Myelodysplastic syndromes (MDS) are among the most common hematological malignancies. Polycythemia vera (PV) is a myeloproliferative disorder that causes the neoplastic proliferation of hematopoietic progenitor cells. Limited data exist on the population-level burden of MDS and PV globally. This ecological study utilized publicly available data from the Hospital Episode Statistics database in England and the Patient Episode Database for Wales for the period from April 1999 to April 2020. The hospital admission rate was 71.6% (from 72.62 [95% confidence interval [CI]: 71.89-73.35] in 1999 to 124.60 [95% CI 123.71-125.50] in 2020 per 100,000 persons, trend test, P < .05). MDS and PV-related admissions increased by 85.3% and 24.2%, respectively. In males, the admission rate increased by 86.1% (from 88.36 [95% CI: 87.21-89.52] in 1999 to 164.48 [95% CI: 163.02-165.94] in 2020 per 100,000 persons), whereas in females, there was an increase of 48.5% (from 57.62 [95% CI: 56.71-58.53] in 1999 to 85.55 [95% CI: 84.51-86.60] in 2020 per 100,000 persons). During the past 21 years, there has been a substantial rise in MDS and PV-related hospital admissions in England and Wales. Further studies are needed to establish the population factors contributing to these trends in order to inform public health measures.

This study aims to identify programmed cell death (PCD)-associated genes linked to breast cancer prognosis for the construction of a prognostic model. Transcriptomic and clinical information was imported from the The Cancer Genome Atlas (TCGA) and GEO databases. Modulatory genes related to 18 types of PCD were evaluated. Furthermore, the TCGA and GEO datasets were employed as the training and validation datasets, respectively. A risk score prognostic model based on PCD-related genes was generated via univariate, LASSO, and multivariate Cox regression analyses. Further, differences in drug sensitivity, tumor mutation burden (TMB), immune-related pathways and cell infiltration, and immune checkpoints were compared between high-risk and low-risk cohorts to elucidate the clinical applicability of the model. Lastly, the model gene's expression was verified by RT-PCR. The data revealed 1480 PCD-related genes from the TCGA breast cancer gene expression matrix. Differential expression analysis identified 186 differentially expressed PCD genes. Furthermore, a prognostic model was generated according to the risk scores using multivariate Cox regression. The model comprised 8 PCD-related genes (BRSK2, CD24, IFNG, LAMB3, PDX1, PMAIP1, SLC7A11, and TRIML2). Moreover, breast cancer cases were divided into high-risk and low-risk cohorts per the median risk score. The results indicated that low-risk patients had better prognoses, and the model showed good predictive performance in the GEO validation cohort. The area under the curve values were 0.819, 0.731, and 0.674 for the nomogram's 3, 5, and 8 years overall survival, respectively. Functional enrichment analysis revealed that the prognostic model was markedly linked with the modulation of the immune microenvironment and tumor progression in breast cancer. Immune infiltration assessment revealed that low-risk patients had increased activity in immune-related pathways and infiltration of immune cells. In addition, the low-risk cohort had lower TMB and elevated immune checkpoint-related levels. Correlation analysis between immune checkpoints and risk scores indicated that low-risk patients were more responsive to immunotherapy. Drug sensitivity analysis showed variations in the IC50 values between the risk cohorts, suggesting potential variations in drug efficacy across different risk cohorts. Gene expression was verified by RT-PCR.A prognostic risk model for breast cancer based on 8 PCD-related genes was constructed and its predictive value was validated. The established model may provide novel biomarkers and effective therapeutic targets for breast cancer diagnosis and treatment.

BackgroundArtificial intelligence (AI) increasingly supports clinical decision making. ChatGPT-5 (OpenAI, San Francisco, CA) and OpenEvidence (OpenEvidence Inc, Miami, FL) are regularly used by physicians, yet the limits of their reliability in decision-making remain poorly defined. This study evaluated both platforms against the National Comprehensive Cancer Network® (NCCN) Guidelines for Rectal Cancer to define where AI tools perform well and where they fall short.MethodsThe NCCN Guidelines for Rectal Cancer (Version 2.2025) were reviewed. Three questions were generated per decision-making page and classified into workup/diagnosis, treatment, and surveillance domains, yielding 138 clinical scenarios. Both platforms were queried. Responses were scored independently by two physicians on a 5-point Likert scale (5 = completely correct; 1 = absolutely incorrect). Two performance thresholds were defined: Correctness (≥3) and Accuracy (≥4). Proportions were compared with Fisher's exact test and score distributions with the Mann-Whitney U test.ResultsBoth platforms demonstrated high overall guideline concordance. ChatGPT-5 achieved Correctness in 136 (98.6%) and Accuracy in 116 (84.1%), compared to 128 (92.8%) and 112 (81.2%) for OpenEvidence, respectively. Overall Correctness favored ChatGPT-5 (P = 0.035), while Accuracy showed no significant difference (P = 0.634). Mean Likert scores were 4.57 vs 4.37 (P = 0.089). Both platforms achieved >90% Correctness across all domains.ConclusionBoth platforms demonstrate reliable identification of the broad direction of care but exhibit important limitations in completeness, nuance, and the handling of preference-sensitive decisions. These findings define the appropriate role of AI-assisted decision support as an adjunct to, rather than a substitute for, multidisciplinary review in rectal cancer management.

