TY - JOUR A1 - Righesso, L. A. R. A1 - Terekhov, M. A1 - Götz, H. A1 - Ackermann, M. A1 - Emrich, T. A1 - Schreiber, L. M. A1 - Müller, W. E. G. A1 - Jung, J. A1 - Rojas, J. P. A1 - Al-Nawas, B. T1 - Dynamic contrast-enhanced magnetic resonance imaging for monitoring neovascularization during bone regeneration — a randomized in vivo study in rabbits JF - Clinical Oral Investigations N2 - Objectives Micro-computed tomography (μ-CT) and histology, the current gold standard methods for assessing the formation of new bone and blood vessels, are invasive and/or destructive. With that in mind, a more conservative tool, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), was tested for its accuracy and reproducibility in monitoring neovascularization during bone regeneration. Additionally, the suitability of blood perfusion as a surrogate of the efficacy of osteoplastic materials was evaluated. Materials and methods Sixteen rabbits were used and equally divided into four groups, according to the time of euthanasia (2, 3, 4, and 6 weeks after surgery). The animals were submitted to two 8-mm craniotomies that were filled with blood or autogenous bone. Neovascularization was assessed in vivo through DCE-MRI, and bone regeneration, ex vivo, through μ-CT and histology. Results The defects could be consistently identified, and their blood perfusion measured through DCE-MRI, there being statistically significant differences within the blood clot group between 3 and 6 weeks (p = 0.029), and between the former and autogenous bone at six weeks (p = 0.017). Nonetheless, no significant correlations between DCE-MRI findings on neovascularization and μ-CT (r =−0.101, 95% CI [−0.445; 0.268]) or histology (r = 0.305, 95% CI [−0.133; 0.644]) findings on bone regeneration were observed. Conclusions These results support the hypothesis that DCE-MRI can be used to monitor neovascularization but contradict the premise that it could predict bone regeneration as well. KW - animal experimentation KW - bone regeneration KW - multiparametric magnetic resonance imaging KW - neovascularization, physiologic KW - tissue engineering KW - translational medical research Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307614 SN - 1432-6981 SN - 1436-3771 VL - 25 IS - 10 ER - TY - JOUR A1 - Lenz, Dominic A1 - Pahl, Jens A1 - Hauck, Fabian A1 - Alameer, Seham A1 - Balasubramanian, Meena A1 - Baric, Ivo A1 - Boy, Nikolas A1 - Church, Joseph A. A1 - Crushell, Ellen A1 - Dick, Anke A1 - Distelmaier, Felix A1 - Gujar, Jidnyasa A1 - Indolfi, Giuseppe A1 - Lurz, Eberhard A1 - Peters, Bianca A1 - Schwerd, Tobias A1 - Serranti, Daniele A1 - Kölker, Stefan A1 - Klein, Christoph A1 - Hoffmann, Georg F. A1 - Prokisch, Holger A1 - Greil, Johann A1 - Cerwenka, Adelheid A1 - Giese, Thomas A1 - Staufner, Christian T1 - NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency JF - Journal of Clinical Immunology N2 - Purpose Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell–intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of naïve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity. KW - NBAS KW - inborn error of immunity KW - NK cell deficiency KW - B cell deficiency KW - vesicle trafficking KW - familial hemophagocytic lymphohistiocytosis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308362 SN - 0271-9142 SN - 1573-2592 VL - 41 IS - 8 ER - TY - JOUR A1 - Holländer, Olivia A1 - Schwender, Kristina A1 - Böhme, Petra A1 - Fleckhaus, Jan A1 - Haas, Cordula A1 - Han, Yang A1 - Heidorn, Frank A1 - Klein-Unseld, Rachel A1 - Lichtenwald, Julia A1 - Naue, Jana A1 - Neubauer, Jacqueline A1 - Poetsch, Micaela A1 - Schneider, Peter M. A1 - Wagner, Wolfgang A1 - Vennemann, Marielle T1 - Forensische DNA-Methylierungsanalyse T1 - Forensic DNA methylation analysis : First technical collaborative exercise by the working group on molecular age estimation of the German Society of Legal Medicine BT - Erster, technischer Ringversuch der Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin JF - Rechtsmedizin N2 - Die quantitative Analyse der relativen DNA-Methylierung gilt als eine der vielversprechendsten Methoden der molekularen Altersschätzung. Viele Studien der letzten Jahre identifizierten geeignete Positionen im Genom, deren DNA-Methylierung sich altersabhängig verändert. Für den Einsatz dieser Methode in der Routine- bzw. Fallarbeit ist es von großer Bedeutung, angewandte Analysetechniken zu validieren. Als ein Teilaspekt dieser Validierung sollte die Vergleichbarkeit der Analyseergebnisse zur DNA-Methylierung mithilfe der Mini- und Pyrosequenzierung zwischen verschiedenen Laboren evaluiert werden. Die Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin (DGRM) führte hierzu den ersten, technischen Ringversuch durch, der 4 Positionen in den Genen PDE4C, EDARADD, SST und KLF14 umfasste. Diese Marker waren in vorangegangenen Studien als altersabhängige Biomarker charakterisiert worden. Am Ringversuch nahmen 12 Labore teil, wobei jedes die Wahl zwischen der Minisequenzierung und/oder der Pyrosequenzierung für die quantitative Methylierungsanalyse hatte. Jedem teilnehmenden Labor wurden Blut- und Speichelproben von 3 