@article{PalladinoChiocchettiFranketal.2020,
  author    = {Palladino, Viola Stella and Chiocchetti, Andreas G. and Frank, Lukas and Haslinger, Denise and McNeill, Rhiannon and Radtke, Franziska and Till, Andreas and Haupt, Simone and Br{\"u}stle, Oliver and G{\"u}nther, Katharina and Edenhofer, Frank and Hoffmann, Per and Reif, Andreas and Kittel-Schneider, Sarah},
  title     = {Energy metabolism disturbances in cell models of PARK2 CNV carriers with ADHD},
  series = {Journal of Clinical Medicine},
  volume    = {9},
  journal   = {Journal of Clinical Medicine},
  number    = {12},
  issn      = {2077-0383},
  doi       = {10.3390/jcm9124092},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-220074},
  year      = {2020},
  abstract  = {The main goal of the present study was the identification of cellular phenotypes in attention-deficit-/hyperactivity disorder (ADHD) patient-derived cellular models from carriers of rare copy number variants (CNVs) in the PARK2 locus that have been previously associated with ADHD. Human-derived fibroblasts (HDF) were cultured and human-induced pluripotent stem cells (hiPSC) were reprogrammed and differentiated into dopaminergic neuronal cells (mDANs). A series of assays in baseline condition and in different stress paradigms (nutrient deprivation, carbonyl cyanide m-chlorophenyl hydrazine (CCCP)) focusing on mitochondrial function and energy metabolism (ATP production, basal oxygen consumption rates, reactive oxygen species (ROS) abundance) were performed and changes in mitochondrial network morphology evaluated. We found changes in PARK2 CNV deletion and duplication carriers with ADHD in PARK2 gene and protein expression, ATP production and basal oxygen consumption rates compared to healthy and ADHD wildtype control cell lines, partly differing between HDF and mDANs and to some extent enhanced in stress paradigms. The generation of ROS was not influenced by the genotype. Our preliminary work suggests an energy impairment in HDF and mDAN cells of PARK2 CNV deletion and duplication carriers with ADHD. The energy impairment could be associated with the role of PARK2 dysregulation in mitochondrial dynamics.},
  language  = {en}
}
@article{EckardtStasikKrameretal.2021,
  author    = {Eckardt, Jan-Niklas and Stasik, Sebastian and Kramer, Michael and R{\"o}llig, Christoph and Kr{\"a}mer, Alwin and Scholl, Sebastian and Hochhaus, Andreas and Crysandt, Martina and Br{\"u}mmendorf, Tim H. and Naumann, Ralph and Steffen, Bj{\"o}rn and Kunzmann, Volker and Einsele, Hermann and Schaich, Markus and Burchert, Andreas and Neubauer, Andreas and Sch{\"a}fer-Eckart, Kerstin and Schliemann, Christoph and Krause, Stefan W. and Herbst, Regina and H{\"a}nel, Mathias and Frickhofen, Norbert and Noppeney, Richard and Kaiser, Ulrich and Baldus, Claudia D. and Kaufmann, Martin and R{\´a}cil, Zdenek and Platzbecker, Uwe and Berdel, Wolfgang E. and Mayer, Jiř{\´i} and Serve, Hubert and M{\"u}ller-Tidow, Carsten and Ehninger, Gerhard and St{\"o}lzel, Friedrich and Kroschinsky, Frank and Schetelig, Johannes and Bornh{\"a}user, Martin and Thiede, Christian and Middeke, Jan Moritz},
  title     = {Loss-of-function mutations of BCOR are an independent marker of adverse outcomes in intensively treated patients with acute myeloid leukemia},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {9},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13092095},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236735},
  year      = {2021},
  abstract  = {Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6\%) and 53 patients (3.5\%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95\%-Confidence Interval (CI): 1.005-2.134), p = 0.047), relapse-free survival (HR = 1.904 (95\%-CI: 1.163-3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95\%-CI: 0.990-2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.},
  language  = {en}
}
@article{ManchiaAdliAkulaetal.2013,
