An intimate yet less known relation between human brain and gut is rapidly emerging as several recent studies have identified various alterations within brain as a result of gastrointestinal disorders and reported comparable variations in gastrointestinal system due to altered brain outputs. These relationships are collectively termed as brain-gut axis and a deeper understanding of its exact nature and operation can lead to development of novel diagnosis, drugs and precision treatment for both neurological and gastrointestinal disorders. The first step towards establishing a comprehensive understanding of brain-gut axis is to identify suitable phenotypes that can be used to describe certain disease state and serve as basis for further investigations into operation of brain-gut axis. In this study, a multiomics based data analysis approach is proposed to search for exclusive and generalizable phenotypes of a certain gastrointestinal disorder. Our multiomics data consist of multimodal imagery of brain and gut, clinical diagnostics, microbial profiling, questionnaire based disease evaluations, genetic and molecular representations taken from carefully designed cohorts of patients and healthy controls. Our data analyses will employ a variety of techniques including digital image processing, computer vision, machine learning and statistical methods to determine covariate factors in omics, which will be then used to identify representative biomarkers for gastrointestinal disorders. We also aim to develop a novel diagnosis system for gastrointestinal disease based on novel biomarkers through a combination of neuroimaging and digital image processing pipeline . Our research is expected to excel the existing knowledge on brain-gut axis by exposing critical phenotypes, employing them for early diagnostic and paving way towards deeper understanding of brain-gut axis.

Schizophrenia (SCZ) affects 20 million people worldwide and antipsychotics remain the only effective pharmacological intervention. However, one-third of people with SCZ do not respond to first-line antipsychotic drugs. In the absence of clinical biomarkers to stratify SCZ subtypes, all individuals receive the same initial intervention, and it takes >4 years on average before people with resistant forms of the condition receive suitable treatment. My overall aim is to unravel the pre-symptomatic cell-type-specific genetic circuits contributing to differential treatment response in SCZ. To achieve my aim I will use an interdisciplinary approach that improves my technical and soft skills and further extends my international network through a two-year stay at Yale University, and three months secondment at Harvard Medical School. During the return phase, I will establish myself as an independent researcher and a suitable candidate for leadership of a to-be-established stem cell lab at the host institute. Objectives are (O1) to identify cell-type-specific neuronal pathways associated with distinct neurotransmission imbalances in each SCZ subgroup using a human-based neurodevelopmental model. (O2) To determine the functional link between SCZ-associated risk variants and response to antipsychotics. Method: I will couple advanced stem cell models (region-specific brain organoids) with single-cell RNA sequencing to generate cell-type-specific transcriptomic profiles of patient-derived brain organoids from treatment-responsive and treatment-resistant forms of SCZ. I will integrate the potential risk variants from SCZ-GWAS and use published functional genomics data to determine the genetic pathways and associated regulators implicated in the etiopathophysiology of differential response to antipsychotics. Impact: identify distinct genetic makeup for each SCZ subgroup to serve as potential predictive biomarkers and points of therapeutic intervention.