Personen unterschiedlichen Alters übersandt. Die Wahl der Reagenzien für die Probenbearbeitung wurde den Teilnehmern freigestellt. Die Ergebnisse der Minisequenzierung zeigten systematische Abweichungen zwischen den Laboren, die am ehesten auf die Verwendung unterschiedlicher Reagenzien und Analyseplattformen zurückzuführen sein können. Die Resultate der Pyrosequenzierung hingegen wiesen nicht auf systematische Abweichungen zwischen den Laboren hin, hier zeigte sich jedoch die Tendenz einer markerabhängigen Abweichung. Darüber hinaus konnten Unterschiede hinsichtlich technischer Probleme zwischen Laboren mit mehr Erfahrung in der jeweiligen Sequenzierungsmethode und Laboren mit weniger Erfahrung festgestellt werden. Sowohl die Beobachtung von systematischen als auch die von markerabhängigen Abweichungen lässt den Schluss zu, dass eine Übertragung von Analysemethoden zwischen Laboren grundsätzlich möglich ist, eine Anpassung des jeweiligen Modells zur Altersschätzung jedoch notwendig sein kann. N2 - Quantitative analysis of relative DNA methylation is currently one of the most promising methods of molecular age estimation. In recent years numerous studies identified potential DNA methylation markers showing age-dependent changes in their relative methylation state. For routine application of this method validation is an important prerequisite. One aspect of validation is the degree of comparability of analytical data between laboratories. The working group on molecular age estimation of the German Society for Legal Medicine (DGRM) conducted a first technical proficiency test comprising four age estimation markers within the genes PDE4C, EDARADD, SST and KLF14. These positions were previously characterized as age-dependent biomarkers. A total of 12 laboratories participated using pyrosequencing and/or minisequencing techniques for quantitative analysis of DNA methylation. Each laboratory received blood and buccal swab samples from three individuals of different ages. Laboratories were free in their choice of reagents and material for sequencing. Minisequencing results showed systematic deviations between laboratories, which are believed to originate from differing reagents and sequencing platforms. The results of pyrosequencing did not show clear signs of systematic deviation but did show differences in the comparability between markers. Different levels of technical problems were reported, which correlated with the amount of experience with the sequencing technology. Both systematic and specific differences between analytical data produced in different laboratory settings lead to the conclusion that while it is generally possible to transfer an age estimation method to another laboratory, a mathematical model for age estimation might need to be adjusted accordingly. KW - DNA-Methylierung KW - Pyrosequenzierung KW - Minisequenzierung KW - Ergebnisreproduzierbarkeit KW - Laborleistungstests KW - DNA methylation KW - minisequencing KW - pyrosequencing KW - reproducibility of results KW - laboratory proficiency testing Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307131 SN - 0937-9819 SN - 1434-5196 VL - 31 IS - 3 ER - TY - JOUR A1 - Adolph, Jonas E. A1 - Fleischhack, Gudrun A1 - Gaab, Christine A1 - Mikasch, Ruth A1 - Mynarek, Martin A1 - Rutkowski, Stefan A1 - Schüller, Ulrich A1 - Pfister, Stefan M. A1 - Pajtler, Kristian W. A1 - Milde, Till A1 - Witt, Olaf A1 - Bison, Brigitte A1 - Warmuth-Metz, Monika A1 - Kortmann, Rolf-Dieter A1 - Dietzsch, Stefan A1 - Pietsch, Torsten A1 - Timmermann, Beate A1 - Tippelt, Stephan T1 - Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies JF - Journal of Neuro-Oncology N2 - Purpose Survival in recurrent ependymoma (EPN) depends mainly on the extent of resection achieved. When complete resection is not feasible, chemotherapy is often used to extend progression-free and overall survival. However, no consistent effect of chemotherapy on survival has been found in patients with recurrent EPN. Methods Systemic chemotherapeutic treatment of 138 patients enrolled in the German HIT-REZ-studies was analyzed. Survival depending on the use of chemotherapy, disease-stabilization rates (RR), duration of response (DOR) and time to progression (TTP) were estimated. Results Median age at first recurrence was 7.6 years (IQR: 4.0–13.6). At first recurrence, median PFS and OS were 15.3 (CI 13.3–20.0) and 36.9 months (CI 29.7–53.4), respectively. The Hazard Ratio for the use of chemotherapy in local recurrences in a time-dependent Cox-regression analysis was 0.99 (CI 0.74–1.33). Evaluable responses for 140 applied chemotherapies were analyzed, of which sirolimus showed the best RR (50%) and longest median TTP [11.51 (CI 3.98; 14.0) months] in nine patients, with the strongest impact found when sirolimus was used as a monotherapy. Seven patients with progression-free survival > 12 months after subtotal/no-resection facilitated by chemotherapy were found. No definitive survival advantage for any drug in a specific molecularly defined EPN type was found. Conclusion No survival advantage for the general use of chemotherapy in recurrent EPN was found. In cases