Ny forskning om jente- og kvinnehelse

Maternal perceived stress, mental health, and physiological dysregulation during pregnancy can alter the intrauterine environment, shaping infant development through fetal programming processes. Nonetheless, few longitudinal studies in low- and middle-income countries (LMICs) have jointly examined psychological and biological factors in relation to infant outcomes. This longitudinal study followed 146 Pakistani mother-infant dyads at early to mid-gestation (T1), mid- to late gestation (T2), and postpartum (T3). Maternal perceived stress, depressive symptoms, and social support were measured across all timepoints, whereas pregnancy-related anxiety and an allostatic load index of physiological dysregulation were measured during pregnancy. Infant developmental outcomes across five domains were assessed using the Ages and Stages Questionnaire (ASQ-3). Perceived stress at each timepoint, depressive symptoms at T1 and T3, and allostatic load at T1 were associated with poorer infant fine motor skills. Perceived stress at T3 was linked to poorer infant problem solving. Communication, gross motor, and personal-social skills in infants showed no associations. Higher T3 social support attenuated the relationship between prenatal perceived stress and fine motor skills. Moreover, an exploratory interaction showed that T1 allostatic load related to lower fine motor skills when T3 stress is high. Psychological and biological pathways may link maternal prenatal risk to infant fine motor development, with the postpartum environment possibly influencing whether prenatal vulnerabilities translate into delays. Interventions strengthening social resources and reducing postpartum stress may help disrupt intergenerational stress transmission in LMICs.

Triple-negative breast cancer (TNBC) is an aggressive subtype that lacks targeted therapy, and robust prognostic biomarkers remain scarce. L-type amino acid transporter 1 (LAT1/SLC7A5) drives tumor amino acid metabolism and proliferation, whereas CD163 + M2-like tumor-associated macrophages (TAMs) constitute a hallmark of an immunosuppressive microenvironment. We investigated the expression, clinicopathological associations, and prognostic significance of tumor LAT1 and CD163 + macrophage density in 172 patients with TNBC. LAT1 and CD163 were assessed by immunohistochemistry and dichotomized at the cohort median. High LAT1 expression was strongly associated with high histologic grade, larger tumor size, advanced stage, and elevated Ki-67 (all p <0.001) and predicted inferior overall survival (OS) and disease-free survival (DFS; both p <0.05). CD163 + macrophage density showed no association with conventional clinicopathological features. LAT1 and CD163 expression were weakly but significantly correlated (Pearson's r =0.191, p =0.012; Spearman's ρ =0.220, p =0.004). In multivariable analysis, the adjusted DFS associations of both markers were model-dependent: high CD163 was independently associated with DFS after adjustment for tumor size [hazard ratio (HR)=2.11, p =0.034] but only borderline after ordinal-stage adjustment (HR=1.87, p =0.076), and the LAT1 effect on DFS was likewise stage-dependent. For OS, high LAT1 remained independently prognostic after adjustment for stage and age (HR=3.6, p =0.02), whereas CD163 did not. These findings indicate that LAT1 and CD163 convey significant prognostic information in TNBC and support the further evaluation of LAT1-directed metabolic and macrophage-targeted therapeutic strategies.

Adequate analgesia after cesarean delivery is a priority in women with preeclampsia, in whom opioid-sparing strategies are desirable. Nonsteroidal anti-inflammatory drugs (NSAIDs) were historically avoided in hypertensive disorders of pregnancy because of a presumed effect on blood pressure, but randomized trials and meta-analyses have since shown no clinically meaningful blood-pressure effect, and current guidance supports their postpartum use when otherwise appropriate. Metamizole (dipyrone) is a non-opioid analgesic widely used in Brazil, Latin America, and parts of Europe, but its regulatory status varies internationally. It is not approved in the United States, and agranulocytosis is a recognized rare but potentially serious adverse reaction. European regulatory guidance also advises against its use during breastfeeding. No randomized trial has directly compared metamizole with an NSAID after cesarean delivery in women with preeclampsia. To compare metamizole and ibuprofen for analgesic effectiveness and short-term safety, with particular attention to blood pressure trajectory and renal function, after cesarean delivery in women with preeclampsia with severe features. Quadruple-blind (participant, care provider, investigator, outcome assessor), randomized, active-comparator, phase 4 trial at a tertiary maternity hospital in northeastern Brazil. Seventy-four women received oral metamizole 1 g or ibuprofen 400 mg every 6 hours for up to 5 days, with intravenous tramadol available as rescue analgesia. Co-primary outcomes, as prospectively registered, were postoperative pain-categorized as mild, moderate, or severe by visual analogue scale (VAS)-and acute kidney injury (AKI). Continuous VAS, the D1-to-D2 mean reduction in VAS, the clinically interpretable threshold VAS ≥4, the Faces Pain Scale-Revised, peri-incisional pressure pain thresholds by algometry, rescue analgesia, serial blood pressure, hypertensive episodes, laboratory values, satisfaction, and length of stay were secondary or supportive outcomes. Effects were estimated with risk differences, risk ratios, exact tests, Hodges-Lehmann differences, standardized effect sizes with Holm correction, and linear mixed-effects models. Thirty-eight women were allocated to metamizole and 36 to ibuprofen. The registered three-category pain distribution did not differ between groups on day 1 (exact P=.45) or day 2 (exact P=.55). Median VAS was 4 (IQR 2-5) in both groups on day 1 and 2 (IQR 2-4) versus 3 (IQR 2-4) on day 2; the mean D1-to-D2 VAS reduction was 1.0 (SD 2.1) versus 0.6 (SD 2.4), with a mean between-group difference in reduction of 0.36 points (95% CI -0.70 to 1.42; P=.50). Rescue analgesia on day 1 was required by 18.4% versus 38.9% (risk difference -20.5 percentage points, 95% CI -39.1 to 0.1). AKI occurred in 3 of 38 (7.9%) versus 1 of 36 (2.8%) (risk ratio 2.84; 95% CI 0.31-26.08; Fisher P=.62; risk difference +5.1 percentage points, 95% CI -7.4 to 18.2). Linear mixed-effects models showed no group-by-time interaction for systolic (P=.14) or diastolic (P=.18) blood pressure; robust GEE sensitivity analyses were concordant. Severe hypertensive episodes were rare in both arms. In this randomized trial, no clear between-group difference was detected in postoperative pain or blood-pressure trajectory. The trial was not designed as an equivalence or non-inferiority study. AKI was numerically more frequent with metamizole, but the estimate was highly imprecise; comparative renal safety remains uncertain and requires adequately powered studies.

