07 Fakultät Konstruktions-, Produktions- und Fahrzeugtechnik

Permanent URI for this collectionhttps://elib.uni-stuttgart.de/handle/11682/8

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    ROSIE : RObust Sparse ensemble for outlIEr detection and gene selection in cancer omics data
    (2022) Jensch, Antje; Lopes, Marta B.; Vinga, Susana; Radde, Nicole
    The extraction of novel information from omics data is a challenging task, in particular, since the number of features (e.g. genes) often far exceeds the number of samples. In such a setting, conventional parameter estimation leads to ill-posed optimization problems, and regularization may be required. In addition, outliers can largely impact classification accuracy. Here we introduce ROSIE, an ensemble classification approach, which combines three sparse and robust classification methods for outlier detection and feature selection and further performs a bootstrap-based validity check. Outliers of ROSIE are determined by the rank product test using outlier rankings of all three methods, and important features are selected as features commonly selected by all methods. We apply ROSIE to RNA-Seq data from The Cancer Genome Atlas (TCGA) to classify observations into Triple-Negative Breast Cancer (TNBC) and non-TNBC tissue samples. The pre-processed dataset consists of 16,600 genes and more than 1,000 samples. We demonstrate that ROSIE selects important features and outliers in a robust way. Identified outliers are concordant with the distribution of the commonly selected genes by the three methods, and results are in line with other independent studies. Furthermore, we discuss the association of some of the selected genes with the TNBC subtype in other investigations. In summary, ROSIE constitutes a robust and sparse procedure to identify outliers and important genes through binary classification. Our approach is ad hoc applicable to other datasets, fulfilling the overall goal of simultaneously identifying outliers and candidate disease biomarkers to the targeted in therapy research and personalized medicine frameworks.
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    Lernen und üben wir das Richtige? : Kritische Erfolgsfaktoren der Bewältigung des Massenanfalls von Verletzten : Ergebnisse einer FMEA und einer Analyse von MANV-bezogenen Curricula
    (2021) Drews, Patrick; Berger, Maximilian; Sautter, Johannes; Rohde, Annika
    Der Massenanfall von Verletzten (MANV) ist eine Ausnahmesituation für Rettungsdienst und andere Einsatzkräfte. Trotz niedriger Inzidenz müssen sich die Einsatzkräfte sowohl auf ärztlicher als auch auf nichtärztlicher Seite auf diesen Einsatzfall vorbereiten. In der vorliegenden Pilotstudie wurden anhand einer Fehlermöglichkeits- und -einflussanalyse (FMEA) die kritischen Einsatzfaktoren im MANV ermittelt und mit den Ausbildungscurricula verglichen. Die herangezogenen Curricula waren Notfallsanitäter:in, organisatorische:r Leiter:in, Konzept zur katastrophenmedizinischen Ausbildung im studentischen Unterricht an deutschen Hochschulen, Nationaler Kompetenz-basierter Lernzielkatalog Medizin (NKLM), Zusatz-Weiterbildung Notfallmedizin und Fortbildung zum:zur leitenden Notarzt:ärztin. Die Ergebnisse lassen vermuten, dass in der praktischen Ausbildung der MANV eine eher untergeordnete Rolle spielt. Weitere empirische Untersuchungen sind aus Sicht der Autoren notwendig.
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    Mathematical modeling of the pituitary-thyroid feedback loop: role of a TSH-T3-shunt and sensitivity analysis
    (2018) Berberich, Julian; Dietrich, Johannes W.; Hoermann, Rudolf; Müller, Matthias A.
    Despite significant progress in assay technology, diagnosis of functional thyroid disorders may still be a challenge, as illustrated by the vague upper limit of the reference range for serum thyrotropin (TSH). Diagnostical problems also apply to subjects affected by syndrome T, i.e. those 10% of hypothyroid patients who continue to suffer from poor quality of life despite normal TSH concentrations under substitution therapy with levothyroxine (L-T4 ). In this paper, we extend a mathematical model of the pituitary-thyroid feedback loop in order to improve the understanding of thyroid hormone homeostasis. In particular, we incorporate a TSH-T3 –shunt inside the thyroid, whose existence has recently been demonstrated in several clinical studies. The resulting extended model shows good accordance with various clinical observations, such as a circadian rhythm in free peripheral triiodothyronine (FT3). Furthermore, we perform a sensitivity analysis of the derived model, revealing the dependence of TSH and hormone concentrations on different system parameters. The results have implications for clinical interpretation of thyroid tests, e.g. in the differential diagnosis of subclinical hypothyroidism.
