Background Mechanisms that preclude lung metastasis are still barely understood. The possible consequences of allergic airways inflammation on cancer dissemination were studied in a mouse model of breast cancer. Methods Balb/c mice were immunized and daily exposed to ovalbumin (OVA) from day 21. They were subcutaneously injected with 4T1 mammary tumor cells on day 45 and sacrificed on day 67. Lung metastases were measured by biophotonic imaging (IVIS® 200 Imaging System) and histological measurement of tumor area (Cytomine software). Effects of CCL11 were assessed in vivo by intratracheal instillations of recCCL11 and in vitro using Boyden chambers. CCR3 expression on cell surface was assessed by flow cytometry. Results The extent of tumor metastases was significantly higher in lungs of OVA-exposed mice and increased levels of CCL11 expression were measured after OVA exposure. Migration of 4T1 cells and neutrophils was stimulated in vitro and in vivo by recCCL11. 4T1 cells and neutrophils express CCR3 as shown by flow cytometry and a selective CCR3 antagonist (SB-297006) inhibited the induction of 4T1 cells migration and proliferation in response to recCCL11 . Conclusions Allergic inflammation generated by exposure to allergens triggers the implantation of metastatic cells from primary breast tumor into lung tissues plausibly in a CCL11–CCR3-dependent manner. This indicates that asthma related inflammation in lungs might be a risk factor for lung metastasis in breast cancer patients.

Open Science calls for transparent science and involvement of various stakeholders. Here are examples of and advice for meaningful stakeholder engagement.

AbstractThis chapter seeks to provide insight into the ways in which Member States leveraged the regulatory discretion afforded to them by the GDPR. Specifically, it reviews the biobank regulatory environment; whether and how derogations under Article 89(2) GDPR are enabled; the legal basis for scientific research and the role of consent in biobanking post-GDPR; the balance between individual rights and public interest in national law; and finally, the GDPR’s impact and future possibilities for biobanking. In exercising self-determination, Member States can, to a certain extent, align data protection requirements with their values and aspirations. Such alignment, though, could jeopardize collaborative research. In light of the need to bridge divergent legal and ethical requirements at a national and supranational level, the role of Research Ethics Committees (RECs) might prove to be essential.

AbstractThis contribution aims to present in a clear and concise manner the intricate legal framework for biobank research in Belgium. In Part 1, we describe the Belgian biobank infrastructure, with a focus on the concept of biobank. In Part 2, we provide an overview of the applicable legal framework, namely the Act of 19 December 2008 on Human Body Material (HBM), and its amendments. Attention is given to an essential piece of self-regulation, namely the Compendium on biobanks issued by the Federal Agency on Medicine Products and Health (FAMPH). Furthermore, we delineate the interplay with relevant data protection rules. Part 3 is dedicated to the main research oversight bodies in the field of biobanking. In Part 4, we provides several examples of the ‘law in context’. In particular, we discuss issues pertaining to presumed consent, processing of personal data associated with HBM, and information provided to the donor of HBM. Finally, Part 5 and 6 addresses the impact of the EU General Data Protection Regulation (GDPR), suggests lines for further research, and outline the future possibilities for biobanking in Belgium.

Aim: Maximal handgrip strength is a strong predictor of cardiovascular mortality in economically and socioculturally diverse countries, yet the main determinants of cardiovascular response to change in afterload during handgrip are not well known. We examined the blood pressure (BP) responses during submaximal handgrip (at 25% of grip strength) and the determinants of grip strength. Methods: We studied 2215 participants from a population-based random sample without overt clinical disease (Asklepios Study; mean age 56.2 years). Handgrip testing was performed using a modified Jamar dynamometer with direct visual feedback. Simultaneously, a validated finger plethysmographic device measured continuous BP and heart rate. Results: During handgrip, SBP and DBP rose by, respectively, 20 ± 13 and 10 ± 6 mmHg. These changes were normally distributed and consistently higher in men. The main independent determinants of mean arterial pressure response during handgrip were: grip strength (F = 191.4; P < 0.001), baseline pulse pressure (F = 32.0; P < 0.001), height (F = 16.4; P < 0.001) and age (F = 12.8; P < 0.001). Grip strength was associated with muscle mass, better metabolic health, but also with higher baseline DBP. There was a significant graded increase in maximum pressure achieved and in the magnitude of pressure change during handgrip with increasing BP categories (P for trend <0.001). Conclusion: The population BP response to handgrip is variable and its predominant determinant turned out to be grip strength itself, which should be accounted for in future analyses. Higher baseline BP, even within the normotensive range, acted as an independent and graded predictor of BP increase during handgrip.

