Atrial Fibrillation (AF) is the most common cardiac arrhythmia affecting more than 6 million Europeans with a cost exceeding 1% of the EU health care system budget (13.5 billion annually). New treatment strategies and the progress achieved in research on AF mechanisms and substrate evaluation methods to date have not been commensurate with an equivalent development of the knowledge and technologies required to individually characterize each patient in search of the most efficient therapy. PersonalizeAF addresses this challenge by delivering an innovative multinational, multi-sectorial, and multidisciplinary research and training programme in new technologies and novel strategies for individualized characterization of AF substrate to and increase treatments’ efficiency. From the research point of view, PersonalizeAF will integrate data and knowledge from in-vitro, in silico, ex vivo and in vivo animal and human models to: 1) generate an individual description of the state of the atrial muscle identifying the disease mechanisms and characteristics; 2) understanding the potential effect that different therapies have on different atrial substrates; and 3) combining this information to generate a specific profile of the patient and the best therapy for each patient. With this purpose, PersonalizeAF partnership aggregates relevant scientific staff from the academic and clinical world with highly specialised biomedical companies which will be involved in a high-level personalised training programme that will train a new generation of highly skilled professionals and guarantee ESRs and future PhD students outstanding Career Opportunities in the biomedical engineering, cardiology services and medical devices sectors. PersonalizeAF will disseminate results to a wide spectrum of stakeholders, create awareness in the general public about atrial fibrillation and encourage vocational careers among young students.

BACKGROUND: Adolescents are at particularly high risk for digital technology overuse, including in response to the COVID pandemic, and are therefore vulnerable for its potential harmful effects on mental health. Problematic usage of the internet (PUI) is thought to represent a marker of disrupted self-management, with major consequences for individual and societal health and wellbeing. AIM: Bootstrap brings together a multidisciplinary consortium aiming to initiate health and social policy and practice change designed to reduce the harmful effects of digitalization on mental health, particularly for young people. APPROACH: We will co-create a digital screening and assessment platform to understand which individuals are at-risk for developing PUI. Algorithm-based models will be used to predict which individual will benefit from which type of self-management intervention, and these preventative behavioral interventions will be tested for their (cost)effectiveness. Finally, we will develop a policy toolkit in co-design with stakeholders, to promote human digital rights accountability at the local, national, and European level. IMPACT: Bootstrap will provide unprecedented scientific knowledge on the psychological mechanisms underlying (risk for) PUI and potential interventions. Improved self-management and tools to optimize healthy internet usage will promote mental health and prevent mental ill health in adolescents, and contribute to reducing stigma. In addition, our policy toolkit will empower policy makers and private companies to (self)regulate with the intent to protect vulnerable groups. In the long run, Bootstrap will thus contribute to improving mental wellbeing across Europe and beyond.

Pregnancy involves biological adaptations that are necessary for the onset, maintenance and regulation of maternal behavior. We were the first group to find (1, 2) that pregnancy is associated with consistent, pronounced and long-lasting reductions in cerebral gray matter (GM) volume in areas of the social-cognition network. The aim of BEMOTHER is to develop an integrative model of the adaptations for motherhood that occur during pregnancy and the postpartum period by: i) establishing when the brain of pregnant women begins to change and how it evolves; ii) characterizing the dynamics of cognitive performance, theory-of-mind, maternal-infant bonding and psychiatric measures; iii) assessing the effect of environmental and/or psychological factors in the maternal adaptations, iv) identifying the metabolomics biomarkers associated with maternal adaptations, and v) integrating the previous findings within the Research Domain Criteria framework (RDoC) (3). We will use a prospective longitudinal design at 5 time points (1 pre-pregnancy session, 2 intra-pregnancy sessions and 2 postpartum sessions) during which neuroimaging, psychological, behavioral and metabolomics data will be acquired in 3 groups of women: a group of nulliparous women who will be undergoing a full-term pregnancy, another group of nulliparous women whose same-sex partners will undergo a full-term pregnancy, and a group of control nulliparous women. We will provide the longitudinal RDoC-based model at the end of the study, but we will also deliver intermediate longitudinal evaluations after the postpartum session, as well as cross-sectional analyses after the first intra-pregnancy session and the postpartum session. BEMOTHER is timely and innovative. It adopts the translational RDoC framework in order to provide a pioneering, comprehensive and dynamic characterization of the adaptations for motherhood, addressing the interaction among different functional domains at different levels of analysis.

Cell therapy based on regulatory T cells (Treg) transfer has acquired great interest for the treatment of autoimmune diseases, graft rejection or graft versus host disease (GVHD). Until now, this therapy has not rendered definitive clinical results in humans mainly due to the low number and limited quality of differentiated Treg purified from adult peripheral blood. To overcome these limitations, the host group has developed a new technology to produce massive amounts of GMP Treg derived from the thymic tissue (thyTreg), which are being employed in a clinical trial as an autologous cell therapy in transplanted children. However, the massive amount of thyTreg obtained from each thymus make possible to produce hundreds of doses that could be also employed allogenically to treat a range of immune diseases and patients. My experience and acquired skills in immunology will provide the host with the adequate knowledge to develop the allogenic use of thyTreg. The goal of my research will be to investigate the immunogenicity of thyTreg and confirm that its immature phenotype makes possible its “off-the-self” use, and secondly to initiate a clinical trial to evaluate the safety/feasibility of a therapy with allogenic thyTreg in patients with GVHD. The project will establish the basis for the development of allogenic thyTreg cell therapies to suppress the harmful immune response underlying autoimmune diseases, transplant rejection, GvHD, and cytokine release syndrome associated with CAR-T therapy or clinical progress in COVID-19 patients. This innovative project will reinforce my expertise in immune disorders, gaining experience in translational research from the pre-clinical stages to the development of clinical trials and transfer of technology. Being part of this host institution participating in leading projects and international partnerships provides the ideal environment to complete my training and to develop my leadership abilities to become an independent researcher.

Reconstructive surgeries frequently require multiple, often complex, procedures at high social and economic costs. A shape-morphing implant that can be implanted using less invasive procedures and that then undergoes predesigned shape changes, leading to tissue expansion and allowing for complete degradation coupled with tissue regeneration, is a radically new treatment concept. BIOMET4D aims to create a new generation of shape-shifting and load-bearing implants for dynamic tissue restoration and to introduce a revolutionary paradigm in how actuators can be implemented in biomedicine. Science-towards-technology breakthroughs will be demonstrated with new shape-morphing metamaterials, 4D smart metallic actuators, advanced multi-domain optimization tools, and finally proof-of-concept for two potential clinical applications. Technologically, this vision also goes beyond existing paradigms because of the step-by-step actuation mechanisms, enabled through the additive manufacturing of multi-material degradable metallic structures, that are targeted for an order of magnitude improvement compared to the state-of-the-art. A futuristic long-term vision of this breakthrough technology is to dynamically regenerate entire tissues, such as a nose or an ear, and proof-of-concept will be demonstrated for craniosynostosis treatment and skin expansion. This long-term vision can only be achieved through an interdisciplinary approach and will likely have high social and economic impact as well as provide a new line of research for applications of smart metamaterials in medicine and engineering.