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Mechanistic/data-driven hybrid modeling is a key approach when the mechanistic details of the processes at hand are not sufficiently well understood, but also inferring a model purely from data is too complex. By the integration of first principles into a data-driven approach, hybrid modeling promises a feasible data demand alongside extrapolation. In this work, we introduce a learning strategy for tree-structured hybrid models to perform a binary classification task. Given a set of binary labeled data, the challenge is to use them to develop a model that accurately assesses labels of new unlabeled data. Our strategy employs graph-theoretic methods to analyze the data and deduce a function that maps input features to output labels. Our focus here is on data sets represented by binary features in which the label assessment of unlabeled data points is always extrapolation. Our strategy shows the existence of small sets of data points within given binary data for which knowing the labels allows for extrapolation to the entire valid input space. An implementation of our strategy yields a notable reduction of training-data demand in a binary classification task compared with different supervised machine learning algorithms. As an application, we have fitted a tree-structured hybrid model to the vital status of a cohort of COVID-19 patients requiring intensive-care unit treatment and mechanical ventilation. Our learning strategy yields the existence of patient cohorts for whom knowing the vital status enables extrapolation to the entire valid input space of the developed hybrid model. [ABSTRACT FROM AUTHOR]

Introduction: Though xenogeneic acellular scaffolds are frequently used for surgical reconstruction, knowledge of their mechanical properties is lacking. This study compared the mechanical, histological and ultrastructural properties of various native and acellular specimens. Materials and Methods: Porcine esophagi, ureters and skin were tested mechanically in a native or acellular condition, focusing on the elastic modulus, ultimate tensile stress and maximum strain. The testing protocol for soft tissues was standardized, including the adaption of the tissue’s water content and partial plastination to minimize material slippage as well as templates for normed sample dimensions and precise cross-section measurements. The native and acellular tissues were compared at the microscopic and ultrastructural level with a focus on type I collagens. Results: Increased elastic modulus and ultimate tensile stress values were quantified in acellular esophagi and ureters compared to the native condition. In contrast, these values were strongly decreased in the skin after acellularization. Acellularization-related decreases in maximum strain were found in all tissues. Type I collagens were well-preserved in these samples; however, clotting and a loss of cross-linking type I collagens was observed ultrastructurally. Elastins and fibronectins were preserved in the esophagi and ureters. A loss of the epidermal layer and decreased fibronectin content was present in the skin. Discussion: Acellularization induces changes in the tensile properties of soft tissues. Some of these changes appear to be organ specific. Loss of cross-linking type I collagen may indicate increased mechanical strength due to decreasing transverse forces acting upon the scaffolds, whereas fibronectin loss may be related to decreased load-bearing capacity. Potentially, the alterations in tissue mechanics are linked to organ function and to the interplay of cells and the extracellular matrix, which is different in hollow organs when compared to skin. [ABSTRACT FROM AUTHOR]

Introduction: Acellular scaffolds are increasingly used for the surgical repair of tendon injury and ligament tears. Despite this increased use, very little data exist directly comparing acellular scaffolds and their native counterparts. Such a comparison would help establish the effectiveness of the acellularization procedure of human tissues. Furthermore, such a comparison would help estimate the influence of cells in ligament and tendon stability and give insight into the effects of acellularization on collagen. Material and Methods: Eighteen human iliotibial tract samples were obtained from nine body donors. Nine samples were acellularized with sodium dodecyl sulphate (SDS), while nine counterparts from the same donors remained in the native condition. The ends of all samples were plastinated to minimize material slippage. Their water content was adjusted to 69%, using the osmotic stress technique to exclude water content-related alterations of the mechanical properties. Uniaxial tensile testing was performed to obtain the elastic modulus, ultimate stress and maximum strain. The effectiveness of the acellularization procedure was histologically verified by means of a DNA assay. Results: The histology samples showed a complete removal of the cells, an extensive, yet incomplete removal of the DNA content and alterations to the extracellular collagen. Tensile properties of the tract samples such as elastic modulus and ultimate stress were unaffected by acellularization with the exception of maximum strain. Discussion: The data indicate that cells influence the mechanical properties of ligaments and tendons in vitro to a negligible extent. Moreover, acellularization with SDS alters material properties to a minor extent, indicating that this method provides a biomechanical match in ligament and tendon reconstruction. However, the given protocol insufficiently removes DNA. This may increase the potential for transplant rejection when acellular tract scaffolds are used in soft tissue repair. Further research will help optimize the SDS-protocol for clinical application. [ABSTRACT FROM AUTHOR]