0071]). Central systolic pressure was higher in PE (109.8 [SD 11.4]) than in sPTD (99.3 [SD 13.88]) or controls (98.4 [SD 8.94], [ p = 0.0069]). CPP was higher in PE (34.2, SD 3.62) than in sPTD (30.8, SD 3.34) and controls (30.3, SD 3.67 [ p = 0.0027]). Vascular and inflammatory markers in PE or sPTD 2-3 years postpartum are higher compared with reference controls. Future studies should investigate vascular and inflammatory function in larger cohorts and prospectively evaluate contribution to CVD risk.

We sought to define the prevalence of obesity in the first trimester of pregnancy among women with inflammatory bowel disease (IBD) and evaluate its association with adverse pregnancy outcomes. First-trimester body mass index (BMI) was assessed in pregnancies with and without IBD. Pregnancies reaching 24 weeks were propensity-score matched 1:6 by maternal age, BMI, smoking status and gravidity to assess whether IBD conferred additional pregnancy risk. Overall, 22.6% (64/283; 95% CI 17.7%-27.5%) of pregnancies in women with IBD met ethnicity-adjusted criteria for obesity. Increasing obesity class was associated with stepwise increases in gestational diabetes, pre-eclampsia, venous thromboembolism (VTE), emergency caesarean section and high birthweight. Matching yielded 177 IBD pregnancies and 1062 controls. Obesity was independently associated with the composite adverse pregnancy outcome (OR 1.63; 95% CI 1.15-2.33; p = 0.007), whereas no statistically significant additional association was identified for IBD diagnosis alone (OR 0.74; 95% CI 0.53-1.03; p = 0.073). Among IBD pregnancies, aspirin was recommended in 39.3% (86/219). Low-molecular-weight heparin (LMWH) was prescribed in 21.6% (19/88) of pregnancies classified post hoc as intermediate or high VTE risk. More than one in five pregnancies in women with IBD were complicated by obesity. Obesity was strongly associated with adverse pregnancy outcomes, whereas this study did not identify a significant additional effect attributable to IBD diagnosis alone. Preventive prescribing with aspirin and LMWH represents an opportunity for improved antenatal care.

In pregnancy, antiretroviral drug-drug interactions must be interpreted against dynamic changes in gastrointestinal physiology, plasma-protein binding, renal elimination, hepatic enzyme activity and membrane transporter expression. Interaction studies quantify geometric mean exposure ratios relative to nonpregnant adults, but these measures describe relative pharmacokinetic change rather than whether effective exposure is preserved. For HIV treatment, validated exposure-response targets remain reasonable starting anchors when pregnancy-specific targets are unavailable. No evidence indicates that gestational immune adaptation alone requires a different intrinsic antiviral target. Pregnancy alters target attainment by altering drug disposition and variability, and it can modify the pharmacokinetics of both the victim antiretroviral and the perpetrator drug. For long-acting injectable PrEP, protective exposure, dosing interval and pharmacokinetic tail require separate consideration from treatment targets. This review evaluates candidate evidentiary anchors, including protein-adjusted in vitro inhibitory concentrations, exposure-response relationships, therapeutic drug-monitoring targets and model-informed probability of target attainment. Evidence from integrase inhibitors, protease inhibitors, non-nucleoside reverse transcriptase inhibitors, tenofovir formulations and long-acting agents demonstrates that similar proportional reductions in exposure can have different clinical implications depending on therapeutic margin, resistance barrier, interaction mechanism, formulation and pharmacologically relevant matrix. A newly proposed six-domain framework integrates clinical context, active analyte, exposure metric, evidentiary anchor, distributional target attainment and clinical outcomes. Physiologically based and population pharmacokinetic models provide evidence when pregnancy-specific data are unavailable, but their use should reflect model verification and uncertainty. The central objective is therefore not to define a universal pregnancy threshold but to determine whether pharmacologically effective exposure is maintained in the setting of gestational physiology and concomitant medicines.

Tumor microenvironment is closely involved in breast cancer progression and metastatic spread. Therefore, it is essential to develop a combination therapy to suppress tumor progression by regulating TME. Herein, Ru486-loaded doxorubicin (DOX)-chondroitin sulfate (chondroitin sulfate) nanomicelles (R/D-CS) were prepared for combined delivery. A "MCF-7 + MRC-5" dual-cell model and "4T1 + NIH-3T3" cell-bearing mouse model were established to recapitulate TME in vitro and in vivo, respectively. Interestingly, R/D-CS nanomicelles internalized cancer-associated fibroblasts and tumor cells and reduced tumor proliferation and migration markedly by downregulating expression of P-gp, vimentin, and CXCR4. Moreover, the in vivo antitumor studies were performed on a tumor-bearing mouse model, R/D-CS nanomicelles showed stronger antiproliferative and antimetastatic effects. Overall, the combination therapy based on R/D-CS nanomicelles was potent for breast cancer treatment.

