Polycystic ovary syndrome(PCOS) is increasingly recognized for its substantial depressive burden, however, the underlying mechanism remains unclear. In this study, the neuro-metabolic pathway was explored to unravel the mechanism in PCOS-related depression.

Participants recruited from the UK Biobank comprised a cross-sectional population, the outcome as female depression, with 2,826 individuals among whom 471 diagnosed with PCOS. Progressive regression, interaction and mediation analyses, linearity and threshold examinations, relative weight analysis and principal component analysis(PCA), as well as stratified analyses were conducted in this study.

The two brain magnetic resonance imaging(MRI) metrics as volume of grey matter in frontal orbital cortex(FOC GMVol) and mean thickness of caudalanteriorcingulate(CaudalAntCing Thk) showed prominent links with PCOS-related depression, with CaudalAntCing Thk serving as the final common executor to depression. FOC GMVol and CaudalAntCing Thk interacted with PCOS in a metabolic-dependent and a metabolic-independent way respectively. A PCOS×free androgen index(FAI)×FOC GMVol three-way interaction was observer only in normal body mass index(BMI) individuals with high FAI. The FOC GMVol-CaudalAntCing Thk association, correlated with concurrent increases in BMI and FAI, existed exclusively in non-PCOS. Metabolic factors exhibited mediating effects (BMI and FAI) and formed a network among which BMI served as a hub linking the antagonistic FAI and the auxiliary triglyceride-glucose index(TyG), while systemic immune-inflammation index(SII) acted as an independent risk factor irrelevant to PCOS. A two-tiered brain protective hypothesis was proposed against depression: neural compensation reflected the protective FOC GMVol-CaudalAntCing Thk coupling in non-PCOS, and protective threshold patterns of both FOC GMVol and CaudalAntCing Thk in PCOS, with FAI playing pivotal and distinct roles at both peripheral and central levels across the entire pathways.

Given the intricate neuro-metabolic correlates underlying PCOS-related depression, further studies were warranted and a synergistic therapeutic strategy of androgen suppression plus weight management might be considered.

Gastric adenocarcinoma characterized by deficient mismatch repair (dMMR)/high microsatellite instability (MSI-H) represents a distinct subtype with high tumor immunogenicity and inherent sensitivity to immune checkpoint inhibitors. While neoadjuvant dual immunotherapy or chemoimmunotherapy has demonstrated high pathological complete response (pCR) rates in locally advanced dMMR/MSI-H gastric cancer, evidence supporting neoadjuvant monotherapy with Cadonilimab remains scarce. Cadonilimab is a PD-1/CTLA-4 bispecific antibody. We herein present the case of a 72-year-old man with locally advanced gastric antral adenocarcinoma (cT3N0M0, dMMR/MSI-H, PD-L1 CPS = 30) who received three cycles of neoadjuvant Cadonilimab (625 mg, Q3W) followed by radical surgery. Postoperative pathological assessment confirmed a pCR (TRG0), with no residual tumor identified in the gastric specimen or any of the 32 dissected lymph nodes. This case offers compelling evidence that Cadonilimab monotherapy can induce a profound pathological response with a favorable safety profile, supporting its further investigation as a personalized neoadjuvant strategy for this disease subset.

The optimal timing of surgery after conversion therapy for initially unresectable hepatocellular carcinoma (uHCC) remains unclear. This study aimed to evaluate whether surgical timing can be optimized by integrating major pathological response (MPR), defined as residual viable tumor (RVT) ≤15%, with preoperative treatment duration.

This multicenter retrospective study enrolled patients with initially uHCC who underwent curative-intent hepatectomy after comprehensive conversion therapy at seven tertiary hospitals between January 2020 and December 2025. The prognostic cutoff for MPR was determined using restricted cubic spline (RCS) models. Patients were categorized into three groups according to the interval from initiation of conversion therapy to surgery: <12 weeks, 12-24 weeks, and >24 weeks. MPR rates, survival outcomes, and perioperative safety were compared among the three groups.

A total of 257 patients were included. RCS analysis showed that a higher RVT proportion was associated with increased risks of poor overall survival (OS) and recurrence-free survival (RFS), with the most pronounced change in risk observed at an RVT threshold of 15%. Therefore, RVT ≤15% was defined as MPR in this study. The overall MPR rate was 63.4% (163/257). MPR was an independent protective factor for both OS and RFS. The MPR rate increased progressively with longer treatment duration (41.3% in the <12-week group, 66.2% in the 12-24-week group, and 73.0% in the >24-week group). OS differed significantly among the three duration groups, whereas the difference in RFS was not statistically significant. The incidences of severe postoperative complications and high-grade adverse events were low across all groups and did not increase markedly with prolonged therapy.

