It remains unclear whether breastfeeding in infancy is associated with risk of metabolic dysfunction-associated steatohepatitis (MASH) and adverse liver outcomes in adulthood.

We analyzed data from the prospective UK Biobank. Breastfeeding in infancy was ascertained via self-report. In a cross‑sectional analysis involving 26,850 participants with liver MRI data, metabolic dysfunction-associated steatotic liver disease (MASLD) was defined as PDFF > 5.5%, and MASH as PDFF > 5.5% combined with cT1 > 800 ms. Additionally, a longitudinal analysis of 378,702 participants assessed associations with incident cirrhosis, hepatocellular carcinoma (HCC), and liver‑related mortality.

In MRI-based analysis, breastfeeding in infancy was associated with lower odds of MASLD (OR 0.89, 95% CI 0.80-0.99) and MASH (OR 0.79, 95% CI 0.65-0.97) in females but not males, with a significant sex interaction for MASH (P for interaction = 0.023) but not for MASLD (P for interaction = 0.301). Over a median follow‑up of 14.9 years, breastfeeding was associated with reduced risks of cirrhosis (HR 0.71, 95% CI 0.60-0.83), HCC (HR 0.52, 95% CI 0.33-0.82), and liver‑related mortality (HR 0.63, 95% CI 0.46-0.86) in females. No such associations were observed in males (P for interaction = 0.047, 0.030, and 0.008, respectively). Mediation analysis revealed that circulating insulin-like growth factor-1 (IGF-1) mediated the association specifically in females, with a sex difference in the indirect effect (FDR < 0.001).

Breastfeeding in infancy confers a long-term protective effect against MASH and adverse liver outcomes in women, but not in men. This sex-specific protective association was mediated by circulating IGF-1, suggesting a potential underlying mechanism.

Mast cell tumours are the most common skin neoplasms in dogs, accounting for up to 21% of all cutaneous tumours. They typically appear as firm nodules, most often on the trunk, limbs, or head, and their biological behaviour depends on the grade. Diagnosis is based on cytology and histopathology, while surgical excision with adequate margins remains the treatment of choice, often requiring reconstructive techniques in anatomically sensitive areas, such as the eyelid.

The article describes two cases of lower eyelid mast cell tumours in dogs, surgically treated using the lip-to-lid technique with lymphadenectomy of the sentinel lymph node. This method allowed complete excision while preserving eyelid function and appearance. Histopathology revealed different tumour grades, resulting in distinct prognoses and postoperative strategies regarding adjuvant chemotherapy. In both cases the final outcome was positive, with no local reoccurrence or distant metastases.

The use of lip-to-lid technique can be successfully used for the reconstruction of the lower eyelid defect after mast cell tumour removal. Sentinel lymph node mapping plays an essential role in perioperative staging for these tumours, and provides crucial information about prognosis. Multimodal approach for diagnosis and treatment of mast cell tumours is important to achieve a good long-term outcome. These cases contribute to the limited literature on lower eyelid mast cell tumours and support the integration of advanced staging techniques, including sentinel lymph node mapping, with reconstructive surgery in the management of periocular MCTs.

Serous cystadenoma (SCA), pancreas is a rare benign neoplasm comprising < 1% of primary pancreatic lesions. Although preoperative imaging and biochemical cyst fluid analysis have been described for SCA, the pathognomic features are appreciable only in a handful of cases. Endoscopic ultrasound guided fine needle aspiration/Biopsy (EUS FNA/B) and cell block of SCA suffers from low cellular yield and nonspecific diagnosis.

This was a combined retrospective and prospective study conducted during a period of 6 years (January 2017-December 2023) at a tertiary care referral centre. Clinical history, primary imaging and EUS characteristics were noted. Immunohistochemical (IHC) expression of alpha inhibin, Calponin, Glucose transporter 1 (GLUT 1), Synaptophysin and Chromogranin was evaluated in the cases of SCA and compared with expression of these immunomarkers in 20 cases of neuroendocrine tumour, pancreas (Grades I and II).

Fourteen cases of indeterminate SCA were identified over a period of 6 years (January 2017-December 2023). Cell block supplemented with immunohistochemistry(IHC) was able to provide a definitive diagnosis in 92.3% (12/13) cases in this series. Thus, diagnostic certainty improved from 30.8% on the basis of morphology alone to 92.3% with FNA/B and cell block and IHC.