Objectives: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer. Mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK), as well as protein kinase B (AKT), are potential therapeutic targets for TNBC. Programmed death-ligand 1 (PD-L1) is implicated in TNBC progression and is associated with AKT and ERK signaling pathways. In addition, reactive oxygen species (ROS) act upstream of MAPK/AKT and PD-L1. In this study, we aimed to clarify the role of PD-L1 in TNBC progression and to delineate the underlying signaling mechanisms. Methods: Western blotting and reverse transcription-polymerase chain reaction were used to analyze protein and mRNA levels, respectively. Transwell migration and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays were used to assess cell migration and proliferation, respectively. Results: The ERK inhibitor (PD98059) suppressed MDA-MB-231 cell migration but not proliferation, whereas PD-L1 siRNA and the ROS scavenger dithiothreitol (DTT) reduced both cell migration and proliferation. However, PD-L1 siRNA and DTT did not reduce the activities of ERK, JNK, or AKT. Whereas PD98059 and DTT suppressed PD-L1 protein expression, PD-L1 mRNA expression could be reduced by DTT only. Taken together, ROS and ERK may activate different pathways to regulate PD-L1 expression and MDA-MB-231 cell progression. Consistently, DTT combined with PD98059 additively inhibited MDA-MB-231 cell migration. Similar observations were noted in another TNBC cell line, Hs578T, which exhibits motility, but not in MDA-MB-453 cells, which lack motility. Conclusion: Since PD-L1 appears to function downstream of ERK and ROS and is required for TNBC progression, co-targeting both ERK and ROS signaling pathways may represent a promising therapeutic strategy for TNBC.

Backgrounds: Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with a unique tumor microenvironment, and while Programmed cell death protein 1/Programmed cell death ligand 1 (PD-1/PD-L1) blockade represents a standard immunotherapy, most patients develop primary or acquired resistance, with few alternative immunotherapeutic targets currently available. Therefore, we aimed to identify potential immune checkpoint-related molecules involved in TNBC-macrophage crosstalk, clarify the underlying molecular mechanism mediated by small extracellular vesicles (sEVs), and provide a theoretical basis for the future development of novel immunotherapeutic targets against TNBC. Methods: Single-cell RNA-sequencing (scRNA-seq) datasets for various breast cancer subtypes were used. Pseudotime trajectory, cell‒cell communication and Tumor Immune Estimation Resource 2.0 (TIMER2) analyses were conducted to characterize the tumour microenvironment (TME). Immunochemistry and immunofluorescence were used to confirm the results of the above analyses. Single-nucleus RNA sequencing (snRNA-seq) was conducted on three pairs of TNBC tumour and adjacent normal tissues. The functions of tumour-associated macrophages (TAMs) and sEVs in TNBC metastasis were explored by Western blotting, flow cytometry and cell-based experiments. Results: A total of nearly 60,000 high-quality single cells were subjected to scRNA-seq analysis, from which seven major cell types were identified. An overall increase in immune cell proportion was observed in TNBC compared with other subtypes, with the immune cell fraction in TNBC tissues being ~1.8-fold higher than that in luminal A/HER2+ subtypes (p < 0.001). Cell‒cell communication analysis indicated that TNBC cells mainly interact with macrophages. Interestingly, HAVCR2, an immune checkpoint, is expressed mainly in macrophages in the TNBC TME. HAVCR2 is associated with macrophage pseudotime progression in TNBC, which was validated by immunofluorescence staining. Moreover, analysis of The Cancer Genome Atlas (TCGA) bulk RNA-seq data revealed that HAVCR2 expression is significantly correlated with M2-like macrophage gene signatures and computationally inferred macrophage infiltration levels in TNBC, and this tissue-level transcriptional correlation is associated with poor patient prognosis. Notably, bulk RNA-seq data cannot define discrete cell subsets, and the identification of HAVCR2+ M2 macrophage subsets was independently validated by scRNA-seq and snRNA-seq at the single-cell level. Furthermore, treatment with TNBC-derived sEVs is associated with concurrent increases in the expression of HAVCR2 and M2-associated markers (CD163, CD206) in macrophages. These findings reflect a correlative association rather than a demonstrated causal or regulatory relationship between HAVCR2 and M2-associated marker upregulation. Conclusion: sEVs derived from TNBC cells are associated with the upregulation of M2-associated markers and concomitant HAVCR2 upregulation in macrophages, both of which correlate with TNBC progression and metastasis. We propose that HAVCR2 may serve as a candidate prognostic marker associated with M2-like macrophage features in TNBC, and these foundational in vitro findings from Human acute monocytic leukemia cell line (THP-1) macrophages warrant further validation in primary human monocyte-derived macrophages and in vivo TNBC models.

