In the vast majority of cardiovascular diseases (CVDs), there are well-described differences between women and men in epidemiology, pathophysiology, clinical manifestations, effects of therapy, and outcomes.^1–3 These differences arise on one hand from biological differences among women and men, which are called sex differences. They are due to differences in gene expression from the sex chromosomes and subsequent differences in sexual hormones leading to differences in gene expression and function in the CV system, e.g. in vascular function and NO signalling, in myocardial remodelling under stress, or metabolism of drugs by sex-specific cytochrome expression. Sex differences are frequently reproducible in animal models. In contrast, gender differences are unique to the human. They arise from sociocultural processes, such as different behaviours of women and men; exposure to specific influences of the environment; different forms of nutrition, lifestyle, or stress; or attitudes towards treatments and prevention. These are equally important for CVDs. Both sex and gender (S&G) influence human development (Figure 1). Since it is almost impossible to distinguish properly between effects of S&G in the medical field, the EUGenMed writing group decided to discuss both of them together and to use the term S&G for all medical relevant differences between women and men in the present review.

Background: Human-centered design (HCD) approaches to health care strive to support the development of innovative, effective, and person-centered solutions for health care. Although their use is increasing, there is no integral overview describing the details of HCD methods in health innovations. Objective: This review aims to explore the current practices of HCD approaches for the development of health innovations, with the aim of providing an overview of the applied methods for participatory and HCD processes and highlighting their shortcomings for further research. Methods: A narrative review of health research was conducted based on systematic electronic searches in the PubMed, CINAHL, Embase, Cochrane Library, Web of Science, PsycINFO, and Sociological Abstracts (2000-2020) databases using keywords related to human-centered design, design thinking (DT), and user-centered design (UCD). Abstracts and full-text articles were screened by 2 reviewers independently based on predefined inclusion criteria. Data extraction focused on the methodology used throughout the research process, the choice of methods in different phases of the innovation cycle, and the level of engagement of end users. Results: This review summarizes the application of HCD practices across various areas of health innovation. All approaches prioritized the user’s needs and the participatory and iterative nature of the design process. The design processes comprised several design cycles during which multiple qualitative and quantitative methods were used in combination with specific design methods. HCD- and DT-based research primarily targeted understanding the research context and defining the problem, whereas UCD-based work focused mainly on the direct generation of solutions. Although UCD approaches involved end users primarily as testers and informants, HCD and DT approaches involved end users most often as design partners. Conclusions: We have provided an overview of the currently applied methodologies and HCD guidelines to assist health care professionals and design researchers in their methodological choices. HCD-based techniques are challenging to evaluate using traditional biomedical research methods. Previously proposed reporting guidelines are a step forward but would require a level of detail that is incompatible with the current publishing landscape. Hence, further development is needed in this area. Special focus should be placed on the congruence between the chosen methods, design strategy, and achievable outcomes. Furthermore, power dimensions, agency, and intersectionality need to be considered in co-design sessions with multiple stakeholders, especially when including vulnerable groups.

Humans with primary biliary cirrhosis (PBC), a disease characterized by the destruction of small bile ducts, exhibit signature autoantibodies against mitochondrial Pyruvate Dehydrogenase Complex E2 (PDC-E2) that crossreact onto the homologous enzyme of Novosphingobium aromaticivorans, an ubiquitous alphaproteobacterium. Here, we show that infection of mice with N. aromaticivorans induced signature antibodies against microbial PDC-E2 and its mitochondrial counterpart but also triggered chronic T cell-mediated autoimmunity against small bile ducts. Disease induction required NKT cells, which specifically respond to N. aromaticivorans cell wall alpha-glycuronosylceramides presented by CD1d molecules. Combined with the natural liver tropism of NKT cells, the accumulation of N. aromaticivorans in the liver likely explains the liver specificity of destructive responses. Once established, liver disease could be adoptively transferred by T cells independently of NKT cells and microbes, illustrating the importance of early microbial activation of NKT cells in the initiation of autonomous, organ-specific autoimmunity.

The importance of sex and gender as modulators of disease biology and treatment outcomes is well known in other disciplines of medicine, such as cardiology, but remains an undervalued issue in oncology. Considering the increasing evidence for their relevance, European Society for Medical Oncology decided to address this topic and organized a multidisciplinary workshop in Lausanne, Switzerland, on 30 November and 1 December 2018. Twenty invited faculty members and 40 selected physicians/scientists participated. Relevant content was presented by faculty members on the basis of a literature review conducted by each speaker. Following a moderated consensus session, the final consensus statements are reported here. Clinically relevant sex differences include tumour biology, immune system activity, body composition and drug disposition and effects. The main differences between male and female cells are sex chromosomes and the level of sexual hormones they are exposed to. They influence both local and systemic determinants of carcinogenesis. Their effect on carcinogenesis in non-reproductive organs is largely unknown. Recent evidence also suggests differences in tumour biology and molecular markers. Regarding body composition, the difference in metabolically active, fat-free body mass is one of the most prominent: in a man and a woman of equal weight and height, it accounts for 80% of the man's and 65% of the woman's body mass, and is not taken into account in body-surface area based dosing of chemotherapy. Sex differences in cancer biology and treatment deserve more attention and systematic investigation. Interventional clinical trials evaluating sex-specific dosing regimens are necessary to improve the balance between efficacy and toxicity for drugs with significant pharmacokinetic differences. Especially in diseases or disease subgroups with significant differences in epidemiology or outcomes, men and women with non-sex-related cancers should be considered as biologically distinct groups of patients, for whom specific treatment approaches merit consideration.