@article{CampanaCiaramellaBorzi2021, author = {Campana, Francesca Cal{\`a} and Ciaramella, Gabriele and Borz{\`i}, Alfio}, title = {Nash Equilibria and Bargaining Solutions of Differential Bilinear Games}, series = {Dynamic Games and Applications}, volume = {11}, journal = {Dynamic Games and Applications}, number = {1}, doi = {10.1007/s13235-020-00351-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283897}, pages = {1-28}, year = {2021}, abstract = {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.}, language = {en} } @article{PotreckMutkeWeylandetal.2021, author = {Potreck, Arne and Mutke, Matthias A. and Weyland, Charlotte S. and Pfaff, Johannes A. R. and Ringleb, Peter A. and Mundiyanapurath, Sibu and M{\"o}hlenbruch, Markus A. and Heiland, Sabine and Pham, Mirko and Bendszus, Martin and Hoffmann, Angelika}, title = {Combined Perfusion and Permeability Imaging Reveals Different Pathophysiologic Tissue Responses After Successful Thrombectomy}, series = {Translational Stroke Research}, volume = {12}, journal = {Translational Stroke Research}, number = {5}, issn = {1868-4483}, doi = {10.1007/s12975-020-00885-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308946}, pages = {799-807}, year = {2021}, abstract = {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.}, language = {en} } @article{LiPamporakiFliedneretal.2021, author = {Li, Minghao and Pamporaki, Christina and Fliedner, Stephanie M. J. and Timmers, Henri J. L. M. and N{\"o}lting, Svenja and Beuschlein, Felix and Prejbisz, Aleksander and Remde, Hanna and Robledo, Mercedes and Bornstein, Stefan R. and Lenders, Jacques W. M. and Eisenhofer, Graeme and Bechmann, Nicole}, title = {Metastatic pheochromocytoma and paraganglioma: signs and symptoms related to catecholamine secretion}, series = {Discover Oncology}, volume = {12}, journal = {Discover Oncology}, issn = {2730-6011}, doi = {10.1007/s12672-021-00404-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-309901}, year = {2021}, abstract = {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.}, language = {en} } @article{FleuchausBlumWildeetal.2021, author = {Fleuchaus, Paul and Blum, Philipp and Wilde, Martina and Terhorst, Birgit and Butscher, Christoph}, title = {Retrospective evaluation of landslide susceptibility maps and review of validation practice}, series = {Environmental Earth Sciences}, volume = {80}, journal = {Environmental Earth Sciences}, issn = {1866-6280}, doi = {10.1007/s12665-021-09770-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308911}, year = {2021}, abstract = {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.}, language = {en} } @article{LeimeisterStieglitzMatzneretal.2021, author = {Leimeister, Jan Marco and Stieglitz, Stefan and Matzner, Martin and Kundisch, Dennis and Flath, Christoph and R{\"o}glinger, Maximilian}, title = {Quo Vadis Conferences in the Business and Information Systems Engineering (BISE) Community After Covid}, series = {Business \& Information Systems Engineering}, volume = {63}, journal = {Business \& Information Systems Engineering}, number = {6}, issn = {2363-7005}, doi = {10.1007/s12599-021-00707-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308902}, pages = {741-749}, year = {2021}, language = {en} } @article{MinnerSchreinerSaeger2021, author = {Minner, S. and Schreiner, J. and Saeger, W.}, title = {Adrenal cancer: relevance of different grading systems and subtypes}, series = {Clinical and Translational Oncology}, volume = {23}, journal = {Clinical and Translational Oncology}, number = {7}, issn = {1699-048X}, doi = {10.1007/s12094-020-02524-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308479}, pages = {1350-1357}, year = {2021}, abstract = {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.}, language = {en} } @article{NowotnyAhmedBensingetal.2021, author = {Nowotny, Hanna and Ahmed, S. Faisal and Bensing, Sophie and Beun, Johan G. and Br{\"o}samle, Manuela and Chifu, Irina and Claahsen van der Grinten, Hedi and Clemente, Maria and Falhammar, Henrik and Hahner, Stefanie and Husebye, Eystein and Kristensen, Jette and Loli, Paola and Lajic, Svetlana and Reisch, Nicole}, title = {Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis}, series = {Endocrine}, volume = {71}, journal = {Endocrine}, number = {3}, organization = {Endo ERN (MTG1)}, issn = {1355-008X}, doi = {10.1007/s12020-021-02649-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308769}, pages = {586-594}, year = {2021}, abstract = {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.}, language = {en} } @article{AdolphFleischhackGaabetal.2021, author = {Adolph, Jonas E. and Fleischhack, Gudrun and Gaab, Christine and Mikasch, Ruth and Mynarek, Martin and Rutkowski, Stefan and Sch{\"u}ller, Ulrich and Pfister, Stefan M. and Pajtler, Kristian W. and Milde, Till and Witt, Olaf and Bison, Brigitte and Warmuth-Metz, Monika and Kortmann, Rolf-Dieter and Dietzsch, Stefan and Pietsch, Torsten and Timmermann, Beate and Tippelt, Stephan}, title = {Systemic chemotherapy of pediatric recurrent ependymomas: results from the German HIT-REZ studies}, series = {Journal of Neuro-Oncology}, volume = {155}, journal = {Journal of Neuro-Oncology}, number = {2}, organization = {German GPOH HIT-Network}, issn = {0167-594X}, doi = {10.1007/s11060-021-03867-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308302}, pages = {193-202}, year = {2021}, abstract = {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.}, language = {en} } @article{LenzPahlHaucketal.2021, author = {Lenz, Dominic and Pahl, Jens and Hauck, Fabian and Alameer, Seham and Balasubramanian, Meena and Baric, Ivo and Boy, Nikolas and Church, Joseph A. and Crushell, Ellen and Dick, Anke and Distelmaier, Felix and Gujar, Jidnyasa and Indolfi, Giuseppe and Lurz, Eberhard and Peters, Bianca and Schwerd, Tobias and Serranti, Daniele and K{\"o}lker, Stefan and Klein, Christoph and Hoffmann, Georg F. and Prokisch, Holger and Greil, Johann and Cerwenka, Adelheid and Giese, Thomas and Staufner, Christian}, title = {NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency}, series = {Journal of Clinical Immunology}, volume = {41}, journal = {Journal of Clinical Immunology}, number = {8}, issn = {0271-9142}, doi = {10.1007/s10875-021-01110-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308362}, pages = {1781-1793}, year = {2021}, abstract = {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 na{\"i}ve 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.}, language = {en} } @article{DanyszDekundyScheschonkaetal.2021, author = {Danysz, Wojciech and Dekundy, Andrzej and Scheschonka, Astrid and Riederer, Peter}, title = {Amantadine: reappraisal of the timeless diamond—target updates and novel therapeutic potentials}, series = {Journal of Neural Transmission}, volume = {128}, journal = {Journal of Neural Transmission}, number = {2}, doi = {10.1007/s00702-021-02306-2}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-330133}, pages = {127-169}, year = {2021}, abstract = {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.}, language = {en} }