To develop and empirically characterize a domain-specific, block-structured annotation schema and an expert-annotated reference corpus for German-language head and neck squamous cell carcinoma (HNSCC) pathology reports.

We retrieved 631 pathology reports from 145 patients treated at University Hospital Würzburg between January 2021 and March 2024 and split them at the patient level into training, validation, and evaluation subsets. Reports were manually annotated using a hierarchical, span-based schema supporting overlapping and nested annotations. The resulting corpus contains 45 unique labels organized into clinically meaningful blocks and an average of 37-39 annotations per report across subsets. Label frequencies and normalized category distributions were broadly comparable across the three subsets. Fine-grained labels were predominantly applied within their designated blocks, indicating adherence to the intended block structure. The corpus provides a domain-specific reference resource for developing and evaluating structured information-extraction approaches for German HNSCC pathology reports.

Taxane-related chemotherapy-induced peripheral neuropathy (CIPN) is highly prevalent among breast cancer survivors and significantly impairs quality of life, yet established treatments are lacking. This study investigated the preliminary efficacy and safety of multimodal Japanese-style acupuncture and moxibustion (MJAM)-a program combining filiform needle acupuncture, non-insertive needle (Teishin) therapy, motion-style acupuncture, indirect moxibustion, hot pack application, and self-care instruction-for taxane-related CIPN.

In this single-center, single-arm study, we enrolled breast cancer survivors who had completed curative treatment for stage I-III breast cancer at least 3 months previously and who had moderate-to-severe taxane-related CIPN pain (BPI item 5 score of 4 or greater) at the time of enrollment. Participants received 12 weekly sessions of a standardized MJAM program. The primary endpoint was the change in Brief Pain Inventory (BPI) item 5 (average pain) from baseline to week 16.

Between October 2022 and April 2024, 30 women (median age 58.0 years) were enrolled. Median time since chemotherapy completion was 2.47 years. Mean baseline BPI item 5 score was 5.3 (SD 1.7). Twenty-eight participants (93.3%) completed the treatment. Nine participants (30.0%) experienced mild (grade 1) adverse events. BPI item 5 scores significantly decreased over time. Changes from baseline were -0.1 (95%CI, -0.6 to 0.3; p = 0.56) at week 4, -0.7 (95%CI, -1.2 to -0.2; p = 0.008) at week 8, -1.1 (95%CI, -1.7 to -0.6; p = 0.0003) at week 12, and -1.2 (90%CI, -1.7 to -0.8; p < 0.0001) at week 16.

MJAM was safe, feasible, and associated with a reduction in pain in breast cancer survivors with persistent taxane-related CIPN. A confirmatory randomized clinical trial is warranted.

UMIN-CTR UMIN000048478.

Objectives: YTH N6-Methyladenosine RNA Binding Protein F2 (YTHDF2) had been implicated in nasopharyngeal carcinoma (NPC) progression. Increasing evidence indicated that numerous circular RNAs (circRNAs) were involved in regulating tumor progression. However, how the regulation of circRNAs by YTHDF2 contributes to NPC progression remains to be uncovered. In this study, we aimed to elucidate the role and mechanism of YTHDF2-mediated circRNA regulation in NPC migration and invasion. Methods: YTHDF2 expression in NPC was assessed using GEO datasets and immunohistochemistry. Functional experiments were performed in HNE1 and 5-8F cells, with migration/invasion evaluated by wound healing and transwell assays, and epithelial-mesenchymal transition (EMT) markers by Western blotting. CircRNA candidates were screened through circRNA sequencing. CircRNA m6A modification was assessed by methylated RNA immunoprecipitation-quantitative PCR (MeRIP-qPCR). The SELECT method (single-base elongation- and ligation-based qPCR amplification) was used to identify the specific m6A modification site. RNA stability was measured by actinomycin D assay. circRNA-miRNA and miRNA-target interactions were validated by luciferase reporter assays. Results: YTHDF2 expression was upregulated in NPC tissues and was found to promote in vitro migration and invasion phenotypes. Mechanistically, m6A-modified circ_0015508 was recognized and degraded by YTHDF2. YTHDF2-mediated pro-migration and pro-invasion effects were reversed by circ_0015508. FOXN3 was identified as a target of miR-496. Circ_0015508 was found to sequester miR-496, thereby de-repressing FOXN3 expression. Conclusion: In this study, a potential oncogenic pathway was delineated in which NPC migration and invasion were facilitated by YTHDF2 via degradation of circ_0015508, thereby the sponging effect of miR-496 was abolished and FOXN3 expression was suppressed.

