8 research outputs found

    What Characteristics does a Full-Immersive Multiplayer-VR-Simulation have in Comparison to the Application of Software for Video Conferences in the Processes of Group Work?

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    Der Einsatz von vollimmersiven VR-Lernumgebungen fördert bei Lernenden die individuellen FĂ€higkeiten und ihr Vorwissen. Konkrete Lerneffekte und Integrationskonzepte sind jedoch noch nicht ausreichend untersucht. Im Rahmen eines vom BMBF geförderten Forschungsprojektes soll mit diesem Beitrag deshalb der Frage nachgegangen werden: Welche didaktisch-gestalterischen sowie kommunikativ-interaktiven Unterschiede zeigen vollimmersive virtuelle Lernumgebungen gegenĂŒber dem Einsatz von Videokonferenzsoftware im Kontext der Gruppenarbeit? Das Ziel ist es, den Einsatz von Multiplayer-VR-Szenarien der Nutzung von Videokonferenztools fĂŒr Gruppenarbeitsprozesse im Rahmen der Fallarbeit gegenĂŒberzustellen und deren Vor- und Nachteile aufzuzeigen. Die Ergebnisse zeigen, dass sich fĂŒr Gruppenarbeitsprozesse in beiden Formaten Vor- und Nachteile finden lassen. Die Umsetzung des Konzeptes der Fallarbeit fĂ€llt jedoch in beiden Formaten positiv aus. Folglich ist der Erfolg einer Gruppenarbeit von der konzeptionellen Einbindung der Methode in den Lehrkontext abhĂ€ngig, sodass die Form der Umsetzung vorwiegend Einfluss auf die Performanz nimmt. ZukĂŒnftig gilt es, konkrete Implementierungskonzepte fĂŒr den Einsatz von VR-Anwendungen in der Lehre zu entwickeln und zu erproben.The use of full-immersive VR learning environments promotes the individual skills and prior knowledge of students. However, more specific effects on learning and concepts for integration are not sufficiently studied yet. As part of a BMBF-funded research project, this article pursues the following question: What are the design and didactical as well as communicative-interactive differences between full-immersive virtual learning environments and the usage of tools for video conferences in the context of group work? The goal is to compare the use of multiplayer VR scenarios with tools for video conferences for working in groups within the framework of casework and to point out their advantages and disadvantages. Results show that both formats render advantages and disadvantages for working in groups, though the implementation of the concept of casework turns out to be positive in both formats. Consequently, the success of working in groups depends on the conceptual inclusion of one of the methods in the learning context, so that its performance is mainly influenced by the way of how it is implemented. Prospectively, specific concepts for the implementation of VR applications in teaching processes need to be developed and evaluated

    Sarcoma treatment in the era of molecular medicine

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    Sarcomas are heterogeneous and clinically challenging soft tissue and bone cancers. Although constituting only 1% of all human malignancies, sarcomas represent the second most common type of solid tumors in children and adolescents and comprise an important group of secondary malignancies. More than 100 histological subtypes have been characterized to date, and many more are being discovered due to molecular profiling. Owing to their mostly aggressive biological behavior, relative rarity, and occurrence at virtually every anatomical site, many sarcoma subtypes are in particular difficult-to-treat categories. Current multimodal treatment concepts combine surgery, polychemotherapy (with/without local hyperthermia), irradiation, immunotherapy, and/or targeted therapeutics. Recent scientific advancements have enabled a more precise molecular characterization of sarcoma subtypes and revealed novel therapeutic targets and prognostic/predictive biomarkers. This review aims at providing a comprehensive overview of the latest advances in the molecular biology of sarcomas and their effects on clinical oncology; it is meant for a broad readership ranging from novices to experts in the field of sarcoma.Peer reviewe

    Molecular features and vulnerabilities of recurrent chordomas

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    Background!#!Tumor recurrence is one of the major challenges in clinical management of chordoma. Despite R0-resection, approximately 50% of chordomas recur within ten years after initial surgery. The underlying molecular processes are poorly understood resulting in the lack of associated therapeutic options. This is not least due to the absence of appropriate cell culture models of this orphan disease.!##!Methods!#!The intra-personal progression model cell lines U-CH11 and U-CH11R were compared using array comparative genomic hybridization, expression arrays, RNA-seq, and immunocytochemistry. Cell line origin was confirmed by short tandem repeat analysis. Inter-personal cell culture models (n = 6) were examined to validate whether the new model is representative. Cell viability after HOX/PBX complex inhibition with small peptides was determined by MTS assays.!##!Results!#!Using whole genome microarray analyses, striking differences in gene expression between primary and recurrent chordomas were identified. These expression differences were confirmed in the world's first intra-personal model of chordoma relapse consisting of cell lines established from a primary (U-CH11) and the corresponding recurrent tumor (U-CH11R). Array comparative genomic hybridization and RNA-sequencing analyses revealed profound genetic similarities between both cell lines pointing to transcriptomic reprogramming as a key mechanism of chordoma progression. Network analysis of the recurrence specific genes highlighted HOX/PBX signaling as a common dysregulated event. Hence, HOX/PBX complexes were used as so far unknown therapeutic targets in recurrent chordomas. Treating chordoma cell lines with the complex formation inhibiting peptide HXR9 induced cFOS mediated apoptosis in all chordoma cell lines tested. This effect was significantly stronger in cell lines established from chordoma relapses.!##!Conclusion!#!Clearly differing gene expression patterns and vulnerabilities to HOX/PBX complex inhibition in highly therapy resistant chordoma relapses were identified using the first intra-personal loco-regional and further inter-personal chordoma progression models. For the first time, HOX/PBX interference was used to induce cell death in chordoma and might serve as the basic concept of an upcoming targeted therapy for chordomas of all progression stages