The SHARC (SHAring Reward & Credit) interest group (IG) is an interdisciplinary group set up in the framework of RDA (Research Data Alliance) to improve crediting and rewarding mechanisms in the sharing process throughout the data life cycle. Notably, one of the objectives is to promote data sharing activities in research assessment schemes at national and European levels. To this aim, the RDA-SHARC IG is developing assessment grids using criteria to establish if data are compliant to the FAIR principles (findable /accessible / interoperable / reusable). The grid is aiming to be extensive, generic and trans-disciplinary. It is meant to be used by evaluators to assess the quality of the sharing practice of the researcher/scientist over a given period, taking into account the means & support available over that period. The grid displays a mind-mapped tree-graph structure based on previous works on FAIR data management (Reymonet et al., 2018; Wilkinson et al., 2016; Wilkinson et al., 2018; and E.U.Guidelines about FAIRness Data Management Plans). The criteria used are based on the work from FORCE 11*, and the Open Science Career Assessment Matrix designed by the EC Working group on Rewards under Open science. The criteria are organised in 5 clusters: ‘Motivations for sharing’; ‘Findable’, ‘Accessible’, ‘Interoperable’ and ‘Reusable’. For each criterion, 4 graduations are proposed (‘Never / Not Assessable’; ‘If mandatory’; ‘Sometimes’; ‘Always’). Only one value must be selected per criterion. Evaluation should be done by cluster; the final overall assessment will be based on the sum of the number of each ticked value / total number of criteria in each cluster; the ‘motivations for sharing’ should be appreciated qualitatively in the final interpretation. The final goals are to develop a graduated assessment of the researcher FAIRness literacy and help identifying needs to build FAIRness guidelines to improve the sharing capacity of researchers.

The Bioresource center Ghent is the central hospital-integrated biobank of Ghent University Hospital. Our mission is to facilitate translational biomedical research by collecting, storing and providing high quality biospecimens to researchers. Several of our biobank partners store large amounts of cell lines. As cell lines are highly important both in basic research and preclinical screening phases, good annotation, authentication, and quality of these cell lines is pivotal in translational biomedical science. A Biobank Information Management System (BIMS) was implemented as sample and data management system for human bodily material. The samples are annotated by the use of defined datasets, based on the BRISQ (Biospecimen Reporting for Improved Study Quality) and Minimum Information About Biobank data Sharing (MIABIS) guidelines completed with SPREC (Standard PREanalytical Coding) information. However, the defined dataset for human bodily material is not ideal to capture the specific cell line data. Therefore, we set out to develop a rationalized cell line dataset. Through comparison of different datasets of online cell banks (human, animal, and stem cell), we established an extended cell line dataset of 156 data fields that was further analyzed until a smaller dataset-the survey dataset of 54 data fields-was obtained. The survey dataset was spread throughout our campus to all cell line users to rationalize the fields of the dataset and their potential use. Analysis of the survey data revealed only small differences in preferences in data fields between human, animal, and stem cell lines. Hence, one essential dataset for human, animal and stem cell lines was compiled consisting of 33 data fields. The essential dataset was prepared for implementation in our BIMS system. Good Clinical Data Management Practices formed the basis of our decisions in the implementation phase. Known standards, reference lists and ontologies (such as ICD-10-CM, animal taxonomy, cell line ontology…) were considered. The semantics of the data fields were clearly defined, enhancing the data quality of the stored cell lines. Therefore, we created an essential cell line dataset with defined data fields, useable for multiple cell line users.

