Dimitra C Tsakona, Nikolaos A Papanikolaou
The final fully constrained model showed good fit. At the between-person level, random intercept correlations among the four domains were not statistically significant in the complete-case model. At the within-person level, selected healthy dietary behaviors and physical activity showed reciprocal temporal associations, as did physical activity and emotion. Fitness performance was associated with subsequent physical activity, whereas selected healthy dietary behaviors, physical activity, and emotion were not directly associated with subsequent fitness performance. Formal multigroup tests detected no statistically significant sex differences in the main cross-lagged paths.
Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors remains the principal barrier to durable responses in non-small cell lung cancer (NSCLC), yet how the molecular interaction networks underlying this resistance reorganize over time is poorly understood. We reasoned that a systems-level signature of resistance should be visible in the way protein interaction networks remodel under sustained drug exposure, and therefore applied time-resolved network analysis to isogenic gefitinib-sensitive PC9 and gefitinib-resistant PC9R cells across 24 h of gefitinib treatment, computing network entropy and centrality measures for temporal protein interaction networks and interrogating co-expression-augmented networks for candidate resistance-associated bottleneck proteins. Network entropy rose in both phenotypes, indicating that entropic remodeling is a general response to EGFR pathway perturbation rather than a signature of resistance. In contrast, eigenvector entropy was higher in resistant cells at the earliest post-treatment time point, and resistant cells preserved giant-component connectivity and small-world topology early before fragmenting later. Temporal centrality analysis nominated BIRC3 as a resistant-cell-associated high-centrality node at 24 h, and co-expression analysis identified delta-catenin (CTNND1) as a high-betweenness bottleneck in the PC9R network, topologically bridging EGFR, VAV3, HIF3A, and NOTCH2. These findings nominate early post-treatment eigenvector entropy and a CTNND1-centered, EGFR-enriched subnetwork as candidate resistance-associated features that require validation in independent datasets and functional models.