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Globalization and the call for global citizenship education have enabled virtual exchange to prepare healthcare students as emerging healthcare professionals for working in an increasingly interconnected and diverse world. Integrating virtual exchange opportunities into undergraduate curricula in higher education equips students with the knowledge, skills, and attributes needed to be responsive to global healthcare challenges. This study reports on the perceptions of undergraduate healthcare students from geographically distant locations on how (if any) participating in an international virtual exchange project fostered their intercultural competence. Anchored in social constructivism and adopting a qualitative methodology, data was collected using an online, open-ended reflective questionnaire. Findings from the thematic analysis highlight that integrating virtual exchange into curriculum design can foster intercultural competence, preparing healthcare students as emerging professionals for the world of work that necessitates an appreciation for diverse ways of knowing, being, and doing to ensure optimal healthcare.

This study explores the captivating world of toy unboxing videos as a space for emergent bilingual children to engage in translanguaging practices. Through the lens of translanguaging, which encourages the unrestricted use of full linguistic repertoires, this research examines the experiences of two five-year-old immigrant and emergent bilingual children, who employ linguistic repertoires from both English and Korean, within toy unboxing play. Toy unboxing play is not exclusive to these children alone but extends beyond as a shared phenomenon of new play among children across the globe. This ethnographic case study seeks to understand when and how translanguaging is employed in their toy unboxing play and explores the possibilities it opens for fostering inclusive views on linguistic practices among emergent bilingual children. In our findings, we argue that toy unboxing play can be a way of creating translanguaging space facilitating the deployment of children's linguistic repertoires and contributing to their meaning-making and learning processes. The translanguaging practices exhibited by the children in their toy unboxing play demonstrate linguistic flexibility across three key domains: (1) playful interaction with toys and self, (2) emotional interaction with families and intimate others, and (3) transcultural interaction with peers and virtual audience. The study contributes valuable insights into the potentialities of translanguaging within the context of children's play. Translanguaging emerges not only as a linguistic phenomenon but as a holistic approach to communication, reflecting the multifaceted nature of emergent bilingual children's identities and experiences. The hybridized approach observed in their play underscores the importance of recognizing translanguaging as a way of being and belonging for children and families with transnational and transcultural backgrounds. By shedding light on the intricate interplay between language, culture, and play, this research deepens our understanding of inclusive and liberating translanguaging spaces for emergent bilingual children.

The natural curiosity of young children, makes the preschool period an important time for introducing and reinforcing engineering practices. Engineering here is defined as goal-oriented thinking that addresses problems and decisions within constraints by drawing on available resources. Engineering encompasses hands-on activity, inquiry, teamwork, and other instructional practices that develop children's critical thinking, communication, collaboration, and creativity. However, exposure to engineering in early childhood education is mostly incidental, rather than exclusively through engineering. Further, while there is an emerging body of literature on engineering curricula and activities in early childhood, little information is provided about what preschool engineering looks like, as well as reflections from such implementation. The purpose of this study was to implement engineering challenges in a preschool classroom framed in an inquiry-based teaching approach, and to document teacher reflections and lessons learned. The study was conducted in a private preschool program for students aged 3-5, including children with or at-risk for developmental delays. Thirteen preschool students and one preschool teacher participated in this study, wherein, four engineering activities were implemented in the classroom over a four-week period. The teacher's reflections reveal the importance of engineering activities in providing a platform for preschool students with diverse needs to work together, practice skills from a multitude of domains, and engage in authentic peer interactions. Implications for early childhood educators seeking to incorporate engineering experiences in their classroom are shared. Recommendations for practice including how preschool students can meaningfully participate in similar inquiry-driven activities as well as the teacher's role in supporting their participation is discussed.