  author    = {Manchia, Mirko and Adli, Mazda and Akula, Nirmala and Arda, Raffaella and Aubry, Jean-Michel and Backlund, Lena and Banzato, Claudio E. M. and Baune, Bernhard T. and Bellivier, Frank and Bengesser, Susanne and Biernacka, Joanna M. and Brichant-Petitjean, Clara and Bui, Elise and Calkin, Cynthia V. and Cheng, Andrew Tai Ann and Chillotti, Caterina and Cichon, Sven and Clark, Scott and Czerski, Piotr M. and Dantas, Clarissa and Del Zompo, Maria and DePaulo, J. Raymond and Detera-Wadleigh, Sevilla D. and Etain, Bruno and Falkai, Peter and Fris{\´e}n, Louise and Frye, Mark A. and Fullerton, Jan and Gard, S{\´e}bastien and Garnham, Julie and Goes, Fernando S. and Grof, Paul and Gruber, Oliver and Hashimoto, Ryota and Hauser, Joanna and Heilbronner, Urs and Hoban, Rebecca and Hou, Liping and Jamain, St{\´e}phane and Kahn, Jean-Pierre and Kassem, Layla and Kato, Tadafumi and Kelsoe, John R. and Kittel-Schneider, Sarah and Kliwicki, Sebastian and Kuo, Po-Hsiu and Kusumi, Ichiro and Laje, Gonzalo and Lavebratt, Catharina and Leboyer, Marion and Leckband, Susan G. and L{\´o}pez Jaramillo, Carlos A. and Maj, Mario and Malafosse, Alain and Martinsson, Lina and Masui, Takuya and Mitchell, Philip B. and Mondimore, Frank and Monteleone, Palmiero and Nallet, Audrey and Neuner, Maria and Nov{\´a}k, Tom{\´a}s and O'Donovan, Claire and {\"O}sby, Urban and Ozaki, Norio and Perlis, Roy H. and Pfennig, Andrea and Potash, James B. and Reich-Erkelenz, Daniela and Reif, Andreas and Reininghaus, Eva and Richardson, Sara and Rouleau, Guy A. and Rybakowski, Janusz K. and Schalling, Martin and Schofield, Peter R. and Schubert, Oliver K. and Schweizer, Barbara and Seem{\"u}ller, Florian and Grigoroiu-Serbanescu, Maria and Severino, Giovanni and Seymour, Lisa R. and Slaney, Claire and Smoller, Jordan W. and Squassina, Alessio and Stamm, Thomas and Steele, Jo and Stopkova, Pavla and Tighe, Sarah K. and Tortorella, Alfonso and Turecki, Gustavo and Wray, Naomi R. and Wright, Adam and Zandi, Peter P. and Zilles, David and Bauer, Michael and Rietschel, Marcella and McMahon, Francis J. and Schulze, Thomas G. and Alda, Martin},
  title     = {Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0065636},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130938},
  pages     = {e65636},
  year      = {2013},
  abstract  = {Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.},
  language  = {en}
}
@article{KimLiessStolteetal.2021,
  author    = {Kim, Jin Hong and Liess, Andreas and Stolte, Matthias and Krause, Ana-Maria and Stepanenko, Vladimir and Zhong, Chuwei and Bialas, David and Spano, Frank and W{\"u}rthner, Frank},
  title     = {An Efficient Narrowband Near-Infrared at 1040 nm Organic Photodetector Realized by Intermolecular Charge Transfer Mediated Coupling Based on a Squaraine Dye},
  series = {Advanced Materials},
  volume    = {33},
  journal   = {Advanced Materials},
  number    = {26},
  doi       = {10.1002/adma.202100582},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-256374},
  year      = {2021},
  abstract  = {A highly sensitive short-wave infrared (SWIR, λ > 1000 nm) organic photodiode (OPD) is described based on a well-organized nanocrystalline bulk-heterojunction (BHJ) active layer composed of a dicyanovinyl-functionalized squaraine dye (SQ-H) donor material in combination with PC\(_{61}\)BM. Through thermal annealing, dipolar SQ-H chromophores self-assemble in a nanoscale structure with intermolecular charge transfer mediated coupling, resulting in a redshifted and narrow absorption band at 1040 nm as well as enhanced charge carrier mobility. The optimized OPD exhibits an external quantum efficiency (EQE) of 12.3\% and a full-width at half-maximum of only 85 nm (815 cm\(^{-1}\)) at 1050 nm under 0 V, which is the first efficient SWIR OPD based on J-type aggregates. Photoplethysmography application for heart-rate monitoring is successfully demonstrated on flexible substrates without applying reverse bias, indicating the potential of OPDs based on short-range coupled dye aggregates for low-power operating wearable applications.},