Hypertensive disorders of pregnancy (HDPs) are major causes of maternal and perinatal morbidity. While observational studies suggest physical activity may reduce HDP risk, confounding and reverse causality limit causal inference. We conducted a two-sample Mendelian randomization study using genetic instruments for 11 activity traits from UK Biobank and outcome data for gestational hypertension and pre-eclampsia from FinnGen. Light do-it-yourself (DIY) activities were associated with lower risks of gestational hypertension ( β[Formula: see text] = -3.56, P = 0.002) and pre-eclampsia ( β = -3.54, P = 0.029). Aerobic exercise was associated with lower pre-eclampsia risk ( β = -3.56, P = 0.017). No significant associations were found for vigorous activity, moderate-to-vigorous activity, or the three specific sedentary behaviors examined (time spent using a computer, time spent watching television, and time spent driving). This study provides causal evidence that specific physical activities confer protection against HDPs. Genetically predicted light DIY activities were associated with lower risks of both gestational hypertension and pre-eclampsia, while aerobic exercise was associated with lower pre-eclampsia risk. The three sedentary behaviors examined showed no causal associations. These findings highlight light-intensity domestic activities and aerobic exercise as accessible strategies for HDP prevention in prenatal care.

Cervical cancer treatment faces challenges from chemotherapy resistance. Inducing ferroptosis is a promising strategy. Calycosin (Cal), an active component of Astragalus membranaceus , exhibits antitumor activity, but its role in cervical cancer, particularly regarding epithelial-mesenchymal transition (EMT) and ferroptosis, remains unclear. Cell Counting Kit-8, colony formation and Transwell assays assessed Cal's effects on cell viability, migration and invasion. Ferroptosis was evaluated by detecting reactive oxygen species (ROS), malondialdehyde, glutathione and ferrous iron (Fe 2+ ) levels, mitochondrial morphology and expression of ferroptosis-related proteins. EMT markers and signaling pathways (TGF-β/Smad and Hippo/YAP) were analyzed using western blot. TGF-β1 knockdown was used to investigate the functional link between EMT and ferroptosis in vitro and in vivo . Cal inhibited proliferation and induced ferroptosis in cervical cancer cells, evidenced by mitochondrial shrinkage, lipid peroxidation and altered glutathione peroxidase 4/solute carrier family 7 member 11/acyl-CoA synthetase long-chain family member 4 expression. However, Cal also promoted migration and invasion, upregulated mesenchymal markers, and activated TGF-β/Smad while inhibiting Hippo/YAP signaling. Importantly, TGF-β1 knockdown suppressed both Cal-induced EMT and ferroptosis, indicating a synergistic relationship. In vivo studies confirmed these findings, showing Cal inhibited primary tumor growth but promoted metastasis, effects attenuated by TGF-β1 knockdown. Cal exerts dual effects in cervical cancer: Inducing ferroptosis to inhibit growth while promoting EMT-associated metastasis via TGF-β/Smad and Hippo/YAP pathways. Crucially, Cal-induced EMT synergistically enhances ferroptosis sensitivity. These findings highlight the complex pharmacology of Cal and suggest that combining with EMT inhibitors may optimize its therapeutic potential while mitigating pro-metastatic risks.

A late-preterm girl (35 + 1 weeks; birth weight 2440 g) was born after preterm labor in the setting of meconium-stained amniotic fluid and a tight body cord. At birth, she presented with abdominal distension and right upper quadrant ecchymosis. Within hours, she developed progressive respiratory distress requiring escalation from continuous positive airway pressure to intubation in the setting of worsening abdominal distension. Gastric decompression yielded bilious fluid, and she was started on intravenous fluids and antibiotics. Initial radiographs demonstrated paucity of bowel gas without pneumoperitoneum or calcifications. After transfer to a tertiary neonatal intensive care unit for suspected intra-abdominal pathology, she was pale with sluggish capillary refill and had a tense, distended abdomen with absent bowel sounds. Laboratory evaluation revealed anemia and coagulopathy, and abdominal ultrasonography demonstrated massive ascites with internal debris and abnormal hepatic venous flow. Despite stabilization, abdominal distension progressed over several days. On day of life 4, thin dark-green fluid drained from the vaginal introitus in the setting of otherwise normal external genitalia and anorectal anatomy. What is the most likely diagnosis?

To examine the knowledge and perceptions of female pelvic floor disorders (PFDs) among men in active or former long-term relationships. Men 45 years and older previously or currently in a long-term (≥3 years) intimate relationship with a woman were recruited from a urology clinic. Respondents completed the validated Prolapse and Incontinence Knowledge Questionnaire, with supplemental questions assessing attitudes on PFDs. The primary outcome was knowledge proficiency in the pelvic organ prolapse (POP) and urinary incontinence (UI) domains, defined as ≥50% and >75% correct, respectively. Multivariable logistic regression analysis assessed factors associated with proficiency in both domains. Secondary outcomes included rates of high response confidence, defined as responding with "don't know" less than 50% of the time. Of the 134 respondents, 22% demonstrated proficiency in the POP and 13% in the UI domain, with median scores of 1/12 and 3.5/12, respectively. Employed men were more likely to demonstrate knowledge proficiency (POP: aOR 6.24, p <0.01; UI: aOR 6.94, p=0.024) and exhibit higher rates of response confidence (POP: aOR 5.39, p=0.01; UI: aOR 5.54, p<0.01), relative to retired men. Higher education, older age, and having a partner with POP were associated with proficiency in the POP domain only. Fewer than 25% of men felt they should be involved in treatment decisions related to PFD. Men in long-term relationships exhibited low PFD knowledge. Future research is needed to determine if a relationship exists between improved knowledge among male partners and care-seeking behavior among women with PFDs.

