TSPAN6 is a suppressor of Ras-driven cancer

Oncogenic mutations in the small GTPase RAS contribute to ~30% of human cancers. In a Drosophila genetic screen, we identified novel and evolutionary conserved cancer genes that affect Ras-driven tumorigenesis and metastasis in Drosophila including confirmation of the tetraspanin Tsp29Fb. However, it was not known whether the mammalian Tsp29Fb orthologue, TSPAN6, has any role in RAS-driven human epithelial tumors. Here we show that TSPAN6 suppressed tumor growth and metastatic dissemination of human RAS activating mutant pancreatic cancer xenografts. Whole-body knockout as well as tumor cell autonomous inactivation using floxed alleles of Tspan6 in mice enhanced Kras(G12D)-driven lung tumor initiation and malignant progression. Mechanistically, TSPAN6 binds to the EGFR and blocks EGFR-induced RAS activation. Moreover, we show that inactivation of TSPAN6 induces an epithelial-to-mesenchymal transition and inhibits cell migration in vitro and in vivo. Finally, low TSPAN6 expression correlates with poor prognosis of patients with lung and pancreatic cancers with mesenchymal morphology. Our results uncover TSPAN6 as a novel tumor suppressor receptor that controls epithelial cell identify and restrains RAS-driven epithelial cancer

Development of Harmonized COVID-19 Occupational Questionnaires

Harmonized tools and approaches for data collection can help to detect similarities and differences within and between countries and support the development, implementation, and assessment of effective and consistent preventive strategies. We developed open source occupational questionnaires on COVID-19 within COVID-19 working groups in the OMEGA-NET COST action (Network on the Coordination and Harmonisation of European Occupational Cohorts, omeganetcohorts.eu), and the EU funded EPHOR project (Exposome project for health and occupational research, ephor-project.eu). We defined domains to be included in order to cover key working life aspects of the COVID-19 pandemic. Where possible, we selected questionnaire items and instruments from existing questionnaire resources. Both a general occupational COVID-19 questionnaire and a specific occupational COVID-19 questionnaire are available. The general occupational COVID-19 questionnaire covers key working life aspects of the COVID-19 pandemic, including the domains: COVID-19 diagnosis and prevention, Health and demographics, Use of personal protective equipment and face covering, Health effects, Work-related effects (e.g. change in work schedule and work–life balance), Financial effects, Work-based risk factors (e.g. physical distancing, contact with COVID-19-infected persons), Psychosocial risk factors, Lifestyle risk factors, and Personal evaluation of the impact of COVID-19. For each domain, additional questions are available. The specific occupational COVID-19 questionnaire focusses on occupational risk factors and mitigating factors for SARS-CoV2 infection and COVID-19 disease and includes questions about the type of job, amount of home working, social distancing, human contact (colleagues, patients, and members of the public), commuting, and use of personal protective equipment and face coverings. The strength of this initiative is the broad working life approach to various important issues related to SARS-CoV-2 infection, COVID-19 disease, and potentially future pandemics. It requires further work to validate the questionnaires, and we welcome collaboration with researchers willing to do this. A limitation is the moderate number of questions for each of the domains in the general questionnaire. Only few questions on general core information like ethnicity, demographics, lifestyle factors, and general health status are included, but the OMEGA-NET questionnaires can be integrated in existing questionnaires about sociodemographic and health-related aspects. The questionnaires are freely accessible from the OMEGA-NET and the EPHOR homepages

Recognition of COVID-19 with occupational origin: a comparison between European countries

Objectives This study aims to present an overview of the formal recognition of COVID-19 as occupational disease (OD) or injury (OI) across Europe. Methods A COVID-19 questionnaire was designed by a task group within COST-funded OMEGA-NET and sent to occupational health experts of 37 countries in WHO European region, with a last update in April 2022. Results The questionnaire was filled out by experts from 35 countries. There are large differences between national systems regarding the recognition of OD and OI: 40% of countries have a list system, 57% a mixed system and one country an open system. In most countries, COVID-19 can be recognised as an OD (57%). In four countries, COVID-19 can be recognised as OI (11%) and in seven countries as either OD or OI (20%). In two countries, there is no recognition possible to date. Thirty-two countries (91%) recognise COVID-19 as OD/OI among healthcare workers. Working in certain jobs is considered proof of occupational exposure in 25 countries, contact with a colleague with confirmed infection in 19 countries, and contact with clients with confirmed infection in 21 countries. In most countries (57%), a positive PCR test is considered proof of disease. The three most common compensation benefits for COVID-19 as OI/OD are disability pension, treatment and rehabilitation. Long COVID is included in 26 countries. Conclusions COVID-19 can be recognised as OD or OI in 94% of the European countries completing this survey, across different social security and embedded occupational health systems.This publication is based on work from COST Action CA16216 (OMEGA-NET), supported by COST (European Cooperation in Science and Technology)

AIF-regulated oxidative phosphorylation supports lung cancer development

International audienc

Burden of infectious disease studies in Europe and the United Kingdom: a review of methodological design choices

This systematic literature review aimed to provide an overview of the characteristics and methods used in studies applying the disability-adjusted life years (DALY) concept for infectious diseases within European Union (EU)/European Economic Area (EEA)/European Free Trade Association (EFTA) countries and the United Kingdom. Electronic databases and grey literature were searched for articles reporting the assessment of DALY and its components. We considered studies in which researchers performed DALY calculations using primary epidemiological data input sources. We screened 3053 studies of which 2948 were excluded and 105 studies met our inclusion criteria. Of these studies, 22 were multi-country and 83 were single-country studies, of which 46 were from the Netherlands. Food- and water-borne diseases were the most frequently studied infectious diseases. Between 2015 and 2022, the number of burden of infectious disease studies was 1.6 times higher compared to that published between 2000 and 2014. Almost all studies (97%) estimated DALYs based on the incidence- and pathogen-based approach and without social weighting functions; however, there was less methodological consensus with regards to the disability weights and life tables that were applied. The number of burden of infectious disease studies undertaken across Europe has increased over time. Development and use of guidelines will promote performing burden of infectious disease studies and facilitate comparability of the results