Silke F Metzelthin,1,2 Jette Thuesen,3,4 Hanne Tuntland,5 Magnus Zingmark,6 Yun-Hee Jeon,7 Hanne Kaae Kristensen,8,9 Lee-Fay Low,7 Christopher J Poulos,10,11 Jackie Pool,12 Miia Rahja,13 Erik Rosendahl,14 Marjolein E de Vugt,15 Clarissa Giebel,16 Maud JL Graff,17 Linda Clare18 1Department of Health Services Research, Maastricht University, Maastricht, the Netherlands; 2Living Laboratory in Ageing and Long-Term Care, Maastricht, the Netherlands; 3REHPA, The Danish Knowledge Centre for Rehabilitation and Palliative Care, Nyborg, Denmark; 4Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 5Department of Health and Functioning, Western Norway University of Applied Sciences, Bergen, Norway; 6Department of Occupational Therapy, Institution of Community Medicine and Rehabilitation, Umeå University, Umeå, Sweden; 7Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia; 8Centre for Innovative Medical Technology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 9Health Sciences Research Centre UCL University College, Odense, Denmark; 10Faculty of Medicine & Health, University of New South Wales, Sydney, NSW, Australia; 11HammondCare, Sydney, NSW, Australia; 12Dementia PAL, Southampton, UK; 13Flinders Health and Medical Research Institute, Flinders University, Adelaide, SA, Australia; 14Department of Community Medicine and Rehabilitation, Umeå University, Umeå, Sweden; 15Department of Psychiatry and Neuropsychology, Alzheimer Center Limburg, Mental Health and Neuroscience Research Institute, Maastricht University, Maastricht, the Netherlands; 16Department of Primary Care and Mental Health, University of Liverpool & NIHR Applied Research Collaboration North West Coast, Liverpool, UK; 17Department of Rehabilitation & Department of IQ health, Radboudumc Alzheimer Center, Radboud University Medical Center Nijmegen, Nijmegen, the Netherlands; 18University of Exeter Medical School and NIHR Applied Research Collaboration South-West Peninsula, Exeter, UKCorrespondence: Silke F Metzelthin, Department of Health Services Research, Maastricht University, Duboisdomein 30, Maastricht, 6229 GT, the Netherlands, Tel +31 6 38 59 49 90, Email s.metzelthin@maastrichtuniversity.nlAbstract: The World Health Organization (WHO) recognizes the right of individuals with dementia and their family caregivers to access interventions that enhance their participation in society. Reablement is an approach that enables older people to participate in meaningful daily and social activities. Over the past decade, a growing body of evidence has underscored reablement as a promising approach within dementia care, including positive outcomes for people with dementia and their family caregivers, and cost-effectiveness. However, the dissemination of knowledge about and practical implementation of reablement remain slow. This position paper, authored by the ReableDEM research network, aims to address key issues related to implementing reablement in dementia care. To expedite the adoption of reablement within dementia care, we propose five critical areas of focus: 1) Changing the attitudes and expectations of stakeholders (eg health and social care staff, policy makers, funders) – encouraging people to think about dementia as a disability from a biopsychosocial perspective; 2) Disrupting health and social care - A radical change is needed in the way services are organized so that they are more holistic, personalized and resource-oriented; 3) Investing in capacity-building and creating a supportive environment – the workforce needs to be trained and supported to implement reablement in dementia care; 4) Involving, educating and supporting family caregivers - services and staff that are equipped to provide reablement will be better able to involve family caregivers and the person’s social network; 5) Providing robust evidence about reablement in dementia care by conducting high-quality research with long-term follow-up.Keywords: ageing, sustainability, autonomy, capacity-building, functioning, social participation

Abstract Background Undiagnosed hypertension (HTN) and diabetes mellitus (DM) are major public health challenges worldwide. We aimed to investigate the prevalence of undiagnosed HTN and DM, and their correlates, in a large-scale population-based cohort study. Methods In this cross-sectional study, data collected during the enrollment phase of the Tabari Cohort study (TCS) were utilized. Data were collected in the TCS using a standard questionnaire, blood collection, and measurement of anthropometric indices and blood pressure. Data were analyzed using the chi-squared test and univariate and multivariate logistic regression analyses. Undiagnosed HTN included those who were not aware of HTN at the time of enrollment but had systolic and diastolic blood pressures ≥ 140 mm or ≥ 90 mmHg, respectively. Undiagnosed DM included participants who were unaware of their DM at the time of enrollment and had FBS levels ≥ 126 mg/dL. Results The total prevalence of undiagnosed HTN and DM were 5% (508) and 4.7% (485), respectively. The findings of multivariable logistic regression analysis showed that young age (OR: 0.40, P