The Clinical Practice Guidelines: Pregnancy Care aim to ensure that women in Australia receive consistent, high-quality, evidence-based maternity care. We undertook an impact evaluation to assess the awareness, value and use of the Pregnancy Care Guidelines. We used mixed methods, involving online surveys and semi-structured interviews. Online surveys collecting both quantitative and qualitative data were distributed to (1) health professionals providing maternity care in Australia and (2) policy makers/decision makers involved in pregnancy care. They explored participants' awareness and use of the guideline, resources used to guide clinical practice and policy making, the perceived value of the guideline, and their perceived strengths, limitations and opportunities for improvement. Interviews were conducted with purposively sampled representatives to supplement the survey data, and further explore guideline use, strengths, limitations and opportunities for improvement. A total of 357 surveys were received and 12 interviews were conducted. Participants described the value of the guidelines in providing a strong, evidence-based foundation from which to guide pregnancy care in Australia. Awareness and use of the guidelines, however, was limited. Many participants felt that the guidelines do not adequately cover all the important areas of clinical practice for pregnancy care. The need for active dissemination, translation and implementation of the guidelines was emphasised, along with the need to ensure that recommendations are kept up to date. The Pregnancy Care Guidelines are a valuable resource for providers of pregnancy care in Australia. However more active promotion and support for implementation into practice are needed if they are to achieve their potential to improve care for women during pregnancy, and outcomes for mothers and babies. The findings of this impact evaluation will be used to inform the next updated version of these guidelines and their transition into living guidelines.

Pregnancies of unknown location (PUL) require repeated visits to exclude ectopic pregnancy (EP). We externally validated the M6P (with progesterone) and M6NP (without progesterone) risk models. In this prospective single-centre cohort (Rennes University Hospital, 2024-2026), consecutive women with a PUL and initial hCG of 25-3,510 IU/L were included. The models were applied directly, without the first progesterone step of two-step triage, at a 5% risk threshold, and were not available to clinicians. We estimated sensitivity, specificity, predictive values and AUC, and compared the models in women evaluable by both (exact McNemar and DeLong tests). Among 456 women included, 444 were analysable for M6NP (127 EP, 28.6%) and 252 for M6P (105 EP, 41.7%). Sensitivity was 96.2% (95% CI 90.6-98.5) for M6P and 96.1% (91.1-98.3) for M6NP; negative predictive values were 94.4% and 97.1%; specificities were 46.3% and 53.0%. In the 252 women evaluable by both models, sensitivity, specificity and AUC did not differ significantly (all p>0.5). Both models were highly sensitive but only moderately specific, and a low-risk result did not exclude EP. The absence of a significant difference does not demonstrate equivalence, and progesterone testing was not random. M6P and M6NP identify a low-risk subgroup of PUL; interpretation must integrate clinical and ultrasound findings. Prospective evaluation of risk-adapted follow-up is warranted.

Ageratina adenophora is an invasive plant known for its toxicity to livestock. Many advantageous endophytes, extracts, and metabolites with antibacterial, antioxidant, and anti-inflammatory properties have been identified from A. adenophora in recent years. However, there is little information about the antiproliferative activity of these plant resources. Therefore, this study aims to screen and identify endophytic fungi from Ageratina adenophora that show favourable antiproliferative properties in vitro. Firstly, putative strains antiproliferative activity were screened and identified using the Cell Counting Kit-8 (CCK-8) method, and the chemical constituents of the extract were characterized by LC-MS/MS analysis, then potential targets and pathways were predicted through network pharmacologyand further explored through molecular docking and in vitro experiments. Our results showed that, Alternaria alternata Y-13 endophyte exhibited potent antiproliferative activity at IC₅₀ value of (15.90 ± 2.54) μg/mL against HeLa S3 cells. The network pharmacology identified 157 potential targets, and 10 core genes including AKT1 and CASP3; KEGG enrichment revealed pathways such as cancer, PI3K-Akt, and apoptosis; the molecular docking suggested that theputatively annotated metabolites could bound to AKT1 and EGFR. In vitro experiments showed that Y-13 ethyl acetate extracts (EAE) regulated the expression of apoptosis-related genes and proteins. This is the first study to show that extracts from endophytic fungus, Alternaria alternata Y-13 isolated from A. adenophora exerts prominent antiproliferative effects against cervical cancer cells, providing preliminary insights into its potential molecular mechanisms and a basis for further investigation of its bioactive constituents.

To compare, using Bayesian network meta-analysis, the effectiveness and safety of treatments and embolic agents for symptomatic uterine fibroids. A PRISMA-compliant systematic review of randomized controlled trials (PubMed, Embase, Cochrane Library; inception through July 2026) compared, via two prespecified Bayesian network meta-analyses, (1) uterine artery embolization (UAE) with hysterectomy, myomectomy, magnetic resonance-guided focused ultrasound, microwave ablation, and laparoscopic uterine artery occlusion, and (2) embolic agents used during UAE. Primary outcomes were technical success and major complications for treatment strategies, and complete/near-complete fibroid infarction for embolic agents; reintervention was secondary in both networks. Twenty-three RCTs (N=2,055 women) were included. Technical success and major complication rates did not differ significantly across treatment strategies or embolic agents in the Bayesian analysis, though frequentist analysis showed slightly higher technical success with hysterectomy than UAE (RR, 1.09; 95% CI, 1.02-1.17). Myomectomy had significantly lower reintervention than UAE (OR, 0.21; 95% CrI, 0.10-0.40). Several Bayesian associations emerged for polyvinyl alcohol (PVA) particles versus tris-acryl gelatin microspheres (TAGM), including higher complete infarction (OR, 4.8; 95% CrI, 1.0-40), higher reintervention (OR, 5.3; 95% CrI, 1.4-28), and divergent findings with PVA700-900; none was reproduced in the frequentist analysis. UAE did not differ significantly from alternative strategies in procedural success or safety, but myomectomy showed greater durability. Evidence is insufficient to establish definitive embolic-agent differences. Treatment strategy appears to influence outcomes more than embolic material, supporting individualized selection and larger trials.