  language  = {en}
}
@article{DietlSchwinnDietletal.2016,
  author    = {Dietl, Sebastian and Schwinn, Stefanie and Dietl, Susanne and Riedl, Simone and Deinlein, Frank and Rutkowski, Stefan and von Bueren, Andre O. and Krauss, J{\"u}rgen and Schweitzer, Tilmann and Vince, Giles H. and Picard, Daniel and Eyrich, Matthias and Rosenwald, Andreas and Ramaswamy, Vijay and Taylor, Michael D. and Remke, Marc and Monoranu, Camelia M. and Beilhack, Andreas and Schlegel, Paul G. and W{\"o}lfl, Matthias},
  title     = {MB3W1 is an orthotopic xenograft model for anaplastic medulloblastoma displaying cancer stem cell- and Group 3-properties},
  series = {BMC Cancer},
  volume    = {16},
  journal   = {BMC Cancer},
  number    = {115},
  doi       = {10.1186/s12885-016-2170-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145877},
  year      = {2016},
  abstract  = {Background Medulloblastoma is the most common malignant brain tumor in children and can be divided in different molecular subgroups. Patients whose tumor is classified as a Group 3 tumor have a dismal prognosis. However only very few tumor models are available for this subgroup. Methods We established a robust orthotopic xenograft model with a cell line derived from the malignant pleural effusions of a child suffering from a Group 3 medulloblastoma. Results Besides classical characteristics of this tumor subgroup, the cells display cancer stem cell characteristics including neurosphere formation, multilineage differentiation, CD133/CD15 expression, high ALDH-activity and high tumorigenicity in immunocompromised mice with xenografts exactly recapitulating the original tumor architecture. Conclusions This model using unmanipulated, human medulloblastoma cells will enable translational research, specifically focused on Group 3 medulloblastoma.},
  language  = {en}
}
@unpublished{StennettBissingerGriesbecketal.2019,
  author    = {Stennett, Tom E. and Bissinger, Philipp and Griesbeck, Stefanie and Ullrich, Stefan and Krummenacher, Ivo and Auth, Michael and Sperlich, Andreas and Stolte, Matthias and Radacki, Krzysztof and Yao, Chang-Jiang and W{\"u}rthner, Frank and Steffen, Andreas and Marder, Todd B. and Braunschweig, Holger},
  title     = {Near-Infrared Quadrupolar Chromophores Combining Three-Coordinate Boron-Based Superdonor and Superacceptor Units},
  series = {Angewandte Chemie, International Edition},
  journal   = {Angewandte Chemie, International Edition},
  doi       = {10.1002/anie.201900889},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-180391},
  year      = {2019},
  abstract  = {In this work, two new quadrupolar A-π-D-π-A chromophores have been prepared featuring a strongly electron- donating diborene core and strongly electron-accepting dimesitylboryl F(BMes2) and bis(2,4,6-tris(trifluoromethyl)phenyl)boryl (BMes2) end groups. Analysis of the compounds by NMR spectroscopy, X-ray crystallography, cyclic voltammetry and UV-vis-NIR absorption and emission spectroscopy indicated that the compounds possess extended conjugated π-systems spanning their B4C8 cores. The combination of exceptionally potent π-donor (diborene) and π- acceptor (diarylboryl) groups, both based on trigonal boron, leads to very small HOMO-LUMO gaps, resulting in strong absorption in the near-IR region with maxima in THF at 840 and 1092 nm, respectively, and very high extinction coefficients of ca. 120,000 M-1cm-1. Both molecules also display weak near-IR fluorescence with small Stokes shifts.},
  language  = {en}
}
@article{KistlerSiwyFranketal.2011,
  author    = {Kistler, Andreas D. and Siwy, Justyna and Frank, Breunig and Jeevaratnam, Praveen and Scherl, Alexander and Mullen, William and Warnock, David G. and Wanner, Christoph and Hughes, Derralynn A. and Mischak, Harald and W{\"u}thrich, Rudolf P. and Serra, Andreas L.},
  title     = {A Distinct Urinary Biomarker Pattern Characteristic of Female Fabry Patients That Mirrors Response to Enzyme Replacement Therapy},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {6},
