In childhood, adolescence and young adults (CAYA), melanoma is under-studied and non-existing tailored clinical guidelines and standardized approaches lead to a very low diagnostic accuracy. The MELCAYA project aims to understand risk factors and determinants of melanoma to improve the prevention, diagnosis and prognosis of melanomas in CAYAs through a strong international consortium with experts from 10 countries in different disciplines (e.g. oncology, paediatrics, ethics, policy making), and sectors (e.g. academic centers, SMEs, hospitals, patient associations). MELCAYA will work on different approaches. 1) By integrating existing reference European cohorts and registries, studies of genetic and environmental risk factors and progression of melanoma in CAYA will be performed through different omic methods, and a novel taxonomy of CAYA melanoma will be generated. 2) MELCAYA will also develop image-based robust and trustworthy machine learning tools and a pan-European second-opinion platform for better diagnosis specifically designed for CAYA. 3) Moreover, the validation of minimally and non-invasive disruptive tools based on artificial intelligence and volatilomics detection from exhaled breath and skin will lead to earlier detection and more accurate prognosis of melanoma in CAYA. 4) Finally, through the evidence gathered, MELCAYA will design and implement public health strategies and will actively involve patients and the general population. The results of MELCAYA will maximize its impact by making its data and results accessible and re-usable through integration into UNCAN.eu. This action is part of the Cancer Mission cluster of projects on ‘‘Understanding".

Clear evidence supports associations between endocrine disrupting chemical (EDC) exposure and impaired neurodevelopment. Yet, current hazard assessment of EDCs does not address developmental neurotoxicity. This is due to lack of scientific knowledge on how endocrine disruption is linked to developmental neurotoxicity (DNT). Thus there is an urgent need for novel testing and screening tools to address ED-induced DNT, based on new scientific knowledge. This calls for rapid advances in basic research as well as in the development of screening and testing tools close to the end-users. ENDpoiNTs will address this need by i) integrating advanced expertise in the EDC and DNT fields, two so far rather independent toxicology communities, and ii) continuous interaction with European and international key stakeholders. By combining state-of-the-art in silico and in vitro tools, innovative experimental designs and technologies, and advanced biostatistics on human epidemiological and biomonitoring data, ENDpoiNTs will 1) Generate the necessary scientific insights on the correlative and causal links between endocrine disruption and DNT; 2) Develop predictive in silico tools for chemical screening using machine learning and combination of evidence; 3) Develop and validate in vitro tools for chemical screening and testing that address sex- and species differences; 4) Develop novel molecular endpoints for existing animal-based test guidelines by integrating in vitro, in vivo, and human omics data with behavioural outcomes; 5) Ensure human relevance by linking experimental and epidemiological evidence; 6) Develop an integrated testing approach based on the developed in silico, in vitro, and in vivo assays and molecular markers; 7) Ensure regulatory relevance by developing strategies for implementation of these tools and endpoints into regulatory frameworks. In this way, ENDpoiNTs will meet the scientific, regulatory, and societal needs for improved hazard and risk assessment of EDCs

The aim of the research is to study the effects of smallest traffic related ultrafine- or nanoparticles beyond the lung on brain health. Air pollutants have been shown to cause a vast amount of different adverse health effects. These effects include impairment of many respiratory (e.g. asthma, COPD) and cardiovascular (ischemic heart disease, infarction, stroke) diseases. However, in recent years, the evidence showing effects beyond the lungs and circulatory system are becoming more evident. Neurological diseases, namely Alzheimer´s disease (AD) has shown to be associated with living near traffic. However, reason for this has remained unresolved until today. This consortium aims on revealing the mechanisms and exposures both behind cardiorespiratory diseases and beyond the current knowledge in neurological diseases. This consortium includes experts in areas of aerosol technology, emission research, engine and fuel research, human clinical studies, epidemiology, emission inventories, inhalation toxicology, neurotoxicology and disease mechanism studies. This enables research of resolving the effects of nanoparticles from different traffic modes for both air quality and concomitant toxic effect of these air pollutants. In this study, we will investigate adverse effects of air pollutants using cell cultures, animal exposures and volunteered human exposures as well as the material from epidemiological cohort study. These are going to be compared according to inflammatory, cytotoxic and genotoxic changes and furthermore beyond the current state of the art to neurotoxic and brain health effects. With this approach, we are aiming in to a comprehensive understanding of the adverse effects of nanoparticles from traffic. In current situation only particles above 23nm are measured in regulations, traditional toxicological methods are used in risk assessment and emission inventories and regulations are largely based on old technology engines. Our project will change this.

The vision of the ONTOX consortium is to provide a functional and sustainable solution for advancing human risk assessment of chemicals without the use of animals in line with the principles of 21st century toxicity testing and next generation risk assessment. Specifically, ONTOX will deliver a generic strategy to create innovative new approach methodologies (NAMs) in order to predict systemic repeated dose toxicity effects that, upon combination with tailored exposure assessment, will enable human risk assessment. This strategy can be applied to any type of chemical and systemic repeated dose toxicity effect. However, for proof-of-concept purposes, focus will be put on 6 specific NAMs addressing adversities in the liver (steatosis and cholestasis), kidneys (tubular necrosis and crystallopathy) and developing brain (neural tube closure and cognitive function defects) induced by a variety of chemicals, including from the pharmaceutical, cosmetics, food and biocide sectors. The 6 NAMs will each consist of a computational system based on cutting-edge artificial intelligence (AI) and will be primarily fed by available biological/mechanistic, toxicological/epidemiological, physico-chemical and kinetic data. Data will be consecutively integrated in physiological maps, quantitative adverse outcome pathway networks and ontology frameworks. Data gaps, as identified by AI, will be filled by targeted state-of-the-art in vitro and in silico testing. The 6 NAMs will be evaluated and applied in collaboration with industrial and regulatory stakeholders in order to maximise end-user acceptance and regulatory confidence. This is anticipated to expedite implementation in risk assessment practice and to facilitate commercialisation. ONTOX will have a deep and long-lasting impact at many levels, in particular by consolidating Europe’s world-leading position regarding the development, exploitation, regulation and application of animal-free methods for human risk assessment of chemicals.