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The Adverse Outcome Pathway (AOP) framework contributes to understanding how specific and measurable biological perturbations cause adverse effects on human and environmental health. Recognizing the value of AOPs to support regulatory decisions around the world, the Organisation for Economic Co-operation and Development (OECD) launched the AOP Programme in 2012, which sought to promote and guide the development of AOPs to ensure their suitability for the downstream applications in the context of regulatory safety assessment. OECD published the initial guidance on AOP development and assessment in 2013, which has been expanded as practices have evolved and matured. AOP development requires adherence to specific principles and considerations for identifying and describing key events (KEs) and representing and assessing the weight of evidence for the key event relationships (KERs). Ultimately, the structured and consistent application of the principles helps build confidence in the applicability of the knowledge represented in the AOP for decision making in the regulatory context. To assist new AOP developers, in 2019, the OECD introduced a coaching program. This program primarily aims to pair novices with experienced AOP developers (ie, coaches). International partnerships in the coaching program contribute to harmonizing and promoting AOP development according to the OECD guidance. Coaches have also helped to identify and initiate "Gardening" efforts that remove redundant/synonymous KEs in the AOP-Wiki, allowing for improved AOP network creation, promoting the re-use of extensively reviewed KEs, and ensuring the development of high-quality AOPs. The AOP Coaching Program represents the latest international activity to ensure that AOPs are developed in a consistent manner that is designed to enhance their use for supporting public health decisions around the world.
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http://dx.doi.org/10.1093/etojnl/vgaf173 | DOI Listing |
Environ Mol Mutagen
September 2025
Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.
Long-duration spaceflight exposes astronauts to various stressors that can alter human physiology, potentially causing immediate and long-term health effects. These stressors can damage biomolecules, cells, tissues, and organs, leading to adverse outcomes. Developing adverse outcome pathways (AOPs) relevant to radiation exposure can guide research priorities and inform risk assessments of future space exploration activities.
View Article and Find Full Text PDFAge Ageing
August 2025
Department of Social Determinants of Health, Division of Healthier Populations, World Health Organization, Geneva, Switzerland.
The Abuse of Older People - Intervention Accelerator (AOP-IA) project aims to accelerate the development of effective interventions to prevent and reduce AOP aged 60 and older within the framework of the United Nations Decade of Healthy Ageing (2021-2030). The AOP-IA was launched in response to the global need for interventions with proven effectiveness, as few existing approaches have been rigorously evaluated. This paper focuses on the first two phases of the AOP-IA project, which involved conducting a systematic search, screening and evaluation process to identify candidate interventions ready to be rigorously evaluated in future stages of the project, as well as establishing a network of intervention developers.
View Article and Find Full Text PDFAnn Hematol
September 2025
Department of Internal Medicine I, Division of Hematology and Hemostaseology, Medical University of Vienna, Vienna, Austria.
In a subset of patients with systemic mastocytosis (SM), an associated hematologic neoplasm (AHN) is identified. Most AHN are myeloid neoplasms, whereas lymphoid neoplasms are uncommon. We report on a 70-year-old female patient with bone marrow mastocytosis (BMM) associated with primary cutaneous follicle center lymphoma (PCFCL).
View Article and Find Full Text PDFOpen Heart
September 2025
Cardiology Department, Sahlgrenska University Hospital, Gothenburg, Sweden.
Aims: We investigated the prevalence of coronary microvascular dysfunction (CMD) and its association with severity of heart failure in patients with reduced or mildly reduced ejection fraction (HFrEF and HFmrEF).
Method: Patients with stable, symptomatic heart failure with left ventricular ejection fraction (LVEF) <50% were enrolled. Data collection included physical examination, blood samples, Kansas City Cardiomyopathy Questionnaire (KCCQ), carotid to femoral pulse wave velocity, echocardiography and adenosine-based transthoracic Doppler echocardiography to assess coronary flow reserve (CFR).
ALTEX
August 2025
Department of Biomedical Engineering, Institute for Quantitative Health Science and Engineering, Michigan State University, East Lansing, MI, USA.
Sonic hedgehog (SHH) is a major intercellular signaling pathway involved in the orchestration of embryogenesis, including orofacial morphogenesis. The SHH pathway is sensitive to disruption, including both genetic predisposition and chemical-induced disruption at multiple molecular targets including antagonism of the SHH signal transducer Smoothened (SMO). Here we report the adverse outcome pathway (AOP) 460 describing the linkage between antagonism of the SMO receptor, a key intermediate in the hedgehog signaling, and orofacial clefts (OFCs).
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