  doi       = {10.1371/journal.pone.0020534},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133526},
  pages     = {e20534},
  year      = {2011},
  abstract  = {Female patients affected by Fabry disease, an X-linked lysosomal storage disorder, exhibit a wide spectrum of symptoms, which renders diagnosis, and treatment decisions challenging. No diagnostic test, other than sequencing of the alpha-galactosidase A gene, is available and no biomarker has been proven useful to screen for the disease, predict disease course and monitor response to enzyme replacement therapy. Here, we used urine proteomic analysis based on capillary electrophoresis coupled to mass spectrometry and identified a biomarker profile in adult female Fabry patients. Urine samples were taken from 35 treatment-naive female Fabry patients and were compared to 89 age-matched healthy controls. We found a diagnostic biomarker pattern that exhibited 88.2\% sensitivity and 97.8\% specificity when tested in an independent validation cohort consisting of 17 treatment-naive Fabry patients and 45 controls. The model remained highly specific when applied to additional control patients with a variety of other renal, metabolic and cardiovascular diseases. Several of the 64 identified diagnostic biomarkers showed correlations with measures of disease severity. Notably, most biomarkers responded to enzyme replacement therapy, and 8 of 11 treated patients scored negative for Fabry disease in the diagnostic model. In conclusion, we defined a urinary biomarker model that seems to be of diagnostic use for Fabry disease in female patients and may be used to monitor response to enzyme replacement therapy.},
  language  = {en}
}
@article{HanfsteinLausekerHehlmannetal.2014,
  author    = {Hanfstein, Benjamin and Lauseker, Michael and Hehlmann, R{\"u}diger and Saussele, Susanne and Erben, Philipp and Dietz, Christian and Fabarius, Alice and Proetel, Ulrike and Schnittger, Susanne and Haferlach, Claudia and Krause, Stefan W. and Schubert, J{\"o}rg and Einsele, Hermann and H{\"a}nel, Mathias and Dengler, Jolanta and Falge, Christiane and Kanz, Lothar and Neubauer, Andreas and Kneba, Michael and Stengelmann, Frank and Pfreundschuh, Michael and Waller, Cornelius F. and Spiekerman, Karsten and Baerlocher, Gabriela M. and Pfirrmann, Markus and Hasford, Joerg and Hofmann, Wolf-Karsten and Hochhaus, Andreas and M{\"u}ller, Martin C.},
  title     = {Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib},
  series = {Haematologica},
  volume    = {99},
  journal   = {Haematologica},
  number    = {9},
  issn      = {1592-8721},
  doi       = {10.3324/haematol.2013.096537},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115476},
  pages     = {1441-1447},
  year      = {2014},
  abstract  = {The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 x 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 x 109/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier: 00055874)},
  language  = {en}
}
@article{SausseleHehlmannFabariusetal.2018,
  author    = {Saussele, Susanne and Hehlmann, Ruediger and Fabarius, Alice and Jeromin, Sabine and Proetel, Ulrike and Rinaldetti, Sebastien and Kohlbrenner, Katharina and Einsele, Hermann and Falge, Christine and Kanz, Lothar and Neubauer, Andreas and Kneba, Michael and Stegelmann, Frank and Pfreundschuh, Michael and Waller, Cornelius F. and Oppliger Leibundgut, Elisabeth and Heim, Dominik and Krause, Stefan W. and Hofmann, Wolf-Karsten and Hasford, Joerg and Pfirrmann, Markus and M{\"u}ller, Martin C. and Hochhaus, Andreas and Lauseker, Michael},
  title     = {Defining therapy goals for major molecular remission in chronic myeloid leukemia: results of the randomized CML Study IV},
  series = {Leukemia},
  volume    = {32},
  journal   = {Leukemia},
  number    = {5},
  doi       = {10.1038/s41375-018-0055-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-227528},
