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Change surface regression for nonlinear subgroup identification with application to warfarin pharmacogenomics data.
Biometrics
January 2025
Department of Statistics and Data Science, National University of Singapore, Singapore 117546, Singapore.
Pharmacogenomics stands as a pivotal driver toward personalized medicine, aiming to optimize drug efficacy while minimizing adverse effects by uncovering the impact of genetic variations on inter-individual outcome variability. Despite its promise, the intricate landscape of drug metabolism introduces complexity, where the correlation between drug response and genes can be shaped by numerous nongenetic factors, often exhibiting heterogeneity across diverse subpopulations. This challenge is particularly pronounced in datasets such as the International Warfarin Pharmacogenetic Consortium (IWPC), which encompasses diverse patient information from multiple nations.
View Article and Find Full Text PDFDevelopment and Clinical Validation of Model-Informed Precision Dosing for Everolimus in Liver Transplant Recipients.
ACS Pharmacol Transl Sci
January 2025
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea.
Everolimus presents significant dosing challenges due to between- and within-patient pharmacokinetic variabilities. This study aimed to develop and validate a model-informed precision dosing strategy for everolimus in liver transplant recipients. The dosing strategy was initially developed using retrospective data, employing nonlinear mixed-effects modeling.
View Article and Find Full Text PDFFrom "isolation" to "me-time": linguistic shifts enhance solitary experiences.
Cogn Emot
January 2025
School of Communication, The Ohio State University, Columbus, OH, USA.
Spending time alone is a virtually inevitable part of daily life that can promote or undermine well-being. Here, we explore how the language used to describe time alone - such as "me-time", "solitude", or "isolation" - influences how it is perceived and experienced. In Study 1 ( = 500 U.
View Article and Find Full Text PDFAwakening not associated with an increased rate of cortisol secretion.
Proc Biol Sci
January 2025
Laboratory for Integrative Neuroscience and Endocrinology, University of Bristol, Bristol BS1 3NY, UK.
Cortisol is released upon activation of the hypothalamic-pituitary-adrenal axis, varies across the day, possesses an underlying diurnal rhythm and is responsive to stressors. The endogenous circadian peak of cortisol occurs in the morning, and increases in cortisol observed post-awakening have been named the cortisol awakening response (CAR) based on the belief that the act of waking up stimulates cortisol secretion. However, objective evidence that awakening induces cortisol secretion is limited.
View Article and Find Full Text PDFMechanisms for dysregulation of excitatory-inhibitory balance underlying allodynia in dorsal horn neural subcircuits.
PLoS Comput Biol
January 2025
Department of Mathematics and Statistics, Middlebury College, Middlebury, Vermont, United States of America.
Chronic pain is a wide-spread condition that is debilitating and expensive to manage, costing the United States alone around $600 billion in 2010. In a common symptom of chronic pain called allodynia, non-painful stimuli produce painful responses with highly variable presentations across individuals. While the specific mechanisms remain unclear, allodynia is hypothesized to be caused by the dysregulation of excitatory-inhibitory (E-I) balance in pain-processing neural circuitry in the dorsal horn of the spinal cord.
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