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| http://dx.doi.org/10.1371/journal.pntd.0000645 | DOI Listing |
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Machine Learning Prediction of On/Off Target-driven Clinical Adverse Events.
Pharm Res
August 2024
Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, Ann Arbor, MI, 48109, United States.
Objective: Currently, 90% of clinical drug development fails, where 30% of these failures are due to clinical toxicity. The current extensive animal toxicity studies are not predictive of clinical adverse events (AEs) at clinical doses, while current computation models only consider very few factors with limited success in clinical toxicity prediction. We aimed to address these issues by developing a machine learning (ML) model to directly predict clinical AEs.
View Article and Find Full Text PDFRemoving Neighboring Ring Influence in Monocyclic B-OH Diazaborines: Properties and Reactivity as Phenolic Bioisosteres with Dynamic Hydroxy Exchange.
J Am Chem Soc
July 2024
Department of Chemistry, University of Alberta, Centennial Centre for Interdisciplinary Science, Edmonton, Alberta T6G 2G2, Canada.
The design of small molecules with unique geometric profiles or molecular connectivity represents an intriguing yet neglected challenge in modern organic synthesis. This challenge is compounded when emphasis is placed on the preparation of new chemotypes that have distinct and practical functions. To expand the structural diversity of boron-containing heterocycles, we report herein the preparation of novel monocyclic hemiboronic acids, diazaborines.
View Article and Find Full Text PDFLipoprotein(a) in the Year 2024: A Look Back and a Look Ahead.
Arterioscler Thromb Vasc Biol
July 2024
University of California San Diego, La Jolla.
In fitting with the American Heart Association’s 100th anniversary of its founding and organizing a Centennial Collection to celebrate this event, lipoprotein(a) [Lp(a)] celebrates its 61 birthday in November 2024. There has been substantial progress in understanding the biology and pathophysiology of Lp(a) in the last 6 decades, including its discovery as a unique β-lipoprotein containing the pathognomonic apolipoprotein(a) moiety covalently bound to apolipoprotein B-100, its independent monogenetic association with cardiovascular disease and calcific aortic valve disease, its increased content of pro-atherogenic and pro-inflammatory of oxidized phospholipids relative to other lipoproteins and the development of RNA therapeutics to lower plasma Lp(a) levels. The validation or refutation of the “Lp(a) hypothesis”, namely that lowering plasma Lp(a) will lead to clinical benefit, is ongoing in 3 clinical outcomes trials.
View Article and Find Full Text PDFSalt Sensitivity of Blood Pressure.
Circ Res
May 2024
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN (J.A., C.L.L., A.K.).
The year 2024 marks the centennial of the initiation of the American Heart Association. Over the past 100 years, the American Heart Association has led groundbreaking discoveries in cardiovascular disease including salt sensitivity of blood pressure, which has been studied since the mid-1900s. Salt sensitivity of blood pressure is an important risk factor for cardiovascular events, but the phenotype remains unclear because of insufficient understanding of the underlying mechanisms and lack of feasible diagnostic tools.
View Article and Find Full Text PDFCelebrating the centennial of the most famous experiment in embryology: Hilde Mangold, Hans Spemann and the organizer.
Cells Dev
June 2024
Department of Cell and Developmental Biology, University College London, Gower Street, London WC1E 6BT, UK. Electronic address:
This Issue of Cells & Development celebrates the centennial of the Spemann-Mangold organizer experiment. This was the most famous experiment in embryology and its reverberations have greatly influenced developmental biology. This historical issue describes the impact of the discovery and is a prelude to the second volume of this Festschrift, which will consist of the proceedings of the international meeting to be held in Freiburg University, at the place where the organizer was discovered.
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