with incomplete resection, chemotherapy was able to extend survival in individual cases. Sirolimus showed the best RR, DOR and TTP out of all drugs analyzed and may warrant further investigation. KW - ependymoma KW - chemotherapy KW - recurrence KW - children KW - sirolimus Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308302 SN - 0167-594X SN - 1573-7373 VL - 155 IS - 2 ER - TY - JOUR A1 - Loos, Jacqueline A1 - Krauss, Jochen A1 - Lyons, Ashley A1 - Föst, Stephanie A1 - Ohlendorf, Constanze A1 - Racky, Severin A1 - Röder, Marina A1 - Hudel, Lennart A1 - Herfert, Volker A1 - Tscharntke, Teja T1 - Local and landscape responses of biodiversity in calcareous grasslands JF - Biodiversity and Conservation N2 - Across Europe, calcareous grasslands become increasingly fragmented and their quality deteriorates through abandonment and land use intensification, both affecting biodiversity. Here, we investigated local and landscape effects on diversity patterns of several taxonomic groups in a landscape of highly fragmented calcareous grassland remnants. We surveyed 31 grassland fragments near Göttingen, Germany, in spring and summer 2017 for vascular plants, butterflies and birds, with sampling effort adapted to fragment area. Through regression modelling, we tested relationships between species richness and fragment size (from 314 to 51,395 m\(^2\)), successional stage, habitat connectivity and the per cent cover of arable land in the landscape at several radii. We detected 283 plant species, 53 butterfly species and 70 bird species. Of these, 59 plant species, 19 butterfly species and 9 bird species were grassland specialists. Larger fragments supported twice the species richness of plants than small ones, and hosted more species of butterflies, but not of birds. Larger grassland fragments contained more grassland specialist plants, but not butterfly or bird specialists. Increasing amounts of arable land in the landscape from 20 to 90% was related to the loss of a third of species of plants, and less so, of butterflies, but not of birds. Per cent cover of arable land negatively correlated to richness of grassland specialist plants and butterflies, but positively to grassland specialist birds. We found no effect by successional stages and habitat connectivity. Our multi-taxa approach highlights the need for conservation management at the local scale, complemented by measures at the landscape scale. KW - abandonment KW - birds KW - butterflies KW - land use intensification KW - nature conservation KW - vascular plants Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308595 SN - 0960-3115 SN - 1572-9710 VL - 30 IS - 8-9 ER - TY - JOUR A1 - Kanzow, Christian A1 - Lechner, Theresa T1 - Globalized inexact proximal Newton-type methods for nonconvex composite functions JF - Computational Optimization and Applications N2 - Optimization problems with composite functions consist of an objective function which is the sum of a smooth and a (convex) nonsmooth term. This particular structure is exploited by the class of proximal gradient methods and some of their generalizations like proximal Newton and quasi-Newton methods. The current literature on these classes of methods almost exclusively considers the case where also the smooth term is convex. Here we present a globalized proximal Newton-type method which allows the smooth term to be nonconvex. The method is shown to have nice global and local convergence properties, and some numerical results indicate that this method is very promising also from a practical point of view. KW - globalized proximal Newton-type method KW - nonconvex smooth term Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283715 VL - 78 IS - 2 ER - TY - JOUR A1 - Glinz, Jonathan A1 - Šleichrt, Jan A1 - Kytýř, Daniel A1 - Ayalur-Karunakaran, Santhosh A1 - Zabler, Simon A1 - Kastner, Johann A1 - Senck, Sascha T1 - Phase-contrast and dark-field imaging for the inspection of resin-rich areas and fiber orientation in non-crimp vacuum infusion carbon-fiber-reinforced polymers JF - Journal of Materials Science N2 - In this work, we present a multimodal approach to three-dimensionally quantify and visualize fiber orientation and resin-rich areas in carbon-fiber-reinforced polymers manufactured by vacuum infusion. Three complementary image modalities were acquired by Talbot–Lau grating interferometer (TLGI) X-ray microcomputed tomography (XCT). Compared to absorption contrast (AC), TLGI-XCT provides enhanced contrast between polymer matrix and carbon fibers at lower spatial resolutions in the form of differential phase contrast (DPC) and dark-field contrast (DFC). Consequently, relatively thin layers of resin, effectively indiscernible from image noise in AC data, are distinguishable. In addition to the assessment of fiber orientation, the combination of DPC and DFC facilitates the quantification of resin-rich areas, e.g., in gaps between fiber layers or at binder yarn collimation sites. We found that resin-rich areas between fiber layers are predominantly developed in regions characterized by a pronounced curvature. In contrast, in-layer resin-rich areas are mainly caused by the collimation of fibers by binder yarn. Furthermore, void volume around two adjacent 90°-oriented fiber layers is increased by roughly 20% compared to a random distribution over the whole specimen. Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-351581 VL - 56 IS - 16 ER - TY - JOUR A1 - Denk, S. A1 - Schmidt, S. A1 - Schurr, Y. A1 - Schwarz, G. A1 - Schote, F. A1 - Diefenbacher, M. A1 - Armendariz, C. A1 - Dejure, F. A1 - Eilers, M. A1 - Wiegering, Armin T1 - CIP2A regulates MYC translation (via its 5′UTR) in colorectal cancer JF - International Journal of Colorectal Disease N2 - Background Deregulated expression of MYC is a driver of colorectal carcinogenesis, suggesting that decreasing MYC expression may have significant therapeutic value. CIP2A is an oncogenic factor that regulates MYC expression. CIP2A is overexpressed in colorectal cancer (CRC), and its expression levels are an independent marker for long-term outcome of CRC. Previous studies suggested that CIP2A controls MYC protein expression on a post-transcriptional level. Methods To determine the mechanism by which CIP2A regulates MYC in CRC, we dissected MYC translation and stability dependent on CIP2A in CRC cell lines. Results Knockdown of CIP2A reduced MYC protein levels without influencing MYC stability in CRC cell lines. Interfering with proteasomal degradation of MYC by usage of FBXW7-deficient cells or treatment with the proteasome inhibitor MG132 did not rescue the effect of CIP2A depletion on MYC protein levels. Whereas CIP2A knockdown had marginal influence on global protein synthesis, we could demonstrate that, by using different reporter constructs and cells expressing MYC mRNA with or without flanking UTR, CIP2A regulates MYC translation. This interaction is mainly conducted by the MYC 5′UTR. Conclusions Thus, instead of targeting MYC protein stability as reported for other tissue types before, CIP2A specifically regulates MYC mRNA translation in CRC but has only slight effects on global mRNA translation. In conclusion, we propose as novel mechanism that CIP2A regulates MYC on a translational level rather than affecting MYC protein stability in CRC. KW - CIP2A KW - MYC KW - translation KW - colon cancer Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-280092 VL - 36 IS - 5 ER - TY - JOUR A1 - Reddersen, Kirsten A1 - Güllmar, André A1 - Tonndorf-Martini, Silke A1 - Sigusch, Bernd W. A1 - Ewald, Andrea A1 - Dauben, Thomas J. A1 - Martin, Karin A1 - Wiegand, Cornelia T1 - Critical parameters in cultivation of experimental biofilms using the example of Pseudomonas fluorescens JF - Journal of Materials Science: Materials in Medicine N2 - Formation and treatment of biofilms present a great challenge for health care and industry. About 80% of human infections are associated with biofilms including biomaterial centered infections, like infections of prosthetic heart valves, central venous catheters, or urinary catheters. Additionally, biofilms can cause food and drinking water contamination. Biofilm research focusses on application of experimental biofilm models to study initial adherence processes, to optimize physico-chemical properties of medical materials for reducing interactions between materials and bacteria, and to investigate biofilm treatment under controlled conditions. Exploring new antimicrobial strategies plays a key role in a variety of scientific disciplines, like medical material research, anti-infectious research, plant engineering, or wastewater treatment. Although a variety of biofilm models exist, there is a lack of standardization for experimental protocols, and designing experimental setups remains a challenge. In this study, a number of experimental parameters critical for material research have been tested that influence formation and stability of an experimental biofilm using the non-pathogenic model strain of Pseudomonas fluorescens. These parameters include experimental time frame, nutrient supply, inoculum concentration, static and dynamic cultivation conditions, material properties, and sample treatment during staining for visualization of the biofilm. It was shown, that all tested parameters critically influence the experimental biofilm formation process. The results obtained in this study shall support material researchers in designing experimental biofilm setups. KW - biomaterials KW - biomedical engineering and bioengineering KW - regenerative medicine/tissue engineering KW - polymer sciences KW - ceramics, glass, composites, natural materials KW - surfaces and interfaces, thin films Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-309911 SN - 0957-4530 SN - 1573-4838 VL - 32 IS - 9 ER - TY - JOUR A1 - Nowotny, Hanna A1 - Ahmed, S. Faisal A1 - Bensing, Sophie A1 - Beun, Johan G. A1 - Brösamle, Manuela A1 - Chifu, Irina A1 - Claahsen van der Grinten, Hedi A1 - Clemente, Maria A1 - Falhammar, Henrik A1 - Hahner, Stefanie A1 - Husebye, Eystein A1 - Kristensen, Jette A1 - Loli, Paola A1 - Lajic, Svetlana A1 - Reisch, Nicole T1 - Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis JF - Endocrine N2 - Adrenal insufficiency (AI) is a life-threatening condition requiring