Background: Breast cancer treatment is complex, incorporating all modern day treatment options which means that many different professions are involved in this pathway. However it is widely known that the patients’ care and service pathway associated with breast cancer through early detection, diagnostic procedures and treatments to the follow- up phase is still discontinuous. Cancer detection, diagnosis and care coordination comprise timely and appropriate care, provided by interprofessional team including medical, nursing and allied health professionals. There is a need for this kind of education both at the basic education level of these health care professionals, in-house training of cancer clinics and learning materials for independent continuous professional development (CPD). An online learning package is a great resource to resolve the issue at some level.Objectives, methods to achieve them and outcomes of the project:Objective 1. (IO1) To review and create evidence based knowledge about interprofessional breast cancer care and treatments. For this purpose, methodology of integrative literature review, observational study and qualitative questionnaire study are used. As a result, the project will produce new research knowledge to develop healthcare teachers’ and staff understanding about breast cancer care and therapies.Objective 2: Improving the quality of breast cancer care and therapies and health care staff education related to this.To fulfill this objective, three e-learning modules comprising of 13 ECTS credits are developed by using evidence-based approach. The pedagogical principle with the interprofessional orientation to be used in the e-learning course will also follow the same evidence based approach. Module 1/IO2 focuses on interprofessional aspects of cancer care and treatment (3 ects). Module 2/IO3 focuses on breast cancer treatments and therapies (5 ects) Module 3/IO4 focuses on ensuring patient safety in breast cancer care and therapies (5 ects). Using evidence-based approach in the development and implementation of the e-learningpackages will facilitate the development of life-long learning competences among the students and health care professionals who are taking part of the courses.Objective 3: Testing and implementing the e-learning package at the European level. For this purpose, e-learning modules created in the process will be developed, tested within the partnership, improved based on the feedback obtained from the participants, experts and the steering committee members, and made available as open access resources. This will lead to the most obvious results of the project, which is better competences related to interprofessional co-operation in breast cancer therapeutic phase among the teachers, students and health professionals who take part in the preparation and testing of the educational packages. Also, teaching and training activity C1- an intensive week will be carried out (on site + online) to introduce the course content and usage to potential users of the online course Target groups of project for IO1 to IO4. Inside the partnership: two cancer clinic nurses, biomedical laboratory scientists (n=about 30), higher education institutions staff (n=20) and students (n=about 80 annually) who will be participating, teaching and studying the topics. Outside the partnership, target groups are European (+wider globally) cancer clinics’ staff and higher education institutions teachers and students (n= several thousand in Europe only). At intensive course activity C1, there will be 15 participants who`s expenses are covered by project grant taking part on site + at least 15 participating with their own cost on site and about 10 online. In addition, HESAV (Swiss associate partner) will apply for funding from Swiss national agency Movetia to send 4 to 5 teachers for the Intensive course.Impacts: The most important impact on the participating organizations as well as on other organizations that take the e-learning package in their educational use will be the harmonization of quality and contents of education in the field of interprofessional breast cancer treatment and its safety. The e-learning package linked also to EU EPALE dissemination platform gives open access resources for education also for such educational and health care institutions who otherwise could not afford or for some other reason are not able to have that kind of learning resources. At participant level this means equal possibility for health care professionals like radiation therapists, radiographers, biomedical laboratory scientists and nurses and their educators to acquire competences on e-learning in general, interprofessional breast cancer treatment and how to ensure its safety. In addition, studying from such of e-learning materials increases health care staff and ordering clinical units’ understanding about different phases, procedures, actors and safety issues associated with breast cancer therapeutic phase.

In high-grade serous ovarian cancer (HGSOC) there is an urgent medical need for effective treatment options for the patients with a limited response to both standard chemotherapy and emerging PARP inhibitors. Apart from the mutations in DNA repair pathways, targetable point mutations in tumour suppressors are uncommon in HGSOC tumours. Instead, patients present unique and highly variable combinations of copy number aberrations, structural variations and additional subclonal changes, significantly complicating classification and targeting of intratumoral chemoresistance-associated heterogeneity across patients. Thus, innovative personalised approaches are required to help these patients. To overcome treatment resistance in HGSOC, we propose to implement a novel concept: to unbiasedly detect the distinct tumour subpopulations that confer resistance to current therapies, and then to predict and test which drugs they respond to. We propose to implement this concept by combining [i] a novel, unbiased, and robust algorithm to reliably identify the resistant tumour cell subpopulations from single cell transcriptomic data of HGSOC tumours and matched organoids, [ii] drug response prediction and screening in organoid cultures, using single cell readouts, and [iii] validation of the resulting personalised drug predictions in independent samples, in both organoid cultures and in vivo patient-derived xenografts, co-treated with chemotherapy. Our novel approach enables the design of effective personalised treatments of HGSOC to complement chemotherapy by targeting the specific chemoresistance mechanisms active in each patient’s tumour cell subpopulations. The resulting tools and biomarkers can be used for screening and prioritisation; first, in early-phase patient-centric studies, and then in larger trials. The overall approach can be extended to other diseases where subpopulations provide treatment resistance, towards a paradigm shift in personalised oncology.

