The SYSCID consortium aims to develop a systems medicine approach for disease prediction in CID. We will focus on three major CID indications with distinct characteristics, yet a large overlap of their molecular risk map: inflammatory bowel disease, systemic lupus erythematodes and rheumatoid arthritis. We have joined 15 partners from major cohorts and initiatives in Europe (e.g.IHEC, ICGC, TwinsUK and Meta-HIT) to investigate human data sets on three major levels of resolution: whole blood signatures, signatures from purified immune cell types (with a focus on CD14 and CD4/CD8) and selected single cell level analyses. Principle data layers will comprise SNP variome, methylome, transcriptome and gut microbiome. SYSCID employs a dedicated data management infrastructure, strong algorithmic development groups (including an SME for exploitation of innovative software tools for data deconvolution) and will validate results in independent retrospective and prospective clinical cohorts. Using this setup we will focus on three fundamental aims : (i) the identification of shared and unique "core disease signatures” which are associated with the disease state and independent of temporal variation, (ii) the generation of "predictive models of disease outcome"- builds on previous work that pathways/biomarkers for disease outcome are distinct from initial disease risk and may be shared across diseases to guide therapy decisions on an individual patient basis, (iii) "reprogramming disease"- will identify and target temporally stable epigenetic alterations in macrophages and lymphocytes in epigenome editing approaches as biological validation and potential novel therapeutic tool . Thus, SYSCID will foster the development of solid biomarkers and models as stratification in future long-term systems medicine clinical trials but also investigate new causative therapies by editing the epigenome code in specific immune cells, e.g. to alleviate macrophage polarization defects.

The management and reconstruction of bone defects is a significant global healthcare challenge. While autografts offer ideal compatibility, they are often not suitable for large bone defects, and allografts suffer from potential immunorejection.The limited efficacy of conventional treatment strategies for large bone defects and the increasing aged population, has inspired the consortium to propose a SMART RESORBABLE BONE (SRB) IMPLANT embedding stem cells and bioactive agents with the aim of a controllable and fast restoration. The proposed solution includes 3D printed medical grade polymers enriched with electrospun fibers (for increased mechanical properties) that can be customized for patient physiology, pathology, and gender. The scaffold design will ensure easy and minimal Injury placement, and will embed different sensors for monitoring e.g. pressure, pH value and temperature based on biocompatible conductive inks. The smart implant will thus be able to provide vital information of implant performance in terms of bone growth and infection/inflammation. The proposed method is unique because it includes a customized smart implant (3D printed parts with adjustable sensors and communication electronic system), together with tissue engineering methods i.e. in-vitro programming of stem cells for embedding into the smart implant. The proposed solution introduces an innovative regenerative chain, from early testing and characterization (identification/adjustement of the proper specifications) and embedding regenerative stem cells and particulate bioactive agents into the smart implant in preclinical research (in-vitro). The in vivo proof of concept of SBR solution will be tested in (large animal model) preclinical studies within the scope of the project. Finally the regulatory and commercialization strategy on how to further explore the proposed concept and deliver it for clinical testing will be elaborated.

RURACTIVE aims to foster a just and sustainable transition of rural areas by developing smart, community-led, tailor-made, place-based and inclusive solutions within local Multi-Actor Rural Innovation Ecosystems (RIEs) in 12 pilot area (Dynamos - Ds) in 7 EU, 2 Associated Countries and Switzerland. RURACTIVE will unlock the innovation potential of rural communities by addressing six integrated Rural Development Drivers (RDDs) – namely multimodal mobility, energy transition, agri-food and agroecology, culture and cultural innovation, health and wellbeing, nature-based and cultural tourism – and transversally integrating climate change mitigation and adaption, biodiversity and social justice and inclusion. RURACTIVE will empower rural communities to act for societal change, by making available existing knowledge around smart solutions that integrate various forms of innovation (digital and technological, technical, organizational and social, business models and financial) and enhancing rural communities' capacities and skills, by providing training, capacity building, and knowledge transfer. Implementing a methodology for RIEs establishment in 12 Ds, RURACTIVE will work towards inclusive decision-making processes for all, including vulnerable groups and people at risk of exclusion, providing RIEs with instruments and capacities to collaboratively co-develop, co-implement and co-monitor smart and community-led solutions. Also, by offering an open set of data-driven tools (Decision Support Tool, Adaptive Monitoring tool), a digital infrastructure (RURACTIVE Digital Hub), and defining a programme for external Innovators, RURACTIVE will provide a fertile ground for change in rural areas. Results will be out-scaled through knowledge exchanges and networking at EU level (open contest for Additional Ds and RURACTIVE Forum), the deployment of training and capacity building activities for further rural communities and the creation of open e-learning courses and MOOC.

ProgrammE in Costing, resource use measurement and outcome valuation for Use in multi-sectoral National and International health economic evaluAtions (PECUNIA) addresses the call SC1-PM-20-2017 Methods research for improved health economic evaluation. The consortium brings together 10 partners from 6 countries with complementary methodological expertise. It represents differing health care systems with varying feasibility and acceptability of economic evaluations in evidence-informed decision making. Some countries have established national unit cost programmes (DE, NL, UK), some early stage initiatives (AT, ES, HU). Availability of health utility value sets for outcome evaluations and requirements in terms of the primary analytical perspective of economic evaluations (health & social care vs. societal) also differ. Over 36 months, PECUNIA will develop standardised, harmonised and validated multi-sectoral, multi-national and multi-person methods, tools and information for 1) self-reported resource use measurement, 2) reference unit cost valuation, 3) cross-national health utility assessment, and 4) broader wellbeing measurement. To achieve the widest impact possible and exploit its disruptive innovation potential for end users, decision makers, payers and the industry, the work will be executed in close collaboration with 5) external scientific advisors and broad outreach to all relevant stakeholders. Considering feasibility and relevant societal challenges in the European health systems, selected mental health disease areas (depression, schizophrenia, PTSD) will be used as illustrative examples for cost assessment. PECUNIA will lead to better understanding of the variations in costs and outcomes within and across countries, improve the quality, comparability and transferability of economic evaluations in Europe, and support the feasibility of broader economic and societal impacts measurement and valuation in multi-sectoral economic evaluations also for HTA.