166 research outputs found

    OpenML Benchmarking Suites

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    Machine learning research depends on objectively interpretable, comparable, and reproducible algorithm benchmarks. Therefore, we advocate the use of curated, comprehensive suites of machine learning tasks to standardize the setup, execution, and reporting of benchmarks. We enable this through software tools that help to create and leverage these benchmarking suites. These are seamlessly integrated into the OpenML platform, and accessible through interfaces in Python, Java, and R. OpenML benchmarking suites are (a) easy to use through standardized data formats, APIs, and client libraries; (b) machine-readable, with extensive meta-information on the included datasets; and (c) allow benchmarks to be shared and reused in future studies. We also present a first, carefully curated and practical benchmarking suite for classification: the OpenML Curated Classification benchmarking suite 2018 (OpenML-CC18)

    Physics of Brain Cancer:Multiscale Alterations of Glioblastoma Cells under Extracellular Matrix Stiffening

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    The biology and physics underlying glioblastoma is not yet completely understood, resulting in the limited efficacy of current clinical therapy. Recent studies have indicated the importance of mechanical stress on the development and malignancy of cancer. Various types of mechanical stress activate adaptive tumor cell responses that include alterations in the extracellular matrix (ECM) which have an impact on tumor malignancy. In this review, we describe and discuss the current knowledge of the effects of ECM alterations and mechanical stress on GBM aggressiveness. Gradual changes in the brain ECM have been connected to the biological and physical alterations of GBM cells. For example, increased expression of several ECM components such as glycosaminoglycans (GAGs), hyaluronic acid (HA), proteoglycans and fibrous proteins result in stiffening of the brain ECM, which alters inter-and intracellular signaling activity. Several mechanosensing signaling pathways have been identified that orchestrate adaptive responses, such as Hippo/YAP, CD44, and actin skeleton signaling, which remodel the cytoskeleton and affect cellular properties such as cellā€“cell/ECM interactions, growth, and migration/invasion of GBM cells. In vitro, hydrogels are used as a model to mimic the stiffening of the brain ECM and reconstruct its mechanics, which we also discuss. Overall, we provide an overview of the tumor microenvironmental landscape of GBM with a focus on ECM stiffening and its associated adaptive cellular signaling pathways and their possible therapeutic exploitation

    The Unfolded Protein Response Sensor PERK Mediates Stiffness-Dependent Adaptation in Glioblastoma Cells

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    Glioblastoma multiforme (GBM) is the most aggressive brain tumor in adults. In addition to genetic causes, the tumor microenvironment (TME), including stiffening of the extracellular matrix (ECM), is a main driver of GBM progression. Mechano-transduction and the unfolded protein response (UPR) are essential for tumor-cell adaptation to harsh TME conditions. Here, we studied the effect of a variable stiff ECM on the morphology and malignant properties of GBM stem cells (GSCs) and, moreover, examined the possible involvement of the UPR sensor PERK herein. For this, stiffness-tunable human blood plasma (HBP)/alginate hydrogels were generated to mimic ECM stiffening. GSCs showed stiffness-dependent adaptation characterized by elongated morphology, increased proliferation, and motility which was accompanied by F-Actin cytoskeletal remodeling. Interestingly, in PERK-deficient GSCs, stiffness adaptation was severely impaired, which was evidenced by low F-Actin levels, the absence of F-Actin remodeling, and decreased cell proliferation and migration. This impairment could be linked with Filamin-A (FLN-A) expression, a known interactor of PERK, which was strongly reduced in PERK-deficient GSCs. In conclusion, we identified a novel PERK/FLNA/F-Actin mechano-adaptive mechanism and found a new function for PERK in the cellular adaptation to ECM stiffening

    Bioinspired Processing:Complex Coacervates as Versatile Inks for 3D Bioprinting

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    3D bioprinting is a powerful fabrication technique in biomedical engineering, which is currently limited by the number of available materials that meet all physicochemical and cytocompatibility requirements for biomaterial inks. Inspired by the key role of coacervations in the extrusion and spinning of many natural materials, hyaluronic acid-chitosan complex coacervates are proposed here as tunable biomaterial inks. Complex coacervates are obtained through an associative liquid-liquid phase separation driven by electrostatic attraction between oppositely charged macromolecules. They offer bioactive properties as well as facile modulation of their mechanical properties through mild physicochemical changes in the environment, rendering them attractive for 3D bioprinting. Fine-tuning the salt concentration, pH, and molecular weight of the constituent polymers results in biomaterial inks that are printable in air and water. The biomaterial ink, initially a viscoelastic fluid, transitions into a viscoelastic solid upon printing due to dehydration (for printing in air) or due to a change in pH and ionic composition (for printing in water). Consequently, scaffolds printed using the complex coacervate inks are stable without the need for post-printing processing. Cell culture scaffolds fabricated in this way are cytocompatible and show long-term topological stability. These results pave the way to a new class of easy-to-handle tunable biomaterials for biofabrication

    Long-term results after transplantation of pediatric liver grafts from donation after circulatory death donors

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    Background Liver grafts from donation after circulatory death (DCD) donors are increasingly accepted as an extension of the organ pool for transplantation. There is little data on the outcome of liver transplantation with DCD grafts from a pediatric donor. The objective of this study was to assess the outcome of liver transplantation with pediatric DCD grafts and to compare this with the outcome after transplantation of livers from pediatric donation after brain death (DBD) donors. Method All transplantations performed with a liver from a pediatric donor ( Results In total, 74 liver transplantations with pediatric grafts were performed; twenty (27%) DCD and 54 (73%) DBD. The median donor warm ischemia time (DWIT) was 24 min (range 15-43 min). Patient survival rate at 10 years was 78% for recipients of DCD grafts and 89% for DBD grafts (p = 0.32). Graft survival rate at 10 years was 65% in recipients of DCD versus 76% in DBD grafts (p = 0.20). If donor livers in this study would have been rejected for transplantation when the DWIT >= 30 min (n = 4), the 10-year graft survival rate would have been 81% after DCD transplantation. The rate of non-anastomotic biliary strictures was 5% in DCD and 4% in DBD grafts (p = 1.00). Other complication rates were also similar between both groups. Conclusions Transplantation of livers from pediatric DCD donors results in good long-term outcome especially when the DWIT is kep
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