Thus, EUS FNA/B supplemented with cell block and IHC can provide an unequivocal preoperative diagnosis of SCA. IHC panel comprising alpha inhibin, GLUT 1, synaptophysin and chromogranin can provide a sufficient level of evidence to categorize the lesion as SCA.

Bacterial extracellular vesicles are increasingly recognized as important mediators of microbe-host communication, yet their functional roles within tumour-associated microbiota remain poorly understood. Here, we investigated whether extracellular vesicles derived from Cutibacterium acnes (CEVs) regulate host redox metabolism and ferroptosis in epithelial ovarian cancer (EOC). Using integrated in vitro and in vivo models, we found that CEVs significantly promoted tumour growth and induced transcriptional reprogramming toward antioxidant defence and ferroptosis resistance. Mechanistically, CEVs activated the KEAP1-NRF2 signalling axis through coordinated downregulation of ACSL4 and KEAP1, leading to enhanced glutathione biosynthesis, increased GPX4 activity, reduced lipid peroxidation and decreased intracellular reactive oxygen species levels. These metabolic alterations suppressed ferroptosis and promoted tumour cell survival. Importantly, pharmacological induction of ferroptosis using RSL3 abolished the tumour-promoting effects of CEVs, demonstrating that ferroptosis suppression is essential for CEVs-mediated tumour progression. Collectively, our findings identify bacterial extracellular vesicles as functional modulators of host redox metabolism and ferroptosis, revealing a previously unrecognized mechanism by which tumour-associated microbiota influence cancer progression.

Bile duct carcinoma (BDC) is a highly aggressive malignancy. While epidemiological evidence suggests that acetylsalicylic acid (ASA [aspirin]) reduces BDC risk, the underlying molecular mechanisms have not been fully elucidated. This investigation explored the antineoplastic mechanisms of ASA in BDC cells.

The human BDC cell line SNU-245 was used in all experiments. Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, whereas apoptosis and caspase-3 levels were evaluated using enzyme-linked immunosorbent assay. Protein expression was analyzed using Western blotting and immunofluorescence. Functional pathway interactions were investigated using siRNA-mediated gene silencing.

ASA reduced cell viability and increased apoptosis markers, accompanied by increased Bax and p53 expression and decreased Bcl-2 levels. ASA treatment reduced cyclooxygenase-2 (COX-2) expression and decreased epidermal growth factor receptor (EGFR)levels. COX-2 knockdown markedly attenuated deoxycholic acid (DCA)-induced EGFR phosphorylation, whereas EGFR silencing partially reduced DCA-induced COX-2 expression. These results suggest reciprocal signaling interactions, with COX-2 exerting a relatively stronger upstream influence. ASA increased phosphorylation of AMP-activated protein kinase at threonine 172 (AMPKᵀʰʳ¹⁷²) and reduced insulin like growth factor-1 receptor (IGF-1R)/insulin receptor substrate-1 (IRS-1) signaling and decreased mammalian target of rapamycin (mTOR) phosphorylation. ASA also attenuated epidermal growth factor (EGF)-induced changes in epithelial-mesenchymal transition- related markers, including preservation of E-cadherin and reduction of N-cadherin expression.

In this in vitro model, ASA exposure was associated with coordinated modulation of multiple cell-survival-related signaling pathways in BDC cells, including COX-2/EGFR signaling, AMPK activation, and IGF-1R-mediated mTOR regulation. These findings provide mechanistic insight into the potential antineoplastic effects of ASA and support further translational studies in BDC.

Progastricsin/Pepsinogen C (PGC) is an aspartyl endoprotease predominantly expressed by gastric fundic and chief cells, with additional expression reported in select extragastric tissues. While increased PGC expression has been described in several malignancies, progressive downregulation of PGC has been observed along the spectrum of gastric inflammation to carcinoma. However, data on PGC expression in stomach adenocarcinoma (STAD) from South Asian populations remain limited. Given the distinct genetic, dietary, and environmental context of this region, we investigated the expression profile and epigenetic regulation of PGC in STAD patients from Pakistan.

This observational study integrated experimental analysis of human gastric tissue samples with in silico interrogation of publicly available datasets. Snap-frozen gastric tissues from histopathologically confirmed STAD patients were analyzed for PGC expression using quantitative polymerase chain reaction and immunohistochemistry. Normal gastric tissues, stratified by Helicobacter pylori infection status, were used as controls. Public transcriptomic and DNA methylation datasets were analyzed to validate expression patterns, assess promoter methylation status, and explore associations with survival outcomes.