life-long glucocorticoid (GC) substitution therapy, as well as stress adaptation to prevent adrenal crises. The number of individuals with primary and secondary adrenal insufficiency in Europe is estimated to be 20–50/100.000. A growing number of AI cases are due to side effects of GC treatment used in different treatment strategies for cancer and to immunotherapy in cancer treatment. The benefit of hormone replacement therapy is evident but long-term adverse effects may arise due to the non-physiological GC doses and treatment regimens used. Given multiple GC replacement formulations available comprising short-acting, intermediate, long-acting and novel modified-release hydrocortisone as well as subcutaneous formulations, this review offers a concise summary on the latest therapeutic improvements for treatment of AI and prevention of adrenal crises. As availability of various glucocorticoid formulations and access to expert centers across Europe varies widely, European Reference Networks on rare endocrine conditions aim at harmonizing treatment and ensure access to specialized patient care for individual case-by-case treatment decisions. To improve the availability across Europe to cost effective oral and parenteral formulations of hydrocortisone will save lives. KW - adrenal insufficiency KW - congenital adrenal hyperplasia KW - adrenal crisis KW - glucocorticoid replacement KW - hydrocortisone KW - stress instructions Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308769 SN - 1355-008X SN - 1559-0100 VL - 71 IS - 3 ER - TY - JOUR A1 - Fleuchaus, Paul A1 - Blum, Philipp A1 - Wilde, Martina A1 - Terhorst, Birgit A1 - Butscher, Christoph T1 - Retrospective evaluation of landslide susceptibility maps and review of validation practice JF - Environmental Earth Sciences N2 - Despite the widespread application of landslide susceptibility analyses, there is hardly any information about whether or not the occurrence of recent landslide events was correctly predicted by the relevant susceptibility maps. Hence, the objective of this study is to evaluate four landslide susceptibility maps retrospectively in a landslide-prone area of the Swabian Alb (Germany). The predictive performance of each susceptibility map is evaluated based on a landslide event triggered by heavy rainfalls in the year 2013. The retrospective evaluation revealed significant variations in the predictive accuracy of the analyzed studies. Both completely erroneous as well as very precise predictions were observed. These differences are less attributed to the applied statistical method and more to the quality and comprehensiveness of the used input data. Furthermore, a literature review of 50 peer-reviewed articles showed that most landslide susceptibility analyses achieve very high validation scores. 73% of the analyzed studies achieved an area under curve (AUC) value of at least 80%. These high validation scores, however, do not reflect the high uncertainty in statistical susceptibility analysis. Thus, the quality assessment of landslide susceptibility maps should not only comprise an index-based, quantitative validation, but also an additional qualitative plausibility check considering local geomorphological characteristics and local landslide mechanisms. Finally, the proposed retrospective evaluation approach cannot only help to assess the quality of susceptibility maps and demonstrate the reliability of such statistical methods, but also identify issues that will enable the susceptibility maps to be improved in the future. KW - landslides KW - hazard maps KW - predictive performance KW - review KW - Swabian Alb Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308911 SN - 1866-6280 SN - 1866-6299 VL - 80 ER - TY - JOUR A1 - Li, Minghao A1 - Pamporaki, Christina A1 - Fliedner, Stephanie M. J. A1 - Timmers, Henri J. L. M. A1 - Nölting, Svenja A1 - Beuschlein, Felix A1 - Prejbisz, Aleksander A1 - Remde, Hanna A1 - Robledo, Mercedes A1 - Bornstein, Stefan R. A1 - Lenders, Jacques W. M. A1 - Eisenhofer, Graeme A1 - Bechmann, Nicole T1 - Metastatic pheochromocytoma and paraganglioma: signs and symptoms related to catecholamine secretion JF - Discover Oncology N2 - Background The presence or future development of metastatic pheochromocytomas or paragangliomas (mPPGLs) can be difficult to diagnose or predict at initial presentation. Since production of catecholamines from mPPGLs is different from non-metastatic tumors (non-mPPGLs), this study aimed to clarify whether presenting catecholamine-related signs and symptoms (cSS) might also differ. Methods The study included 249 patients, 43 with mPPGL and 206 with non-mPPGL. Clinical data at the time of biochemical diagnosis (i.e. at entry into the study) were used to generate a cumulative score of cSS for each patient. Results Patients with mPPGL were significantly younger (43.3 ± 14 vs. 48.9 ± 16.1 years) and included a lower proportion of females (39.5% vs. 60.7%) than patients with non-mPPGLs. Frequencies of signs and symptoms did not differ between the two groups. Patients with mPPGLs had lower (P < 0.001) urinary excretion of epinephrine (3.5 (IQR, 1.9—6.5) µg/day) than