Abstract Background The implementation of social innovations for addressing societal challenges, particularly in health, leverages community participation and technology to optimally meet social needs compared to traditional approaches. A key feature of these innovations is their ability to utilize existing capacities for contributing to resolving infectious disease outbreaks, which has attracted significant attention from health organizations. Given the potential of these innovations, this study has investigated social innovations in the prevention and control of infectious diseases as one of the major global challenges in the form of a comprehensive literature review. Methods This review study examined the relevant literature from January 1, 2010 to December 31, 2022. Based on inclusion and exclusion criteria, 50 documents were retained and fully examined. The documents were analyzed by applying a thematic analysis, and important content related to the application of social innovations for the prevention and control of pandemic infectious diseases was extracted using a data collection form. Results Five major themes concerning social innovation in the prevention and control of epidemic diseases were discerned as follows: new products, novel processes and policies, empowerment, innovative practices and behaviors, and community engagement. New products include technological products for control and management of epidemics, preventive products, diagnostic and therapeutic products. Novel processes and policies are related to reorienting and reorganizing care methods, control and monitoring policies, participatory and creative strategies. Empowerment is focused on enhancing the capabilities of health workers, community leaders, and communities. Innovative practices and behaviors involve technology-based participation and support mechanisms. Community engagement is related to awareness, consultation, community mobilization, and participation in production and support. Conclusions During the outbreak of infectious diseases, governments are faced with many challenges, including health, economic and social challenges. To answer these challenges, tools should be used that have the ability to answer the problem from several aspects. Social innovation as an appropriate process in response to health crises has led to new forms of relationships and empowered the communities. And to promote public health, it provides the opportunity for all members of the society to participate in crisis resolution and optimal use of resources.

Artikkel on teine osa algajate eesti keele õppijate ja eesti keelt emakeelena kõnelejate suulist interaktsiooni käsitlevast pikiuuringust. Informantideks on viis täiskasvanud keeleõppijat, kellest neljaga on nende aastasel eesti keele intensiivkursusel osalemise perioodil salvestatud neli, ühega kaks vaba vestlust emakeelekõnelejatega, vestluste vahe on keskmiselt kaks kuud. Artiklis käsitletakse suulises interaktsioonis toimuvaid muutusi eesti keele õppijate keeleoskuse täienemise käigus. Pikiuurimuse materjali analüüs näitas, et õppijate keeleoskuse arenedes suureneb õppija voorust põhjustatud tähendusläbirääkimiste hulk ning mitmekesistuvad õppijate kasutatud abiotsimisstrateegiad. Seejuures toetuvad keeleõppijad muudele interaktsioonis osalejate ühistele keeltele kogu uurimisperioodi vältel ning võtavad eesti vestluspartnerite pakutud keelelise toetuse enamasti vestluses vastu keelendite vahetu kordamise teel. Eesti emakeelega osalejate tekstis esineb ka keeleõppesituatsioonile omaseid suulise korrigeeriva tagasiside andmise juhtumeid. "Changes in the interactions between learners of Estonian and native speakers over one year." This article is the second part of a longitudinal study of the oral interactions of learners of Estonian as a second language (L2) and native speakers (L1). The informants in the research are five adult language learners (native languages English, Romanian, Udmurt and Russian), who studied Estonian in an intensive course and who did not know Estonian prior to the beginning of their studies. As partners of the language learners three speakers of Estonian as a native language participated in the research; all of them had prior experience in teaching Estonian as a second language but none of them had taught the informants. During the year the research was conducted, four free-form conversations with native speakers were recorded with four of the language learners and two with one of them; the average length of the conversations was 20 minutes and the average interval between the conversations was two months. The article examines the particularities of the L1 and L2 learners’ interactions and changes over the period of the year as the Estonian language competence of the learners continues to grow.

