AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.

Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

Evaluating the utility and challenges associated with "unknown" and fictional patients in the electronic medical record.

Electronic medical records (EMRs) allow for the creation of "fictional" and unknown patients within the EMR production environment. Surprisingly, there is sparse literature regarding the use cases for these patients or the challenges associated with their existence in the EMR. Here, we identified three classes of patients in regular use at our institution: true fictional patients with medical record numbers (MRNs) used to test EMR functions in the production environment, "confidential patients" used to store sensitive data, and "unknown" patients that are assigned temporary MRNs in emergency situations until additional information can be acquired.

Affordance norms for 2825 concrete nouns.

Objects are commonly described based on their relations to other objects (e.g., associations, semantic similarity, etc.

Tyrosine Kinase 2 Inhibition With Zasocitinib (TAK-279) in Psoriasis: A Randomized Clinical Trial.

Importance: New, effective, and well-tolerated oral therapies are needed for treating psoriasis. Zasocitinib, a highly selective allosteric tyrosine kinase 2 (TYK2) inhibitor, is a potential new oral treatment for this disease.

Objective: To assess the efficacy, safety, and tolerability of zasocitinib in patients with moderate to severe plaque psoriasis.

Multidisciplinary considerations for implementing Bayesian borrowing in basket trials.

Drug development has historically relied on phase I-III clinical trials including participants sharing the same disease. However, drug development has evolved as the discovery of mechanistic drivers of disease demonstrated that the same therapeutic target may provide benefits across different diseases. A basket trial condenses evaluation of one therapy among multiple related diseases into a single trial and presents an opportunity to borrow information across them rather than viewing each in isolation.