Background: Although epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibition produces substantial initial benefit in EGFR-mutant non-small cell lung cancer, durable disease control is frequently compromised by the emergence of drug-resistant tumor cells. We therefore examined whether loss of cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) supports the resistant phenotype by altering redox control and the cellular threshold for ferroptotic injury. Methods: The Gene Expression Omnibus (GEO) datasets GSE172002 and GSE236654 were analyzed to identify resistance-associated pathways. cGAS was depleted in parental cells and restored in resistant derivatives, followed by phenotypic, redox, mitochondrial, and signaling assessments in cultured cells and xenografts; pathway relationships were further examined by rescue experiments and structural modeling. Results: Bioinformatics analysis indicated significant alteration of DNA repair-related pathways in epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI)-resistant models. Resistant PC-9/GR and H1975/OR cells displayed increased half-maximal inhibitory concentration (IC₅₀) values and attenuated inhibition of phosphorylated EGFR (p-EGFR), Phosphorylated Protein Kinase B1 (p-AKT1), and phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) after matched EGFR-TKI treatment. In parental cells, EGFR-TKI exposure was associated with increased DNA damage, cytosolic double-stranded DNA (dsDNA) accumulation, cGAS induction, ferroptosis-related staining patterns, reduced glutathione (GSH), and increased malondialdehyde (MDA), whereas these changes were less evident in resistant cells and were partly attenuated by Ferrostatin-1. Functionally, cGAS knockdown was associated with enhanced proliferative, migratory/invasive, and xenograft growth phenotypes, together with a redox pattern consistent with reduced ferroptosis susceptibility. Conversely, cGAS overexpression in resistant cells produced opposite effects. Altering cGAS abundance redistributed total and Ser40-phosphorylated nuclear factor erythroid 2-related factor 2 (Nrf2) between cellular compartments and concurrently changed sirtuin 3 (SIRT3) abundance and deacetylase activity. Nrf2 or SIRT3 manipulation partially reversed cGAS-associated phenotypes. Conclusions: These findings identify low cGAS abundance as a feature of the resistant state and support its involvement in an Nrf2-SIRT3-dependent antioxidant program that raises the threshold for ferroptotic damage.

Surgical resection often leaves residual lesions that lead to tumor recurrence and high mortality across various cancer types, a challenge that is particularly pronounced in oral squamous cell carcinoma. Herein, we developed a sprayable hydrogel loaded with fusion cellular vesicles (Fus-CVs) and characterized its structural and mechanical properties for the prevention of postoperative tumor recurrence. Fus-CVs co‑express PD‑1 to engage PD‑L1 on tumor cells and CD36 to competitively bind oxidized lipids in the tumor microenvironment, thereby effectively reversing T cell exhaustion and restoring T cell effector function. Additionally, the sprayable hydrogel, formed by crosslinking sodium alginate (SA) with the ionic solution (calcium chloride, CaCl₂; manganese chloride, MnCl₂), enables sustained local delivery of Fus‑CVs to potentiate T cell‑mediated killing of residual tumor cells.

In vitro experiments and primary tumor model confirmed that Fus‑CVs specifically achieve dual targeting of PD-L1 on tumor cells and oxidized lipids in the tumor microenvironment, reverse T cell exhaustion and achieve combination therapy. In an established postoperative recurrence mouse model, the SA solution containing Fus-CVs and the ionic solution could be co-sprayed to rapidly form a conformal, uniform and stable layer on irregular tissue surfaces, enabling sustained local release of Fus-CVs and achieve effective tumor recurrence suppression.