  pages     = {1222-1228},
  year      = {2018},
  abstract  = {Major molecular remission (MMR) is an important therapy goal in chronic myeloid leukemia (CML). So far, MMR is not a failure criterion according to ELN management recommendation leading to uncertainties when to change therapy in CML patients not reaching MMR after 12 months. At monthly landmarks, for different molecular remission status Hazard ratios (HR) were estimated for patients registered to CML study IV who were divided in a learning and a validation sample. The minimum HR for MMR was found at 2.5 years with 0.28 (compared to patients without remission). In the validation sample, a significant advantage for progression-free survival (PFS) for patients in MMR could be detected (p-value 0.007). The optimal time to predict PFS in patients with MMR could be validated in an independent sample at 2.5 years. With our model we provide a suggestion when to define lack of MMR as therapy failure and thus treatment change should be considered. The optimal response time for 1\% BCR-ABL at about 12-15 months was confirmed and for deep molecular remission no specific time point was detected. Nevertheless, it was demonstrated that the earlier the MMR is achieved the higher is the chance to attain deep molecular response later.},
  language  = {en}
}
@article{KarakayaBiderFranketal.2022,
  author    = {Karakaya, Emine and Bider, Faina and Frank, Andreas and Teßmar, J{\"o}rg and Sch{\"o}bel, Lisa and Forster, Leonard and Schr{\"u}fer, Stefan and Schmidt, Hans-Werner and Schubert, Dirk Wolfram and Blaeser, Andreas and Boccaccini, Aldo R. and Detsch, Rainer},
  title     = {Targeted printing of cells: evaluation of ADA-PEG bioinks for drop on demand approaches},
  series = {Gels},
  volume    = {8},
  journal   = {Gels},
  number    = {4},
  issn      = {2310-2861},
  doi       = {10.3390/gels8040206},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-267317},
  year      = {2022},
  abstract  = {A novel approach, in the context of bioprinting, is the targeted printing of a defined number of cells at desired positions in predefined locations, which thereby opens up new perspectives for life science engineering. One major challenge in this application is to realize the targeted printing of cells onto a gel substrate with high cell survival rates in advanced bioinks. For this purpose, different alginate-dialdehyde—polyethylene glycol (ADA-PEG) inks with different PEG modifications and chain lengths (1-8 kDa) were characterized to evaluate their application as bioinks for drop on demand (DoD) printing. The biochemical properties of the inks, printing process, NIH/3T3 fibroblast cell distribution within a droplet and shear forces during printing were analyzed. Finally, different hydrogels were evaluated as a printing substrate. By analysing different PEG chain lengths with covalently crosslinked and non-crosslinked ADA-PEG inks, it was shown that the influence of Schiff's bases on the viscosity of the corresponding materials is very low. Furthermore, it was shown that longer polymer chains resulted in less stable hydrogels, leading to fast degradation rates. Several bioinks highly exhibit biocompatibility, while the calculated nozzle shear stress increased from approx. 1.3 and 2.3 kPa. Moreover, we determined the number of cells for printed droplets depending on the initial cell concentration, which is crucially needed for targeted cell printing approaches.},
  language  = {en}
}
@article{LuekeHallerUtpateletal.2022,
  author    = {L{\"u}ke, Florian and Haller, Florian and Utpatel, Kirsten and Krebs, Markus and Meidenbauer, Norbert and Scheiter, Alexander and Spoerl, Silvia and Heudobler, Daniel and Sparrer, Daniela and Kaiser, Ulrich and Keil, Felix and Schubart, Christoph and T{\"o}gel, Lars and Einhell, Sabine and Dietmaier, Wolfgang and Huss, Ralf and Dintner, Sebastian and Sommer, Sebastian and Jordan, Frank and Goebeler, Maria-Elisabeth and Metz, Michaela and Haake, Diana and Scheytt, Mithun and Gerhard-Hartmann, Elena and Maurus, Katja and Br{\"a}ndlein, Stephanie and Rosenwald, Andreas and Hartmann, Arndt and M{\"a}rkl, Bruno and Einsele, Hermann and Mackensen, Andreas and Herr, Wolfgang and Kunzmann, Volker and Bargou, Ralf and Beckmann, Matthias W. and Pukrop, Tobias and Trepel, Martin and Evert, Matthias and Claus, Rainer and Kerscher, Alexander},
