Abstract

Abstract

Abstract
Background: Aberrant or loss of cell adhesion drives invasion and metastasis, key hallmarks of cancer progression. In this work, we hypothesized that a gene signature related to cell adhesion could predict breast cancer prognosis. Methods: Highly variant genes were tested for association with overall survival using Cox regression. Adhesion-related genes were identified through gene ontology analysis and multivariate Cox regression, with AIC selection, defined the prognostic signature. The AdhesionScore was then calculated as a weighted sum of gene expression, with risk stratification assessed by Kaplan-Meier and log-rank tests. Results: We found that the AdhesionScore was a significant independent predictor of poor survival in three large independent datasets, as it provided a robust stratification of patient prognosis in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) (HR: 2.65; 95% CI: 2.33-3.0, p = 2.34 x 10-51), The Cancer Genome Atlas (TCGA) (HR: 3.46; 95% CI: 2.35-5.09, p = 3.50 x 10-10), and the GSE96058 (HR: 2.83; 95% CI: 2.20-3.65, p = 6.29 x 10-16) datasets. The 5-year risk of death in the high-risk group was 32.41% for METABRIC, 27.8% for TCGA, and 17.54% for GSE96058 datasets. Consistently, HER2-enriched and triple-negative breast carcinomas (TNBC) cases showed higher AdhesionScores than luminal subtypes, indicating an association with aggressive tumor biology. Conclusions: We have developed, for the first time, a molecular signature based on cell adhesion, as well as an associated AdhesionScore that can predict patient prognosis in invasive breast cancer, with potential clinical application. We developed a novel adhesion-based molecular signature, the AdhesionScore, that robustly predicts prognosis in breast cancer across independent cohorts, highlighting its potential clinical utility for patient risk stratification.

Abstract
BackgroundTobacco smoke is the main cause of preventable mortality worldwide. Smoking increases the risk of developing many diseases and has been proposed as an aging accelerator. Yet, the molecular mechanisms driving smoking-related health decline and aging acceleration in most tissues remain unexplored.MethodsHere, we use data from the Genotype-Tissue Expression Project (GTEx) to perform a characterization of the effect of cigarette smoking across human tissues. We perform a multi-tissue analysis across 46 human tissues. Our multi-omics characterization includes analysis of gene expression, alternative splicing, DNA methylation, and histological alterations. We further analyze ex-smoker samples to assess the reversibility of these molecular alterations upon smoking cessation.ResultsWe show that smoking impacts tissue architecture and triggers systemic inflammation. We find that in many tissues, the effects of smoking significantly overlap those of aging. Specifically, both age and smoking upregulate inflammatory genes and drive hypomethylation at enhancers (odds ratio (OR) = 2). In addition, we observe widespread smoking-driven hypermethylation at target regions of the Polycomb repressive complex (OR = 2), which is a well-known aging effect. Smoking-induced epigenetic changes overlap causal aging CpGs, suggesting that these methylation changes may directly mediate the aging acceleration observed in smokers. Finally, we find that smoking effects that are shared with aging are more persistent over time.ConclusionOverall, our multi-tissue and multi-omic analysis of the effects of cigarette smoking provides an extensive characterization of the impact of tobacco smoke across tissues and unravels the molecular mechanisms driving smoking-induced tissue homeostasis decline and aging acceleration.

Abstract
Events like Valentine's Day and Christmas can influence user intent when interacting with search engines. For example, a user searching for gift around Valentine's Day is likely to be looking for Valentine's-themed options, whereas the same query close to Christmas would more likely suggest an interest in Holiday-themed gifts. These shifts in user intent, driven by temporal factors, are often implicit but important to determine the relevance of search results. In this demo, we explore how incorporating temporal awareness can enhance search relevance in an e-commerce setting. We constructed a database of 2K events and, using historical purchase data, developed a temporal model that estimates each event's importance on a specific date. The most relevant events on the date the query was issued are then used to enrich search results with event-specific items. Our demo illustrates how this approach enables a search system to better adapt to temporal nuances, ultimately delivering more contextually relevant products.

Abstract
The presence of missing data poses a common challenge for time series analysis in general since the most usual requirement is that the data is equally spaced in time and therefore imputation methods are required. For time series of counts, the usual imputation methods which usually produce real valued observations, are not adequate. This work employs Bayesian principles for handling missing data within time series of counts, based on first-order integer-valued autoregressive (INAR) models, namely Approximate Bayesian Computation (ABC) and Gibbs sampler with Data Augmentation (GDA) algorithms. The methodologies are illustrated with synthetic and real data and the results indicate that the estimates are consistent and present less bias when the percentage of missing observations decreases, as expected. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2025.