RVT ≤15% may serve as a prognostically meaningful criterion for MPR after conversion therapy for uHCC. To balance the degree of pathological response, long-term survival benefit, and perioperative safety, a treatment-to-surgery interval of 12 to 24 weeks may be optimal.

To develop and externally validate an interpretable deep learning model for pre-treatment prediction of early clinically significant immune-related adverse events in patients with hepatocellular carcinoma receiving immune checkpoint inhibitor-based therapy.

We conducted a multicenter retrospective cohort study of patients with hepatocellular carcinoma receiving immune checkpoint inhibitor-based therapy, with atezolizumab plus bevacizumab serving as the representative regimen in this cohort. The study population was divided into a training cohort and an independent external validation cohort. Early immune-related adverse events were defined as clinically significant events occurring within three months after treatment initiation. Five prediction models were constructed using baseline clinical and circulating immunological variables obtained prior to treatment, including TabNet, logistic regression, random forest, extreme gradient boosting, and support vector machine models. Model performance was evaluated using discrimination, calibration, and clinical utility metrics, and model interpretability was assessed using feature attribution analyses.

Among all models, the TabNet model showed the most favorable overall performance profile, considering discrimination, calibration, clinical utility, and external validation performance. Calibration analysis showed good agreement between predicted risks and observed event rates, while decision curve analysis and clinical impact assessment indicated meaningful clinical utility across a range of threshold probabilities. Interpretability analyses identified the CD4 to CD8 ratio, serum immunoglobulin G level, albumin, platelet count, and the proportion of CD19-positive B cells as key contributors to model-predicted early immune-related adverse event risk. Risk-stratified feature clustering further suggested that immune-related features and host functional reserve may represent complementary dimensions associated with model-predicted early immune-related toxicity risk.

An interpretable deep learning model was developed and externally validated for pre-treatment prediction of early clinically significant immune-related adverse events in hepatocellular carcinoma patients receiving immune checkpoint inhibitors.

Relapse remains the most significant cause of mortality after allogeneic transplant for leukemia despite advances in understanding of disease biology and newer, targeted treatment modalities. Cure after allogeneic transplant is mediated through the graft-vs-leukemia effect, as donor immune cells recognize and reject leukemic cells, largely through recognition of mismatched HLA and/or minor histocompatibility antigens. There is growing evidence that adjuvant but non-engrafting cellular therapies, either alone or in conjunction with conventional allogeneic transplant, improves leukemia outcomes and immune responses to such therapies have also been described during solid-organ transplants and following double cord unit transplantation, and are there associated with clinical consequences. We review these immune responses induced by third party and non-engrafting leukocytes and suggest possible mechanisms for the action of such cells. We further suggest that improved understanding of the nature of such responses might allow development of transplant technologies to make allogeneic transplants both better and safer, by targeting the immune response of the allogeneic immune system more specifically to leukemia.

To explore oncology nurses' perspectives on performing cancer treatments with parenteral antineoplastic agents in patients' homes.

A descriptive qualitative study utilizing interviews.

Semi-structured interviews were performed with oncology nurses at a hospital oncology daycare ward between October and November 2022. The interview data were inductively analysed with thematic content analysis.

Five themes were identified: (1) Establishing rapport in the home environment, (2) The complexity of a home, (3) Adverse events-not practicalities, (4) Solitary nursing and (5) Planning enables performance. The nurses believed patients would benefit from home treatment with antineoplastic agents but were concerned about adverse events and working alone. For successful home treatments, nurses believed sufficient resources, education and support were necessary. Practicalities such as transporting, administering and waste handling were not considered complex. Neither did the antineoplastic agents handling seem problematic.

Although positive, especially from the patient perspective, the nurses identified concerns that need to be addressed before implementing oncology hospital-at-home services.

Working in different contexts than the hospital can lead to extended roles and further responsibilities for oncology nurses and possibly facilitate more person-centred care.

This study explored oncology nurses' perspectives on performing parenteral cancer treatments with antineoplastic agents in patients' homes. In general, the nurses were positive, but challenges were identified. The study provides insights into how healthcare developers can incorporate the needs of nurses when designing future hospital-at-home programmes.