To assess the association between human papillomavirus (HPV) vaccination following cervical intraepithelial neoplasia (CIN) and subsequent invasive cervical cancer (CC) diagnoses. We conducted a retrospective cohort study using the TriNetX Global Collaborative Network. Patients diagnosed with CIN (ICD-10-CM: N87, N87.0, N87.1, D06) during 2020-2022 who underwent regular cervical screening (Z12.4) were compared according to subsequent HPV vaccination records. Propensity score matching (PSM) incorporated demographic characteristics, selected diagnosis, and cervical procedures. Outcomes were assessed for day 1 through year 3 after the CIN diagnosis. Patients with CC recorded before diagnosis were excluded. Exploratory analyses evaluated code-defined CIN1-2 and CIN3 subgroups. Matching yielded 7397 patients per cohort. After outcome-specific exclusions, 7194 vaccinated patients and 7233 comparators remained, with 47 and 92 CC diagnoses, respectively (HR 0.56, 95% CI 0.39-0.79; p=0.001). By CIN grade, a significant association was observed in CIN3 patients (HR 0.32; 95% CI 0.20-0.53; p < 0.001), but not CIN1-2 patients (HR 0.98; 95% CI 0.51-1.92; p=0.96). Recorded HPV vaccination was associated with fewer CC diagnosis overall and in CIN3 patients. Exposure misclassification, residual confounding, differential observation, and non-proportional hazards limit casual interpretation.

Complete gross tumor resection is an important prognostic factor in advanced ovarian cancer (AOC), and total parietal peritonectomy (TPP) is a key method to achieve it. Despite undergoing complete gross resection, some patients experience thoracic recurrence, which is associated with a poor prognosis. Clinicopathological factors associated with such recurrence remain unclear. We hypothesized that occult lymphovascular invasion within the subdiaphragmatic peritoneum, the lymphatic interface between the peritoneal and thoracic cavities, may be associated with thoracic recurrence. We retrospectively analyzed patients with International Federation of Gynecology and Obstetrics stage IIIB-IVB ovarian cancer who underwent complete resection using TPP. Clinicopathological factors evaluated were stage, neoadjuvant chemotherapy, homologous recombination deficiency status, and intraoperative macroscopic findings. The subdiaphragmatic regions were microscopically assessed for lymphovascular invasion using D2-40 and CD31 immunohistochemistry. Thoracic recurrence was analyzed using Fine-Gray model. Seventy-four patients were included: 47 (63.5%) and 27 (36.5%) had stage III and IV disease, respectively. Neoadjuvant chemotherapy was administered to 38 (51.4%) patients. Subdiaphragmatic lymphatic invasion (SLI) was detected in 37 patients (50.0%), including seven without macroscopic lesions; venous invasion was rare (n = 1). During a median follow-up of 30.9 months, 20 (27.0%) and 18 (24.3%) patients developed thoracic and abdominal recurrence, respectively. Thoracic recurrence was significantly higher with SLI (43.2% vs. 10.8%); SLI independently predicted thoracic recurrence (subdistribution hazard ratios, 16.5, 95% confidence interval, 5.1-53.9; p < 0.001). SLI was independently associated with thoracic recurrence after complete gross resection in AOC, supporting a potential transdiaphragmatic pathway of tumor dissemination.

To investigate the pro‑metastatic effects of low-dose bisphenol S (BPS) and characterize the underlying molecular pathway in breast cancer (BC). HER2‑amplified MMTV‑Erbb2 mice received BPS‑laced drinking water (50 μg/L) to assess tumor growth and metastasis. BC cell migration, invasion, and proliferation were evaluated after BPS treatment. RNA‑seq and bioinformatics identified key pathways. PINK1 or DRP1 knockdown, together with pharmacological inhibition of DRP1 (Mdivi‑1), were employed to verify the role of mitophagy in vitro and in vivo. Clinical relevance was assessed via immunohistochemistry and public databases (TCGA, GEO). Environmentally relevant BPS exposure accelerated BC progression in mice, increasing primary tumor burden, lung/liver metastasis and an EMT‑like signature (upregulated FN, MMP‑2, Snail; downregulated E‑cadherin) with elevated oxidative stress. In vitro, BPS promoted migration and invasion without affecting proliferation in MCF-7 and BT474 cells. RNA‑seq revealed transcriptomic changes; KEGG enrichment identified mitophagy as a central pathway. BPS induced mitochondrial dysfunction (depolarization, ROS accumulation, ATP depletion) and activated PINK1/Parkin‑mediated mitophagy (increased MAP1LC3B-II, reduced P62/TOM20). Genetic knockdown of PINK1 or DRP1, as well as pharmacological inhibition of DRP1 by Mdivi‑1, reversed BPS‑induced mitophagy, restored mitochondrial homeostasis (mitochondrial length and membrane potential), and suppressed the pro‑migratory and pro‑invasive phenotypes. In vivo, Mdivi‑1 attenuated BPS‑driven tumor progression and metastasis. Clinically, elevated DRP1 and PINK1 in BC tissues correlated with lymph node metastasis, advanced TNM stage, and worse overall survival. Environmental‑level BPS exposure promotes BC metastasis via DRP1/PINK1‑dependent mitophagy. DRP1 and PINK1 are identified as potential prognostic biomarkers and therapeutic targets for reducing cancer risk from environmental carcinogens.