  title     = {Identification of disparities in personalized cancer care — a joint approach of the German WERA consortium},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {20},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14205040},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290311},
  year      = {2022},
  abstract  = {(1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in W{\"u}rzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy.},
  language  = {en}
}
@article{GutknechtPoppWaideretal.2015,
  author    = {Gutknecht, Lise and Popp, Sandy and Waider, Jonas and Sommerlandt, Frank M. J. and G{\"o}ppner, Corinna and Post, Antonia and Reif, Andreas and van den Hove, Daniel and Strekalova, Tatyana and Schmitt, Angelika and Colaςo, Maria B. N. and Sommer, Claudia and Palme, Rupert and Lesch, Klaus-Peter},
  title     = {Interaction of brain 5-HT synthesis deficiency, chronic stress and sex differentially impact emotional behavior in Tph2 knockout mice},
  series = {Psychopharmacology},
  volume    = {232},
  journal   = {Psychopharmacology},
  doi       = {10.1007/s00213-015-3879-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-154586},
  pages     = {2429 -- 2441},
  year      = {2015},
  abstract  = {Rationale While brain serotonin (5-HT) function is implicated in gene-by-environment interaction (GxE) impacting the vulnerability-resilience continuum in neuropsychiatric disorders, it remains elusive how the interplay of altered 5-HT synthesis and environmental stressors is linked to failure in emotion regulation. Objective Here, we investigated the effect of constitutively impaired 5-HT synthesis on behavioral and neuroendocrine responses to unpredictable chronic mild stress (CMS) using a mouse model of brain 5-HT deficiency resulting from targeted inactivation of the tryptophan hydroxylase-2 (Tph2) gene. Results Locomotor activity and anxiety- and depression-like behavior as well as conditioned fear responses were differentially affected by Tph2 genotype, sex, and CMS. Tph2 null mutants (Tph2\(^{-/-}\)) displayed increased general metabolism, marginally reduced anxiety- and depression-like behavior but strikingly increased conditioned fear responses. Behavioral modifications were associated with sex-specific hypothalamic-pituitary-adrenocortical (HPA) system alterations as indicated by plasma corticosterone and fecal corticosterone metabolite concentrations. Tph2\(^{-/-}\) males displayed increased impulsivity and high aggressiveness. Tph2\(^{-/-}\) females displayed greater emotional reactivity to aversive conditions as reflected by changes in behaviors at baseline including increased freezing and decreased locomotion in novel environments. However, both Tph2\(^{-/-}\) male and female mice were resilient to CMS-induced hyperlocomotion, while CMS intensified conditioned fear responses in a GxE-dependent manner. Conclusions Our results indicate that 5-HT mediates behavioral responses to environmental adversity by facilitating the encoding of stress effects leading to increased vulnerability for negative emotionality.},
  language  = {en}
}
@article{SeydelmannLiuKraemeretal.2016,
  author    = {Seydelmann, Nora and Liu, Dan and Kr{\"a}mer, Johannes and Drechsler, Christiane and Hu, Kai and Nordbeck, Peter and Schneider, Andreas and St{\"o}rk, Stefan and Bijnens, Bart and Ertl, Georg and Wanner, Christoph and Weidemann, Frank},
  title     = {High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease},
  series = {Journal of the American Heart Association},
  volume    = {5},
  journal   = {Journal of the American Heart Association},
