Severe deficits in social interactions are one of the hallmarks of schizophrenia. Prominent hypotheses have suggested that social deficits are primarily the result of impaired social skills or deficits in social cognition. The role of nonverbal communication, and in particular speech synchronization, has been little studied in schizophrenia to date despite its fundamental importance in human interaction. While recent work has demonstrated that embodied conversational agents (ECAs) can engage people with social deficits in various forms of social learning, the acceptability and benefit of their use remain largely unexplored in schizophrenia. This project draws on recent advances in ECA modeling, psychological science, and movement science to assess whether the production of non-verbal social cues combining gestures and speech generated by an ECA can promote the maintenance of patient-ECA social interaction and their generalization to patient-human interactions. Our project is technically and epistemologically ambitious because it leans on recent advances in movement science, computational modeling, clinical psychology and embodied conversational agents, to assess whether social skills and nonverbal communication of individuals with schizophrenia can be enhanced through repeated interactions with an ECA. This translational research project will thus allow a transfer of knowledge in both directions: both from basic research to patient application and from patient observations to basic research.

FORGETDIABETES introduces a radically new approach to Type 1 Diabetes (T1D) treatment, by developing an immuno-optimized, fully-implantable, fully-automated, Bionic Invisible Pancreas (BIP). BIP targets physiological intraperitoneal hormone delivery, enabling an optimal glycemic control. T1D patient number is rising, projected at 63-94 million in 2045. T1D patients require exogenous insulin, resulting in an exorbitant number of actions: 100.000-500.000 in one patient’s life. BIP will free T1D subjects from therapeutic actions and from related psychological burden. BIP will become a life-condition (like wearing glasses), allowing T1D patients to live just as everybody else. An interdisciplinary team with top experts in micro-nano mechatronics, control engineering, biomaterials, endocrinology, surgery and behavioural sciences has been assembled to develop what was regarded as impossible for decades: a long-lasting system relying on a physiological glucose sensing and hormone delivery, orchestrated by personalized adaptive algorithms with advanced self-diagnostic capabilities. Pump refilling through a weekly oral recyclable drug pill will free T1D subjects from the burden of painful and awkward daily measurement and treatment actions. Wireless power transfer and data transmission to cloud-based data management system round-up to a revolutionary treatment device for this incurable chronic disease. In this project, the key technologies enabling BIP will be developed. Furthermore, extensive in vivo preclinical experiments along with massive in silico testing will establish the proof-of-principle, paving the way to the ambitious first-in-human inpatient trial of BIP. This paradigm will revolutionize diabetes treatment and stimulate an innovation ecosystem including research bodies, SMEs, patient organizations, diabetes societies and clinicians. By investing in efforts like FORGETDIABETES, Europe will stand at the forefront of technological innovations for T1D treatment.

It will be a radically new approach for long-term continuous monitoring of insulin-treated persons with diabetes (ITD) moving from a glucose-only to a multi-metabolite monitoring - glucose, lactate and 3 ß OH-butyrate– paradigm. Multi-metabolite monitoring will also lead to a diabetes therapy breakthrough by algorithmically driving a continuous physiologic insulin delivery by a maintenance-free implanted MEMS pump using the peritoneal route enabling an optimal therapy for subjects with ITD. Our vision is a fully implantable artificial organ to replace insulin secretion loss by targeting metabolic health instead of mere glucose control and mimicking physiological insulin action. While offering a really burden-free life for insulin-treated children and adults, it is expected to allow a dramatic reduction of metabolic variations, hence a minimization of acute and long-term complications and an abating of the still high mortality of T1D patients. Unobtrusive living with diabetes will be reached by the calibration-free, implantable, long-term multi-metabolite monitoring solution connected wirelessly to a novel highly miniaturized silicon MEMS micropump, with down to 50 nl stroke volume, able to operate a newly developed U1000 insulin and enabling reservoir refill cycles of 180 days up to 365 days. Both devices hold durable battery operating life of more than 8 years without recharge and are suitable for children. Newly designed control algorithms based upon multiple signal inputs will drive automated insulin delivery without the need of obtrusive meal and physical exercise announcements.

The current COVID-19 pandemic put the world in an unprecedented situation, with a wide influence on our daily lives. Increasing evidence indicates that short- and long-term neurological complications are associated to SARS-CoV-2 infection. However, minimal information regarding the impact of the virus on the central nervous system is available. In particular, the lack of mechanistic insights dampens our understanding of the COVID-19-induced neuropathological features (neuroCOVID), thus preventing the elaboration of suitable treatments. Here, we propose to determine the molecular and cellular impact of SARS-CoV-2 on the human brain cortex using human stem-cell-derived cerebral organoids and organotypic culture of post-mortem human brain slices. We will first fully characterize these models and evaluate the permissiveness and replication kinetic profiles of SARS-CoV-2 in the major neural cell types. In parallel, we will investigate how SARS-CoV-2 infection and/or exposure affects neurological synapse formation and monitor the perturbation of neuronal electrical activity. Finally, differential proteomics on single organoids allowed us to identify a subset of host factors significantly modulated upon SARS-CoV-2 infection and we will decipher the consequences of protein expression perturbation in order to find the origin of neurological dysfunctions in infected patients. Together, this work shall provide seminal knowledge regarding the molecular mechanisms leading to SARS-CoV-2-induced neurological disorders.

Drug hypersensitivity to antibiotics, mainly Beta-lactams (BLCs) affects more than 2.5 million European citizens. Moreover, preventable adverse drug reactions are estimated in additional hospitalization costs of 1750-4500 €/patient. Currently, the allergy diagnosis is mainly based on the information given by invasive, single, and risky in vivo assays. In daily practice, few in vitro diagnostic methods are available and only used at the tertiary health services. These tests also lack of sensitivity (>0.35 kUA/L) and selectivity (98%), multiplexed (10 BLCs), rapid (30 min), and low-cost (2.4 €/allergen) drug allergy test. The solution involves an advanced approach to the diagnosis and management of drug allergy with the aim to ameliorate patient safety. The consortium comprises multidisciplinary knowledge on optics, electronics, advanced materials, biotechnology, smart microstructures, microfluidics, surface/organic chemistry, allergy, manufacturing systems, and telecom networking. Also, the key industrial actors, present in the consortium, will contribute to the manufacturing and placing the product on the IVD market.