those with non-mPPGLs (19.1 (IQR, 4.3—70.2) µg/day). There was no difference in urinary excretion of norepinephrine. In patients with mPPGLs a high cSS score was associated with high urinary excretion of norepinephrine and normetanephrine. In contrast, in patients with non-mPPGLs, a high cSS was associated with high urinary excretion of epinephrine and metanephrine. Conclusion Although presenting signs and symptoms were associated with production of norepinephrine in patients with mPPGLs and of epinephrine in patients with non-mPPGLs, there were no differences in signs and symptoms between the two groups. Therefore, consideration of signs and symptoms does not appear helpful for distinguishing patients with and without mPPGLs. KW - pheochromocytoma KW - paraganglioma KW - metastatic KW - signs KW - symptoms KW - catecholamines Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-309901 SN - 2730-6011 VL - 12 ER - TY - JOUR A1 - Leimeister, Jan Marco A1 - Stieglitz, Stefan A1 - Matzner, Martin A1 - Kundisch, Dennis A1 - Flath, Christoph A1 - Röglinger, Maximilian T1 - Quo Vadis Conferences in the Business and Information Systems Engineering (BISE) Community After Covid BT - What Can Stay, What Should Go, What Do We Need to Change for Our Future Scientific Conferences? JF - Business & Information Systems Engineering KW - IT in Business KW - business and management Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308902 SN - 2363-7005 SN - 1867-0202 VL - 63 IS - 6 ER - TY - JOUR A1 - Minner, S. A1 - Schreiner, J. A1 - Saeger, W. T1 - Adrenal cancer: relevance of different grading systems and subtypes JF - Clinical and Translational Oncology N2 - Purpose The subclassification of adrenal cancers according to the WHO classification in ordinary, myxoid, oncocytic, and sarcomatoid as well as pediatric types is well established, but the criteria for each subtype are not sufficiently determined and the relative frequency of the different types of adrenal cancers has not been studied in large cohorts. Therefore, our large collection of surgically removed adrenal cancers should be reviewed o establish the criteria for the subtypes and to find out the frequency of the various types. Methods In our series of 521 adrenal cancers the scoring systems of Weiss et al., Hough et al., van Slooten et al. and the new Helsinki score system were used for the ordinary type of cancer (97% of our series) and the myxoid type (0.8%). For oncocytic carcinomas (2%), the scoring system of Bisceglia et al. was applied. Results Discrepancies between benign and malignant diagnoses from the first thee classical scoring systems are not rare (22% in our series) and could be resolved by the Helsinki score especially by Ki-67 index (more than 8% unequivocally malignant). Since all our cancer cases are positive in the Helsinki score, this system can replace the three elder systems. For identification of sarcomatoid cancer as rarest type in our series (0.2%), the scoring systems are not practical but additional immunostainings used for soft tissue tumors and in special cases molecular pathology are necessary to differentiate these cancers from adrenal sarcomas. According to the relative frequencies of the different subtypes of adrenal cancers the main type is the far most frequent (97%) followed by the oncocytic type (2%), the myxoid type (0.8%) and the very rare sarcomatoid type (0.2%). Conclusions The Helsinki score is the best for differentiating adrenal carcinomas of the main, the oncocytic, and the myxoid type in routine work. Additional scoring systems for these carcinomas are generally not any longer necessary. Signs of proliferation (mitoses and Ki-67 index) and necroses are the most important criteria for diagnosis of malignancy. KW - adrenal KW - cancer KW - cancer types KW - classification Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308479 SN - 1699-048X SN - 1699-3055 VL - 23 IS - 7 ER - TY - JOUR A1 - Danysz, Wojciech A1 - Dekundy, Andrzej A1 - Scheschonka, Astrid A1 - Riederer, Peter T1 - Amantadine: reappraisal of the timeless diamond—target updates and novel therapeutic potentials JF - Journal of Neural Transmission N2 - The aim of the current review was to provide a new, in-depth insight into possible pharmacological targets of amantadine to pave the way to extending its therapeutic use to further indications beyond Parkinson’s disease symptoms and viral infections. Considering amantadine’s affinities in vitro and the expected concentration at targets at therapeutic doses in humans, the following primary targets seem to be most plausible: aromatic amino acids decarboxylase, glial-cell derived neurotrophic factor, sigma-1 receptors, phosphodiesterases, and nicotinic receptors. Further three targets could play a role to a lesser extent: NMDA receptors, 5-HT3 receptors, and potassium channels. Based on published clinical studies, traumatic brain injury, fatigue [e.g., in multiple sclerosis (MS)], and chorea in Huntington’s disease should be regarded potential, encouraging indications. Preclinical investigations suggest amantadine’s therapeutic potential in several further indications