Limited efficacy of glioblastoma treatment with temozolomide (TMZ) due to resistance has prompted researchers to look for adjuvants capable of enhancing TMZ-associated cytotoxicity. The aim of our in vitro study was to evaluate such effects of erucic acid when combined with TMZ in human U87 MG cells. Cells were treated for 24 or 72 h with vehicle (control), TMZ (200 ng/mL), or TMZ plus EA (20, 40, 80, or 160 µg/mL). Cell viability was assessed using the MTT assay, membrane integrity with lactate dehydrogenase (LDH) release, and intracellular redox balance by measuring total antioxidant capacity (TAC) and total oxidant status (TOS). The mRNA expression of apoptosis-related genes (p53, p21, Bax, Bcl-2, Bcl-xL, and caspase-3) was analysed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Compared with the vehicle control, TMZ plus EA reduced cell viability and increased LDH release, with more pronounced effects at higher EA concentrations and at 72 h. These changes were accompanied by lower TAC and higher TOS, indicating a shift toward a pro-oxidant intracellular environment. At the transcriptional level, the combination induced increased pro-apoptotic Bax, caspase-3, p53, and p21 expression and reduced Bcl-2 and Bcl-xL expression. In conclusion, EA potentiated TMZ-associated cytotoxic responses in U87 MG cells with accompanying oxidative imbalance and apoptosis-related transcriptional changes.

Targeting transcriptional condensates is an emerging paradigm for cancer therapy. A key player is the transcriptional coactivator YAP (Yes-associated protein), which drives tumor-specific programs that fuel tumor progression and therapeutic resistance. Cyclin K, partnered with cyclin-dependent kinases (CDKs) CDK12/CDK13, is essential for transcription elongation, but its role in specific oncogenic programs was unclear. Here, we identify Cyclin K as an essential vulnerability across multiple cancer types. The CDK12/Cyclin K complex binds YAP via Cyclin K and forms a regulatory condensate to bridge YAP phosphorylation by CDK12. Such a phosphorylation at threonine-398 impedes YAP inhibition by its canonical LATS kinases, stabilizes YAP, and enables its further condensation with TEAD4 to stimulate YAP oncogenic activity. Coexpression of CDK12/Cyclin K and YAP predicts sensitivity to Cyclin K inhibitors in hepatocellular carcinoma cells and patient-derived xenografts. Thus, we define CDK12/Cyclin K as a critical regulator of YAP-driven transcriptional addiction and a biomarker for patient stratification who mostly benefit from therapies targeting the CDK12/Cyclin K-YAP axis.

Background and objectives Polycystic ovary syndrome (PCOS) is a heterogeneous endocrine-metabolic disorder with unclear etiology, influenced by genetic, environmental, and epigenetic factors. This study investigated the role of gene-specific DNA methylation and transcriptional regulation in North Indian women with PCOS stratified by body mass index (BMI). Methods Thirty women with PCOS (19 obese, 11 non-obese) and 10 healthy controls (age-matched to both PCOS groups; BMI-matched to non-obese PCOS) were recruited. BMI stratification was intentional to assess obesity-specific epigenetic modifications. Clinical, hormonal, and metabolic parameters were assessed. Promoter-methylation and mRNA expression of 17 candidate genes involved in epigenetic regulation, steroidogenesis, insulin signalling, and cell proliferation were analysed using methylation-specific PCR and qRT-PCR. Correlation matrices were constructed to evaluate associations between methylation and clinical traits. Receiver operating characteristic (ROC) based modelling was used to assess the predictive utility of methylation markers. Results PCOS-obese participants exhibited significantly elevated testosterone, Luteinising Hormone (LH), and cholesterol levels compared to controls. Vitamin D₃ deficiency was observed in both PCOS subgroups. Epigenetic analysis revealed hypermethylation and downregulation of TET1 and INSIG1, and hypomethylation-linked overexpression of SF1, CYP11A1, and cell cycle regulators. Correlation analyses revealed associative methylation expression signatures linked with key hormonal parameters (e.g., testosterone, LH/FSH ratio) and, to a lesser extent, metabolic traits (associative findings but not mechanistic conclusions). Interpretation and conclusions This integrative study highlights distinct methylation-expression signatures as hypothesis-generating markers that show statistical association with certain clinical traits, particularly in the obese-PCOS subgroup, but require validation in larger cohorts.