    Prognostic Relevance and In Vitro Targeting of Concomitant PTEN and p16 Deficiency in Chordomas

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    Chordomas are rare bone tumors arising along the spine. Due to high resistance towards chemotherapy, surgical resection—often followed by radiation therapy—is currently the gold standard of treatment. So far, targeted systemic therapies have not been approved. The most frequent molecular alterations include the loss of PTEN and CDKN2A (encoding p16), being associated with poor prognoses in chordoma patients. Specific inhibitors of the PI3K/AKT/mTOR pathway as well as CDK4/6 have shown antitumor activity in preclinical studies and have recently been under investigation in phase II clinical trials; however, the clinical impacts and therapeutic consequences of concomitant PTEN and p16 deficiency have not yet been investigated in chordomas. In a cohort of 43 chordoma patients, 16% of the cases were immunohistochemically negative for both markers. The simultaneous loss of PTEN and p16 was associated with a higher KI-67 index, a tendency to metastasize, and significantly shorter overall survival. Additionally, 30% of chordoma cell lines (n = 19) were PTEN-/p16-negative. Treating these chordoma cells with palbociclib (CDK4/6 inhibitor), rapamycin (mTOR inhibitor) or the pan-PI3K inhibitor buparlisib significantly reduced cell viability. Synergistic effects were observed when combining palbociclib with rapamycin. In conclusion, we show that patients with PTEN-/p16-negative chordomas have poor prognoses and provide strong preclinical evidence that these patients might benefit from a Palbociclib/rapamycin combination treatment

    Comorbidities, biomarkers and cause specific mortality in patients with irritable bowel syndrome: A phenome-wide association study

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    BackgroundIrritable bowel syndrome (IBS) is one of the most common functional digestive disorders. Our understanding about its comorbidities, biomarkers, or long-term risks is still incomplete. ObjectiveTo characterize comorbidities and biomarkers for IBS and establish the effect of IBS on overall- and cause specific mortality. MethodsWe analyzed data from the population-based cohort of the UK Biobank (UKB) with 493,974 participants, including self-reported physician-diagnosed (n = 20,603) and ICD-10 diagnosed (n = 7656) IBS patients, with a mean follow-up of 11 years. We performed a phenome-wide association study (PheWAS) and competing risk analysis to characterize common clinical features in IBS patients. ResultsIn PheWAS analyses, 260 PheCodes were significantly overrepresented in self-reported physician-diagnosed IBS patients, 633 in patients with ICD-10 diagnosed IBS (ICD-10-IBS), with 221 (40%) overlapping. In addition to gastrointestinal diseases, psychiatric, musculoskeletal, and endocrine/metabolic disorders represented the most strongly associated PheCodes in IBS patients. Self-reported physician-diagnosed IBS was not associated with increased overall mortality and the risk of death from cancer was decreased (hazard ratio [HR] = 0.78 [95% CI = 0.7-0.9]). Lastly, we evaluated changes in serum metabolites in IBS patients and identified glycoprotein acetyls (GlycA) as a potential biomarker in IBS. One standard deviation increase in GlycA raised the risk of self-reported IBS/ICD-10 coded by 9%-20% (odds ratio [OR] = 1.09 [95% CI = 1.1-1.1]/OR = 1.20 [95% CI = 1.1-1.3]) and the risk of overall mortality in ICD-10-IBS patients by 28% (HR = 1.28 [95% CI = 1.1-1.5]). ConclusionOur large-scale association study determined IBS patients having an increased risk of several different comorbidities and that GlycA was increased in IBS patients

    Data_Sheet_1_Omega-3 intake is associated with liver disease protection.pdf

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    BackgroundNon-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease are among the most common liver diseases worldwide, and there are currently no Food and Drug Administration (FDA)-approved treatments. Recent studies have focused on lifestyle changes to prevent and treat NAFLD. Omega-3 supplementation is associated with improved outcomes in patients with chronic liver disease. However, it is unclear whether Omega-3 supplementation can prevent the development of liver disease, particularly in individuals at an increased (genetic) risk.MethodsIn this UK Biobank cohort study, we established a multivariate cox proportional hazards model for the risk of incident liver disease during an 11 year follow up time. We adjusted the model for diabetes, prevalent cardiovascular disorders, socioeconomic status, diet, alcohol consumption, physical activity, medication intake (insulin, biguanides, statins and aspirin), and baseline characteristics.ResultsOmega-3 supplementation reduced the risk of incident liver disease (HR = 0.716; 95% CI: 0.639, 0.802; p = 7.6 × 10−9). This protective association was particularly evident for alcoholic liver disease (HR = 0.559; 95% CI: 0.347, 0.833; p = 4.3 × 10−3), liver failure (HR = 0.548; 95% CI: 0.343, 0.875; p = 1.2 × 10−2), and non-alcoholic liver disease (HR = 0.784; 95% CI: 0.650, 0.944; p = 1.0 × 10−2). Interestingly, we were able to replicate the association with reduced risk of NAFLD in a subset with liver MRIs (HR = 0.846; 95% CI: 0.777, 0.921; p = 1.1 × 10−4). In particular, women benefited from Omega-3 supplementation as well as heterozygous allele carriers of the liver-damaging variant PNPLA3 rs738409.ConclusionsOmega-3 supplementation may reduce the incidence of liver disease. Our study highlights the potential of personalized treatment strategies for individuals at risk of metabolic liver disease. Further evaluation in clinical trials is warranted before Omega-3 can be recommended for the prevention of liver disease.</p
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