such as: depression, recovery after spinal cord injury, neuroprotection in MS, and cutaneous pain. Query in the database http://www.clinicaltrials.gov reveals research interest in several further indications: cancer, autism, cocaine abuse, MS, diabetes, attention deficit-hyperactivity disorder, obesity, and schizophrenia. KW - Amantadine Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-330133 VL - 128 IS - 2 ER - TY - JOUR A1 - Naue, Jana A1 - Pfeifer, Manuel A1 - Augustin, Christa A1 - Becker, Julia A1 - Fleckhaus, Jan A1 - Grabmüller, Melanie A1 - Han, Yang A1 - Heidorn, Frank A1 - Hollaender, Olivia A1 - Klein-Unseld, Rachel A1 - Kulstein, Galina A1 - Lichtenwald, Julia A1 - Neubauer, Jacqueline A1 - Suarez, Philippe A1 - Haas, Cordula A1 - Schneider, Peter M. A1 - Vennemann, Marielle A1 - Böhme, Petra T1 - Forensische DNA-Methylierungsanalyse T1 - Forensic DNA methylation analysis : Second technical collaborative exercise by the working group on “molecular age estimation” of the German Society of Legal Medicine BT - Zweiter, technischer Ringversuch der Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin JF - Rechtsmedizin N2 - Mit der Entdeckung altersabhängiger epigenetischer Veränderungen, der DNA-Methylierung (DNAm), hat sich eine neue Möglichkeit aufgezeigt, das Alter eines Individuums zu schätzen. Die Methode wurde intensiv erforscht und ihre Anwendung in der forensischen Fallarbeit durch die Aktualisierung des § 81e der Strafprozessordnung (StPO) in Deutschland reguliert. Zur Untersuchung des DNAm-Grades müssen neue Techniken etabliert und validiert werden. Dies macht die Prüfung der Vergleichbarkeit von Messergebnissen aus verschiedenen forensischen Laboren erforderlich. Hierzu führte die Arbeitsgruppe „Molekulare Altersschätzung“ der Deutschen Gesellschaft für Rechtsmedizin (DGRM) im Winter 2019/2020 den 2. Ringversuch (RV) zur quantitativen DNAm-Analyse mithilfe der Mini- und der Pyrosequenzierung durch. Dieser basierte auf den Erfahrungen des 1. RV 2018/2019, dessen Ergebnisse in dieser Ausgabe ebenfalls vorgestellt werden. Die aktuelle Studie umfasst Analyseergebnisse aus 12 Laboren (ingesamt 14 teilnehmende Labore), von denen einige beide Methoden angewandt haben. Zusätzlich führten 4 Labore eine Altersschätzung an den RV-Proben mit eigenen Markerkombinationen und Modellen durch. Da diese auf unterschiedlichen Referenzdaten und Markerkombinationen beruhen, erfolgte kein qualitativer Vergleich der Modelle, sondern das grundsätzliche Potenzial der Methodik wurde verdeutlicht. Ziele des RV waren die Evaluierung der Vergleichbarkeit der DNAm-Messungen und die Bewertung möglicher Einflussfaktoren, wie Extraktionsmethode und verwendetes Gerät. Die Ergebnisse zeigen, dass sich die gemessenen DNAm-Werte der untersuchten Marker sowohl zwischen Mini- und Pyrosequenzierung als auch innerhalb der jeweiligen Methode zwischen den Laboren unterscheiden können, sodass mit Schwankungen gerechnet werden muss. N2 - With the discovery of age-related epigenetic changes DNA methylation (DNAm) has shown new possibilities for the estimation of the age of an individual. The method has been intensively researched and its application in forensic casework is regulated by an amendment of § 81e of the German Code of Criminal Procedures (StPO). To investigate the degree of DNAm new techniques must be established and validated. This necessitates investigation of the comparability of measurement results from different forensic laboratories. In winter 2019/2020 the molecular age estimation working group of the German Society of Legal Medicine (DGRM) conducted a second proficiency test to investigate this comparability using minisequencing and pyrosequencing for quantitative analysis of DNAm. This was based on the experience from the first proficiency test in 2018/2019, the results of which are presented in this edition of the journal. The current study includes the results of DNAm analysis from 12 laboratories (in total 14 participating laboratories), some of which have used both methods. In addition, four laboratories performed an age estimation using their own marker combinations and models. As these are based on different reference data and marker combinations, no qualitative comparison of the models was done but the fundamental potential of the methodology was clarified. The aim of the interlaboratory comparison was to evaluate the comparability of the DNAm measurements and to assess possible influencing factors, such as the extraction method and the device used. The results showed that the measured DNAm values of the investigated markers can differ between minisequencing and pyrosequencing as well as within the respective method between laboratories, so that fluctuations are to be expected. KW - Epigenetik KW - Biomarker KW - Minisequenzierung KW - Pyrosequenzierung KW - Laborleistungstests KW - epigenetics KW - biomarker KW - minisequencing KW - pyrosequencing KW - laboratory proficiency testing Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-307129 SN - 0937-9819 SN - 1434-5196 VL - 31 IS - 3 ER - TY - JOUR A1 - Campana, Francesca Calà A1 - Ciaramella, Gabriele A1 - Borzì, Alfio