We tested whether early pregnancy insulin resistance and insulin deficiency are associated with infant birthweight percentile and postpartum glucose in women with diabetes risk factors. This was a secondary analysis of data from the prospective Study of Pregnancy Regulation of Insulin and Glucose (SPRING). Participants were enrolled at 7-14 weeks' gestation and underwent a 2-hour oral glucose tolerance test (OGTT) with hourly glucose and insulin measures. Exposures were first-trimester (7-14 weeks' gestation) log-transformed insulin resistance and insulin secretory response, determined using the Matsuda index and Stumvoll first-phase estimate. Primary outcomes were birthweight percentile and 2-hour OGTT glucose at 6-24 weeks postpartum. Secondary outcomes included fasting, 30-min, and 1-hour OGTT glucose postpartum. We used covariate-adjusted linear regression models to quantify associations between standardized exposures and outcomes. Among 150 participants, greater first-trimester insulin resistance was associated with higher birthweight percentile (adjusted β: 5.11%, 95% CI: 0.04, 10.18 per 1 SD decrease in log Matsuda index), but not with postpartum glucose. Lower first-trimester insulin secretory response was not associated with birthweight percentile, but it was associated with higher postpartum 2-hour OGTT glucose (adjusted β: 13.96 mg/dL, 95% CI: 7.24, 20.69 per 1 SD decrease in log Stumvoll estimate), as well as glucose at the fasting, 30-min, and 1-hour post-OGTT time points postpartum. Insulin resistance and insulin deficiency in the first trimester are differentially associated with maternal and fetal outcomes. Assessing the underlying mechanisms of hyperglycemia in pregnancy may enable more personalized risk assessment.

Breast cancer is a heterogeneous malignancy shaped by genetic alterations and cytokine-mediated immune interactions. However, integrative characterization of cytokine-related regulators using genetic, single-cell, and computational approaches remains limited. This study aimed to identify genetically supported cytokine-related candidates in breast cancer, characterize their immune and cellular contexts, and explore their potential regulatory and therapeutic relevance. Bulk transcriptomic datasets were integrated to identify differentially expressed cytokine-cytokine receptor interaction-related genes, followed by two-sample Mendelian randomization (MR), functional enrichment, immune infiltration, single-cell RNA sequencing, CellChat analysis, in silico gene perturbation, AI-assisted compound screening, and molecular docking. A total of 882 differentially expressed genes and 20 cytokine-related candidates were identified. MR provided the most consistent support for CXCL10, with genetically predicted higher expression associated with increased breast cancer risk (OR = 1.112, 95% CI: 1.026-1.206, p = 0.010). PRLR was significant only in the IVW analysis and was therefore considered a candidate requiring further validation. The CXCL10/PRLR model achieved an AUC of 0.810 (95% CI: 0.774-0.846) for discriminating breast cancer from normal samples. CXCL10 was predominantly associated with immune-cell populations, interferon-related programs, and predicted chemokine communication. In silico perturbation, AI-assisted screening, and docking further generated computational hypotheses regarding CXCL10-associated regulation and candidate compounds. CXCL10 represents a genetically supported immune-associated candidate in breast cancer. Overall, the findings are computational and hypothesis-generating and require validation in independent cohorts and experimental models.

www.clinicaltrials.gov identifier is NCT06382948; EU Clinical Trials identifier is EUCT 2024-512926-27-00. What type of study is this? ADELA is a global, multicenter, double-blind, placebo-controlled, randomized phase III trial. The study is designed to compare the efficacy of elacestrant combined with everolimus versus elacestrant with placebo. Who is eligible for this study? Patients who are eligible for the trial are women (premenopausal, perimenopausal, or postmenopausal) and men with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Additionally, patients must have tumors with estrogen receptor 1 ( ESR1 ) mutations and have experienced disease progression on prior treatment with endocrine therapy plus a CDK4/6 inhibitor. What is the study looking at? ER+/HER2− advanced breast cancer often initially responds well to endocrine therapy, but over time cancer cells may develop resistance, making the disease more difficult to control. More effective endocrine therapy-based options are needed for patients whose disease has progressed after endocrine therapy and CDK4/6 inhibitor. The ADELA study specifically focuses on those patients, evaluating whether combining two medicines that work in different ways may help control the disease for longer than current treatment approaches. The primary objective is to determine whether the combination of elacestrant and everolimus, compared with elacestrant plus placebo, can prolong progression-free survival, which is the length of time that patients remain alive without their cancer growing, spreading, or getting worse after starting study treatment. More information can be found at ClinicalTrials.gov by searching for NCT06382948 or at euclinicaltrials.eu by searching for EUCT 2024-512926-27-00.

The combination of topotecan and bevacizumab is a treatment option for platinum-resistant ovarian cancer. However, the efficacy and safety of the standard 5-day topotecan regimen in real-world practice remain unclear. This study evaluated the clinical outcomes of 5-day topotecan plus bevacizumab in a heavily pretreated population. This two-institution retrospective analysis included patients with platinum-resistant recurrent ovarian, fallopian tube, or primary peritoneal cancers treated with a 5-day topotecan plus bevacizumab regimen. Progression-free survival (PFS), overall survival (OS), antitumor efficacy, and treatment-related toxicities were assessed. Cox proportional hazards models were used to identify the prognostic factors. Fifty-four patients were included. The median number of prior chemotherapy regimens was 3, and 85% had previously received bevacizumab. The median PFS and OS were 4.0 and 11.0 months, respectively. No clinical variables were significantly associated with PFS in univariate analysis; however, histological subtype was associated with PFS in the multivariable model. The objective response rate was 18.5%, and the disease control rate was 57.4%. Hematologic toxicities were frequent and severe: grade ≥ 3 neutropenia occurred in 81.5% of patients, and grade ≥ 3 thrombocytopenia occurred in 37.0%. Gastrointestinal perforation occurred in two patients. The combination of 5-day topotecan and bevacizumab showed limited clinical benefits and substantial hematologic toxicity in heavily pretreated patients with platinum-resistant ovarian cancer. This regimen may not provide an optimal balance between efficacy and tolerability, underscoring the need for prospective studies to identify patients who may benefit from and optimize treatment sequencing in this era of prior bevacizumab and PARP inhibitor exposure.

