The Project eBrain-Health will deliver a distributed research platform for modeling and simulating complex neurobiological phenomena of human brain function and dysfunction in a data protection compliant environment. It will provide thousands of multilevel virtual brains from patients and healthy human controls for research and innovation. Brain data from multiple sources will be pre-processed. Solving the societal grand challenge of dementia is a big task. Yet it appears feasible in a collective approach. Therefore, we will build an interdisciplinary digital twin for dementia for modeling and simulating complex phenomena at the service of research infrastructure communities. EBRAINS-Health-Cloud will offer end-to-end services for personalized complex brain modeling and simulations in distributed e-infrastructures with data protection by design and by default and simulation-ready human multiscale brain data that range from molecular (genomics, proteomics, metabolomics) and cellular to electrophysiology and imaging to behavioural, clinical, life-style and environmental data as well as data from wearables. Brain data are pre-processed and annotated such that they all relate to a common reference 3D brain space. EBRAINS-Health-Cloud constitutes a blend of three large-scale research programs: the FET Flagship Human Brain Project with its EBRAINS Research Infrastructure, the EOSC project Virtual Brain Cloud with its Virtual Research Environment for sensitive data and the H2020 project AI-MIND with intelligent tools for dementia risk estimation. The project will have synergies to topics of the Digital Europe Program, such as artificial intelligence, cybersecurity and supercomputing and the Health Data Space. EBRAINS-Health-Cloud offers a next generation clinical research infrastructure and creates an open yet protected space for groundbreaking digital health innovation by the research infrastructure communities comprising academia and the private sector.

"PROPHET - a PeRsOnalized Prevention roadmap for the future HEalThcare" will develop a Strategic Research and Innovation Agenda (SRIA) for Personalized Prevention, in order to support the implementation of innovative, sustainable and effective personalized programmes to prevent common chronic diseases. Technological biomedical advances (including omics data and digital tools) make risk stratification at the individual level possible. However, development of Personalized Prevention approaches must be accompanied by healthcare system transition, including citizen engagement, healthcare professional education and addressing organisational, social and legal issues. PROPHET will be centred around stakeholder engagement and the SRIA co-creation process in relation to three main strands of activities: Mapping, Assessment, and Building. Firstly, we will summarize, evaluate and discuss with the relevant stakeholders the extent to which all these new technologies can synergise (Mapping). Secondly, we will design a holistic framework (the PROPHET Framework) that will include all the necessary aspects to appraise Personalized Prevention approaches and their adoption by Public Health Authorities (Assessment). Thirdly, we will support the introduction of Personalised Prevention Programmes by providing guidelines for their design, engaging with healthcare professionals (especially those working with policy makers), and increasing health literacy at the population level on the benefits of Personalized Prevention (Building). PROPHET will liaise with other key current and forthcoming initiatives at EU level, such as ICPerMed, European Partnership (EP) PerMed, the CSA Beyond 1 Million Genomes (B1MG), and the EP on Transforming Health and Care Systems. The consortium consists of 18 beneficiaries and 2 affiliated entities across 12 EU Countries, and a large number of stakeholders already engaged from different Target Groups.

