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Pancreatic ductal adenocarcinoma (PDAC) poses a significant threat due to its tendency to evade early detection, frequent metastasis, and the subsequent challenges in devising effective treatments. Processes that govern epithelial-mesenchymal transition (EMT) in PDAC hold promise for advancing novel therapeutic strategies. SAMD1 (SAM domain-containing protein 1) is a CpG island-binding protein that plays a pivotal role in the repression of its target genes. Here, we revealed that SAMD1 acts as a repressor of genes associated with EMT. Upon deletion of SAMD1 in PDAC cells, we observed significantly increased migration rates. SAMD1 exerts its effects by binding to specific genomic targets, including CDH2, encoding N-cadherin, which emerged as a driver of enhanced migration upon SAMD1 knockout. Furthermore, we discovered the FBXO11-containing E3 ubiquitin ligase complex as an interactor and negative regulator of SAMD1, which inhibits SAMD1 chromatin-binding genome-wide. High FBXO11 expression in PDAC is associated with poor prognosis and increased expression of EMT-related genes, underlining an antagonistic relationship between SAMD1 and FBXO11. In summary, our findings provide insights into the regulation of EMT-related genes in PDAC, shedding light on the intricate role of SAMD1 and its interplay with FBXO11 in this cancer type.

Background Lung ultrasound (LUS) has emerged as a useful tool in the acute phase of patients admitted for ST‐segment–elevation myocardial infarction. However, its long‐term significance remains uncertain, and risk scores do not include LUS findings as a predictor. This study aims to assess the 1‐year prognostic value of LUS and its ability to enhance existing risk scores. Methods and Results This is a multicenter prospective cohort study involving 373 patients with ST‐segment–elevation myocardial infarction. LUS was performed during the first 24 hours after angiography. LUS results were assessed both as a categorical (wet/dry lung) and continuous variable (LUS score). The primary end point comprised the following major adverse cardiovascular events: all‐cause mortality or hospitalization for heart failure, acute coronary syndrome, or stroke within 1 year. We also evaluated whether LUS could enhance the predictive value of the GRACE (Global Registry of Acute Coronary Events) score. Major adverse cardiovascular events occurred in 51 (13.7%) patients over a median follow‐up of 368 days. After multivariate analysis, the LUS score was an independent predictor (hazard ratio [HR], 1.06 [95% CI, 1.01–1.10]; P=0.009] for each additional B‐line), whereas the categorical classification was an independent predictor in patients with ST‐segment–elevation myocardial infarction Killip I (HR, 3.12 [95% CI, 1.34–7.31]; P=0.009). Incorporating LUS into GRACE resulted in a net reclassification index of 31.6% and a significant increase in the area under the curve; GRACE alone scored 0.705 compared with GRACE+LUS 0.791 (P=0.002). Conclusions Detecting B‐lines on LUS at the acute phase predicts major adverse cardiovascular events at 1 year in patients with ST‐segment–elevation myocardial infarction and enhances the predictive value of the GRACE score. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04526535.

RESUMO Objetivo Verificar a associação entre a restrição à participação decorrente de perda auditiva e a autopercepção da saúde, do suporte social e da qualidade de vida em pessoas idosas. Método Estudo com delineamento transversal, observacional, descritivo e com abordagem quantitativa dos dados. Foi utilizado um banco de dados com informações coletadas em um município brasileiro de médio porte, sendo incluídas no estudo 235 pessoas cadastradas em cinco unidades de Estratégia de Saúde da Família. Utilizou-se informações sociodemográficas, de saúde e os resultados dos questionários: avaliação à restrição à participação (Hearing Handicap Inventory for the Elderly Screening Version - HHIE-S), Suporte Social (Escala de Apoio Social do MOS), Avaliação Subjetiva de Saúde e a Qualidade de Vida (Short-Form 6 dimensions- SF-6D). Comparou-se os grupos com restrição e sem restrição à participação segundo as variáveis sociodemográficas, de saúde, suporte social e qualidade de vida. Um método de regressão logística binária multivariado foi utilizado para avaliar as associações entre as variáveis independentes e a restrição à participação. Resultados O grupo com restrição à participação é mais velho, possui menor qualidade de vida e pior autopercepção de saúde. Esta se mostrou ser o único preditor da restrição à participação relacionada à perda auditiva. Conclusão A restrição à participação está associada a uma pior autopercepção de saúde. O estudo revela a importância de avaliar a autopercepção dos indivíduos quanto às questões biopsicossociais, além de considerar o contexto ambiental para a compreensão dos impactos sociais e emocionais da perda auditiva.

Purpose: To verify the association between participation restriction due to hearing loss and self-perception of health, social support, and quality of life in elderly people., Methods: This is a cross-sectional, observational, and descriptive study with a quantitative data approach. A database with information collected in a medium-sized Brazilian municipality was used. The study was conducted with 235 elderly people registered in five Family Health Strategy Units. Sociodemographic and health information and the results of the following questionnaires were used: Hearing Handicap Inventory for the Elderly - Screening Version (HHIE-S), Medical Outcomes Study (MOS) Social Support Survey, Subjective Health Assessment, and Short-Form 6-Dimension (SF-6D) Health and Quality of Life Index. Groups with and without participation restriction were compared according to sociodemographic, health, social support, and quality of life variables. A multivariate binary logistic regression method was employed to evaluate the associations between the independent variables and participation restriction., Results: The group with participation restriction is composed of older individuals with lower quality of life and poorer self-perception of health. Poorer self-perception of health was the only predictor of participation restriction related to hearing loss., Conclusion: Participation restriction is associated with poorer self-perception of health. The study highlights the importance of assessing individuals' self-perception regarding biopsychosocial issues, in addition to considering the environmental context to understand the social and emotional impacts caused by hearing loss.