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Intranasal oxytocin for apathy in people with frontotemporal dementia (FOXY): a multicentre, randomised, double-blind, placebo-controlled, adaptive, crossover, phase 2a/2b superiority trial.
Lancet Neurol
February 2025
Department of Clinical Neurological Sciences, University of Western Ontario, London, ON, Canada; Department of Cognitive Neurology, St Joseph's Health Care London, London, ON, Canada. Electronic address:
Background: No treatments exist for apathy in people with frontotemporal dementia. Previously, in a randomised double-blind, placebo-controlled, dose-finding study, intranasal oxytocin administration in people with frontotemporal dementia improved apathy ratings on the Neuropsychiatric Inventory over 1 week and, in a randomised, double-blind, placebo-controlled, crossover study, a single dose of 72 IU oxytocin increased blood-oxygen-level-dependent signal in limbic brain regions. We aimed to determine whether longer treatment with oxytocin improves apathy in people with frontotemporal dementia.
View Article and Find Full Text PDFMachine Learning-Assisted Drug Repurposing Framework for Discovery of Aurora Kinase B Inhibitors.
Pharmaceuticals (Basel)
December 2024
Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania.
Aurora kinase B (AurB) is a pivotal regulator of mitosis, making it a compelling target for cancer therapy. Despite significant advances in protein kinase inhibitor development, there are currently no AurB inhibitors readily available for therapeutic use. This study introduces a machine learning-assisted drug repurposing framework integrating quantitative structure-activity relationship (QSAR) modeling, molecular fingerprints-based classification, molecular docking, and molecular dynamics (MD) simulations.
View Article and Find Full Text PDFOverview of Novel Antipsychotic Drugs: State of the Art, New Mechanisms, and Clinical Aspects of Promising Compounds.
Biomedicines
January 2025
Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy.
Antipsychotic medications are a vast class of drugs used for the treatment of psychotic disorders such as schizophrenia. Although numerous compounds have been developed since their introduction in the 1950s, several patients do not adequately respond to current treatments, or they develop adverse reactions that cause treatment discontinuation. Moreover, in the past few decades, discoveries in the pathophysiology of psychotic disorders have opened the way for experimenting with novel compounds that have alternative mechanisms of action, with some of them showing promising results in early trials.
View Article and Find Full Text PDFRescue of Mutant CFTR Channel Activity by Investigational Co-Potentiator Therapy.
Biomedicines
January 2025
Biosystems & Integrative Sciences Institute, Faculty of Sciences, University of Lisbon, 1749-016 Lisbon, Portugal.
The potentiator VX-770 (ivacaftor) has been approved as a monotherapy for over 95 cystic fibrosis (CF)-causing variants associated with gating/conductance defects of the CF transmembrane conductance regulator (CFTR) channel. However, despite its therapeutic success, VX-770 only partially restores CFTR activity for many of these variants, indicating they may benefit from the combination of potentiators exhibiting distinct mechanisms of action (i.e.
View Article and Find Full Text PDFDual anti-CTLA-4 and anti-PD-1 blockade in metastatic basal cell carcinoma.
NPJ Precis Oncol
January 2025
University of California at San Diego Moores Cancer Center, La Jolla, CA, USA.
We report the basal cell cancer (BCC) cohort of the SWOG/NCI 1609 Dual Anti-CTLA-4 & Anti-PD-1 blockade in Rare Tumors (DART), a phase II prospective, multicenter basket trial of nivolumab and ipilimumab. The primary endpoint was objective response rate (ORR) (RECIST v1.1).
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