Trastuzumab deruxtecan (T-DXd) has shown remarkable efficacy in phase III trials in patients with HER2-positive early- and late-stage breast cancer and HER2-low/ultra-low metastatic breast cancer (mBC). However, toxicities remain prevalent and clinically relevant, leading to dose reductions/interruptions or discontinuation. A survey was conducted across oncologists in 13 countries worldwide to collect experiences in managing T-DXd-related toxicities, focusing on nausea/vomiting, fatigue, and interstitial lung disease (ILD) as key areas of clinical concern. Ninety-nine experts participated in the survey. Nausea and fatigue were the most common toxicities, reported by 91.9% and 94.9% of respondents, respectively. 5-HT3 receptor antagonists, NK1 receptor antagonists, and corticosteroids were "very often" prescribed for prophylaxis. The frequency of use of second‑generation 5‑HT3 receptor antagonists varied among respondents. Most frequently, they employed an NK1 receptor antagonist combined with corticosteroids and 5‑HT3 receptor antagonists. Forty-four percent of respondents prescribed 4‑drug regimens incorporating NK1 receptor antagonists and olanzapine to all patients with nausea/vomiting above grade 1 in the first cycle, 35% reserved them for high‑risk patients, and 21% used them for all patients from cycle one. For all respondents, patients receiving T‑DXd experienced fatigue, with 65% observing it in more than 60% of patients, and most considered nausea/vomiting and fatigue to moderately or significantly affect daily activities and quality of life. ILD was reported as rare or occasional and was generally monitored using computed tomography. Real-life management of T-DXd-related toxicities is complex and needs an ongoing comprehensive evaluation of patients before, during and after therapy, with a highly trained/skilled multidisciplinary team.

The association between excessive sugar intake and breast cancer risk has been considered, however, results are unclear. This study aimed to examine the association between high-sugar foods intake and breast cancer in a prospective cohort study. This study included 92,314 women aged 40-69 years from the Health Examinees-Gem (HEXA-G) study (2004-2013). High-sugar foods were defined as sugar-rich food groups identified from the food frequency questionnaire. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer risk according to high-sugar foods consumption were estimated using Cox proportional hazards models. A total of 713 breast cancer cases occurred over an average follow-up of 9.20 years. The top three foods contributing to total sugar intake were fruits (42.89%), Korean traditional tea (5.60%), and ice cream (2.51%). Overall, consuming more than two servings of total high-sugar foods per week was associated with a 28% higher risk compared to less than once per month (HR = 1.28; 95% CI 1.02-1.61, P for trend = 0.05), with particularly significant associations observed for sugary cereals and ice cream. Notably, fruit intake, which accounted for the largest proportion of dietary sugar intake in this population, was not associated with breast cancer risk. Higher consumption of high-sugar foods was associated with an increased risk of breast cancer, whereas fruit intake was not. These findings suggest that sugar sources, rather than total sugar intake alone, may be important when considering dietary strategies for breast cancer prevention.

Anger-related irritability is a leading reason for referral to child and adolescent mental health services. However, studies on longitudinal patterns of irritability typically rely on caregiver reports, yielding limited insights into youths' own experiences. Furthermore, there has been little focus on potential sex differences during the transition to adolescence. Using data from the Adolescent Brain Cognitive Development (ABCD) Study® (n = 9,411, 48% females), this study compared caregiver and youth reports of anger-related irritability from ages 9 to 13, focusing on a high-persistent irritability classification (defined as ≥2 'very true' and ≥1 'somewhat true' ratings of "hot temper" across time points) and examined sex differences. High-persistent irritability was reported by 5.1% of youths, whereas caregiver reports indicated 1.6%. Among four irritability classifications (low, low-to-moderate, moderate, and high-persistent) there was limited agreement between informants (Cohen's κ= 0.22, SE=0.01), particularly among females. This discrepancy was primarily driven by poor concordance on the latter three classifications, while agreement on the low class was comparatively greater. When females reported high-persistent irritability, 3.9% of their caregivers reported the same, compared to 9.5% among males. During the transition to adolescence, most youths experience low irritability levels, whereas a small minority display persistently high, anger-related irritability. Agreement between caregivers and youths on which individuals belong to this high‑persistent classification was low. These findings highlight the importance of incorporating youth self‑reports-particularly for females-because reliance on caregiver reports alone may miss critical aspects of the informant-specific longitudinal patterns of irritability.

The uniform biennial mammography approach currently used in Japan's population-based breast cancer screening program has limitations. We developed a radiomics-based machine learning method with feature-level transparency to analyze image-derived patterns associated with future breast cancer occurrence using Japanese screening mammograms. The dataset comprised 208 mediolateral oblique mammograms obtained at the Tsukuba Comprehensive Health Screening Center, including 104 pre-symptomatic screening mammograms from 104 women subsequently diagnosed with breast cancer and 104 mammograms from 104 women with no abnormal findings. The pre-symptomatic mammograms were acquired 2-6 years before diagnosis and showed no definite suspicious findings at screening interpretation. For the future breast cancer group, 128 × 128-pixel regions of interest (ROIs) were extracted from lesion-corresponding areas on pre-symptomatic screening mammograms. For the healthy group, ROIs were extracted from the entire breast region. Following the Image Biomarker Standardization Initiative, 185 radiomics features were calculated per ROI. The least absolute shrinkage and selection operator selected 11 radiomics features. Using these features, five classifiers were compared: decision tree, k-nearest neighbors, naïve Bayes, linear support vector machine, and regularized discriminant analysis (RDA). In patient-level 5-fold cross-validation repeated five times using common fixed partitions, RDA achieved the highest mean ROI-based AUROC of 0.872 ± 0.003. After hyperparameter optimization using the same repeated cross-validation partitions, the final model achieved a breast-level AUROC of 0.803 (95% CI, 0.693-0.894) on the independent evaluation dataset. These findings suggest that local radiomic patterns in pre-symptomatic screening mammograms may contain discriminative information associated with future breast cancer occurrence in a case-control setting.

