Optimization of Potent and Selective Cyclohexyl Acid ERAP1 Inhibitors Using Structure- and Property-Based Drug Design.

Endoplasmic reticulum aminopeptidase 1 (ERAP1) cleaves the -terminal amino acids of peptides, which can then bind onto major histocompatibility class I (MHC-I) molecules for presentation onto the cell surface, driving the activation of adaptive immune responses. In cancer, overtrimming of mature antigenic peptides can reduce cytotoxic T-cell responses, and ERAP1 can generate self-antigenic peptides which contribute to autoimmune cellular responses. Therefore, modulation of ERAP1 activity has potential therapeutic indications for cancer immunotherapy and in autoimmune disease.

Network analysis of U.S. non-fatal opioid-involved overdose journeys, 2018-2023.

We present a nation-wide network analysis of non-fatal opioid-involved overdose journeys in the United States. Leveraging a unique proprietary dataset of Emergency Medical Services incidents, we construct a journey-to-overdose geospatial network capturing nearly half a million opioid-involved overdose events spanning 2018-2023. We analyze the structure and sociological profiles of the nodes, which are counties or their equivalents, characterize the distribution of overdose journey lengths, and investigate changes in the journey network between 2018 and 2023.

Therapeutic Endoscopic Ultrasound and Endoscopic Ultrasound-Endoscopic Retrograde Cholangiopancreatography Interventions.

Therapeutic endoscopic ultrasound (EUS) encompasses an array of procedures to manage pancreaticobiliary and luminal gastrointestinal disorders. Therapeutic EUS procedures include EUS-guided rendezvous of the pancreatic and biliary ducts, as well as direct drainage of the bile duct, pancreatic duct, and gallbladder, drainage of pancreatic fluid collections, and luminal anastomosis creation. These procedures have a range of required equipment, approaches, clinical outcomes, and adverse events dependent on both procedure-related and patient-related factors.

Endoscopic devices and techniques for the management of gastric varices (with videos).

Background And Aims: Gastric variceal bleeding occurs less commonly than bleeding from esophageal varices (EVs), although it is associated with higher morbidity and mortality. Bleeding from gastroesophageal varices type 1 (GOV1) is treated like EVs. In contrast, other forms of gastric variceal bleeding, including gastroesophageal varices type 2 (GOV2) and isolated gastric varices types 1 (IGV1) and 2 (IGV2), are treated with varying endoscopic approaches.