Background: Guanylate kinase 1 (GUK1) is crucial for nucleotide metabolism, yet its impact on breast cancer (BC) progression remains poorly defined. The objective of the present study is to investigate GUK1 as a prognostic biomarker and therapeutic target. Methods: We employed a multi-omics approach integrating The Cancer Genome Atlas (TCGA) data, machine learning algorithm, High-Definition spatial transcriptomics (Visium HD), single-cell profiling, molecular docking and experimental validation including in vitro knockdown models and Surface Plasmon Resonance (SPR). Results: LASSO regression identified GUK1 as a key metabolic driver. High expression correlated significantly with poor survival and was most pronounced in Human Epidermal Growth Factor Receptor 2 (HER2)-positive and triple-negative subtypes. Spatial transcriptomics revealed GUK1 strongly colocalizes with expanding cancer cell nests, intensifying with disease stage. Single-cell analysis linked GUK1 overexpression to an immunosuppressive microenvironment enriched in exhausted T-cells. Clinically and molecularly, TP53 mutations are highly associated with HSF1 promoter hypomethylation and subsequent HSF1-mediated GUK1 upregulation. We experimentally confirmed this axis, showing that HSF1 or GUK1 knockdown significantly impaired cell migration and suppressed mTOR signaling. Furthermore, while high GUK1 levels predicted resistance to CDK4/6 inhibitors, they enhanced sensitivity to the PI3K/mTOR inhibitor Apitolisib. This therapeutic vulnerability was validated by SPR, which confirmed high-affinity binding between GUK1 and Apitolisib, and by cell viability assays where GUK1 depletion induced drug resistance. Conclusion: GUK1 serves as a robust prognostic biomarker regulated by the TP53-HSF1 axis. Its distinct spatial patterns, immune-suppressive associations, and experimentally validated role in modulating PI3K/mTOR inhibitor sensitivity position GUK1 as a promising target for precision oncology in invasive BC.

To summarize the available evidence on the association between endocrine disruptors and polycystic ovary syndrome (PCOS).

A search was conducted in the MEDLINE (via PubMed); Science direct, Scopus and LILIACS databases for relevant studies published between 2013 and 2025. The inclusion criteria covered cohort, cross-sectional, and case-control studies published in English or Spanish. Data extraction and quality assessment were performed using the Joanna Briggs Institute (JBI) checklists, and the results were synthesized descriptively. The articles retrieved were reviewed by two evaluators; 49 were chosen for full-text review, 30 were included in the qualitative analysis.

This systematic review found that bisphenol A (BPA) is the most frequently associated endocrine disruptor with PCOS. This compound interferes with steroidogenesis by mimicking estrogen, which may contribute to insulin resistance and androgen dysfunction. Additionally, phthalates were found to be related to elevated androgen levels and ovarian dysfunction, while triclosan and cadmium were associated with hormonal imbalances affecting ovarian reserve and testosterone levels. Furthermore, perfluoroalkyl and polyfluoroalkyl substances (PFAS) were linked to reduced ovarian reserve and a higher prevalence of PCOS.

The results of this review highlight the role of endocrine disruptors in the pathophysiology of polycystic ovary syndrome, emphasizing the need for further research to identify emerging disruptors and their potential mechanisms in the development of this disease. Therefore, it is crucial to adopt public health measures aimed at minimizing exposure to these compounds, particularly in women who are more susceptible to developing PCOS.

Dysphagia is associated with increased risk of stroke-associated pneumonia (SAP). The multifactorial pathophysiology of SAP and the interplay of care processes make it challenging to unpack which components are associated with risk of SAP. The aim of the research was to capture contextual aspects of dysphagia management to build knowledge of care processes relevant to SAP.

The methodology was an ethnographic approach. The method was participant observation. Implementation of specialist swallow recommendations, positioning, and oral care processes of 10 stroke patients was observed around mealtimes during the first 72-h of hospital admission. Data was analysed thematically. People affected by stroke were involved in the data analysis process and in the co-generation of themes and implications for clinical practice.