The mean age of STAD patients was 53 years (range: 34-72), with a male predominance. PGC expression was consistently downregulated in STAD tissues compared with non-tumour gastric controls. All local cohort samples were negative for Helicobacter pylori, limiting assessment of infection-specific effects; however, in silico analyses suggested that PGC downregulation may occur independently of infection status. Independent dataset analyses confirmed reduced PGC expression in STAD. Increased promoter methylation of the PGC gene was observed in tumour samples and was inversely associated with gene expression, suggesting epigenetic silencing. Overall PGC expression was not significantly associated with survival in unstratified analyses; however, exploratory subgroup analyses suggested potential ethnicity- and gender-related patterns that did not reach statistical significance.

PGC is consistently downregulated in stomach adenocarcinoma in a South Asian population, with promoter hypermethylation likely contributing to its suppression. Although not independently associated with overall survival, exploratory subgroup observations highlight the need for population- and context-aware analyses. These findings support further evaluation of PGC within integrated biomarker strategies.

This study aims to investigate the prevalence, clinical characteristics, and prognostic significance of anti-neutrophil cytoplasmic antibodies (ANCA) across different subtypes of interstitial lung disease (ILD), specifically idiopathic pulmonary fibrosis (IPF), connective tissue disease-associated ILD (CTD-ILD) without ANCA-associated vasculitis (AAV), and AAV-ILD. A cross-sectional study was conducted to evaluate the positivity rate and clinical characteristics of ANCA in ILD. In the following meta-analysis, PubMed, Web of Science and Scopus were searched for eligible studies reporting positivity rate of ANCA in ILD. The pooled positivity rates of ANCA, MPO and PR3 in ILD were calculated, and survival outcome between ANCA-positive and ANCA-negative ILD patients were compared. Sensitivity analyses, subgroup analyses and meta-regression was also conducted. A total of 217 ILD patients were enrolled in this cross-sectional study, with an ANCA positivity rate of 7%. In the meta-analysis, with 24 studies and 4,424 patients, the pooled positivity rate of ANCA in IPF, CTD-ILD without AAV, and AAV-ILD were 9%, 15% and 97%, respectively. In patients with IPF, patients with ANCA positivity were more likely to develop honeycombing (OR 2.70, 95%CI 1.09, 6.70, p = 0.03). No significant difference was observed in survival time between IPF patients with or without ANCA positivity (HR 1.18, 95%CI 0.73, 1.90). The positivity rate of ANCA varies significantly across different subtypes of ILD. Future research should focus on the characteristics and prognostic value of ANCA positivity in other ILD subtypes.

To estimate the risk projection of temperature on pediatric asthma severity and hospitalization under four Shared Socioeconomic Pathways (SSPs) possible future climate scenarios using the Intergovernmental Panel on Climate Change (IPCC) model. A retrospective study was conducted involving 102,160 pediatric asthma patients from the Taipei Medical University Clinical Research Database (TMUCRD). We utilized global climate model (GCM) outputs to project future temperature for each subject from optimistic (SSP126) to pessimistic (SSP585) projections. A multinomial logistic regression was used to examine the odds ratio of pediatric asthma severity and hospitalization. A 1 °C increase in 1-year, 5-year, and 10-year average temperatures was associated with 1.004-fold (95% CI: 1.003-1.005) and 1.332-fold (95% CI: 1.327-1.338), 1.004-fold (95% CI: 1.002-1.005) and 1.303-fold (95% CI: 1.298-1.308), and 1.005-fold (95% CI: 1.004-1.006) and 1.282-fold (95% CI: 1.278-1.287) increase in the OR for mild persistent and hospitalization of pediatric asthma. We observed a non-linear association between temperature under SSP126, SSP245, SSP370 and SSP585 with moderate persistent pediatric asthma and pediatric asthma hospitalization, with the highest OR increases observed in 2033 at 33.4% and 32.3%, 27.6% and 32.3%, 29.1% and 32.4%, and 27.2% and 32.3%, respectively. Conclusion: Projected future temperature changes as a result of climate change may be associated with a possible increase in pediatric asthma severity and hospitalization in the coming years, with an expected increase of 8.0% and 2.5% per 1 °C increase, respectively. Pediatric asthma patients may be more susceptible to poorer outcomes under climate change in the future. What is Known: • Rising temperatures have been linked to increased asthma severity and hospitalization. • Climate change worsening pediatric asthma outcomes and increasing the healthcare burden. What is New: • Long-term exposure to rising ambient temperatures and PM_2.5 is significantly associated with increased odds of moderate and severe persistent asthma in children. • Theoretical projections linking multiple climate model scenarios (SSP126-SSP585) with future pediatric asthma burden.