BACKGROUND Dermatomyositis is a rare autoimmune condition characterized primarily by proximal muscle weakness and cutaneous rashes, such as Gottron's papules and heliotrope rash, and is classified as a subtype of idiopathic inflammatory myopathies. While the clinical spectrum of dermatomyositis is broad, its initial onset as fulminant rhabdomyolysis (complicated by acute renal failure) is exceedingly rare. Such atypical presentations necessitate proactive clinical vigilance to ensure a prompt and accurate diagnosis. CASE REPORT Our patient was a 53-year-old woman who presented with progressive proximal muscle weakness, dysphagia, dysphonia, elevated creatinine kinase levels, hyperkalemia, and renal impairment. She was initially treated for rhabdomyolysis; however, due to increasing creatinine kinase levels and renal impairment, she required hemodialysis. During hospitalization she developed characteristic skin manifestations, including heliotrope rash and sleeve sign. Further investigation revealed pancreatic adenocarcinoma of the pancreatic head. CONCLUSIONS This report underscores the diagnostic difficulties in differentiating paraneoplastic-associated dermatomyositis from isolated primary rhabdomyolysis. It emphasizes the imperative of screening for occult malignancies in adult patients presenting with profound muscle necrosis and secondary kidney impairment. Identifying unusual clinical patterns of dermatomyositis early, combined with the rapid initiation of immunosuppressant and rigorous cancer surveillance, is essential for improving prognosis. This becomes paramount in scenarios in which the clinical presentation is suggestive of a paraneoplastic origin, notably pancreatic malignancy.

SEMA5B plays an important role in the maintenance of neural development and is highly environment dependent in tumorigenesis. The roles of SEMA5B in prostate cancer remain underexplored. This study investigates SEMA5B's functions in prostate cancer, revealing its role as a tumor suppressor transcriptionally regulated by androgen receptor and uncovering novel biomarkers and potential immunotherapeutic mechanisms. We analyzed SEMA5B's expression in cancer and its spatial association with cells in the tumor microenvironment using single-cell transcriptome sequencing datasets and spatial transcriptome sequencing samples. Using bulk RNA-seq data, we analyzed the immune infiltration of SEMA5B in prostate cancer. The association of SEMA5B with androgen receptor signaling and with metabolic pathways was evaluated by transcriptome and enrichment analysis. The phenotypes, cell cycle, apoptosis, and mitochondrial metabolic function of prostate cancer cell lines were further evaluated. SEMA5B regulation by androgen receptor was examined by gene knockdown, androgen/enzalutamide treatment, and epigenomics. Finally, the effect of SEMA5B on prostate cancer in vivo was detected by tumor xenograft model. Pan-cancer single-cell analysis revealed that SEMA5B's expression showed significant tumor type specificity and spatially correlated with immune cell infiltration. SEMA5B is associated with abundant lymphocyte and immune-inflammatory microenvironment in prostate cancer. SEMA5B overexpression inhibited tumor cell proliferation, migration, and invasion. Moreover, high SEMA5B is associated with oxidative phosphorylation and low glycolytic profile. SEMA5B expression is positively correlated with androgen receptor. Androgen receptor inhibition and androgen stimulation affected the expression of SEMA5B. ChIP confirmed the binding of androgen receptor to the SEMA5B promoter. Finally, SEMA5B was verified to induce cell cycle arrest and apoptosis and reduce tumor growth. SEMA5B inhibits tumor malignant phenotype and is associated with immune-inflammatory tumor microenvironment. SEMA5B can regulate mitochondrial oxidative metabolism and induce cell cycle arrest and cell apoptosis, inhibiting the growth of prostate cancer.