Evidence characterising indoor environmental exposures and their effects on maternal neurobehavioural well-being during pregnancy remains scarce. To estimate the associations between indoor residential environmental exposures (nitrogen dioxide (NO 2 ), temperature, and relative humidity (RH)) and maternal neurobehavioural well-being (measured as perceived stress, sleep quality, and cognitive performance). We included pregnant individuals (n = 906) from the population-based Barcelona Life Study Cohort (BiSC) who were recruited from 2018 to 2021. Weekly average indoor residential NO 2 concentrations, temperature, and RH were objectively measured in participants' homes at ∼ 12 and ∼ 32 weeks of gestation using indoor monitoring devices. Linear, negative binomial, and mixed-effects regression models estimated the associations between indoor environmental exposures and perceived stress (10-item Perceived Stress Scale [PSS-10]), sleep quality (Pittsburgh Sleep Quality Index [PSQI]), and cognitive performance (N-back reaction time and Primary Mental Abilities-Revised [PMA-R]); PSQI was assessed at both visits, while PSS-10 and cognitive tests were performed at ∼ 32 weeks of gestation only. After covariate adjustment, higher indoor NO 2 exposure was associated with higher perceived stress (0.66 points (95 % confidence interval [CI] 0.11, 1.21; p = 0.019)) and a greater increase in PSS-10 scores for a NO 2 interquartile range increase (11.2 µg/m 3 ) but not with sleep quality or cognitive performance. Indoor temperature and RH metrics, including nighttime minima and maxima, were not associated with any outcome. Our findings suggest an association between indoor NO 2 concentration and prenatal perceived stress, indicating that the residential environment may be a relevant factor in maternal antenatal health that warrants further investigation.

"The bed nucleus of the stria terminalis (BNST) is a sexually dimorphic basal forebrain region" is a claim prevalent across rodent and human neuroscience research, arising from the observation that it is substantially larger in male versus female brains. Despite the pervasiveness of this claim, which may have implications for understanding sex differences in anxiety and substance use disorders, inspection of the literature reveals a complex and nuanced picture. Research on volumetric human BNST sex differences comes from a handful of mostly small-scale post-mortem studies and two MRI studies, between them reporting no, moderate, or very large differences. This indicates the need for a more detailed systematic investigation. Addressing this, we developed a novel 3T T1-weighted (T1w) manual segmentation protocol for the BNST, which was applied to sub-millimetre resolution T1w structural MRI data in 170 young human adults. Using a Bayesian modelling approach, taking into account existing data and accounting for total brain volume, age, and sibship, we find substantial evidence favouring no sex difference in total BNST volume. We recommend that researchers exercise caution when reporting evidence of BNST sexual dimorphism, particularly when translating findings from rodent models in which the BNST may play a different, olfaction-focused, role.

Pregnancy per artificial insemination (P/AI) in yearling beef heifers averages approximately 50%, highlighting the need to improve the identification and selection of females with greater reproductive potential. Anogenital distance (AGD) has emerged as a potential indicator of reproductive capacity, as shorter AGD has been associated with greater P/AI in dairy heifers. However, whether AGD is associated with reproductive development and P/AI in beef heifers of different genetic backgrounds remains unclear. The objective of this study was to determine associations of AGD with puberty attainment and P/AI in yearling beef heifers. Three studies were conducted using Bos taurus (Study 1; n = 954), Bos taurus × Bos indicus (Study 2; n = 481), and Bos indicus (Study 3; n = 518) yearling heifers. Heifers were estrous synchronized using GnRH-based (Bos taurus) or estradiol/progesterone-based (Bos taurus × Bos indicus and Bos indicus) protocols and submitted to AI. At protocol initiation, AGD was measured from the anus to the clitoris (AGD-C) and to the dorsal commissure of the vulva (AGD-V). In Bos taurus heifers, both AGD-C and AGD-V were positively associated with body weight and age (P ≤ 0.02). In addition, AGD-C was positively associated with uterine tone, reproductive tract score, corpus luteum presence, estrus expression, and P/AI (P ≤ 0.05), whereas AGD-V tended to be positively associated with uterine tone, reproductive tract score, and estrus expression (P = 0.08). In Bos taurus × Bos indicus heifers, both AGD measures were positively associated with body weight, age, hip height, and uterine score (P < 0.05); but neither was associated with P/AI (P ≥ 0.10). In Bos indicus heifers, AGD-C was positively associated with age and hip height (P < 0.05) and quadratically associated with body weight (P = 0.008), whereas AGD-V was only associated with hip height (P = 0.001). Neither AGD measure was associated with P/AI (P > 0.10). Unlike observations in dairy heifers, greater AGD was not consistently associated with reduced reproductive performance and, in Bos taurus heifers, was positively associated with P/AI. These findings indicate that AGD is more consistently associated with growth and reproductive development than with reproductive outcomes and may reflect developmental status rather than serving as a predictor of reproductive performance in yearling beef heifers.