Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.

The vasodilator hydralazine (HYZ) has been used clinically for ~ 70 years and remains on the World Health Organization's List of Essential Medicines as a therapy for preeclampsia. Despite its longstanding use and the concomitant progress toward a general understanding of vasodilation, the target and mechanism of HYZ have remained unknown. We show that HYZ selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating its metal cofactor and alkylating one of its ligands.

Outcomes Associated With Airway Management of Adult Trauma Patients Admitted to Surgical Intensive Care.

Introduction: Advanced airway management and ventilation of trauma patients are often needed during acute stabilization and resuscitation and later, in those admitted. In addition to endotracheal intubation for advanced airway management, tracheostomy is commonly used in critically ill patients when prolonged mechanical ventilation is required. However, the outcomes associated with airway management approaches and the timing of a tracheostomy in critically ill patients are mixed.

Machine Learning-based Prognostic Subgrouping of Glioblastoma: A Multi-center Study.

Background: Glioblastoma is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification.

Methods: We developed a highly reproducible, personalized prognostication and clinical subgrouping system using machine learning (ML) on routine clinical data, MRI, and molecular measures from 2,838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]).

Patient-derived glioblastoma organoids as real-time avatars for assessing responses to clinical CAR-T cell therapy.

Patient-derived tumor organoids have been leveraged for disease modeling and preclinical studies but rarely applied in real time to aid with interpretation of patient treatment responses in clinics. We recently demonstrated early efficacy signals in a first-in-human, phase 1 study of dual-targeting chimeric antigen receptor (CAR)-T cells (EGFR-IL13Rα2 CAR-T cells) in patients with recurrent glioblastoma. Here, we analyzed six sets of patient-derived glioblastoma organoids (GBOs) treated concurrently with the same autologous CAR-T cell products as patients in our phase 1 study.