Fus‑CVs-loaded sprayable hydrogel not only achieves dual functionality in immune checkpoint blockade and lipid metabolic regulation but also offers localized controlled release, and reduced systemic toxicity, thereby presenting a clinically translatable strategy for postoperative recurrence prevention.

Chronic obstructive pulmonary disease (COPD) is a leading global health concern, characterized by persistent airflow obstruction and a significant burden on quality of life. Smoking cessation is critical for COPD management, but nicotine addiction poses challenges. Emerging evidence suggests that melatonin may aid in addiction management, though its efficacy in COPD remains underexplored.

This randomized, triple-blind, controlled clinical trial evaluated the impact of melatonin on nicotine dependence and COPD outcomes over 180 days. Sixty male COPD patients with a history of smoking were randomized to receive melatonin (5 mg or placebo). Smoking behavior, psychological well-being, and hospitalization rates were assessed using validated scales.

Both groups exhibited reduced cigarette consumption and improved psychological scores over time, with no significant differences between groups. Hospitalization rates due to COPD exacerbations were lower in the melatonin group (4% vs. 24% in placebo), indicating a nonsignificant trend that warrants further investigation, although the difference was not statistically significant.

While melatonin did not significantly affect smoking cessation or psychological outcomes, the observed reduction in hospitalization rates should be interpreted cautiously as an exploratory finding. Larger, long-term, and adequately powered studies are needed to confirm these results and further investigate the potential role of melatonin as an adjunct therapy in COPD management.

Iranian Registry of Clinical Trials (IRCT): IRCT20190810044500N25.

Variation in pediatric respiratory physiotherapy assessment for asthma and dysfunctional breathing (DB) across NHS services creates inconsistency in clinical reasoning, workforce development, and data harmonization. We aimed to design and implement a standardized, evidence-informed assessment package to support physiotherapists working with children and young people (CYP) with asthma and DB.

Evidence from a previously conducted structured scoping review (PROSPERO ID: 112227) informed key assessment domains. A national collaborative of specialist pediatric respiratory physiotherapists (Kids' Cornerstone Collaborative) co-developed a standardized assessment proforma, competency framework (Agenda for Change Band 5-8), and supporting educational materials. An iterative, problem-driven implementation approach was piloted across five NHS sites and refined using a Theory of Change framework. National dissemination occurred via professional networks and conferences. Uptake was assessed through formal access requests and user agreements.

The final package included a standardized pediatric asthma and DB assessment proforma (digital and paper formats), an implementation playbook, competency framework, and educational resources. Intellectual property agreements enabled free NHS national adoption. Fifty-six NHS Trusts across all UK regions requested access; 30 completed user agreements and received the full package. Pilot implementation informed iterative refinement and strengthened the national collaborative infrastructure.

We developed and nationally disseminated a standardized physiotherapy assessment package for CYP with asthma and/or DB, achieving broad professional engagement across the United KIngdom. This initiative supports consistent evidence-based clinical practice, structured competency development, and future harmonized outcome evaluation across NHS services.

The prevalence and significance of bronchial hyperresponsiveness (BHR) in patients with non-cystic fibrosis (CF) bronchiectasis remain unclear. The objective is to determine the prevalence of BHR, defined as a post-bronchodilator forced expiratory volume in 1 s (FEV1) improvement > 10%, in children with non-CF bronchiectasis and to assess its association with clinical, functional, and radiological characteristics.

This retrospective, observational monocentric study included children with non-CF bronchiectasis followed-up at an university center for rare pediatric respiratory diseases.

Patients were eligible if they had performed spirometry with bronchodilator reversibility testing within 3 years of a diagnostic chest computed tomography (CT).