  number    = {e002839},
  doi       = {10.1161/JAHA.115.002839},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-165682},
  year      = {2016},
  abstract  = {Background High-sensitivity troponin (hs-TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs-TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow-up study to assess longitudinal hs-TNT changes relative to fibrosis and cardiomyopathy progression. Methods and Results For the prospective analysis, hs-TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry-associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs-TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs-TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95\% CI, 3.56-302.59]; P=0.002); patients with elevated baseline hs-TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1-3.3] \%; follow-up, 3.2 [2.3-4.9] \%; P<0.001) and slightly elevated hs-TNT (baseline, 44.7 [30.1-65.3] ng/L; follow-up, 49.1 [27.6-69.5] ng/L; P=0.116) during follow-up. Left ventricular wall thickness and EF of patients with elevated hs-TNT were decreased during follow-up, indicating potential cardiomyopathy progression. Conclusions hs-TNT is an accurate, easily accessible clinical blood biomarker for detecting replacement fibrosis in patients with Fabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs-TNT could be helpful for staging and follow-up of Fabry patients.},
  language  = {en}
}
@unpublished{WernerIlhanLehneretal.2018,
  author    = {Werner, Rudolf A. and Ilhan, Harun and Lehner, Sebastian and Papp, L{\´a}szl{\´o} and Zs{\´o}t{\´e}r, Norbert and Schatka, Imke and Muegge, Dirk O. and Javadi, Mehrbod S. and Higuchi, Takahiro and Buck, Andreas K. and Bartenstein, Peter and Bengel, Frank and Essler, Markus and Lapa, Constantin and Bundschuh, Ralph A.},
  title     = {Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy},
  series = {Molecular Imaging and Biology},
  journal   = {Molecular Imaging and Biology},
  issn      = {1536-1632},
  doi       = {https://doi.org/10.1007/s11307-018-1252-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164624},
  year      = {2018},
  abstract  = {Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed. Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated. Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{BinderMayBaronetal.2011,
  author    = {Binder, Andreas and May, Denisa and Baron, Ralf and Maier, Christoph and T{\"o}lle, Thomas R. and Treede, Rolf-Detlef and Berthele, Achim and Faltraco, Frank and Flor, Herta and Gierthm{\"u}hlen, Janne and Haenisch, Sierk and Huge, Volker and Magerl, Walter and Maih{\"o}fner, Christian and Richter, Helmut and Rolke, Roman and Scherens, Andrea and {\"U}{\c{c}}eyler, Nurcan and Ufer, Mike and Wasner, Gunnar and Zhu, Jihong and Cascorbi, Ingolf},
  title     = {Transient Receptor Potential Channel Polymorphisms Are Associated with the Somatosensory Function in Neuropathic Pain Patients},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {3},
  doi       = {10.1371/journal.pone.0017387},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142782},
  pages     = {e17387},
  year      = {2011},
  abstract  = {Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. Within the German Research Network on Neuropathic Pain (Deutscher Forscbungsverbund Neuropathischer Schmerz) 371 neuropathic pain patients were phenotypically characterized using standardized quantitative sensory testing. Pyrosequencing was employed to determine a total of eleven single nucleotide polymorphisms in transient receptor potential channel genes of the neuropathic pain patients and a cohort of 253 German healthy volunteers. Associations of quantitative sensory testing parameters and single nucleotide polymorphisms between and within groups and subgroups, based on sensory phenotypes, were analyzed. Single nucleotide polymorphisms frequencies did not differ between both the cohorts. However, in neuropathic pain patients transient receptor potential ankyrin 1 710G>A (rs920829, E179K) was associated with the presence of paradoxical heat sensation (p=0.03), and transient receptor potential vanilloid 1 1911A>G (rs8065080, I585V) with cold hypoalgesia (p=0.0035). Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p=0.006, p=0.005 and p<0.001) and transient receptor potential vanilloid 1 1103C>G (rs222747, M315I) to cold hypaesthesia (p=0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients.},
