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Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps.

ABSTRACT: Introduction: The Adverse Outcome Pathway (AOP) concept facilitates rapid hazard assessment for human health risks. AOPs are constantly evolving, their number is growing, and they are referenced in the AOP-Wiki database, which is supported by the OECD. Here, we present a study that aims at identifying well-defined biological areas, as well as gaps within the AOP-Wiki for future research needs. It does not intend to provide a systematic and comprehensive summary of the available literature on AOPs but summarizes and maps biological knowledge and diseases represented by the already developed AOPs (with OECD endorsed status or under validation). Methods: Knowledge from the AOP-Wiki database were extracted and prepared for analysis using a multi-step procedure. An automatic mapping of the existing information on AOPs (i.e., genes/proteins and diseases) was performed using bioinformatics tools (i.e., overrepresentation analysis using Gene Ontology and DisGeNET), allowing both the classification of AOPs and the development of AOP networks (AOPN). Results: AOPs related to diseases of the genitourinary system, neoplasms and developmental anomalies are the most frequently investigated on the AOP-Wiki. An evaluation of the three priority cases (i.e., immunotoxicity and non-genotoxic carcinogenesis, endocrine and metabolic disruption, and developmental and adult neurotoxicity) of the EU-funded PARC project (Partnership for the Risk Assessment of Chemicals) are presented. These were used to highlight under- and over-represented adverse outcomes and to identify and prioritize gaps for further research. Discussion: These results contribute to a more comprehensive understanding of the adverse effects associated with the molecular events in AOPs, and aid in refining risk assessment for stressors and mitigation strategies. Moreover, the FAIRness (i.e., data which meets principles of findability, accessibility, interoperability, and reusability (FAIR)) of the AOPs appears to be an important consideration for further development.

SUBMITTER: Jaylet T

PROVIDER: S-EPMC10958381 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature

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Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps.

Jaylet Thomas T Coustillet Thibaut T Smith Nicola M NM Viviani Barbara B Lindeman Birgitte B Vergauwen Lucia L Myhre Oddvar O Yarar Nurettin N Gostner Johanna M JM Monfort-Lanzas Pablo P Jornod Florence F Holbech Henrik H Coumoul Xavier X Sarigiannis Dimosthenis A DA Antczak Philipp P Bal-Price Anna A Fritsche Ellen E Kuchovska Eliska E Stratidakis Antonios K AK Barouki Robert R Kim Min Ji MJ Taboureau Olivier O Wojewodzic Marcin W MW Knapen Dries D Audouze Karine K

Frontiers in toxicology 20240308

<b>Introduction:</b> The Adverse Outcome Pathway (AOP) concept facilitates rapid hazard assessment for human health risks. AOPs are constantly evolving, their number is growing, and they are referenced in the AOP-Wiki database, which is supported by the OECD. Here, we present a study that aims at identifying well-defined biological areas, as well as gaps within the AOP-Wiki for future research needs. It does not intend to provide a systematic and comprehensive summary of the available literature ...[more]

PMID: 38523647

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Project description:Background: Forensic psychiatric care treats mentally disordered offenders who suffer mainly from psychotic disorders, although comorbidities such as personality disorders, neurodevelopmental disorders, and substance abuse are common. A large proportion of these patients have committed violent crimes. Their care is involuntary, and their caregivers' mission is complex: not only to rehabilitate the patient, but also to consider their risk for reoffending and their risk to society. The objective of this overview of systematic reviews is to identify, appraise, and summarize the existing knowledge in forensic psychiatric care and identify knowledge gaps that require further research. Methods: We undertook a systematic literature search for systematic reviews in five defined domains considered important in daily clinical practice within the forensic psychiatric care: (1) diagnostic assessment and risk assessments; (2) pharmacological treatment; (3) psychological interventions; (4) psychosocial interventions, rehabilitation, and habilitation; and (5) restraint interventions. The target population was mentally disordered offenders (forensic psychiatric patients aged >15 years). Each abstract and full text review was assessed by two of the authors. Relevant reviews then were assessed for bias, and those with moderate or low risk of bias were included. Results: Of 38 systematic reviews meeting the inclusion criteria, only four had a moderate risk of bias. Two aimed to incorporate as many aspects of forensic psychiatric care as possible, one investigated non-pharmacological interventions to reduce aggression in forensic psychiatric care, and one focused on women with intellectual disabilities in forensic care. However, most of the primary studies included in these reviews had high risks of bias, and therefore, no conclusions could be drawn. All of our identified domains must be considered knowledge gaps. Conclusion: We could not answer any of our research questions within the five domains because of the high risk of bias in the primary studies in the included systematic reviews. There is an urgent need for more research on forensic psychiatric care since all of our studied domains were considered knowledge gaps.

Project description:ObjectiveAn individual's understanding of disease risk factors and outcomes is important for the ability to make healthy lifestyle choices and decisions about disease treatment. Peripheral artery disease (PAD) is a condition with increasing global prevalence and high risk of adverse patient outcomes. This study seeks to understand the adequacy of disease understanding in patients with PAD.MethodsThis was an observational study of patients with PAD recruited from vascular surgery outpatient clinic and PAD clinical studies at a single academic medical center over an 8-month period. A 44-item paper survey assessed demographic and socioeconomic information, knowledge of personal medical history, PAD risk factors, consequences of PAD, and health education preferences. Patients with documented presence of PAD were offered the survey. Patients unable to complete the survey or provide informed consent were not considered eligible. Disease "awareness" was defined as correct acknowledgement of the presence or absence of a disease, including PAD, in the personal medical history. "PAD knowledge score" was the percentage of correct responses to questions on general PAD risk factors and consequences. Of 126 eligible patients, 109 participated. Bivariate analysis was used to study factors associated with awareness of PAD diagnosis. Factors associated with the PAD knowledge score were studied using the Pearson correlation coefficient, two-sample t test, or one-way analysis of variance. P value < .05 was considered statistically significant.ResultsThe mean participant age was 69.4 ± 11.0 years, and 39.4% (n = 43) were female. Most participants (78.9%; n = 86) had critical limb-threatening ischemia. Only 65.4% (n = 70) of participants were aware of a diagnosis of PAD, which was less than their awareness of related comorbidities. Factors positively associated with PAD diagnosis awareness were female sex (81.4% vs 54.7%; P = .004) and history of percutaneous leg revascularization (78.6% vs 47.9%; P = .001). Among 17 patients who had undergone major leg amputation, 35% (n = 6) were unaware of a diagnosis of PAD. PAD knowledge scores correlated positively with an awareness of PAD diagnosis (59.1% vs 48.7%; P = .02) and negatively with a history of hypertension (53.4% vs 68.1%; P = .001). Most participants (86.5%; n = 90) expressed a desire to be further educated on PAD. The most popular education topics were dietary recommendations, causes, and treatment for PAD.ConclusionsPatients with PAD have deficits in their awareness of this diagnosis and general knowledge about PAD. Future research priorities should further define these deficits and their causes in order to inform new strategies that foster information-seeking behavior and effective educational programs for PAD.

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Dataset Information

Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps.

Publications

Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps.

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