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Discovery and Optimization of Novel Apo-IDO1 Inhibitors by a Pharmacophore-Based Structural Simplification Strategy.
J Med Chem
March 2025
Jiangsu Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 211198, P. R. China.
Indoleamine 2,3-dioxygenase-1 (IDO1) plays a crucial role in tumor immune escape. However, the limited clinical efficacy of traditional IDO1 inhibitors has impeded their further development. Recently, apo-IDO1 inhibitors that displace the heme to target IDO1 have been discovered, which exhibits a slow dissociation rate reminiscent of irreversible inhibitors.
View Article and Find Full Text PDFserotypes in the genomic era: simplified serotype interpretation from DNA sequence data.
Appl Environ Microbiol
February 2025
Division of Foodborne, Waterborne and Environmental Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.
In the era of genomic characterization of strains for public health microbiology, whole genome sequencing (WGS)-enabled subtyping of provides superior discrimination of strains compared to traditional methods such as serotyping. Nonetheless, serotypes are still very useful; they maintain historical continuity and facilitate clear communication. Genetic determination of serotypes from WGS data is now routine.
View Article and Find Full Text PDFRealigning diabetes regimens in older adults: a 4S Pathway to guide simplification and deprescribing strategies.
Lancet Diabetes Endocrinol
February 2025
Department of Medicine, Upstate Medical University, Syracuse, NY, USA.
Treating older people with diabetes is challenging due to multiple medical comorbidities that might interfere with patients' ability to perform self-care. Most diabetes guidelines focus on improving glycaemia through addition of medications, but few address strategies to reduce medication burden for older adults-a concept known as deprescribing. Strategies for deprescribing might include stopping high-risk medications, decreasing the dose, or substituting for less harmful agents.
View Article and Find Full Text PDFChallenges and ongoing initiatives towards better integrated EU scientific advice.
Front Med (Lausanne)
January 2025
Agenzia Italiana del Farmaco - Italian Medicines Agency, Rome, Italy.
Scientific advice is the main avenue for clarification of EU regulators' scientific evidence requirements during medicines development. There are multiple avenues for seeking scientific advice in the EU with partially overlapping scope which creates room for divergence and contradictions; simplification and better integration among them could help harmonize EU regulators' requirements. Interaction with other decision makers providing advice along the lifecycle of medicines and other healthcare solutions reduces development uncertainties.
View Article and Find Full Text PDFConsensus recommendations for measuring the impact of contraception on the menstrual cycle in contraceptive clinical trials.
Contraception
January 2025
MSI Reproductive Choices, London, England, UK.
Objective: We sought to develop consensus recommendations for measurement and analysis of data on contraceptive-induced menstrual changes (CIMCs) in contraceptive clinical trials. We built upon previous standardization efforts over the last 50 years and prioritized input from a variety of global experts and current regulatory authority guidance on patient-reported outcomes.
Study Design: We completed a formal consensus-building process with an interdisciplinary group of 57 experts from 30 organizations and 14 countries in five global regions who work across academia, nonprofit research organizations, the pharmaceutical industry, and funding agencies.
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