From as early as 2005, different guidelines and quality standards covering biobank activities and sample handling methods have been developed to improve and guarantee the reproducibility of biomarker research. Ten years on, the BBMRI.be Quality working group wanted to gauge the current situation of these aspects in the biobanks of the BBMRI.be network. To this end, two online surveys were launched (fall 2017 and fall 2018) to the biobank quality managers in the BBMRI.be network to determine the status and setup of their current quality management system (QMS) and how their QMS and related practices have evolved over a 14 month time period. All biobanks addressed by the two surveys provided a complete response (12 and 13, respectively). A QMS was implemented in 85% of biobanks, with 4 standards emerging as primary basis. Supplementary guidelines were used, with a strong preference for the ISBER best practices for biobanks. The Standard Preanalytical Code—an indicator of the preanalytical lifecycle of a biospecimen impacting the downstream analysis results—was already implemented in 50% of the biobanks while the other half intends future implementation. To assess and maintain the quality of their QMS, 62% of biobanks used self-assessment tools and 71% participated in proficiency testing schemes. The majority of biobanks had implemented procedures for general and biobank specific activities. However, policies regarding the business and sustainability aspect of biobank were only implemented in a limited number of biobanks. A clear desire for a peer-review audit was expressed by 69% of biobanks, with over half of them intending to implement the recently published biobank standard ISO20387. Overall, the biobanks of the BBMRI.be network have actively implemented a solid quality approach in their practices. The implementation of ISO 20387 may bring further professionalization of activities. Based on the needs expressed in this survey, the Quality working group will be setting up an audit program for the BBMRI.be biobanks, to enhance, harmonize and streamline their activities. On the whole, the biobanks in the BBMRI.be network are able to substantially contribute to translational research, as a primary facilitator guaranteeing high quality standards and reproducibility.

Human biospecimen samples (HBS) and associated data stored in biobanks (also called "biotrusts," "biorepositories," or "biodistributors") are very critical resources for translational research. As HBS quality is decisive to the reproducibility of research results, biobanks are also key assets for new developments in precision medicine. Biobanks are more than infrastructures providing HBS and associated data. Biobanks have pioneered in identifying and standardizing sources of preanalytical variations in HBS, thus paving the way for the current biospecimen science. To achieve this milestone, biobankers have successively assumed the role of "detective," and then "architect," to identify new detrimental impact of preanalytical variables on the tissue integrity. While standardized methods in omics are required to be practiced throughout research communities, the accepted best practices and standards on biospecimen handling are generally not known nor applied by researchers. Therefore, it is mandatory to raise the awareness within omics communities regarding not only the basic concepts of collecting, storing, and utilizing HBS today, but also to suggest insights on biobanking in the cancer omics context.

Thyroid dysfunction is an important public health problem, which affects 10% of the general population and increases the risk of cardiovascular morbidity and mortality. Many aspects of thyroid hormone regulation have only partly been elucidated, including its transport, metabolism, and genetic determinants. Here we report a large meta-analysis of genome-wide association studies for thyroid function and dysfunction, testing 8 million genetic variants in up to 72,167 individuals. One-hundred-and-nine independent genetic variants are associated with these traits. A genetic risk score, calculated to assess their combined effects on clinical end points, shows significant associations with increased risk of both overt (Graves' disease) and subclinical thyroid disease, as well as clinical complications. By functional follow-up on selected signals, we identify a novel thyroid hormone transporter (SLC17A4) and a metabolizing enzyme (AADAT). Together, these results provide new knowledge about thyroid hormone physiology and disease, opening new possibilities for therapeutic targets.

Indexed identifier ? Identification Are each data/dataset identified by an indexed and independant identifier ? Persistent metadata / data link ? Metadata traceability Are the metadata linked to the dataset through a persistent identifier? Metadata & authority linked ? Metadata traceability Are the metadata of each dataset linked to a unique authority (responsible for the datasets at a given time)? Unique, global, persistent ID? Identification Are the data identifiers unique, global and persistent ? Are the data identifiers unique, global and persistent ? Datasets linked to authority ? Metadata traceability Are all datasets linked to an authority (legal entity) through a unique and persistent identifier over time (e.g. institution, association or established body)? In case of a legal reuse restriction (such as personal data, state and public security, national defense secret, confidentiality of external relations, information systems security, secrets in industrial and commercial matters) , is the restriction properly justified?

Bimetra Biobank is the central high quality biorepository of University Hospital Ghent in collaboration with Ghent University (Belgium). Fully operational since 2015 in a new state-of-the-art biobank facility, Bimetra Biobank acts as a core facility for researchers and third parties looking for high-quality annotated clinical biospecimens. Bimetra Biobank stores about 120.000 clinical samples, both historical collections and prospective collections (disease-based collections, population-based collections and basic research collections) within well-defined and ethically approved research projects. Through a clear governance structure compliant with applicable laws, collections are operationally managed by Bimetra biobank personnel and samples releases are coordinated through collection specific coordinators and advisory boards. Biobank collections are open for collaborations to the international scientific community.