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    Cu-doped calcium phosphate supraparticles for bone tissue regeneration
    (2024) Höppel, Anika; Bahr, Olivia; Ebert, Regina; Wittmer, Annette; Seidenstuecker, Michael; Carolina Lanzino, M.; Gbureck, Uwe; Dembski, Sofia
    Calcium phosphate (CaP) minerals have shown great promise as bone replacement materials due to their similarity to the mineral phase of natural bone. In addition to biocompatibility and osseointegration, the prevention of infection is crucial, especially due to the high concern of antibiotic resistance. In this context, a controlled drug release as well as biodegradation are important features which depend on the porosity of CaP. An increase in porosity can be achieved by using nanoparticles (NPs), which can be processed to supraparticles, combining the properties of nano- and micromaterials. In this study, Cu-doped CaP supraparticles were prepared to improve the bone substitute properties while providing antibacterial effects. In this context, a modified sol-gel process was used for the synthesis of CaP NPs, where a Ca/P molar ratio of 1.10 resulted in the formation of crystalline β-tricalcium phosphate (β-TCP) after calcination at 1000 °C. In the next step, CaP NPs with Cu 2+ (0.5-15.0 wt%) were processed into supraparticles by a spray drying method. Cu release experiments of the different Cu-doped CaP supraparticles demonstrated a long-term sustained release over 14 days. The antibacterial properties of the supraparticles were determined against Gram-positive ( Bacillus subtilis and Staphylococcus aureus ) and Gram-negative ( Escherichia coli ) bacteria, where complete antibacterial inhibition was achieved using a Cu concentration of 5.0 wt%. In addition, cell viability assays of the different CaP supraparticles with human telomerase-immortalized mesenchymal stromal cells (hMSC-TERT) exhibited high biocompatibility with particle concentrations of 0.01 mg mL -1 over 72 hours.
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    Different coupling mechanisms for a novel modular plate in acetabular fractures : a comparison using a laparoscopic model
    (2024) Menger, Maximilian M.; Herath, Steven C.; Ellmerer, Andreas E.; Trulson, Alexander; Hoßfeld, Max; Leis, Artur; Ollig, Annika; Histing, Tina; Küper, Markus A.; Audretsch, Christof K.
    Introduction: Acetabular fractures are among the most challenging injuries in traumatology. The complex anatomy usually requires extensive surgical approaches baring the risk for iatrogenic damage to surrounding neurovascular structures. As a viable alternative, minimally invasive endoscopic techniques have emerged during the recent years. This paper reports on the feasibility of different coupling mechanisms for a novel suprapectineal plate especially designed for minimally invasive acetabular surgery. Methods: A total number of 34 participants contributed to the present study, who differed in their arthroscopic and surgical experience. A laparoscopic model was used to compare four different coupling mechanisms by the number of failed attempts, the time required for plate fixation, the influence of surgical experience as well as the learning success for each individual coupling mechanism. Moreover, the feasibility of each mechanism was evaluated by a questionnaire. Results: The results demonstrate that plates employing grooved and pressure-sliding coupling mechanisms exhibit fewer failed attempts and reduce trial times, especially in contrast to sole sliding mechanisms. Furthermore, our study revealed that proficiency in endoscopic procedures significantly influenced the outcome. Notably, the subjective evaluation of the participants show that the pressure base and pressure-slide base plate designs are the most supportive and feasible designs. Conclusions: In summary, the present study evaluates for the first-time different plate and coupling designs for minimal-invasive surgery, indicating a superior feasibility for plates with a grooved and pressure-sliding mechanism.
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    Miniature low-cost γ-radiation sensor for localization of radioactively marked lymph nodes
    (2022) Behling, Merlin; Wezel, Felix; Pott, Peter P.
    Detection of metastasis spread at an early stage of disease in lymph nodes can be achieved by imaging techniques, such as PET and fluoride-marked tumor cells. Intraoperative detection of small metastasis can be problematic especially in minimally invasive surgical settings. A γ-radiation sensor can be inserted in the situs to facilitate intraoperative localization of the lymph nodes. In the minimally invasive setting, the sensor must fit through the trocar and for robot-aided interventions, a small, capsule-like device is favorable. Size reduction could be achieved by using only a few simple electronic parts packed in a single-use sensor-head also leading to a low-cost device. This paper first describes the selection of an appropriate low-cost diode, which is placed in a sensor head (Ø 12 mm) and characterized in a validation experiment. Finally, the sensor and its performance during a detection experiment with nine subjects is evaluated. The subjects had to locate a 137Cs source (138 kBq activity, 612 keV) below a wooden plate seven times. Time to accomplish this task and error rate were recorded and evaluated. The time needed by the subjects to complete each run was 95 ± 68.1 s for the first trial down to 40 ± 23.9 s for the last. All subjects managed to locate the 137Cs source precisely. Further reduction in size and a sterilizable housing are prerequisites for in vitro tests on explanted human lymph nodes and finally in vivo testing.