Lymph node (LN) metastases are a major driver of mortality across solid cancers, including thyroid carcinomas, which are known for high rates of nodal colonization. To elucidate the determinants of nodal spread, we isolated tumor-infiltrating leukocytes from primary thyroid tumors and matched metastatic LNs for single-cell RNA sequencing with validation by multiplex immunohistochemistry. Comparing the microenvironmental alterations between primary tumors and their LNs, we found that thyrocytes and tumor-associated macrophages down-regulate the expression of multiple inflammatory cytokine receptors, including TNFRSF12A and CX3CR1, upon LN colonization. LNs were associated with the induction of regulatory T cells to suppress T cell-mediated cytotoxicity compared to matched primary tumors. Notably, tumor-infiltrating lymphocytes within LNs demonstrated increased expression of activation markers, including interleukin-7 receptor (IL7R). High LN expression of IL7R was significantly correlated with improved outcomes and can serve as a biomarker in this heterogeneous disease. Our findings on the dynamic equilibrium within LN metastases may offer conserved mechanisms for nodal colonization across solid tumors.

Cysteine metabolism plays a crucial role in the growth and survival of non-small cell lung cancer (NSCLC), although the mechanisms governing its regulation are not fully understood. Here, we demonstrate that the RNA demethylase FTO is a therapeutic target that drives cysteine metabolism in NSCLC cells. Genetic or pharmacologic inhibition of FTO reduced cystine uptake and transsulfuration activity, leading to depleted intracellular glutathione, elevated reactive oxygen species (ROS), and ROS-mediated DNA damage and cell death. Mechanistically, FTO promotes the expression of the cystine uptake transporter SLC7A11 and the transsulfuration enzymes cystathionine β-synthase (CBS) and cystathionine γ-lyase (CTH) to promote NSCLC cystine uptake, transsulfuration activity, and survival. FTO inhibition increased lipid peroxidation, reduced tumor growth, and resulted in additive therapeutic benefit in combination with radiotherapy in multiple NSCLC xenograft models. Collectively, our study reveals a role for FTO in cysteine metabolism and highlights the therapeutic potential of targeting cancer epitranscriptomics and cysteine metabolism for NSCLC therapy.

Excessive dynamic airway collapse (EDAC) is defined as a pathological expiratory reduction of ≥ 50% in the cross-sectional area of the tracheobronchial lumen due to increased laxity of the posterior membranous wall while preserving the cartilaginous structure. EDAC frequently coexists with chronic obstructive pulmonary disease (COPD) and may contribute to persistent wheezing and dyspnea despite optimal medical therapy.

This cross-sectional study included 75 stable COPD patients recruited from the outpatient clinic of the Chest Department, Faculty of Medicine, Tanta University Hospitals, between August 2024 and August 2025. All patients underwent detailed history taking, general and local clinical examination, spirometry, dynamic multidetector computed tomography (MDCT) of the chest, and fiberoptic bronchoscopy. Multivariate logistic regression analysis was performed to identify predictors of EDAC.

EDAC was identified in 29 (38.7%) out of 75 COPD patients based on bronchoscopic assessment. Among these 29 patients, dynamic chest CT successfully diagnosed EDAC in 27 cases, resulting in 93.1% (95% CI: 77.2-99.2) sensitivity, 100% (95% CI: 92.3-100.0) specificity, and 97.3% (95% CI: 90.1-100.0) diagnostic accuracy. COPD patients with EDAC showed significantly higher BMI, mMRC, CAT scores, and exacerbation frequency compared with those without EDAC. Conversely, patients with COPD and EDAC showed significantly lower FEV1% predicted and FVC% predicted compared with those without EDAC. BMI, mMRC, and CAT score were independent predictors of EDAC.