The societal burden of brain disorders, such as multiple sclerosis (MS), Alzheimer’s and Parkinson’s disease is enormous and is considered one of the world’s most important health challenges. They affect millions of people worldwide and the annual healthcare costs are high and are increasing with the aging population. There is an immediate need to better understand the underlying molecular mechanisms of these disorders. Inflammation is widely recognized to play an important role in many neurological disorders. Next to the response of microglia, the resident immune cells in the central nervous system (CNS), infiltration of monocytes from the blood occurs, but the exact role of monocyte infiltration and the interplay between microglia and monocytes in vivo is still largely unknown. Clinical trials with chemokine receptor type 2 (CCR2) antagonists, aiming to reduce recruitment of monocytes and thereby reducing neuroinflammation, do not show clinical efficacy. Together, this emphasizes the need to unravel the role of infiltrating monocytes in human disease in vivo. Positron emission tomography (PET) is an imaging technique well suited to serve this purpose. I propose to develop new PET tracers targeting CCR2 as a tool to visualize infiltration of monocytes in the CNS in vivo to help elucidate their role in disease. Newly developed tracers will be evaluated in vitro, ex vivo and in vivo in an animal model of MS. A successful PET tracer will contribute to a better understanding of monocyte infiltration in disease in vivo and could ultimately serve as an important tool to guide drug development and evaluate novel disease-modifying therapies and therapies inhibiting monocyte infiltration. On a personal level, the proposed project will have a significant impact on my career, as new skills in neuroimaging, computer-aided drug design and in vitro target validation techniques will complement my previous expertise in organic chemistry, radiochemistry and PET tracer development.

CAREPATH aims to improve chronic disease management and medication persistence by transforming the care ecosystem, ensuring personalised support for better health outcomes, and reducing healthcare costs. We focus on improving medication adherence and persistence for three prevalent chronic conditions: Obesity (BMI ≥ 30 kg/m2), Type 2 Diabetes Mellitus (T2DM), and cardiovascular diseases (CVD), including chronic heart failure (CHF), across six diverse European countries: Germany, Israel, the Netherlands, Poland, Spain, and Sweden. These countries represent various EU healthcare environments and economic statuses, emphasising the need for tailored approaches to patient care. Our strategy involves integrating localised non-digital and digital health solutions to address the unique healthcare delivery challenges in each region. The CAREPATH toolbox collects, combines, and customises existing solutions into adaptable modules for broad application in both primary and secondary care settings. This toolbox will be tested in four studies across two settings in all six countries in both primary and secondary care. Three pilot studies in different regions as well as a proof-of-concept study in Germany will be conducted. This comprehensive evaluation, including HTA, aims to assess the toolbox's implementation and effectiveness, with a strong focus on learning what works for what groups of patients in which setting. Recognizing the significant impact of obesity, particular emphasis is placed on treatment adherence and persistence of medications that facilitate weight loss, such as dual GIP/GLP-1 receptor agonists, but CAREPATH studies also include patients using lipid-lowering drugs, insulin, and SGLT2 inhibitors. Our goal is to empower patients by improving communication and data sharing among patients, healthcare providers, and other stakeholders, thereby supporting the entire ecosystem and alleviating the burden on healthcare systems.

UMBRELLA is a holistic approach to progress, reshape, and benchmark the overall stroke care pathway and set new and improved standards of care in terms of primary and secondary prevention, rapid access to treatments, early accurate diagnosis, stratification, management and real-time monitoring, therapeutic targets identification, and rehabilitation, recurrent stroke and related cardiovascular events. This innovative approach will transform healthcare systems by improving and harmonizing professionals' workflows in a more patient-centred, digitalized, and communicative manner. UMBRELLA aims to revolutionize stroke management by implementing a comprehensive approach that addresses gaps along the whole continuum of the stroke care pathway. The key paradigm in the project is the multicentric, synergistic "umbrella" strategy for local data collection, harmonization, and standardization along the entire pre-, in-, and post-hospitalization pathway. By establishing specific common data models (CMDs) implemented in each of the 7 top-tier European clinical centres, UMBRELLA will create a federated data platform (U-platform) where Real World Data (RWD)-based AI algorithms can be locally created and validated, to advance personalised diagnosis, risk prediction, and treatment decisions in the acute and post-acute phases of stroke. The algorithms will be then trained in a decentralized manner through a federated learning infrastructure (FL-platform), which preserve data security and privacy, avoiding data centralization or exchange across centres but fostering collective AI-models training. On the other hand, standardized stroke management protocols and procedures will be created and implemented across the participating centres, including the validated usage of advanced digital technologies as solutions to facilitate data collection, visualization, patient engagement, monitoring, outcomes integration, and decision-making across the whole stroke pathway.