COREQ guidelines were used.

No patient or public contribution. WHAT DOES THIS PAPER CONTRIBUTE TO THE WIDER GLOBAL CLINICAL COMMUNITY?: This paper can be used to create tools addressing barriers nurses might have working with hazardous antineoplastic agents in hospital-at-home environments. It emphasizes the importance of education, resources and support to provide nurses with an adequate and safe working environment, improving patient experiences and safety.

To examine temporal trends and demographic and geographic variation in population-level rates of deaths with both Alzheimer's disease (AD) and cancer recorded on death certificates among U.S. adults aged ≥ 65 years from 1999 to 2023.

A population-based descriptive time-trend study using multiple-cause-of-death data.

National mortality data from the CDC WONDER (1999-2023).

Death certificates for U.S. residents aged ≥ 65 years recording both AD (G30) and malignant neoplasms (C00-C97) were included. Age-adjusted mortality rates (AAMRs) were standardized to the 2000 U.S. population; age-group analyses used age-specific crude mortality rates. Joinpoint regression estimated annual percent changes (APCs) and average annual percent changes (AAPCs), with analyses stratified by demographic and geographic characteristics.

Annual deaths increased from 4764 in 1999 to 6240 in 2023, while the overall AAMR declined from 13.96 to 12.05 per 100,000 (AAPC -0.73%, 95% CI -1.39 to -0.06). Significant declines occurred among males, adults aged 75 -84 years, non-Hispanic Black populations, and residents of the Northeast and Midwest, whereas a significant increase occurred among Hispanic populations. Full-period trends among females and non-Hispanic Other populations were not statistically significant. Neither metropolitan nor nonmetropolitan areas showed a significant trend during 1999-2020.

The overall age-adjusted death-certificate mortality rate declined modestly despite increasing annual death counts, with descriptive variation across demographic and geographic groups.

The findings highlight the relevance of coordinated geriatric and oncology nursing assessment and care planning for older adults with complex health needs. Nurses may play an important role in identifying cognitive, functional, treatment-related, and caregiver needs and facilitating multidisciplinary care. These descriptive findings identify areas for clinical attention but do not demonstrate the effectiveness of specific nursing interventions. WHAT PROBLEM DID THE STUDY ADDRESS?: Limited evidence exists on long-term population-level trends in deaths with both AD and cancer recorded on death certificates. WHAT WERE THE MAIN FINDINGS?: The overall age-adjusted mortality rate declined modestly while annual death counts increased. Subgroup-specific trends varied, but no formal between-group comparisons were performed. WHERE AND ON WHOM WILL THE RESEARCH HAVE AN IMPACT?: The findings are relevant to clinicians, policymakers, and public health practitioners involved in the care of older adults with multimorbidity, particularly in underserved populations.

This study adheres to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines.

No Patient or Public Contribution. This study used publicly available, de-identified mortality data and did not involve direct patient or public participation.

Accurate detection of estrogen and progesterone receptors (ER/PR), HER2, and Ki-67 is essential for molecular classification of breast cancer and in deciding upon tailored treatment. In many low- and middle-income countries (LMICs), access to histopathology and immunohistochemistry (IHC) is limited. STRAT4, an automated RT-qPCR assay performed on the widely available GeneXpert platform, offers a potential alternative. We evaluated the performance of STRAT4 on core biopsy, unstained smear of fine-needle aspiration biopsy (FNAB-US), and cellblock samples compared with conventional IHC in 178 histopathology-confirmed breast cancer patients.

Matched core biopsy, cellblock, and FNAB-US samples were analyzed using STRAT4. Concordance with IHC for ER, PR, HER2, and Ki-67 was assessed using percentage agreement and kappa statistics. The effect of alternative dC_t cut-offs used in an earlier study was also examined. Molecular subtype classification derived from STRAT4 was compared with IHC-based classification.

Concordance between STRAT4 and IHC was high for ER across all sample types (κ: 0.78-0.86). PR detection showed substantial agreement for core biopsies (κ = 0.78) and cellblocks (κ = 0.63), but only fair for FNAB-US samples (κ = 0.53). HER2 detection showed moderate agreement (κ = 0.41-0.58), improving with modified cut-offs (κ = 0.57-0.66), especially for FNAB-US. Ki-67 concordance was low (agreement 58.9%-71.0%). Kappa values indicating agreement between molecular subtype classifications using STRAT4 on various samples and routine IHC were as follows: core biopsies = 0.60; cellblocks = 0.61; FNAB-US samples = 0.45.

