Integrated machine learning-driven disulfidptosis profiling: CYFIP1 and EMILIN1 as therapeutic nodes in neuroblastoma.

BACKGROUND: Neuroblastoma (NB), a prevalent pediatric solid tumor, presents formidable challenges due to its high malignancy and intricate pathogenesis. The role of disulfidptosis, a novel form of programmed cell death, remains poorly understood in the context of NB. METHODS: Gaussian mixture model (GMM)-identified disulfidptosis-related molecular subtypes in NB, differential gene analysis, survival analysis, and gene set variation analysis were conducted subsequently. Weighted gene co-expression network analysis (WGCNA) selected modular genes most relevant to the disulfidptosis core pathways. Integration of machine learning approaches revealed the combination of the Least absolute shrinkage and selection operator (LASSO) and Random Survival Forest (RSF) provided optimal dimensionality reduction of the modular genes. The resulting model was validated, and a nomogram assessed disulfidptosis characteristics in NB. Core genes were filtered and subjected to tumor phenotype and disulfidptosis-related experiments. RESULTS: GMM clustering revealed three distinct subtypes with diverse prognoses, showing significant variations in glucose metabolism, cytoskeletal structure, and tumor-related pathways. WGCNA highlighted the red module of genes highly correlated with disulfide isomerase activity, cytoskeleton formation, and glucose metabolism. The LASSO and RSF combination yielded the most accurate and stable prognostic model, with a significantly worse prognosis for high-scoring patients. Cytological experiments targeting core genes (CYFIP1, EMILIN1) revealed decreased cell proliferation, migration, invasion abilities, and evident cytoskeletal deformation upon core gene knockdown. CONCLUSIONS: This study showcases the utility of disulfidptosis-related gene scores for predicting prognosis and molecular subtypes of NB. The identified core genes, CYFIP1 and EMILIN1, hold promise as potential therapeutic targets and diagnostic markers for NB.

Relationship between loneliness and cognitive impairment in community-dwelling elderly in Wuhan / 中华老年医学杂志

Objective To examine the impact of loneliness on cognitive impairment among community-dwelling elderly people.Methods A cross-sectional survey was conducted between July and August 2015 with 895 community-dwelling elderly participants in four residential areas of Wuchang District,Wuhan.The Montreal Cognitive Assessment (MoCA) was used to measure cognitive function.Chi square test,t-test,and multivariate linear regression were used to analyze the data.Results Multivariate linear analysis showed that loneliness was independently and negatively associated with cognitive function among the participants (β=-1.2828,95％ CI:-2.27--0.30).Participants who felt loneliness recorded lower scores on visuospatial executive,attention,and language ability than those who did not (P＜0.05).Multivariate logistic analysis demonstrated that loneliness was also associated with cognitive function after adjustment for age and gender,with OR (95 ％CI) at 1.74(1.05 2.91) / 1.78 (1.07 2.94).Loneliness remained an independent risk factor for cognitive dysfunction after adjustment for age,gender,education level,monthly income,living arrangement,physical activity,mental activity,hypertension,diabetes,frequency of social interaction,and type of social interaction,with OR (95％CI) at 1.69(1.002.87) / 1.72(1.022.90).Conclusions Loneliness is a significant and independent impact factor for cognitive dysfunction among community dwelling elders.

Relationship between loneliness and cognitive impairment in community-dwelling elderly in Wuhan / 中华老年医学杂志

Objective To examine the impact of loneliness on cognitive impairment among community-dwelling elderly people.Methods A cross-sectional survey was conducted between July and August 2015 with 895 community-dwelling elderly participants in four residential areas of Wuchang District,Wuhan.The Montreal Cognitive Assessment (MoCA) was used to measure cognitive function.Chi square test,t-test,and multivariate linear regression were used to analyze the data.Results Multivariate linear analysis showed that loneliness was independently and negatively associated with cognitive function among the participants (β=-1.2828,95％ CI:-2.27--0.30).Participants who felt loneliness recorded lower scores on visuospatial executive,attention,and language ability than those who did not (P＜0.05).Multivariate logistic analysis demonstrated that loneliness was also associated with cognitive function after adjustment for age and gender,with OR (95 ％CI) at 1.74(1.05 2.91) / 1.78 (1.07 2.94).Loneliness remained an independent risk factor for cognitive dysfunction after adjustment for age,gender,education level,monthly income,living arrangement,physical activity,mental activity,hypertension,diabetes,frequency of social interaction,and type of social interaction,with OR (95％CI) at 1.69(1.002.87) / 1.72(1.022.90).Conclusions Loneliness is a significant and independent impact factor for cognitive dysfunction among community dwelling elders.