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Background and Aims: Decoding pancreatic ductal adenocarcinoma heterogeneity and the consequent therapeutic selection remains a challenge. We aimed to characterize epigenetically regulated pathways involved in pancreatic ductal adenocarcinoma progression. Methods: Global DNA methylation analysis in pancreatic cancer patient tissues and cell lines was performed to identify differentially methylated genes. Targeted bisulfite sequencing and in vitro methylation reporter assays were employed to investigate the direct link between site-specific methylation and transcriptional regulation. A series of in vitro loss-of-function and gain-of function studies and in vivo xenograft and the KPC (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx1-Cre) mouse models were used to assess pancreatic cancer cell properties. Gene and protein expression analyses were performed in 3 different cohorts of pancreatic cancer patients and correlated to clinicopathological parameters. Results: We identify Hepatocyte Nuclear Factor 4A (HNF4A) as a novel target of hypermethylation in pancreatic cancer and demonstrate that site-specific proximal promoter methylation drives HNF4A transcriptional repression. Expression analyses in patients indicate the methylation-associated suppression of HNF4A expression in pancreatic cancer tissues. In vitro and in vivo studies reveal that HNF4A is a novel tumor suppressor in pancreatic cancer, regulating cancer growth and aggressiveness. As evidenced in both the KPC mouse model and human pancreatic cancer tissues, HNF4A expression declines significantly in the early stages of the disease. Most importantly, HNF4 loss correlates with poor overall patient survival. Conclusion: HNF4A silencing, mediated by promoter DNA methylation, drives pancreatic cancer development and aggressiveness leading to poor patient survival.

India is one of the world's largest producers of tree nuts, yet it paradoxically remains a net importer of these commodities. This study aims to analyze the demand for imported tree nuts in India, motivated by the need to understand the factors contributing to this imbalance. The primary objective is to calculate income elasticities and own- and cross-price elasticities for five categories of imported tree nuts using the linear approximate almost ideal demand system model. Data is sourced from monthly import records from the United Nations Comtrade database covering 2014 to 2022. The tree nuts considered are almonds, cashews, pistachios, walnuts, and hazelnuts. Key findings reveal all imported tree nuts are normal goods. Cashews exhibit income elasticity (1.2), indicating a significant demand increase with rising incomes, while other nuts show income inelasticity. Cashews are price-elastic (-1.3), while other nuts are price-inelastic. Compensated cross-price elasticities indicate notable substitution effects, particularly between almonds and cashews. The study recommends enhancing domestic cashew production to meet growing demand and developing targeted marketing strategies to address competitive dynamics within the tree nut market. These strategies aim to reduce India's dependency on imports and promote a balanced, sustainable domestic market., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)