Four themes were generated from the data: 1. Patient preparation for mealtimes and medications; 2. Variability in resources, knowledge and implementation of dysphagia care; 3. Swallowing and oral care are everyone's business; and 4. Communication about the person's dysphagia management plan and staff attitudes.

This research enhances understanding of environmental barriers and facilitators that shape how dysphagia care is enacted in acute stroke settings, and how variability in everyday practice may influence circumstances relevant to SAP risk. The findings highlight the role of communication processes, patient and carer information needs, staff awareness of dysphagia diets, mealtime preparation, oral care practices, and access to resources in supporting the implementation of swallowing management plans within routine care.

What is already known on the subject The pathophysiology of stroke-associated pneumonia (SAP) is multifactorial. Patients are most susceptible to SAP during their first 72 h post-stroke. Preventative measures to identify dysphagia as early as possible, such as early dysphagia screening and a specialist swallowing assessment, are associated with reduced risk of SAP. What this paper adds to the existing knowledge Increased understanding of how dysphagia care processes may impact on SAP. Identifies environmental barriers and facilitators to minimising potential risk of SAP, specifically relating to the implementation of the specialist swallowing assessment recommendations, positioning and oral care. Identifies areas for clinical improvement. What are the potential or clinical implications of this work? Swallowing management plans are complex and often only partially enacted, with key elements beyond diet and fluid modification frequently overlooked. Dysphagia management requires a genuinely multidisciplinary and system-wide approach, involving all ward staff and informed family and carers. Effective implementation depends on system-level factors which include: clear, consistent and up-to-date sharing of swallowing plans across all channels; staff, patient and carer education; access to appropriate resources; and supportive ward practices and attitudes.

CFTR modulators are a class of medications prescribed to people with cystic fibrosis (pwCF) who have certain genetic mutations. In 2019, elexacaftor/tezacaftor/ivacaftor (ETI) was approved by the FDA and led to significant health improvements for pwCF. Despite ETI showing significant health improvements compared to prior modulators, little is known about how ETI impacts the lived experience of pwCF.

This study explored how the implementation of ETI in cystic fibrosis treatment has impacted the lived experience of pwCF and what additional resources healthcare providers should be offering to their patients.

We conducted a qualitative study that recruited pwCF from an adult CF center who were over the age of 18 and had been on ETI for at least a year.

We conducted and recorded semi-structured interviews with participants over the Zoom platform. Dedoose was used to code the data and themes were constructed using inductive coding rooted in grounded theory.

Four themes were constructed from the data in this study: (1) "transformation in health" refers to the change in physical health the participants have noticed since starting ETI, (2) "future planning and opportunities" highlights new opportunities becoming available and a new desire to plan for the future, (3) "impact on relationships" describes how participants felt their relationships with their partner, family, and care teams, were impacted by ETI, (4)"new worries and struggles" describes new struggles and concerns that participants have faced.

The data from this study provide evidence that ETI has not only impacted pwCF on a physical level, but may also have an impact on relationships, mental health, and future planning. It also highlights the need for additional resources that CF care teams should be providing to their patients.

Older adults with drug-susceptible pulmonary tuberculosis (DS-PTB) face disproportionately poor treatment outcomes, but practical tools for risk stratification around the time of treatment initiation remain limited.

This retrospective cohort study evaluated the association between the laboratory-based frailty index (FI-Lab) and unfavorable treatment outcomes in adults aged ≥65 years with DS-PTB, who were treated between January 1, 2015, and December 31, 2024, at a tertiary academic medical center in the Republic of Korea. The FI-Lab score was derived from routine blood tests collected within 60 days before to 7 days after treatment initiation, and the primary outcome was a composite of death during treatment, treatment failure, or treatment discontinuation.

Among 627 patients, 119 (19%) experienced an unfavorable outcome. Those in the highest FI-Lab quartile had greater odds of an unfavorable outcome than those in the lowest (odds ratio 3.42, 95% CI 1.75-6.69; p < 0.001; p-for trend = 0.0002), after adjustment for age, sex, comorbidity burden, treatment delay, baseline medications, cavitary disease, and bacteriological status. Results were consistent across seven pre-specified sensitivity analyses and in the Cox proportional hazards model (hazard ratio 3.28, 95% CI 1.60-6.73; p = 0.001).

Higher FI-Lab scores were independently associated with unfavorable treatment outcomes in older adults with DS-PTB. Derived from routinely available blood tests, FI-Lab may offer a practical approach to frailty quantification around the time of treatment initiation, and prospective studies are needed to evaluate whether frailty-targeted interventions improve outcomes.