A novel series of second generation DPP1 inhibitors free from aorta binding liabilities found for earlier compound series was discovered. This work culminated in the identification of compound 30 (AZD7986) as a highly potent, reversible, and selective clinical candidate for COPD, with predicted human PK properties suitable for once daily human dosing.
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http://dx.doi.org/10.1021/acs.jmedchem.6b01127 | DOI Listing |
JMIR Res Protoc
January 2025
Division of Services and Interventions Research, National Institute of Mental Health, Bethesda, MD, United States.
Background: Although substantial progress has been made in establishing evidence-based psychosocial clinical interventions and implementation strategies for mental health, translating research into practice-particularly in more accessible, community settings-has been slow.
Objective: This protocol outlines the renewal of the National Institute of Mental Health-funded University of Washington Advanced Laboratories for Accelerating the Reach and Impact of Treatments for Youth and Adults with Mental Illness Center, which draws from human-centered design (HCD) and implementation science to improve clinical interventions and implementation strategies. The Center's second round of funding (2023-2028) focuses on using the Discover, Design and Build, and Test (DDBT) framework to address 3 priority clinical intervention and implementation strategy mechanisms (ie, usability, engagement, and appropriateness), which we identified as challenges to implementation and scalability during the first iteration of the center.
Codas
January 2025
Faculdade de Medicina, Universidade de São Paulo - USP - São Paulo (SP), Brasil.
Purpose: To identify the most significant risk factors for child development through the application of two risk protocols, namely, the Protocol for the Identification of Risk Factors for Language and Speech Disorders (PIFRAL) and the Language Development Protocol (PDL).
Methods: A retrospective study was carried out with 194 children aged 0 to 5 years and 11 months who were participants of primary health care (PHC) in the municipality of São Paulo, Brazil, from 2016 to 2020. The database was thoroughly analyzed using R software, and the most relevant risk factors were correlated through statistical analysis, generating altered and unaltered PDL results.
Arq Bras Oftalmol
January 2025
Department of Ophthalmology, Guangdong Eye Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences. No. 106 Zhongshan Er Road, Guangzhou 510080, China.
Purpose: Although the orthokeratology effects on corneal biomechanics have been proven with clinical trials, reports of stiffness parameter change are scarce. This study investigated the short-term orthokeratology effects in pediatric myopia and compared stiffness parameter changes to those published in recent clinical investigations. This prospective study aimed to investigate corneal biomechanics changes induced by short-term overnight orthokeratology treatment, focusing on stiffness parameter at A1 and stress-strain index.
View Article and Find Full Text PDFSci Transl Med
January 2025
Department of Surgery, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Pancreatic ductal adenocarcinoma (PDAC) driven by the mutation presents a formidable health challenge because of limited treatment options. MRTX1133 is a highly selective and first-in-class KRAS-G12D inhibitor under clinical development. Here, we report that the advanced glycosylation end product-specific receptor (AGER) plays a key role in mediating MRTX1133 resistance in PDAC cells.
View Article and Find Full Text PDFSci Robot
January 2025
Department of Mechanical Engineering, University of Hong Kong, Pokfulam, Hong Kong, China.
Micro air vehicles (MAVs) capable of high-speed autonomous navigation in unknown environments have the potential to improve applications like search and rescue and disaster relief, where timely and safe navigation is critical. However, achieving autonomous, safe, and high-speed MAV navigation faces systematic challenges, necessitating reduced vehicle weight and size for high-speed maneuvering, strong sensing capability for detecting obstacles at a distance, and advanced planning and control algorithms maximizing flight speed while ensuring obstacle avoidance. Here, we present the safety-assured high-speed aerial robot (SUPER), a compact MAV with a 280-millimeter wheelbase and a thrust-to-weight ratio greater than 5.
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