Abstract Background Asthma, a complex respiratory disease, presents with inflammatory symptoms in the lungs, blood, and other tissues. We investigated the relationship between DNA methylation and 35 clinical markers of asthma. Methods The Illumina Infinium EPIC v1 methylation array was used to evaluate 742,442 CpGs in whole blood from 319 participants from 94 families. They were part of the Netherlands Twin Register from families with at least one member suffering from severe asthma. Repeat blood samples were taken after 10 years from 182 individuals. Principal component analysis on the clinical asthma markers yielded ten principal components (PCs) that explained 92.8% of the total variance. We performed epigenome-wide association studies (EWAS) for each of the ten PCs correcting for familial structure and other covariates. Results 221 unique CpGs reached genome-wide significance at timepoint 1 after Bonferroni correction. PC7, which correlated with loadings of eosinophil counts and immunoglobulin levels, accounted for the majority of associations (204). Enrichment analysis via the EWAS Atlas identified 190 of these CpGs to be previously identified in EWASs of asthma and asthma-related traits. Proximity assessment to previously identified SNPs associated with asthma identified 17 unique SNPs within 1 MB of two of the 221 CpGs. EWAS in 182 individuals with epigenetic data at a second timepoint identified 49 significant CpGs. EWAS Atlas enrichment analysis indicated that 4 of the 49 were previously associated with asthma or asthma-related traits. Comparing the estimates of all the significant associations identified across the two time points yielded a correlation of 0.81. Conclusion We identified 270 unique CpGs that were associated with PC scores generated from 35 clinical markers of asthma, either cross-sectionally or 10 years later. A strong correlation was present between effect sizes at the 2 timepoints. Most associations were identified for PC7, which captured blood eosinophil counts and immunoglobulin levels and many of these CpGs have previous associations in earlier studies of asthma and asthma-related traits. The results point to a robust DNA methylation profile as a new, stable biomarker for asthma.

Background and purpose: Fertility is a key demographic factor influencing population fluctuations. There is a global trend toward delaying childbearing, and Iran is also undergoing significant changes in this regard. This review study examines the factors influencing childbearing and associated obstacles from 2010 to 2022. Materials and methods: This systematic review utilized PubMed, Scopus, SID, and Web of Science databases to analyze articles published in both Farsi and English from 2010 to 2022. The keywords in both Persian and English included childbearing, attitude, women, reasons, fertility, and obstacles. All studies related to obstacles and factors influencing childbearing published in English between 2010 and 2022 and in Persian up to 2022 were included. In this review, the population (P2) refers to married women, intervention (I3) to the effective factors, comparison (C4) is not applicable given this study's reporting nature, and outcome (O5) refers to childbearing. The search within each database was conducted using title searches, with standardized MeSH terms such as childbearing, attitudes, women, reasons, fertility, and obstacles, combined with operators (e.g., AND, OR) to ensure comprehensive retrieval. Results: The search yielded 1,254 articles, of which 36 met the inclusion criteria after applying entry conditions, availability of article files, and removing duplicates. Factors such as social and cultural status, urban versus rural residence, educational level, and individuals’ religious and ethnic beliefs significantly impact couples’ decision-making regarding childbearing. Additionally, governmental policies, including support for pregnant mothers, play an influential role. Conclusion: Analysis of the 1,254 articles showed that economic, social, and cultural factors are significant social determinants of fertility. Ethnic background, education level, family orientation, religiosity, age at marriage, government policies, place of residence, and occupational status were identified as factors influencing childbearing. Religious and traditional values tend to increase fertility rates, especially among families with lower socioeconomic status. Educational programs aimed at improving beliefs and attitudes, promoting positive social norms, and strengthening empowerment skills may significantly enhance Iranian women’s reproductive intentions and behaviors. The findings of this study provide guidance for health policymakers in addressing obstacles to childbearing and supporting population growth in Iran. Additionally, by fostering favorable socio-economic conditions and recognizing diverse fertility behaviors across regions and cultures, reproductive health and pregnancy programs can better align with population growth policies.

Abstract Background In 2016, The World Health Organization introduced HIV self-testing (HIVST) as an alternative to traditional HIV testing (1), the present study aims to study the acceptability of HIV self-testing among Iranian women injecting drug users (WIDUs). The results of this study are expected to provide valuable evidence for the proper implementation of this program in Iran. Methods: This study employed a content analysis approach to gather qualitative data. The investigation was conducted from April to July 2023. We have chosen the following five provinces, namely Mashhad, Tehran, Kurdistan, Mazandaran, and Kerman, as the designated areas for our study. A sample of Iranians (17–62 years) was selected by purposeful and snowball sampling methods to participate in the study, and 31 semi-structured interviews were conducted. The data collection tool was an interview guide, which was designed based on a review of the literature. The data were analyzed using conventional content analysis. The interviews continued until data saturation was reached. Results: Based on our findings, we distilled 2 main themes and 9 categories including Inhibiting factors (Access and Affordability, Accuracy Concerns, Low knowledge, linkage to HIV treatment, the window period, Ignoring the danger) and Focalizing factors (Empowerment and autonomy, Stigma and privacy. Conclusion Iran’s HIV stigma may discourage regular testing, but self-testing can help overcome challenges. Support for counseling, care links, and accurate information dissemination are crucial.