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    Role of rotated head postures on volunteer kinematics and muscle activity in braking scenarios performed on a driving simulator
    (2022) Kempter, Fabian; Lantella, Lorena; Stutzig, Norman; Fehr, Jörg; Siebert, Tobias
    Occupants exposed to low or moderate crash events can already suffer from whiplash-associated disorders leading to severe and long-lasting symptoms. However, the underlying injury mechanisms and the role of muscle activity are not fully clear. Potential increases in injury risk of non-nominal postures, i.e., rotated head, cannot be evaluated in detail due to the lack of experimental data. Examining changes in neck muscle activity to hold and stabilize the head in a rotated position during pre-crash scenarios might provide a deeper understanding of muscle reflex contributions and injury mechanisms. In this study, the influence of two different head postures (nominal vs. rotation of the head by about 63 ± 9° to the right) on neck muscle activity and head kinematics was investigated in simulated braking experiments inside a driving simulator. The braking scenario was implemented by visualization of the virtual scene using head-mounted displays and a combined translational-rotational platform motion. Kinematics of seventeen healthy subjects was tracked using 3D motion capturing. Surface electromyography were used to quantify muscle activity of left and right sternocleidomastoideus (SCM) and trapezius (TRP) muscles. The results show clear evidence that rotated head postures affect the static as well as the dynamic behavior of muscle activity during the virtual braking event. With head turned to the right, the contralateral left muscles yielded higher base activation and delayed muscle onset times. In contrast, right muscles had much lower activations and showed no relevant changes in muscle activation between nominal and rotated head position. The observed delayed muscle onset times and increased asymmetrical muscle activation patterns in the rotated head position are assumed to affect injury mechanisms. This could explain the prevalence of rotated head postures during a crash reported by patients suffering from WAD. The results can be used for validating the active behavior of human body models in braking simulations with nominal and rotated head postures, and to gain a deeper understanding of neck injury mechanisms.
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    Mathematical modeling and simulation of thyroid homeostasis : implications for the Allan-Herndon-Dudley syndrome
    (2022) Wolff, Tobias M.; Veil, Carina; Dietrich, Johannes W.; Müller, Matthias A.
    Introduction: A mathematical model of the pituitary-thyroid feedback loop is extended to deepen the understanding of the Allan-Herndon-Dudley syndrome (AHDS). The AHDS is characterized by unusual thyroid hormone concentrations and a mutation in the SLC16A2 gene encoding for the monocarboxylate transporter 8 (MCT8). This mutation leads to a loss of thyroid hormone transport activity. One hypothesis to explain the unusual hormone concentrations of AHDS patients is that due to the loss of thyroid hormone transport activity, thyroxine (T4) is partially retained in thyroid cells. This hypothesis is investigated by extending a mathematical model of the pituitary-thyroid feedback loop to include a model of the net effects of membrane transporters such that the thyroid hormone transport activity can be considered. A nonlinear modeling approach based on the Michaelis-Menten kinetics and its linear approximation are employed to consider the membrane transporters. The unknown parameters are estimated through a constrained parameter optimization. In dynamic simulations, damaged membrane transporters result in a retention of T4 in thyroid cells and ultimately in the unusual hormone concentrations of AHDS patients. The Michaelis-Menten modeling approach and its linear approximation lead to similar results. The results support the hypothesis that a partial retention of T4 in thyroid cells represents one mechanism responsible for the unusual hormone concentrations of AHDS patients. Moreover, our results suggest that the retention of T4 in thyroid cells could be the main reason for the unusual hormone concentrations of AHDS patients.
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    Data-driven development of sparse multi-spectral sensors for urological tissue differentiation
    (2023) Fischer, Felix; Frenner, Karsten; Granai, Massimo; Fend, Falko; Herkommer, Alois
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    Numerical analysis of the localization of pulmonary nodules during thoracoscopic surgery by ultra-wideband radio technology
    (2021) Battistel, Alberto; Pott, Peter Paul; Möller, Knut
    Worldwide, lung cancer is one of the most common causes of cancer-related death. Detected by computer tomography, it is usually removed through thoracoscopic surgery. During the surgery the lung collapses requiring some strategies to track or localize the new position of the lesion. This is particularly challenging in the case of minimally invasive surgeries when mechanical palpation is not possible. Here we undertake a preliminary study with numerical analysis of an ultra-wideband (UWB) radio technology which can be employed directly during thoracoscopic surgery to localize deep solitary pulmonary nodules. This study was conducted through Finite Difference Time Domain (FDTD) simulations, where a spherical target mimicking a nodule located between 1 and 6 cm of depth and an UWB pulse at several frequencies between 0.5 and 5 GHz was used for localization. This investigation quantifies the influence of several parameters, such frequency, lesion depth, and number of acquisitions, on the final confocal image used to locate a cancer in the lung tissue. We also provide extensive discussion on several artifacts that appear in the images. The results show that the cancer localization was possible at operational frequencies below 1 GHz and for deep nodules (>5 cm), while at lower depths and higher frequencies several artifacts hindered its detection.