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Irreproducibility of research results is one of the major contributing factors to the failure of translating basic research results into tangible bedside progress. To address this, the University Biobank Limburg (UBiLim) was founded by a collaboration between Hasselt University, the Hospital East-Limburg, and the Jessa Hospital. This paper describes the evolution of this process and the barriers encountered on the way. UBiLim evolved from an archival collection over a single-site biobank into a federated structure, supporting translational research at the founding institutions. Currently, UBiLim is a federated biobank, with an established organizational structure and processing, and storage facilities at each of the three sites. All activities are integrated in an ISO15189-accredited Quality Management System and based on (inter)national biobank guidelines. Common methods for processing and storage of a plethora of sample types, suitable for state-of-the-art applications, were validated and implemented. Because the biobank is embedded in two hospitals, the request of researchers to include certain sample types or enroll specific patient groups can quickly be met. Funding has been a major challenge in each step of its evolution and remains the biggest issue for long-term biobank sustainability. To a lesser extent, the Belgian legislation and the operational cost of information management system are also concerns for smooth biobank operations. Nonetheless, UBiLim serves as a facilitator and accelerator for translational research in the Limburg area of Belgium that, given the fields of research, may have an impact on international patient care.

Irreproducibility of research results is one of the major contributing factors to the failure of translating basic research results into tangible bedside progress. To address this, the University Biobank Limburg (UBiLim) was founded by a collaboration between Hasselt University, the Hospital East-Limburg, and the Jessa Hospital. This paper describes the evolution of this process and the barriers encountered on the way. UBiLim evolved from an archival collection over a single-site biobank into a federated structure, supporting translational research at the founding institutions. Currently, UBiLim is a federated biobank, with an established organizational structure and processing, and storage facilities at each of the three sites. All activities are integrated in an ISO15189-accredited Quality Management System and based on (inter)national biobank guidelines. Common methods for processing and storage of a plethora of sample types, suitable for state-of-the-art applications, were validated and implemented. Because the biobank is embedded in two hospitals, the request of researchers to include certain sample types or enroll specific patient groups can quickly be met. Funding has been a major challenge in each step of its evolution and remains the biggest issue for long-term biobank sustainability. To a lesser extent, the Belgian legislation and the operational cost of information management system are also concerns for smooth biobank operations. Nonetheless, UBiLim serves as a facilitator and accelerator for translational research in the Limburg area of Belgium that, given the fields of research, may have an impact on international patient care.

New Findings What is the central question of this study? It remains uncertain whether significant fat-free mass wasting occurs early after coronary artery bypass graft surgery, and the aetiology of this wasting in these particular conditions is unexplored. What is the main finding and its importance? Significant fat-free mass wasting is present after coronary artery bypass graft surgery, and this wasting effect is greater in younger patients and in patients with greater increments in blood cortisol-to-testosterone ratios after surgery. The magnitude and aetiology of muscle wasting early after coronary artery bypass graft (CABG) surgery remains unknown. In the present study, we assessed changes in fat-free mass early after CABG surgery and explored the possible aetiology (relationships with postsurgical changes in blood hormones, insulin resistance, subject characteristics and inflammation) for these changes. Fat-free mass was assessed before and 23(range: 25)days after CABG surgery in 25 subjects. Blood testosterone, cortisol, insulin-like growth factor-1, growth hormone, sex hormone-binding globulin, glucose, insulin, C-peptide and C-reactive protein concentrations were determined, and free androgen index, cortisol-to-testosterone ratio and HOMA-IR index were all calculated before surgery, during the first 3days after surgery and at reassessment of body composition. Relationships between changes in fat-free mass and changes in blood parameters after surgery or subject characteristics were studied. After surgery, free androgen index and blood sex hormone-binding globulin, testosterone and insulin-like growth factor-1 concentrations decreased significantly, while HOMA-IR index, cortisol-to-testosterone ratio, blood growth hormone, insulin and C-reactive protein concentrations increased significantly (P0.80). Whole-body fat-free mass decreased significantly [by -1.9(range: 9.1)kg, P<0.0025, observed =0.99] after surgery. According to regression analysis, greater absolute loss of fat-free mass was observed after CABG surgery in subjects who were younger, who experienced a greater increase in blood cortisol-to-testosterone ratio after surgery and/or who underwent earlier reassessment of body composition (P<0.05). Significant decrements in fat-free mass were observed early after CABG surgery, especially in younger subjects and/or subjects with elevated blood cortisol-to-testosterone ratios after surgery. Interventions to preserve fat-free mass soon after CABG surgery are thus warranted. ; This study was supported by an unrestricted research grant from Hartcentrum Hasselt vzw. L.L. is part of the 'Limburg Clinical Research Program (LCRP) UHasselt-ZOL-Jessa', supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital.