There was and still is a substantial need for the development of high-quality work-based VET in the healthcare sector specialising in the care of patients undergoing appearance altering procedures that result in scarring and body form changes such as cancer, burns, limb loss, mastectomy, plastic surgery and congenital disabilities. As the patients undergo treatment, many have a difficult time to deal with their altered appearance, or they have an unrealistic expectation of the treatment. At the same time, health care professionals do not have the knowledge. A study that surveyed 718 health workers in Europe found that 87% wanted to know more about how to support their patients and 70% wanted to attend an accredited course to address knowledge and skill deficits (Williamson et al., 2017). This proposal was a direct outcome from the COST Action IS1210 network supported by the EU Framework Programme Horizon 2020. Members from the 34 countries involved in this network have concluded that it is paramount to train healthcare professionals in the psychological and psychiatric aspects of care are crucial for the individuals undergoing appearance altering procedures. In particular, feedback from health professionals in Norway, Bulgaria, Italy, Romania and Sweden acknowledge that they do not have the right skills to address with the psychological and/or psychiatric consequences. In many cases, they report that individuals with these problems isolate themselves from society resulting in unemployment and/or poor physical and psychological health. The health care professionals report that they feel inadequate equipped to support their patients; they also experience increased stress and frustration. Extensive research document the significant negative impacts of disfigurement and appearance altering treatment has further indicated that staff report having the insufficient time and little confidence in meeting these patients' information and support needs (Persson et al. 2008; Konradsen et al. 2009). Research by Clarke & Cooper (2001) has shown in addition. However, health professionals do not feel as skilled in delivering psychosocial support to patients that they can very quickly take on this role when given training and access to appropriate resources. The consortium consisted of public health, psychology and pedagogical experts in vocational training in accordance to the EQF framework together with hospitals and NGOs that work directly with individuals undergoing appearance altering procedures, resulted in that a state of the art training material was developed. The training course is in a modular form and was piloted on 46 health professionals in the partners' countries (BG, IT, RO) in order to ensure the effectiveness and cultural adaptation. The project included a purpose-designed pre and post KAPb test. This evaluation questionnaire was developed to measure the participants' levels of knowledge before and after the training. It covers the three dimensions - Knowledge, Attitude and Practice behaviour in relation to the European Qualification Framework level 4. The KAP test consists of 26 questions that are administered before (pre) the training, and after the training (post). The statistical analysis (T-test for paired samples) indicated a significant increase in knowledge. The outcome was a functional continuing education and training package for healthcare professionals who currently have limited or no access to psychological expertise about the psychiatric and psychosocial variables that are associated with disfigurement and appearance altering procedures. As indicated, this issue is a comprehensive European problem, and by utilising a transnational project approach, the consortium was able to generate training materials that functioned effectively in the context of European diversity in social and cultural aspects. By increasing knowledge and awareness of the negative impacts of appearance-related distress amongst partners and their networks, the project promoted a broader social dialogue about the need to encourage positive attitudes towards diversity in appearance, thus enhancing the future social integration of those who are affected by disfigurement – particularly those with additional risk factors for discrimination, including migrants, refugees and those from other socially disadvantaged groups. The longer-term benefits are accelerated enhancements to service provision and the quality of psychological care offered to patients undergoing appearance altering procedures via a succinct and economically viable training module. All the material developed is an open resource and available to download at the website of the project. The dissemination and sustainability plan ensured that a broad group of healthcare professionals across Europe and beyond was reached.