TP53 germline testing and hereditary cancer: how somatic events and clinical criteria affect variant detection rate.

Background: Germline heterozygous pathogenic variants (PVs) in TP53 cause Li-Fraumeni syndrome (LFS), a condition associated with increased risk of multiple tumor types. As the associated cancer risks were refined over time, clinical criteria also evolved to optimize diagnostic yield. The implementation of multi-gene panel germline testing in different clinical settings has led to the identification of TP53 PV carriers outside the classic LFS-associated cancer phenotypes, leading to a broader cancer phenotypic redefinition and to the renaming of the condition as "heritable TP53-related cancer syndrome" (hTP53rc).

Digital Doppelgängers and Lifespan Extension: What Matters?

There is an ongoing debate about the ethics of research on lifespan extension: roughly, using medical technologies to extend biological human lives beyond the current "natural" limit of about 120 years. At the same time, there is an exploding interest in the use of artificial intelligence (AI) to create "digital twins" of persons, for example by fine-tuning large language models on data specific to particular individuals. In this paper, we consider whether digital twins (or digital doppelgängers, as we refer to them) could be a path toward a kind of life extension-or more precisely, a kind of extension-that does not rely on biological continuity.

Angiographic and Histopathological Characteristics of a Novel Polyacrylate Liquid Embolic Agent Compared with Ethylene-Vinyl Alcohol Copolymer in a Large Animal Model.

Purpose: To study the in vivo safety and effectiveness of a novel radiopaque nonadhesive polyacrylate (PA) peripheral liquid embolic system (AMBER SEL-P) relative to ethylene-vinyl alcohol copolymer (EVOH, Onyx) in a healthy swine endovascular model.

Materials And Methods: Twenty-five swine underwent rete mirabile and bilateral kidney embolization with PA or EVOH and were followed up for 24 hours (n = 5) and 30 days (n = 10), and 3 (n = 10) months. Angiographic features (penetrability, radiopacity, catheter entrapment, fragmentation, occlusion, and vasospasm) were evaluated.

Cryo-EM analysis of Pseudomonas phage Pa193 structural components.

The World Health Organization has designated Pseudomonas aeruginosa as a critical pathogen for the development of new antimicrobials. Bacterial viruses, or bacteriophages, have been used in various clinical settings, commonly called phage therapy, to address this growing public health crisis. Here, we describe a high-resolution structural atlas of a therapeutic, contractile-tailed Pseudomonas phage, Pa193.