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Evaluation of the safety, tolerability, pharmacokinetics and pharmacodynamics of SM17 in healthy volunteers: results from pre-clinical models and a first-in-human, randomized, double blinded clinical trial.
Front Immunol
December 2024
SinoMab BioScience Limited, Hong Kong, Hong Kong SAR, China.
Background: Alarmins mediate type 2 T helper cell (Th2) inflammation and serve as upstream signaling elements in allergic inflammation and autoimmune responses. The alarmin interleukin (IL)-25 binds to a multi-domain receptor consisting of IL-17RA and IL-17RB subunits, resulting in the release of Th2 cytokines IL-4, IL-5, IL-9 and IL-13 to drive an inflammatory response. Therefore, the blockage of IL-17RB via SM17, a novel humanized monoclonal antibody, offers an attractive therapeutic target for Th2-mediated diseases, such as asthma.
View Article and Find Full Text PDFForce-Activated Spin-Crossover in Fe and Co Transition Metal Mechanophores.
Inorg Chem
December 2024
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.
Transition metal mechanophores exhibiting force-activated spin-crossover are attractive design targets, yet large-scale discovery of them has not been pursued due in large part to the time-consuming nature of trial-and-error experiments. Instead, we leverage density functional theory (DFT) and external force explicitly included (EFEI) modeling to study a set of 395 feasible Fe and Co mechanophore candidates with tridentate ligands that we curate from the Cambridge Structural Database. Among nitrogen-coordinating low-spin complexes, we observe the prevalence of spin crossover at moderate force, and we identify 155 Fe and Co spin-crossover mechanophores and derive their threshold force for low-spin to high-spin transition ().
View Article and Find Full Text PDFInflammation in the Peri-ACS Period: Ready for Prime Time?
Curr Atheroscler Rep
December 2024
Department of Medicine, Division of Cardiology, New York University Langone Medical Center, NYU Langone Health System, 550 1st Ave, New York, NY, 10010, USA.
Inflammation has been demonstrated to negatively impact patients in the peri-ACS period. This narrative review outlines the inflammatory response in ACS, highlighting the role of the NLRP3 inflammasome pathway following acute plaque rupture and coronary intervention and its potential as a pharmacologic target. RECENT: nvestigators have leveraged medications targeting the NLRP3 inflammasome currently used for other inflammatory pathologies, including colchicine, tocilizumab and anakinra.
View Article and Find Full Text PDFSpeed is associated with polarization during subjective evaluation: no tradeoff, but an effect of the ease of processing.
Cogn Neurodyn
December 2024
Graduate School of Systems Life Sciences, Kyushu University, Fukuoka, Japan.
In human perceptual decision-making, the speed-accuracy tradeoff establishes a causal link between urgency and reduced accuracy. Less is known about how speed relates to the subjective evaluation of visual images. Here, we conducted a set of four experiments to tease apart two alternative hypotheses for the relation between speed and subjective evaluation.
View Article and Find Full Text PDFDifference in Restricted Mean Survival Time (DRMST) has attracted attention and is increasingly used in non-inferiority (NI) trials because of its superior power in detecting treatment effects compared to hazard ratio. However, when treatment switching (also known as crossover) occurs, the widely used intention-to-treat (ITT) analysis can underpower or overpower NI trials. We propose a simulation-based approach, named nifts, to calculate powers and determine the necessary sample size to achieve a desired power for non-inferiority trials that allow treatment switching, in ITT analysis using DRMST.
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