Background and purpose: In 2023, the incidence of tuberculosis (TB) in Golestan Province was reported to be 26.1 cases per 100,000 people, which is three times higher than the national average in Iran. The contagious nature of tuberculosis has economic repercussions and indirect effects on the quality of life of affected individuals. The stigma associated with tuberculosis often leads to social isolation, which can hinder TB control efforts. On the other hand, social support from family, friends, healthcare workers, and community leaders improves quality of life, promotes self-care behaviors, and enhances patient adherence to medication regimens. This study aimed to determine the correlation between stigma, social support, and self-care behaviors in patients with tuberculosis. Materials and methods: This cross-sectional (descriptive-analytical) study was conducted in 2023, surveying 325 tuberculosis patients undergoing treatment in Golestan Province. Data were collected using a demographic information questionnaire, a 12-question stigma questionnaire (patients' perceptions of tuberculosis), the Sherborn and Stewart Perceived Social Support Questionnaire, and the self-care behaviors questionnaire for tuberculosis patients by Herandi et al. The data were analyzed using SPSS version 24 software. To investigate the relationship between perceived stigma and social support with the dimensions of self-care behaviors in tuberculosis patients, Spearman and chi-square tests were used. Logistic regression was employed to predict factors affecting self-care in the studied patients. Results: The average age of the participants was 51.97±17.33 years, with an age range of 19 to 84 years. The overall scores for the stigma questionnaire, perceived social support questionnaire, and self-care behaviors questionnaire were 29.03 ± 5.30, 71.14 ± 14.53, and 84.78 ± 10.17, respectively. Based on the univariate logistic regression model, the variables of race, number of family members, addiction, and age were analyzed for their effects on self-care behaviors. Additionally, the effects of marital status and age on stigma were examined. Significant effects of family size, income, and marital status on social support were observed. Spearman correlation tests showed an inverse and significant correlation between stigma and social support (r= -0.19, P= 0.001), stigma and self-care (r= -0.21, P

Abstract Background Dissemination and outcome reporting biases are a significant problem in clinical research, with far-reaching implications for both scientific understanding and clinical decision-making. This study investigates the prevalence of dissemination- and outcome reporting biases in registered interventional malaria research. Methods All malaria interventional trials registered on ClinicalTrials.gov from 2010 to 2020 were identified. Subsequently, publications that matched the registration were searched. The primary outcome measures were the percentage of registered studies that resulted in subsequent publication of study results, the concordance between registered outcomes, and reported outcomes. Secondary outcomes were compliance with WHO standards for timely publication (issued in 2017) of summary study results in the respective trial registry (within 12 months of study completion) or peer-reviewed publication (within 24 months of study completion) was evaluated. Results A total of 579 trials were identified on ClinicalTrials.gov, of which 544 met the inclusion criteria. Notably, almost 36.6% of these trials (199/544) were registered retrospectively, with 129 (23.7%) registered after the first patient enrolment and 70 (12.9%) following study completion. Publications were identified for 351 out of 544 registered trials (64.5%), involving 1,526,081 study participants. Conversely, publications were not found for 193 of the 544 registrations (35.5%), which aimed to enrol 417,922 study participants. Among these 544 registrations, 444 (81.6%) did not meet the WHO standard to post summary results within 12 months of primary study completion (the last visit of the last subject for collection of data on the primary outcome), while 386 out of 544 registrations (71.0%) failed to publish their results in a peer-reviewed journal within 24 months of primary study completion. Discrepancies were noted in the reported primary outcomes compared to the registered primary outcomes in 47.6% (222/466) of the published trials, and an even higher discordance rate of 73.2% (341/466 publications) for secondary outcomes. Conclusions Non-dissemination remains a significant issue in interventional malaria research, with most trials failing to meet WHO standards for timely dissemination of summary results and peer-reviewed journal publications. Additionally, outcome reporting bias is highly prevalent across malaria publications. To address these challenges, it is crucial to implement strategies that enhance the timely reporting of research findings and reduce both non-dissemination and outcome reporting bias.

