Background: Adverse outcome pathway (AOP) networks are versatile tools in toxicology and risk assessment that capture and visualize mechanisms driving toxicity originating from various data sources. They share a common structure consisting of a set of molecular initiating events and key events, connected by key event relationships, leading to the actual adverse outcome. AOP networks are to be considered living documents that should be frequently updated by feeding in new data. Such iterative optimization exercises are typically done manually, which not only is a time-consuming effort, but also bears the risk of overlooking critical data. The present study introduces a novel approach for AOP network optimization of a previously published AOP network on chemical-induced cholestasis using artificial intelligence to facilitate automated data collection followed by subsequent quantitative confidence assessment of molecular initiating events, key events, and key event relationships. Methods: Artificial intelligence-assisted data collection was performed by means of the free web platform Sysrev. Confidence levels of the tailored Bradford-Hill criteria were quantified for the purpose of weight-of-evidence assessment of the optimized AOP network. Scores were calculated for biological plausibility, empirical evidence, and essentiality, and were integrated into a total key event relationship confidence value. The optimized AOP network was visualized using Cytoscape with the node size representing the incidence of the key event and the edge size indicating the total confidence in the key event relationship. Results: This resulted in the identification of 38 and 135 unique key events and key event relationships, respectively. Transporter changes was the key event with the highest incidence, and formed the most confident key event relationship with the adverse outcome, cholestasis. Other important key events present in the AOP network include: nuclear receptor changes, intracellular bile acid accumulation, bile acid synthesis changes, oxidative stress, inflammation and apoptosis. Conclusions: This process led to the creation of an extensively informative AOP network focused on chemical-induced cholestasis. This optimized AOP network may serve as a mechanistic compass for the development of a battery of in vitro assays to reliably predict chemical-induced cholestatic injury.
The Junior Adverse Drug Event Manager (J-ADEM) team is a multifaceted intervention focusing on real-life education for medical students that has been shown to assist healthcare professionals in managing and reporting suspected adverse drug reactions (ADRs) to the Netherlands Pharmacovigilance Centre Lareb. The aim of this study was to quantify and describe the ADRs reported by the J-ADEM team and to determine the clinical potential of this approach. The J-ADEM team consisted of medical students tasked with managing and reporting ADRs in hospitalized patients. All ADRs screened and reported by J-ADEM team were recorded anonymously, and categorized and analysed descriptively. From August 2018 through January 2020, 209 patients on two wards in an academic hospital were screened for ADR events. The J-ADEM team reported 101 ADRs. Although most ADRs (67%) were first identified by healthcare professionals and then reported by the J-ADEM team, the team also reported an additional 33 not previously identified serious ADRs. In 10% of all reported ADRs, the J-ADEM team helped optimize ADR treatment. The ADR reports were largely well-documented (78%), and ADRs were classified as type A (66%), had a moderate or severe severity (85%) and were predominantly avoidable reactions (69%). This study shows that medical students are able to screen patients for ADRs, can identify previously undetected ADRs and can help optimize ADR management. They significantly increased (by 300%) the number of ADR reports submitted, showing that the J-ADEM team can make a valuable clinical contribution to hospital care.
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Movebite aims to combat the issue of sedentary behavior prevalent among office workers. A recent report of the Nederlandse Sportraad reveal a concerning trend of increased sitting time among Dutch employees, leading to a myriad of musculoskeletal discomforts and significant health costs for employers due to increased sick leave. Recognizing the critical importance of addressing prolonged sitting in the workplace, Movebite has developed an innovative concept leveraging cutting-edge technology to provide a solution. The Movebite app seamlessly integrates into workplace platforms such as Microsoft Teams and Slack, offering a user-friendly interface to incorporate movement into their daily routines. Through scalable AI coaching and real-time movement feedback, Movebite assists individuals in scheduling and implementing active micro-breaks throughout the workday, thereby mitigating the adverse effects of sedentary behavior. In collaboration with the Avans research group Equal Chance on Healthy Choices, Movebite conducts user-centered testing to refine its offerings and ensure maximum efficacy. This includes testing initiatives at sports events, where the diverse crowd provides invaluable feedback to fine-tune the app's features and user experience. The testing process encompasses both quantitative and qualitative approaches based on the Health Belief Model. Through digital questionnaires, Movebite aims to gauge users' perceptions of sitting as a health threat and the potential benefits of using the app to alleviate associated risks. Additionally, semi-structured interviews delve deeper into user experiences, providing qualitative insights into the app's usability, look, and feel. By this, Movebite aims to not only understand the factors influencing adoption but also to tailor its interventions effectively. Ultimately, the goal is to create an environment encouraging individuals to embrace physical activity in small, manageable increments, thereby fostering long-term engagement promoting overall well-being.Through continuous innovation and collaboration with research partners, Movebite remains committed to empowering individuals to lead healthier, more active lifestyles, one micro-break at a time.
