Here, we propose a broad concept of 'Clinical Outcome Pathways' (COPs), which are defined as a series of key molecular and cellular events that underlie therapeutic effects of drug molecules. We formalize COPs as a chain of the following events: molecular initiating event (MIE) → intermediate event(s) → clinical outcome. We illustrate the concept with COP examples both for primary and alternative (i.e., drug repurposing) therapeutic applications. We also describe the elucidation of COPs for several drugs of interest using the publicly accessible Reasoning Over Biomedical Objects linked in Knowledge-Oriented Pathways (ROBOKOP) biomedical knowledge graph-mining tool. We propose that broader use of COP uncovered with the help of biomedical knowledge graph mining will likely accelerate drug discovery and repurposing efforts.
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http://dx.doi.org/10.1016/j.drudis.2022.02.008 | DOI Listing |
Exp Physiol
January 2025
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
There is limited knowledge on diffusing capacity in scoliosis patients. It remains to be determined if impaired pulmonary diffusing capacity is mostly influenced by reduced alveolar-capillary membrane diffusing capacity (D), reduced pulmonary capillary blood volume (V) or both. This study aims to report findings from dual test gas pulmonary diffusing capacity for carbon monoxide and nitric oxide (D) with quantification of pulmonary diffusing capacity for carbon monoxide corrected for haemoglobin with a five s breath-hold (D) and nitric oxide with a five s breath-hold (D), D and V.
View Article and Find Full Text PDFCurr Neuropharmacol
January 2025
Department of Pharmacy, DIFAR, Pharmacology and Toxicology Section, University of Genoa, Viale Cembrano 4, 16148, Genoa, Italy.
The central nervous system (CNS) is not an immune-privileged compartment, but it is intimately intertwined with the immune system. Among the components shared by the two compartments is the complement, a main constituent of innate immunity, which is also produced centrally and controls the development and organization of synaptic connections. Complement is considered a doubled-faced system that, besides controlling the physiological development of the central network, also subserves synaptic engulfment pivotal to the progression of neurodegenerative diseases.
View Article and Find Full Text PDFBMC Res Notes
January 2025
Department of General Surgery, The Royal Marsden Hospital, London, UK.
Research progress and innovation are hindered by barriers, inequalities, and exclusions within academia. Embracing equality, diversity, and inclusion (EDI) is not only an ethical imperative but also essential for advancing knowledge and addressing global challenges. EDI principles ensure that researchers from all backgrounds have equitable opportunities to contribute to and benefit from research.
View Article and Find Full Text PDFBMC Musculoskelet Disord
January 2025
Medical Genetic Diagnosis and Therapy Center, Fujian Maternity and Child Health Hospital, College of Clinical Medicine for Obstetrics and Gynecology and Pediatrics, Fujian Medical University, 18 Daoshan Road, Fuzhou, 350001, China.
Background: Congenital muscular dystrophies (CMDs) and myopathies (CMYOs) are a clinically and genetically heterogeneous group of neuromuscular disorders that share common features, such as muscle weakness, hypotonia, characteristic changes on muscle biopsy and motor retardation. In this study, we recruited eleven families with early-onset neuromuscular disorders in China, aimed to clarify the underlying genetic etiology.
Methods: Essential clinical tests, such as biomedical examination, electromyography and muscle biopsy, were applied to evaluate patient phenotypes.
Sci Rep
January 2025
Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China.
Alzheimer's Disease (AD) significantly aggravates human dignity and quality of life. While newly approved amyloid immunotherapy has been reported, effective AD drugs remain to be identified. Here, we propose a novel AI-driven drug-repurposing method, DeepDrug, to identify a lead combination of approved drugs to treat AD patients.
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