Objective: Training in women's health topics is limited, impacting clinicians' preparedness to address sex-specific concerns. Little is known about the extent neuropsychologists receive structured education in these areas or their comfort with addressing women-specific neurocognitive concerns in practice. This study examined neuropsychologists' self-reported training exposure, clinical comfort, and objective knowledge regarding women's health. Method: A cross-sectional online survey was completed by neuropsychology trainees (29%) and professionals (34% early-, 20% mid-, 17% senior-career) recruited through listservs and social media. Demographics, self-reported training exposure and clinical comfort, and an objective 5-item knowledge quiz were collected. Descriptive statistics examined differences in comfort and knowledge by training, work setting, and career stage. Results: Participants ( n = 122) were predominantly white/non-Hispanic (84%) women (91%) in the United States (89%), with diverse professional roles and work settings. Results showed 59% reported no formal training and 41% reported "slight to no comfort" addressing women's health concerns. Although item-level accuracy on the knowledge quiz was high (68.03-95.08%), 48% of participants answered all items correctly; performance did not differ by training, setting, or career stage. Conclusions: Findings indicate limited formal training, low comfort addressing women-specific neurocognitive issues in clinical care but intact knowledge on common women's health questions. This gap may perpetuate sex-related disparities in patient care and research in this area. Formalized training initiatives are warranted to improve confidence and competence for neuropsychologists.

To evaluate the role of contrast-enhanced ultrasound (CEUS) in preprocedural target localization for cesarean scar pregnancy (CSP) and to assess the outcomes of ultrasound-guided local injection. This retrospective study included 31 patients with CSP who underwent CEUS prior to ultrasound-guided local injection. CEUS was used to identify the hypervascular implantation site. Methotrexate (MTX) (50 mg) was administered locally into the gestational sac, followed by targeted injection toward the implantation site. Serum β-human chorionic gonadotropin (β-hCG) levels and ultrasound findings were monitored during follow-up. Initial treatment success was defined as a satisfactory decline in β-hCG levels after a single injection without additional MTX. CEUS demonstrated earlier enhancement and higher peak intensity at the implantation site than in the surrounding tissues (all p < .001). The hypervascular implantation region delineated by CEUS was significantly larger than that detected by color Doppler imaging (p < .001). Initial treatment success was achieved in 26 of 31 patients (83.87%). The mean time to β-hCG resolution after tissue removal was 21.78 ± 6.96 days. A major complication occurred in 1 patient (3.23%), who required surgical intervention due to severe bleeding. CEUS improves visualization of the hypervascular implantation site and may facilitate target localization before ultrasound-guided local injection. This approach appears feasible and relatively safe for the management of selected CSP patients.

Preeclampsia (PE) is characterized by insufficient extravillous trophoblast (EVT) invasion, but the cytoskeletal mechanisms restraining EVT motility remain unclear. TMT-based placental proteomics identified the cytoskeletal adaptor PDLIM1 as markedly upregulated in PE. In primary trophoblasts and cell lines, PDLIM1 depletion remodeled the actin cytoskeleton and enhanced migration and invasion, whereas trophoblast-restricted Pdlim1 overexpression impaired trophoblast invasion and placental development in mice. Mechanistically, PDLIM1 bounds the rod domain of α-actinin-4 (ACTN4) and competitively displaced USP14, limiting ACTN4 deubiquitination and shifting ACTN4 toward RNF38-associated K48-linked ubiquitination and proteasomal turnover. Importantly, placenta-targeted chondroitin sulfate A-binding nanoparticles delivering Pdlim1 short hairpin RNA (shRNA) alleviated PE-like maternal and fetal phenotypes in mice. Collectively, these findings define a PDLIM1-USP14-ACTN4 proteostatic axis controlling trophoblast invasive homeostasis and identify PDLIM1 as a potential therapeutic target in PE.

To examine the clinical outcomes of tubal factor infertility (TFI) following combined laparoscopic-hysteroscopic surgery and evaluate the time to natural pregnancy, this retrospective study analyzed clinical data from TFI patients with isolated tubal obstruction treated at a Women and Children's Health facility in China. Tubal condition was evaluated using the Gerard Mage scoring system based on the extent of obstruction, integrity of the fimbrial mucosa, and tubal wall quality, with damage classified into four stages (I-IV). Among 174 patients with bilateral fallopian tube obstruction, the overall tubal recanalization rate was 89.7%. Recanalization rates were highest in stages I and II (95.8% and 94.1%, respectively) and lowest in stage IV (80%). Intrauterine pregnancy rates decreased with increasing tubal damage severity, and no pregnancies occurred in stage IV patients (P < 0.05). Preoperative hysterosalpingography showed a tubal obstruction rate of 59.2%, with 95% agreement between diagnostic and surgical findings. The sensitivity and specificity were 94.4% and 86%, respectively. Factors affecting tubal recanalization included early age at first sexual intercourse, pelvic inflammatory disease, history of uterine procedures, tubal ectopic pregnancy treatment, pelvic or abdominal surgeries, and multiple sexual partners (P < 0.05). These findings demonstrate that increasing tubal damage severity is associated with reduced recanalization and pregnancy rates, along with higher infertility and ectopic pregnancy risk.