Asthma symptoms, asthma exacerbations, asthma treatments, allergic markers, infectious exacerbations, causes of bronchiectasis, FEV1, FEV1/forced vital capacity (FVC) ratio, reversibility, and mosaic attenuation on CT were compared between patients with and without BHR.

Among 157 patients, 65 (male/female sex ratio 0.71, mean age 10 years old, asthma symptoms in over 56% of patients, 67% treated with inhaled corticosteroids) met the inclusion criteria. BHR was present in 32.3% of cases. Patients with BHR had a significantly altered lung function (baseline Z-score FEV1 -2.12 vs -0.87; FEV1/FVC -2.28 vs -0.85). No significant association was found between BHR and clinical and radiological characteristics.

BHR is not associated with clinical, radiological or therapeutic characteristics in pediatric non-CF bronchiectasis, except a more severe airflow limitation. These findings highlight the importance of lung function assessment for non-CF bronchiectasis patients.

We report the technique of concomitant heart transplantation and repair of left partial anomalous pulmonary venous return (PAPVR). The patient was a 64-year-old male with a past medical history significant for non-ischaemic cardiomyopathy and a ventricular septal defect. He developed cardiogenic shock requiring insertion of a surgically implanted microaxial pump. He was listed for heart transplantation. Preoperative computed tomography demonstrated left PAPVR draining into the coronary sinus, with a left superior vena cava and patent innominate vein. At explant, the left PAPVR drained into a dilated coronary sinus continuous with the left atrial cuff. The junction of the left PAPVR to the coronary sinus was unroofed, and the septum was resected to form a common chamber. The caudal side of the coronary sinus was closed from both the left atrium and right atrium. The donor left atrium was anastomosed to the common chamber formed by the coronary sinus and left atrial cuff with a running 3-0 polypropylene suture. The rest of the donor heart anastomoses were performed in a standard fashion. The left SVC was identified outside the pericardial space and ligated. The patient was discharged with normal graft function.

High-altitude hypoxia is a sustained environmental stressor that reduces inspired oxygen pressure and challenges tissue oxygen delivery. The male reproductive system is sensitive to oxygen availability, vascular perfusion, testosterone support, Sertoli-cell metabolic function and blood-testis barrier integrity. Human high-altitude exposure studies, mountaineering observations and animal hypobaric hypoxia models indicate that exposure to high altitude or hypobaric hypoxia is associated with reductions in sperm concentration, total sperm count, motility, viability and normal morphology, accompanied in experimental models by testicular structural injury, oxidative stress and reproductive endocrine alterations. However, the magnitude and reversibility of these changes vary substantially across studies. This variability suggests that altitude-related reproductive dysfunction is not a single linear consequence of hypoxia, but a dynamic process governed by exposure intensity, duration, acclimatization, systemic stressors and local testicular compensatory capacity. Building on the classical hypoxia-oxidative stress-germ-cell injury paradigm, this review proposes an integrated framework centered on testicular oxygen homeostasis, dual microenvironmental injury and spermatogonial niche vulnerability. In this model, high-altitude hypoxia first challenges the balance among oxygen delivery, microvascular blood flow, temperature and metabolism. When compensation fails, injury is propagated through two interconnected compartments: the interstitial vascular endothelial niche-Leydig-cell-immune axis and the seminiferous Sertoli-cell-blood-testis barrier-germ-cell support system. Peritubular myoid cells, the basement membrane and extracellular matrix form a boundary layer that links these compartments and participates in the spermatogonial stem-cell niche. The rete testis/efferent ductules, epididymal segmental microenvironment, blood-epididymis barrier and seminal extracellular vesicles are best interpreted as downstream or modifying layers rather than primary mechanisms. Whether injury reaches spermatogonia or the spermatogonial stem-cell niche may determine whether recovery is rapid and complete or delayed and incomplete. The review also identifies evidence gaps, including direct measurement of local testicular oxygen tension, compartment-specific experimental designs, niche-targeted endpoints and longitudinal high-altitude/lowland return cohorts.