Telomeres shorten with age, the major risk factor for atherosclerotic cardiovascular disease (aCVD). The observation of shorter telomeres in aCVD patients thus suggested that critical telomere shortening may contribute to premature biological aging and aCVD. Therefore, telomere length often is suggested as a causal aCVD risk factor, a proposal supported by recent Mendelian randomization studies; however, epidemiological research has shown disappointingly low effect sizes. It therefore remains uncertain whether telomere shortening is a cause of aCVD or merely a consequence. The authors argue that elucidating the mechanistic foundation of these findings is essential for any possible translation of telomere biology to the clinic. Here, they critically evaluate evidence for causality in animal models and human studies, and review popular hypotheses and discuss their clinical implications. The authors identify 4 key questions that any successful mechanistic theory should address, and they discuss how atherosclerosis-associated local telomere attrition may provide the answers.

The RDA-SHARC (SHAring Reward & Credit) interest group is an interdisciplinary volunteer member-based group set up as part of RDA (Research Data Alliance) to unpack and improve crediting and rewarding mechanisms in the sharing process throughout the data life cycle. Background and objectives of this group are reported here. Notably, one of the objectives is to promote the inclusion of data sharing activities in the research (& researchers) assessment scheme at national and European levels. To this aim, the RDA-SHARC-IG is developing two assessment grids using criteria to establish if data are compliant to the F.A.I.R principles (findable /accessible / interoperable / reusable) based on previous works on FAIR data management (Reymonet et al., 2018; Wilkinson et al., 2018; and E.U.Guidelines*): 1/ The self-assessment grid to be used by a scientist as a ‘checklist’ to identify her/his own activities and to pinpoint the hurdles that hinder efficient sharing and reuse of his/her data by all potential users. 2/ The two-level grid (quick/extensive) to be used by the evaluator to assess the quality of the researcher/scientist sharing practice, over a given period, taking into account the means & support available over that period. Assessment criteria are classified according their importance with regards to FAIRness (essential / recommended / desirable) meanwhile good practices are recommended for critical steps. To implement a highly fair assessment of the sharing process, appropriate criteria must be selected in order to design optimal generic assessment grids. This process requires participation, time and input from volunteer scientists data producers/users from various fields.

Telomere length is a prognostic biomarker for aging diseases. As it is unknown whether diet plays a role in these associations, we aimed to assess the impact of diet on telomere length. Moreover, given that telomere length is modulated by oxidative stress and inflammation, an additional goal was to evaluate whether the latter may mediate possible telomere – diet associations. Southern blot measured leukocyte telomere length and food frequency questionnaire data were compared for 2509 apparently healthy men and women (~35 to 55 years) from the Asklepios population. No significant associations were found between telomere length and overall dietary characteristics, such as dietary diversity, quality, equilibrium, and the dietary inflammatory index. Exploratory analysis of individual dietary variables revealed that a higher daily intake of deep fried potato products was associated with shorter telomeres ( P = 0.002, 151 bp per 100 g/day), also in both sexes separately. Deep fried potato product consumption was also significantly associated with C-reactive protein ( P = 0.032) and uric acid ( P = 0.042), but not other inflammation and oxidative stress markers. These results suggest an at most limited association between overall dietary patterns and telomere length in the general population. Nevertheless, the association between telomere length and deep fried potato product intake warrants additional research.

Telomeres shorten with age, the major risk factor for atherosclerotic cardiovascular disease (aCVD). The observation of shorter telomeres in aCVD patients thus suggested that critical telomere shortening may contribute to premature biological aging and aCVD. Therefore, telomere length often is suggested as a causal aCVD risk factor, a proposal supported by recent Mendelian randomization studies; however, epidemiological research has shown disappointingly low effect sizes. It therefore remains uncertain whether telomere shortening is a cause of aCVD or merely a consequence. The authors argue that elucidating the mechanistic foundation of these findings is essential for any possible translation of telomere biology to the clinic. Here, they critically evaluate evidence for causality in animal models and human studies, and review popular hypotheses and discuss their clinical implications. The authors identify 4 key questions that any successful mechanistic theory should address, and they discuss how atherosclerosis-associated local telomere attrition may provide the answers.