Feeding practices in neonatal intensive care units (NICUs) are often compromised by limited lactation support and mother-infant separation. A Comprehensive Lactation Management Centre (CLMC) integrates counselling, bedside lactation assistance and donor human milk banking within the NICU. Evidence on the real-world operationalisation of such centres in tertiary care institutions in India remains limited. This study describes the operationalisation of a CLMC in a tertiary NICU and evaluates its effect on exclusive breastfeeding and structured counselling coverage through a before-after comparison. This retrospective implementation study was conducted in the NICU and CLMC of a public-sector tertiary centre with 4,200-4,500 deliveries annually. Baseline feeding and counselling practices (April-June 2024) were compared with those in the post-implementation period (July 2024-July 2025). Core components included structured lactation counselling, bedside milk expression support, a functional donor human milk pathway, daily multidisciplinary rounds and WhatsApp-based coordination. Feeding and counselling indicators during the baseline and post-implementation periods, monthly operational trends and donor profiles were analysed. The proportion of mothers receiving structured breastfeeding counselling rose from 87/353 (25%) to 1,613/1,841 (88%). Exclusive breastfeeding at discharge increased from 25/56 (45%) to 436/534 (82%). Over the implementation period, 541 neonates received pasteurised donor human milk (PDHM), and the peak monthly donation volume reached 30,009 ml. Early initiation of milk expression, together with hands-on demonstration and lactation counselling, appeared to drive the change. Mother-infant separation and perceived low milk supply remained persistent barriers. CLMC establishment was associated with improved exclusive breastfeeding and structured breastfeeding counselling coverage. As a retrospective analysis, these findings reflect associations rather than causal effects. Sustaining these gains requires ongoing lactation support and system-level coordination.

To examine whether the association between interpregnancy interval and adverse live-birth outcomes differs by the outcome of the preceding pregnancy. We conducted a retrospective population-based cohort study of singleton live births in the 50 U.S. states and the District of Columbia in 2024 (final Natality Public Use File) with at least one previous pregnancy and a classifiable most recent prior pregnancy outcome (live birth vs other outcome). Derived interpregnancy interval was categorized as <6, 6-11, 12-17, 18-23 (reference), 24-59, and ≥60 months. The primary outcome was preterm birth (<37 weeks); secondary outcomes were low birth weight, very low birth weight, neonatal intensive care unit (NICU) admission, and a composite adverse outcome. Modified Poisson regression with robust variance estimated adjusted risk ratios (aRRs) and tested the interval × prior-outcome interaction. Of 1 995 754 births, 420 882 (21.1%) followed a non-live-birth outcome. The association between interval and preterm birth differed by prior outcome (interaction P < 0.001). After a prior live birth, risk was U-shaped (<6 months: aRR 1.61, 95% confidence interval [CI]: 1.57-1.66; ≥60 months: 1.30, 1.27-1.33). After another outcome, intervals <6 months were not associated with increased risk (aRR 0.90, 0.87-0.94), although risk exceeded that after a live birth at every interval of 6 months or longer. Findings were similar for secondary outcomes and robust in sensitivity analyses, including adjustment for parity. The association between interpregnancy interval and adverse outcomes of the subsequent live birth depends on the outcome of the preceding pregnancy and should not be interpreted uniformly across prior pregnancy outcomes.

Our objective was to conduct an exploratory assessment of the incidence and factors associated with severe postpartum hemorrhage (PPH) in women with posterior low-lying placenta and prior cesarean without prenatal suspicion of placenta accreta spectrum (PAS). The study population was derived from the PACCRETA population-based study conducted in the 176 maternity units of 12 French regions from November 2013 through October 2015. All women with posterior low-lying placenta and prior Cesarean without prenatal suspicion of PAS were included in this analysis. The main outcome measure was a composite criterion of severe PPH defined by either estimated blood loss of ≥1500 mL, transfusion of 4 or more units of packed red blood cells, embolization, or surgical treatment. Of the 520 114 women in the source population, 75 met the inclusion criteria (0.14 per 1000 women; 95% confidence interval [CI] 0.11-0.18). Among these women, severe PPH occurred in seven (i.e., severe PPH incidence of 9.3% [95% CI 4.2-18.9]). Unsuspected PAS was diagnosed at delivery in four women of the study population (5.3%). Without these cases of PAS, the severe PPH incidence was 7.0% (95% CI 2.6-16.3). Factors associated with severe PPH were unsuspected PAS diagnosed at delivery (severe PPH incidence of 50% vs. 7%, P = 0.04) and placenta-os distance 1-9 mm compared with 10-19 mm (severe PPH incidence of 19% vs. 0%, P = 0.03). About 1 in 11 women with posterior low-lying and prior cesarean without antenatal suspicion of PAS has severe PPH. Factors associated with severe PPH are unsuspected PAS diagnosed at delivery and 1-9 mm versus 10-19 mm placenta-os distance. These associations should be considered exploratory and require confirmation in larger studies.

Beta-thalassemia can adversely affect pregnancy, but the impact of alpha-thalassemia is less studied. We assessed whether patients with symptomatic alpha-thalassemia have similar pregnancy outcomes as patients with symptomatic beta-thalassemia. We conducted a population-based retrospective cohort study of 1,324,488 pregnancies in Quebec, Canada, between 2006 and 2022. The exposures were maternal symptomatic alpha-thalassemia, symptomatic beta-thalassemia, thalassemia trait, and other thalassemia syndromes. Primary outcomes were severe maternal morbidity, preterm birth, preeclampsia, and other pregnancy complications. We used log-binomial regression models to estimate adjusted risk ratios (RR) and 95% confidence intervals (CI) for the association between each thalassemia and adverse pregnancy outcomes. In total, 825 patients had symptomatic alpha-thalassemia, 681 symptomatic beta-thalassemia, 1,749 thalassemia trait, and 2,377 other thalassemia syndromes. Compared with no thalassemia, alpha-thalassemia (RR 3.05; 95% CI: 2.36-3.94) and beta-thalassemia (RR 2.52; 95% CI: 1.84-3.45) were associated with a greater risk of severe maternal morbidity. However, alpha-thalassemia was additionally associated with preterm birth (RR 1.45; 95% CI: 1.16-1.82), preeclampsia (RR 1.67; 95% CI: 1.27-2.20), and gestational diabetes (RR 1.79; 95% CI: 1.52-2.09). Beta-thalassemia was not associated with these outcomes, and associations were weak for thalassemia trait and other thalassemias. The findings suggest that symptomatic alpha-thalassemia is associated with a wider range of pregnancy complications than symptomatic beta-thalassemia and other thalassemia syndromes. However, symptomatic alpha and beta-thalassemia are both associated with severe maternal morbidity.