Methionine adenosyltransferase genes encode enzymes responsible for the biosynthesis of S-adenosylmethionine, the principal biological methyl donor and precursor of polyamines and glutathione. Mammalian cells express three genes - MAT1A, MAT2A, and MAT2B - with distinct expression and functions. MAT1A is mainly expressed in the liver and maintains the differentiated states of both hepatocytes and bile duct epithelial cells. Conversely, MAT2A and MAT2B are widely distributed in non-parenchymal cells of the liver and extrahepatic tissues. Increasing evidence suggests that methionine adenosyltransferases play significant roles in the development of cancers. Liver cancers, namely hepatocellular carcinoma and cholangiocarcinoma, involve dysregulation of all three methionine adenosyltransferase genes. MAT1A reduction is associated with increased oxidative stress, progenitor cell expansion, genomic instability, and other mechanisms implicated in tumorigenesis. MAT2A/MAT2B induction confers growth and survival advantage to cancerous cells, enhancing tumor migration. Highlighted examples from colon, gastric, breast, pancreas and prostate cancer studies further underscore methionine adenosyltransferase genes' role beyond the liver in cancer development. In this subset of extra-hepatic cancers, MAT2A and MAT2B are induced via different regulatory mechanisms. Understanding the role of methionine adenosyltransferase genes in tumorigenesis helps identify attributes of these genes that may serve as valuable targets for therapy. While S-adenosylmethionine, and its metabolite, methylthioadenosine, have been largely explored as therapeutic interventions, targets aimed at regulation of MAT gene expression and methionine adenosyltransferase protein-protein interactions are now surfacing as potential effective strategies for treatment and chemoprevention of cancers. Impact statement This review examines the role of methionine adenosyltransferases (MATs) in human cancer development, with a particular focus on liver cancers in which all three MAT genes are implicated in tumorigenesis. An overview of MAT genes, isoenzymes and their regulation provide context for understanding consequences of dysregulation. Highlighting examples from liver, colon, gastric, breast, pancreas and prostate cancers underscore the importance of understanding MAT's tumorigenic role in identifying future targets for cancer therapy.

Background: The overlap between eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) has not been extensively examined. We aimed to assess the prevalence of esophageal eosinophilia in patients with IBD. Methods: We conducted a retrospective cohort study using diagnostic codes to identify adults with EoE and IBD between 2008 and 2016 at a tertiary care center. Electronic medical records were reviewed to extract clinical, endoscopic, and treatment data. Patients with esophageal eosinophilia and IBD were compared to EoE cases without IBD. Results: Of 621 EoE patients and 4,814 IBD patients identified, 35 had a code for both diseases and 12 were confirmed to have overlapping IBD and esophageal eosinophilia. The prevalence of esophageal eosinophilia in IBD was 12/4814 (0.25%), and the prevalence of confirmed EoE in IBD was 5/4,814 (0.10%). There were no substantial clinical, endoscopic, or histologic differences between EoE patients with and without IBD. IBD was diagnosed before esophageal eosinophilia 92% of the time, with an average time between diagnoses of 9.6 years. Of the IBD patients, 71% were started on biologic anti-tumor necrosis factor-α therapy an average of 7.6 years prior to developing esophageal eosinophilia. Conclusions: The prevalence of esophageal eosinophilia in IBD is 5 times higher than expected in the general population (0.25 vs. 0.05%) and EoE in IBD is 2 times higher than expected (0.10 vs. 0.05%). Upper gastrointestinal (GI) symptoms in patients with IBD should merit evaluation not only for upper GI Crohn’s disease, but also for esophageal eosinophilia.

This paper presents the current state of the gaming industry, which provides an important background for an effective serious game implementation in mobile crowdsensing. An overview of existing solutions, scientific studies and market research highlights the current trends and the potential applications for citizen-centric platforms in the context of Cyber–Physical–Social systems. The proposed solution focuses on serious games applied in urban water management from the perspective of mobile crowdsensing, with a reward-driven mechanism defined for the crowdsensing tasks. The serious game is designed to provide entertainment value by means of gamified interaction with the environment, while the crowdsensing component involves a set of roles for finding, solving and validating water-related issues. The mathematical model of distance-constrained multi-depot vehicle routing problem with heterogeneous fleet capacity is evaluated in the context of the proposed scenario, with random initial conditions given by the location of players, while the Vickrey–Clarke–Groves auction model provides an alternative to the centralized task allocation strategy, subject to the same evaluation method. A blockchain component based on the Hyperledger Fabric architecture provides the level of trust required for achieving overall platform utility for different stakeholders in mobile crowdsensing.

Alcoholic liver disease (ALD) is a leading cause of liver related morbidity and mortality worldwide. ALD encompasses a spectrum of disorders including asymptomatic steatosis, steatohepatitis, fibrosis, cirrhosis and its related complications, and the acute on chronic state of alcoholic hepatitis. While multidisciplinary efforts continue to be aimed at curbing progression of this spectrum of disorders, there is an urgent need to focus our efforts on effective therapeutic interventions for alcoholic hepatitis (AH), the most severe form of ALD. AH is characterized by an abrupt development of jaundice and complications related to liver insufficiency and portal hypertension in patients with heavy alcohol intake. The mortality of patients with severe AH is very high (20–50% at 3 months). The current therapeutic regimens are limited. The development of new therapies requires translational studies in human samples and suitable animal models that reproduce clinical and histological features of human AH. This review article summarizes the clinical syndrome, pre-clinical translational tools, and pathogenesis of AH at a molecular and cellular level, with the aim to identify new targets of potential therapeutic intervention.

Water supply systems are essential for a modern society. This article presents an overview of the latest research related to information and communication technology systems for water resource monitoring, control and management. The main objective of our review is to show how emerging technologies offer support for smart administration of water infrastructures. The paper covers research results related to smart cities, smart water monitoring, big data, data analysis and decision support. Our evaluation reveals that there are many possible solutions generated through combinations of advanced methods. Emerging technologies open new possibilities for including new functionalities such as social involvement in water resource management. This review offers support for researchers in the area of water monitoring and management to identify useful models and technologies for designing better solutions.