T1 - Nash Equilibria and Bargaining Solutions of Differential Bilinear Games JF - Dynamic Games and Applications N2 - This paper is devoted to a theoretical and numerical investigation of Nash equilibria and Nash bargaining problems governed by bilinear (input-affine) differential models. These systems with a bilinear state-control structure arise in many applications in, e.g., biology, economics, physics, where competition between different species, agents, and forces needs to be modelled. For this purpose, the concept of Nash equilibria (NE) appears appropriate, and the building blocks of the resulting differential Nash games are different control functions associated with different players that pursue different non-cooperative objectives. In this framework, existence of Nash equilibria is proved and computed with a semi-smooth Newton scheme combined with a relaxation method. Further, a related Nash bargaining (NB) problem is discussed. This aims at determining an improvement of all players’ objectives with respect to the Nash equilibria. Results of numerical experiments successfully demonstrate the effectiveness of the proposed NE and NB computational framework. KW - bilinear evolution model KW - Nash equilibria KW - Nash bargaining problem KW - optimal control theory KW - quantum evolution models KW - Lotka-Volterra models KW - Newton methods Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-283897 VL - 11 IS - 1 ER - TY - JOUR A1 - Potreck, Arne A1 - Mutke, Matthias A. A1 - Weyland, Charlotte S. A1 - Pfaff, Johannes A. R. A1 - Ringleb, Peter A. A1 - Mundiyanapurath, Sibu A1 - Möhlenbruch, Markus A. A1 - Heiland, Sabine A1 - Pham, Mirko A1 - Bendszus, Martin A1 - Hoffmann, Angelika T1 - Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy JF - Translational Stroke Research N2 - Despite successful recanalization of large-vessel occlusions in acute ischemic stroke, individual patients profit to a varying degree. Dynamic susceptibility-weighted perfusion and dynamic T1-weighted contrast-enhanced blood-brain barrier permeability imaging may help to determine secondary stroke injury and predict clinical outcome. We prospectively performed perfusion and permeability imaging in 38 patients within 24 h after successful mechanical thrombectomy of an occlusion of the middle cerebral artery M1 segment. Perfusion alterations were evaluated on cerebral blood flow maps, blood-brain barrier disruption (BBBD) visually and quantitatively on ktrans maps and hemorrhagic transformation on susceptibility-weighted images. Visual BBBD within the DWI lesion corresponded to a median ktrans elevation (IQR) of 0.77 (0.41–1.4) min−1 and was found in all 7 cases of hypoperfusion (100%), in 10 of 16 cases of hyperperfusion (63%), and in only three of 13 cases with unaffected perfusion (23%). BBBD was significantly associated with hemorrhagic transformation (p < 0.001). While BBBD alone was not a predictor of clinical outcome at 3 months (positive predictive value (PPV) = 0.8 [0.56–0.94]), hypoperfusion occurred more often in patients with unfavorable clinical outcome (PPV = 0.43 [0.10–0.82]) compared to hyperperfusion (PPV = 0.93 [0.68–1.0]) or unaffected perfusion (PPV = 1.0 [0.75–1.0]). We show that combined perfusion and permeability imaging reveals distinct infarct signatures after recanalization, indicating the severity of prior ischemic damage. It assists in predicting clinical outcome and may identify patients at risk of stroke progression. KW - permeability imaging KW - perfusion imaging KW - mechanical thrombectomy KW - secondary stroke injury KW - hyperperfusion Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308946 SN - 1868-4483 SN - 1868-601X VL - 12 IS - 5 ER - TY - JOUR A1 - Letunic, Ivica A1 - Khedkar, Supriya A1 - Bork, Peer T1 - SMART: recent updates, new developments and status in 2020 JF - Nucleic Acids Research N2 - SMART (Simple Modular Architecture Research Tool) is a web resource (https://smart.embl.de) for the identification and annotation of protein domains and the analysis of protein domain architectures. SMART version 9 contains manually curatedmodels formore than 1300 protein domains, with a topical set of 68 new models added since our last update article (1). All the new models are for diverse recombinase families and subfamilies and as a set they provide a comprehensive overview of mobile element recombinases namely transposase, integrase, relaxase, resolvase, cas1 casposase and Xer like cellular recombinase. Further updates include the synchronization of the underlying protein databases with UniProt (2), Ensembl (3) and STRING (4), greatly increasing the total number of annotated domains and other protein features available in architecture analysis mode. Furthermore, SMART's vector-based protein display engine has been extended and updated to use the latest web technologies and the domain architecture analysis components have been optimized to handle the increased number of protein features available. KW - SMART KW - SMART version 9 KW - protein domains KW - protein domain architectures Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-363816 VL - 49 IS - D1 ER -