Detection of ER from FNAB-US, cellblocks, and core biopsies using STRAT4 showed high concordance with IHC. However, the concordance was low to moderate for other markers.

To explore the perioperative changes in inflammatory-immune-nutritional indicators in patients with advanced gallbladder cancer (GBC), defined as American Joint Committee on Cancer (AJCC) Stage III-IV, and to assess whether individual indicators provide incremental prognostic information beyond conventional clinicopathological factors.

Patients with pathologically confirmed advanced GBC who underwent surgery at the Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, between 2010 and 2022 were retrospectively enrolled. Preoperative and postoperative Day 7 values of the albumin-to-alkaline phosphatase ratio (AAPR), albumin-to-globulin ratio (AGR), albumin-bilirubin score (ALBI), advanced lung cancer inflammation index (ALI), monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), prognostic nutritional index (PNI), and systemic inflammation response index (SIRI) were calculated. Perioperative dynamic changes were compared, and Cox proportional hazards models were constructed to evaluate the incremental prognostic value of these indicators.

Among 103 patients with advanced GBC, all eight inflammatory-immune-nutritional indicators showed significant changes between the preoperative period and postoperative Day 7. Several preoperative and postoperative indicators were associated with cancer-specific survival (CSS) in cutoff-based exploratory analyses. After the incorporation of these indicators into clinicopathological models, most extended models showed varying degrees of improvement in discrimination and goodness of fit.

In this single-center cohort, perioperative inflammatory-immune-nutritional indicators exhibit significant dynamic changes in advanced GBC and can improve, to a certain extent, the prognostic performance of models based on conventional clinicopathological characteristics. These indicators may serve as useful supplementary tools for risk stratification and individualized prognostic assessment in patients with advanced GBC.

Deep learning (DL) methods have shown strong performance in predicting dose distributions from patient anatomy and target structures; however, accurate dose prediction does not guarantee a deliverable plan after conversion into machine parameters and dose recalculation in the treatment planning system (TPS), motivating training objectives that explicitly couple prediction to deliverability. Lymphoma presents substantial clinical heterogeneity in target location, extent, and prescription/fractionation, so fast automated methods that produce deliverable plans are particularly valuable.

To investigate whether a deliverability-aware training framework improves the end-to-end deliverability of DL-generated intensity-modulated radiotherapy (IMRT) plans for lymphoma.

A retrospective single-institution dataset of 619 plans (571 patients; 2009-2021) was used. Clinical volumetric modulated arc therapy (VMAT) plans were converted to standardized 15-field coplanar sliding-window IMRT reference plans in Eclipse using automated scripting. Two DL approaches were compared: a baseline dose-only objective model (DL-DO) and a multi-objective model (DL-MO) trained with dose supervision, fluence supervision, and a dose-fluence-dose cycle-consistency constraint implemented via fixed inverse and forward networks. Predicted fluence maps were imported into the TPS, leaf-sequenced, and recalculated with AcurosXB without further optimization; plan quality was evaluated on a held-out test set (n = 61) using planning target volume (PTV) D₉₈, D₂, and D_max with paired Wilcoxon testing and Holm correction.

DL-MO produced significantly better machine-deliverable plans than DL-DO, improving coverage and reducing hotspots (median paired differences: +12.31 percentage points (pp) in D₉₈, -3.43 pp in D₂, and -3.18 pp in D_max; Holm-corrected p < 0.0001 for all). Mean ± SD PTV metrics were D₉₈ = 90.10 ± 3.74% vs. 78.59 ± 5.92%, D₂ = 106.28 ± 1.13% vs. 109.65 ± 2.40%, and D_max = 110.32 ± 2.20% vs. 113.27 ± 3.03% (DL-MO vs. DL-DO). DL-MO approached the TPS reference IMRT plans (D₉₈ = 91.62 ± 3.45%) with residual hotspot elevation.

Cycle-consistency training improves the end-to-end deliverability of DL-generated IMRT plans for heterogeneous lymphoma, yielding substantially better TPS-recalculated, machine-deliverable plans than conventional dose-only supervision while maintaining sub-second fluence-map generation. However, statistically significant differences from the TPS reference remained for D₉₈, D₂, and D_max.