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Re-examining the pathobiological basis of gait dysfunction in Parkinson's disease.
Trends Neurosci
January 2025
Department of Neurosurgery, Department of Surgery, University of Toronto, Toronto, Ontario, Canada; Krembil Brain Institute, Toronto Western Hospital, Toronto, Ontario, Canada; Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, Ontario, Canada.
Parkinson's disease (PD) is a significant source of morbidity, especially with an aging population. Gait problems, particularly freezing of gait (FOG), remain a persistent issue, causing falls and reduced quality of life without consistent responses to therapies. PD and related symptoms have classically been attributed to dopamine deficiency secondary to substantia nigra degeneration from Lewy body (LB) and Lewy neurite (LN) infiltration.
View Article and Find Full Text PDFUtility of physiologically based pharmacokinetic modeling in predicting and characterizing clinical drug interactions.
Drug Metab Dispos
January 2025
Pharmacokinetics, Dynamics, Metabolism and Bioanalytics, Merck & Co, Inc, Boston, Massachusetts. Electronic address:
Physiologically based pharmacokinetic (PBPK) modeling is a mechanistic dynamic modeling approach that can be used to predict or retrospectively describe changes in drug exposure due to drug-drug interactions (DDIs). With advancements in commercially available PBPK software, PBPK DDI modeling has become a mainstream approach from early drug discovery through to late-stage drug development and is often used to support regulatory packages for new drug applications. This Minireview will briefly describe the approaches to predicting DDI using PBPK and static modeling approaches, the basic model structures and features inherent to PBPK DDI models, and key examples where PBPK DDI models have been used to describe complex DDI mechanisms.
View Article and Find Full Text PDFDoes coronary microvascular dysfunction play a role in heart failure with reduced ejection fraction?
J Mol Cell Cardiol
January 2025
Department of Integrative Medical Sciences, Northeast Ohio Medical University. Electronic address:
Heart failure (HF) is a conundrum in that, current therapies only slow the progression of the disease. We posit, if the causal mechanism were targeted, progression of the disease could be stopped and potentially reversed. We hypothesize that insufficient myocardial blood flow (MBF) produces minute areas of ischemia, that lead to an accumulating injury culminating in HF.
View Article and Find Full Text PDFDiagnostic Performance of the Modified Lung-RADS in a Tuberculosis-endemic Country: The Korean National Lung Cancer Screening Program.
Chest
January 2025
Division of Cancer Early Detection, National Cancer Control Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang 10408, Korea. Electronic address:
Background: In 2019, Korea initiated the world's first national low-dose computed tomography (CT) lung cancer screening (LCS) program, adapting the Lung CT Screening Reporting and Data System (Lung-RADS) to counteract the high false-positive rates driven by prevalent tuberculosis.
Research Question: Does the modified Lung-RADS enhance screening specificity while maintaining sensitivity?
Study Design And Methods: This nationwide, retrospective, cohort study included high-risk current smokers aged 54 to 74 with at least 30 pack-years, participating in the national LCS program from 2019 to 2020. The modified Lung-RADS 1.
Common issues of data science on the eco-environmental risks of emerging contaminants.
Environ Int
January 2025
Key Laboratory of Pollution Processes and Environmental Criteria (Ministry of Education), Carbon Neutrality Interdisciplinary Science Centre, College of Environmental Science and Engineering, Nankai University, Tianjin 300350, China.
Data-driven approaches (e.g., machine learning) are increasingly used to replace or assist laboratory studies in the study of emerging contaminants (ECs).
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