The increasing use of radiation-associated diagnostic and therapeutic procedures have contributed to the improvements of early diagnosis and survival of paediatric patients. While benefits to the patient outweigh the radiation associated risk, the late effects of exposure of children are particularly important to understand in populations with increased survival. The HARMONIC project builds on close collaboration between scientific and medical communities to contribute to improvements in the understanding of the health effects of medical ionising radiation exposure of paediatric patients, focusing on two distinct and complementary populations: (1) Paediatric patients undergoing modern radiotherapy (including proton therapy); (2) Paediatric patients undergoing interventional cardiology. Our project will provide additional insight into exposure to ionising radiation in childhood, exploring potential effects at very early ages, exposure to a wide range of doses from photons, protons and secondary neutrons radiation. We aim at building European cohorts and registries for long term follow-up of paediatric patients treated with ionising radiation, both in cardiology and oncology settings, in the context of very rapid technology evolution. The study will use an integrated approach of conventional epidemiology, based on state-of-the art dosimetry, complemented by non-invasive imaging and molecular epidemiology to assess the following outcomes: endocrine dysfunctions, cardio and neurovascular diseases, societal impact and cancer. Complementary to this effort, we propose to investigate radiation-induced cellular responses in samples of blood and saliva, and the mechanisms involved in the processes that may lead to cancer and vascular diseases. Ultimately, HARMONIC will develop tools and allow definition of guidelines on optimization techniques to guide treatments toward reduction of patient doses in paediatric cardiology and oncology.

This project will provide new knowledge regarding the best regimen, timing, dose, and route of administration of human mesenchymal stem cells (H-MSC) for regenerating the brain damage in infants born preterm; born before 37 of a typical 40 weeks of gestation. Over 15 million babies are born preterm every year it is a leading cause of death and permanent disability, often due to brain damage. The H-MSC that we will comprehensively screen are FDA-approved and in the process of being produced in a GMP grade, making them suitable for future clinical trials in human preterm born infants. These H-MSC will be evaluated in a large number of rodent models mimicking the key insults and brain damage observed in human preterm infants who will develop later motor, cognitive, and behavioral deficits. We will also apply theseH-MSC in two sheep models of injury relevant to brain damage associated with preterm birth. These large animal trials are a key step before initiating clinical trials in this high risk human population. Additional Workpackages will address the mechanisms underlying the regenerative effects of these H-MSC. This project addresses the call text by value adding to current knowledge of stem cell types and applying it to a large patient group with an unmet clinical need – infants with encephalopathy of the preterm born infant. Steps on the innovation chain targeted – preclinical research, proof of concept and to a lesser degree characterization of regenerative mechanisms.

There are three main reasons for an immediate innovation action to apply big data technologies in Healthcare. Firstly, a Healthy nation is a Wealthy nation! An improvement in health leads to economic growth through long-term gains in human and physical capital, which ultimately raises productivity and per capita GDP. Secondly, Healthcare is one of the most expensive sectors, which accounts for 10% of the EU’s GDP continuously becoming more expensive. Thirdly, as healthcare is traditionally very conservative with adopting ICT, while big healthcare data is becoming available, the expected impact of applying big data technologies in Healthcare is enormous. BigMedilytics will transform Europe’s Healthcare sector by using state-of-the-art Big Data technologies to achieve breakthrough productivity in the sector by reducing cost, improving patient outcomes and delivering better access to healthcare facilities simultaneously, covering the entire Healthcare Continuum – from Prevention to Diagnosis, Treatment and Home Care throughout Europe. BigMedilytics produces: • A Big Data Healthcare Analytics Blueprint (defining platforms and components), which enables data integration and innovation spanning all the key players across the Healthcare Data Value Chains • Instantiations of the Blueprint which implement BigMedilytics concepts across 12 large-scale pilots accounting for an estimated 86% of deaths and 77% of the disease burden in Europe • The Best “Big Data technology and Healthcare policy” Practices related to big data technologies, new business models and European and national healthcare data policies and regulations. BigMedilytics will maximize the impact by using its Big Data Healthcare Analytics Blueprint and the Best Practices to scale-up the concepts demonstrated in the 12 pilots, to the whole Healthcare sector in Europe. It will use health records of more than 11 million patients across 8 countries and data from other sectors such as insurance and public sector.

Cancer is the first leading cause of death by non-communicable diseases in children in Europe. During cancer treatment, patients’ morbidity is increased due to physical inactivity, cancer-related fatigue (CRF) and reduced health-related quality of life (HRQoL). Adapted exercise training in cancer patients, called exercise oncology, is an increasingly recognised, promising health care intervention. In adults, exercise oncology revealed notable effects on tolerance and completion rate of cancer treatment. However, in childhood cancer patients, strong evidence for exercise efficiency is lacking. Thus, precision exercise training is not part of standard care in paediatric oncology and does not reach the majority of patients. By pooling the leading expertise on a European and cross-Atlantic level, the FORTEe project aims to evaluate a personalised and standardised exercise intervention for children and adolescents undergoing anti-cancer treatment. In the randomised, controlled FORTEe trial, high evidence for an innovative, patient-centred exercise treatment will be generated. FORTEe promotes exercise oncology that aims at making patients “stronger to fight childhood cancer”. Supervised exercise training intents to increase muscle strength and reduce muscular atrophy due to bedrest. CRF and HRQoL can be improved and in the future, these benefits may help to fight childhood cancer by increasing therapy efficiency and survival rate. Within the project, digital, innovative technologies such as augmented reality will be developed and applied to make the exercise training more effective, age-adapted and personalised. Moreover, FORTEe will stimulate translational research to provide access to paediatric exercise oncology as a new health care intervention. As a progress beyond the current state-of-the-art, FORTEe has the ambition to implement paediatric exercise oncology as an evidence-based standard in clinical care for all childhood cancer patients across the EU and beyond.

Metabolic disorders are a major burden on the European population and health care systems. Moreover, metabolic perturbations contribute substantially to other pathologies such as neurodegenerative disorders and cancer. The causes of metabolic dysregulation are manifold and lead to pathological shifts, often in response to imbalanced nutrition. Likewise, changes in metabolism affect signalling mechanisms and gene regulation, aggravating the pathology. The mechanisms of this interdependence between metabolism and signalling are still not well understood. HubMOL will fill this knowledge gap and open new horizons by exploring the functional duality of a set of small molecules that are involved in all cellular functions - the Hub Molecules Of Life (HubMOLs) including ATP, SAM (S-adenosylmethionine) and the vitamin-derived cofactors, NAD, FAD, and CoA. They are key components of both metabolism and signalling networks and are interconnected, for example, through their participation in posttranslational protein modifications (PTMs). The complexity of this emerging area requires interdisciplinary scientists equipped with comprehensive competences covering experimental, computational and systems biology as well as clinical medicine. Therefore, the main HubMOL goal is to provide world-class training in these areas to 16 DCs enabling them to establish fundamentally new insights into cofactor biology and lay the ground for patient-tailored vitamin supplementation concepts. The strategic exposure of the 16 young researchers to leading European academic institutions, companies and clinical environments combined with systematic training in entrepreneurship and transferable skills will strongly improve their employability for positions in both private and public sectors. HubMOL will impact patients and society by developing therapies for metabolic and regulatory imbalances based on hub molecule biology.