EDAC should be evaluated in all COPD patients who present with more symptoms despite optimal COPD management. Also, obesity in COPD patients represents a contributing factor for EDAC, which should be carefully evaluated and managed. Dynamic CT demonstrated good diagnostic performance in detecting EDAC when compared with bronchoscop.

To assess the association between COVID-19 booster vaccination and hospitalisation and/or death due to COVID-19 among adults with immune-mediated inflammatory diseases (IMIDs).

Adults with IMIDs prescribed steroid-sparing immune-suppressing drugs in Clinical Practice Research Datalink Aurum linked to hospitalisation and mortality records were included. Cases were hospitalised for or died due to COVID-19. Controls were risk-set matched to cases. Exposures were number of COVID-19 booster vaccinations between 16 September 2021 and 13 March 2023; receipt of autumn 2021, spring 2022, autumn 2022 boosters; and time since last booster. Multivariable logistic regression was used. Adjusted OR (aOR) and 95% CIs and adjusted vaccine effectiveness (1 - aORs × 100%) were calculated.

We included 2178 cases and 17 750 controls (mean age 65.5 years; 60.2% women). Hospitalisation and/or death due to COVID-19 was negatively associated with receipt of three (aOR (95% CI) 0.20 (0.15 to 0.28)), two (aOR (95% CI) 0.29 (0.23 to 0.36)) or one booster (aOR (95% CI) 0.56 (0.48 to 0.65), respectively, compared with no booster. The aOR (95% CI) across the booster cycles were: autumn 2021 (aOR (95% CI) 0.40 (0.32 to 0.50)), spring 2022 (aOR (95% CI) 0.52 (0.42 to 0.65)) and autumn 2022 (aOR (95% CI) 0.33 (0.25 to 0.43)). Hospitalisation and/or death due to COVID-19 was negatively associated with booster vaccination within 365 days compared with no booster vaccination. There was no statistically significant association for boosters received more than 365 days ago.

COVID-19 booster vaccination was associated with fewer hospitalisation and/or death due to COVID-19 among adults with IMIDs. These findings support regular booster vaccination in this high-risk population.

Pulmonary tuberculosis (PTB) and chronic respiratory diseases (CRDs) are closely linked. Affected groups present with similar symptoms and share many risk factors (eg, poverty-related factors, smoking, occupational exposures). PTB is itself an independent risk factor for chronic lung disease. However, in many high TB-incidence settings health services for these conditions are provided separately, with little integration of prevention, diagnosis or care.

We describe a transdisciplinary programme of research investigating strategies for integrated TB-CRD care in Arusha, Tanzania, Nairobi, Kenya and Lagos, Nigeria, using clinical, health economic, health systems and qualitative research methods. A prospective clinical cohort study will describe the burden and impact of non-TB respiratory disease (eg, asthma, chronic obstructive pulmonary disease, post-TB lung disease) among adolescents and adults presenting to primary and secondary health facilities with chronic cough who would normally be managed via TB care pathways. Health economics methods will explore patient costs of non-TB respiratory disease, facility-level costs of integrated TB/respiratory diagnostics and will develop a modelling framework to estimate the costs and consequences of integration more broadly. In-depth interviews, focus group discussions, observations and participatory methods will be used to explore lived experiences of chronic respiratory symptoms, disease and exposures among patients and providers, and to identify and address challenges around respiratory health and care. Lastly, existing TB and CRD healthcare services and systems in our three research sites will be described, and local, national and policy level understandings of 'integration' of TB and CRD care will be explored. Together, the findings of this work will be used to develop context-informed model(s) of integrated TB-CRD care and a theory of change and framework for evaluation in future implementation studies.

Ethical approval has been obtained from Imperial College London in the UK, the Scientific Ethics Review Unit in Kenya, University of Lagos in Nigeria and the National Institute of Medical Research in Tanzania. Findings of this study will be presented in research publications and symposia, and will be shared with local communities and stakeholders.