Respiratory tract infections (RTIs) are a leading cause of pediatric hospitalization. Although multiple concurrent viral infections are frequently detected, their impact on clinical outcomes remains unclear. This study evaluated whether viral co-infection in children leads to worse clinical outcomes, higher inflammatory markers, or increased medical management compared to single-virus infections. We retrospectively studied children aged 0-18 years hospitalized with RTIs at a tertiary pediatric center (2017-2024). Inclusion required at least one virus detected by multiplex polymerase chain reaction (PCR). Clinical, laboratory, and hospitalization data were compared between children with single versus multiple viral infections. Multivariable regression models adjusted for age, sex, and season were used to assess associations with clinical outcomes. Of 5,703 hospitalized children, 1,120 (19.6%) had multiple viral infections. Co-infected children were younger (median 0.9 years [IQR 0.5-1.6] vs. 1.2 [IQR 0.4-3.2], p < 0.0001) and more likely to have elevated inflammatory markers, including higher C-reactive protein (CRP) and white blood cell (WBC) counts. Despite these differences, key hospitalization outcomes, including length of stay (median 4 days [IQR 3-6] in both groups), intensive care unit (ICU) admission (8.0% vs. 7.2%), and 30-day rehospitalization rates, did not differ significantly. Co-infected patients were more frequently treated with bronchodilators and steroids.

Viral co-infections were common, particularly among younger children, and were associated with modestly higher inflammatory responses and increased use of anti-inflammatory medications. However, co-infection did not significantly affect hospitalization duration or ICU admission. These findings suggest that multiple viral infections may not substantially worsen disease severity in hospitalized children.

• Viral co-infections are common in pediatric respiratory illness, yet their impact on clinical severity and outcomes remains debated and inconsistent in current literature.

• Co-infection is associated with significantly higher inflammatory markers and increased use of steroids and bronchodilators compared to single-virus infections. • Despite laboratory differences and higher medication use, co-infection does not increase length of stay, ICU admission rates, or 30-day rehospitalization.

Former preterm and term infants are at risk for postanesthesia apnea, but the lack of uniform standards for monitoring and discharge criteria leads to inconsistent practice. The primary aim of this study was to identify major risk factors for postanesthesia apnea. This systematic review and meta-regression analysis used Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Agency for Healthcare Research and Quality guidelines. The literature search included English language case reports, case series, clinical studies, and clinical trials. Major databases were queried from inception to October 2025. A total of 6,191 articles underwent title and abstract screening, 491 underwent full-text screening, and 173 underwent detailed reviews. Data were extracted from 115 of 173 articles (98 studies, 17 case reports or series). Across studies (preterm or full term infants), the median incidence of apnea was 7.6% (range, 0 to 85%). Univariable meta-regression analysis (96 eligible articles) identified five significant predictors of apnea: gestational age, postmenstrual age at time of procedure, birth weight, procedure duration, and year of publication. Odds for apnea incidence decreased with later publication year, older gestational age at birth, older postmenstrual age at time of surgery, higher birth weight, and shorter procedure duration. A multivariable "best fitting model" (64 eligible articles) including publication year (1986 to 2025) and postmenstrual age (32 to 63 weeks) found a decrease in odds of apnea incidence with later publication year (odds ratio [OR], 0.936; CI, 0.91 to 0.964; P < 0.001) and higher postmenstrual age (OR, 0.889; CI, 0.828 to 0.954; P = 0.001). Recommended postanesthesia monitoring duration ranged from 6 to 24 h based on postmenstrual age. Meta-regression showed significantly lower apnea odds with neuraxial versus general anesthesia (OR, 0.236; CI, 0.094 to 0.592; P = 0.003). Postmenstrual age appears to be the strongest and most consistent risk factor for postanesthesia apnea; neuraxial anesthesia may reduce this risk. An individual participant data meta-analysis in a follow-up article will shed further light on the at-risk postmenstrual age threshold for increased risk and help refine monitoring recommendations for these vulnerable infants.