Human cardiac stem cells isolated from atrial appendages based on aldehyde dehydrogenase activity (CASCs) can be expanded in vitro and differentiate into mature cardiomyocytes. In this study, we assess whether Wnt activation stimulates human CASC proliferation, whereas Wnt inhibition induces cardiac maturation. CASCs were cultured as described before. Conventional PCR confirmed the presence of the Frizzled receptors. Small-molecule inhibitors (IWP2, C59, XAV939, and IWR1-endo) and activator (CHIR99021) of the Wnt/beta -catenin signaling pathway were applied, and the effect on beta-catenin and target genes for proliferation and differentiation was assessed by Western blot and RT-qPCR. CASCs express multiple early cardiac differentiation markers and are committed toward myocardial differentiation. They express several Frizzled receptors, suggesting a role for Wnt signaling in clonogenicity, proliferation, and differentiation. Wnt activation increases total and active beta-catenin levels. However, this does not affect CASC proliferation or clonogenicity. Wnt inhibition upregulated early cardiac markers but could not induce mature myocardial differentiation. When CASCs are committed toward myocardial differentiation, the Wnt pathway is active and can be modulated. However, despite its role in cardiogenesis and myocardial differentiation of pluripotent stem-cell populations, our data indicate that Wnt signaling has limited effects on CASC clonogenicity, proliferation, and differentiation. ; This work was funded by a Strategic Basic Research grant of the Flemish Agency for Innovation by Science and Technology (IWT; 121560), a PhD grant of Hasselt University (BOF12DOC21), and the Limburg Clinical Research Center (LCRC) UHasselt-Jessa-ZOL, supported by the foundation Limburg Sterk Merk, province of Limburg, Flemish government, Hasselt University, Jessa Hospital, and Ziekenhuis Oost-Limburg. ; Hendrikx, M (corresponding author), UHasselt, Fac Med & Life Sci, Martelarenlaan 42, B-3500 Hasselt, Belgium. leen.willems@uhasselt.be; annick.daniels@jessazh.be; yanick.fanton@beta-cell.com; loes.linsen@uzleuven.be; lize.evens@uhasselt.be; virginie.bito@uhasselt.be; jeroen.declercq@uzleuven.be; jean-luc.rummens@jessazh.be; karen.hensen@medtronic.com; marc.hendrikx@uhasselt.be

Multiple myeloma (MM) is consistently preceded by precursor conditions recognized clinically as monoclonal gammopathy of undetermined significance (MGUS) or smoldering myeloma (SMM). We interrogate the whole genome sequence (WGS) profile of 18 MGUS and compare them with those from 14 SMMs and 80 MMs. We show that cases with a non-progressing, clinically stable myeloma precursor condition (n=15) are characterized by later initiation in the patient's life and by the absence of myeloma defining genomic events including: chromothripsis, templated insertions, mutations in driver genes, aneuploidy, and canonical APOBEC mutational activity. This data provides evidence that WGS can be used to recognize two biologically and clinically distinct myeloma precursor entities that are either progressive or stable. The factors that are associated with myeloma precursor condition progression are not well understood. Here the authors find that monoclonal gammopathies of undetermined significance and smoldering myelomas that did not progress to multiple myelomas have a distinct genomic profile and emerge later in the patient's life. ; We want to thank Dr. Vincent S Rajkumar for important and useful scientific feedback on the final draft. This work was supported by the Society of Memorial Sloan Kettering, by the Sylvester Comprehensive Cancer Center NCI Core Grant (P30 CA 240139), by the Memorial Sloan Kettering Cancer Center NCI Core Grant (P30 CA 008748), by the Multiple Myeloma Research Foundation (MMRF), by the Perelman Family Foundation, and by the Riney Family Multiple Myeloma Research Program Fund. F.M. is supported by the American Society of Hematology, the International Myeloma Foundation and The Society of Memorial Sloan Kettering Cancer Center. N.B. is funded by the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement no. 817997). K.H.M. is supported by the Royal Australasian College of Physicians Dr. Helen Rarity McCreanor Traveling Fellowship. This study is part of the Limburg Clinical Research Center (LCRC) UHasselt-ZOL-Jessa, supported by the foundation Limburg Sterk Merk (LSM), Hasselt University, Ziekenhuis Oost-Limburg and Jessa Hospital. Additionally, this research is supported by Limburgs Kankerfonds, and LiveALife. ; Maura, F (corresponding author), Mem Sloan Kettering Canc Ctr, Dept Med, Myeloma Serv, 1275 York Ave, New York, NY 10021 USA. Landgren, O; Maura, F (corresponding author), Univ Miami, Sylvester Comprehens Canc Ctr, Myeloma Program, Miami, FL 33124 USA. col15@miami.edu; fxm557@med.miami.edu