Abstract Background Music therapy is the clinical use of musical interventions to improve mental and physical health across multiple domains, including social communication. Autistic children, who have difficulties in social communication and often increased anxiety, tend to show a strong preference for music, because it can be structured and systematic, and therefore more predictable than social interaction. This makes music therapy a promising medium for therapeutic support and intervention. Previous clinical trials of music therapy compared to traditional therapy for autistic children have shown encouraging but nevertheless mixed results. Key aims The primary aim is to conduct a randomised controlled trial (RCT) of improvisational music therapy for autistic children and test its effectiveness in at improving social communication and wellbeing, and to reduce anxiety. Research plan The RCT will be conducted with 200 autistic children in the UK aged 7 to 11 years old. Participants will be randomly assigned to either improvisational music therapy or support as usual. The trial will be an assessor-blind, pragmatic two-arm cluster RCT comparing the impact of 12-weeks of improvisational music therapy in addition to support as usual, vs. support as usual for autistic children. Methods Researchers who are blind to which arm the children are in will conduct assessments and obtain data via caregiver reports. The primary outcome will be the absolute change in the total score of the Brief Observation of Social Communication Change (BOSCC) assessed at baseline, T1 (13 weeks) and T2 (39 weeks) follow-ups. The BOSCC consists of specific items that were developed to identify changes in social-communication behaviours. Secondary outcome measures include: (1) Parent reported anxiety scale for youth with ASD (Note that we do not use the term ‘ASD’ or Autism Spectrum Disorder, because many autistic people feel it is stigmatising. Instead, we use the term ‘autism’) (PRAS-ASD) (2) Young Child Outcome Rating Scale, for wellbeing (YCORS), (3) Strengths and Difficulties Questionnaire (SDQ); and (4) Vineland Adaptive Behaviour Scale (VABS). (5) The Children’s Communication Checklist-2 (CCC-2) will be completed to evaluate pragmatic speech with fluent speakers only; (6) The Music Engagement Scale (MES); and (7) Assessment of the Quality of Relationship (AQR) will be used to evaluate the child-therapist relationships using video-analysis of music therapy sessions. Additional data will be collected by administering the Wechsler Abbreviated Scale of Intelligence (WASI-II), Music at Home Questionnaire (M@H), and children’s versions of the Empathy Quotient (EQ) and Systemizing Quotient (SQ). Audio and video data from the therapy sessions will be collected and analysed (using both human and computer-based feature-coding, e.g., machine learning and AI-driven methods) to identify how music and non-musical interactions foster change throughout the therapy. Discussion This study aims to observe if the interactions, engagement, and therapeutic modalities fostered during music therapy sessions can translate to non-musical contexts and improve autistic children’s social communication skills, identifying possible mediating factors contributing to the effectiveness of music therapy, potentially informing policy making and governance. Trial registration This randomised control trial is registered with the NIH U.S. National Library of Medicine: https://clinicaltrials.gov/search?term=NCT06016621 , clinicalTrials.gov Identifier: NCT0601662, Registration Date 19th August 2023.

Summary: Background: 1H-NMR metabolomics and DNA methylation in blood are widely known biomarkers predicting age-related physiological decline and mortality yet exert mutually independent mortality and frailty signals. Methods: Leveraging multi-omics data in four Dutch population studies (N = 5238, ∼40% of which male) we investigated whether the mortality signal captured by 1H-NMR metabolomics could guide the construction of DNA methylation-based mortality predictors. Findings: We trained DNA methylation-based surrogates for 64 metabolomic analytes and found that analytes marking inflammation, fluid balance, or HDL/VLDL metabolism could be accurately reconstructed using DNA-methylation assays. Interestingly, a previously reported multi-analyte score indicating mortality risk (MetaboHealth) could also be accurately reconstructed. Sixteen of our derived surrogates, including the MetaboHealth surrogate, showed significant associations with mortality, independent of relevant covariates. Interpretation: The addition of our metabolic analyte-derived surrogates to the well-established epigenetic clock GrimAge demonstrates that our surrogates potentially represent valuable mortality signal. Funding: BBMRI-NL, X-omics, VOILA, Medical Delta, NWO, ERC.