Side Chain Investigation of Imidazopyridazine as a Hinge Binder for Targeting Actionable Mutations of RET Kinase.

Actionable mutations of RET kinase have been identified as oncogenic drivers of solid tumors, including thyroid cancer, metastatic colorectal cancer, and nonsmall cell lung cancer. Although multikinase inhibitors and RET selective inhibitors are used to treat patients with RET alterations, there is insufficient research addressing certain issues: which actionable mutations arise from these therapies, how to improve the clinical response rate to RET inhibitors, and how to design new inhibitors to overcome drug resistance. Therefore, the development of sophisticated tool compounds is required to investigate the molecular mechanisms of actionable mutations and to develop breakthrough therapeutics for different RET alterations.

Full-wave Image Reconstruction in Transcranial Photoacoustic Computed Tomography using a Finite Element Method.

Transcranial photoacoustic computed tomography presents challenges in human brain imaging due to skull-induced acoustic aberration. Existing full-wave image reconstruction methods rely on a unified elastic wave equation for skull shear and longitudinal wave propagation, therefore demanding substantial computational resources. We propose an efficient discrete imaging model based on finite element discretization.

De-aberration for transcranial photoacoustic computed tomography through an adult human skull.

Noninvasive transcranial photoacoustic computed tomography (PACT) of the human brain, despite its clinical potential, remains impeded by the acoustic distortion induced by the human skull. The distortion, which is attributed to the markedly different material properties of the skull relative to soft tissue, results in heavily aberrated PACT images -- a problem that has remained unsolved in the past two decades. Herein, we report the first successful experimental demonstration of the de-aberration of PACT images through an ex-vivo adult human skull using a homogeneous elastic model for the skull.

Immunity from NK Cell Subsets Is Important for Vaccine-Mediated Protection in HPV+ Cancers.

High-risk human papillomaviruses (HPVs) are associated with genital and oral cancers, and the incidence of HPV+ head and neck squamous cell cancers is fast increasing in the USA and worldwide. Survival rates for patients with locally advanced disease are poor after standard-of-care chemoradiation treatment. Identifying the antitumor host immune mediators important for treatment response and designing strategies to promote them are essential.