  language  = {en}
}
@article{TonyBurmesterSchulzeKoopsetal.2011,
  author    = {Tony, Hans-Peter and Burmester, Gerd and Schulze-Koops, Hendrik and Grunke, Mathias and Henes, Joerg and K{\"o}tter, Ina and Haas, Judith and Unger, Leonore and Lovric, Svjetlana and Haubitz, Marion and Fischer-Betz, Rebecca and Chehab, Gamal and Rubbert-Roth, Andrea and Specker, Christof and Weinerth, Jutta and Holle, Julia and M{\"u}ller-Ladner, Ulf and K{\"o}nig, Ramona and Fiehn, Christoph and Burgwinkel, Philip and Budde, Klemens and S{\"o}rensen, Helmut and Meurer, Michael and Aringer, Martin and Kieseier, Bernd and Erfurt-Berge, Cornelia and Sticherling, Michael and Veelken, Roland and Ziemann, Ulf and Strutz, Frank and von Wussow, Praxis and Meier, Florian MP and Hunzelmann, Nico and Schmidt, Enno and Bergner, Raoul and Schwarting, Andreas and Eming, R{\"u}diger and Schwarz-Eywill, Michael and Wassenberg, Siegfried and Fleck, Martin and Metzler, Claudia and Zettl, Uwe and Westphal, Jens and Heitmann, Stefan and Herzog, Anna L. and Wiendl, Heinz and Jakob, Waltraud and Schmidt, Elvira and Freivogel, Klaus and D{\"o}rner, Thomas and Hertl, Michael and Stadler, Rudolf},
  title     = {Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID)},
  series = {Arthritis Research \& Therapy},
  volume    = {13},
  journal   = {Arthritis Research \& Therapy},
  number    = {R75},
  doi       = {10.1186/ar3337},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-142856},
  pages     = {1-14},
  year      = {2011},
  abstract  = {Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin's lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0\% with systemic lupus erythematosus, 15.7\% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1\% multiple sclerosis and 10.0\% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0\% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3\% of patients showed no response, 45.1\% showed a partial response and 41.6\% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician's visual analogue scale; mean improvement from baseline of 12.1 mm)},
  language  = {en}
}
@article{GehrkeBalbachRauchetal.2019,
  author    = {Gehrke, Alexander and Balbach, Nico and Rauch, Yong-Mi and Degkwitz, Andreas and Puppe, Frank},
  title     = {Erkennung von handschriftlichen Unterstreichungen in Alten Drucken},
  series = {Bibliothek Forschung und Praxis},
  volume    = {43},
  journal   = {Bibliothek Forschung und Praxis},
  number    = {3},
  issn      = {1865-7648},
  doi       = {10.1515/bfp-2019-2083},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193377},
  pages     = {447 -- 452},
  year      = {2019},
  abstract  = {Die Erkennung handschriftlicher Artefakte wie Unterstreichungen in Buchdrucken erm{\"o}glicht R{\"u}ckschl{\"u}sse auf das Rezeptionsverhalten und die Provenienzgeschichte und wird auch f{\"u}r eine OCR ben{\"o}tigt. Dabei soll zwischen handschriftlichen Unterstreichungen und waagerechten Linien im Druck (z. B. Trennlinien usw.) unterschieden werden, da letztere nicht ausgezeichnet werden sollen. Im Beitrag wird ein Ansatz basierend auf einem auf Unterstreichungen trainierten Neuronalen Netz gem{\"a}ß der U-Net Architektur vorgestellt, dessen Ergebnisse in einem zweiten Schritt mit heuristischen Regeln nachbearbeitet werden. Die Evaluationen zeigen, dass Unterstreichungen sehr gut erkannt werden, wenn bei der Binarisierung der Scans nicht zu viele Pixel der Unterstreichung wegen geringem Kontrast verloren gehen. Zuk{\"u}nftig sollen die Worte oberhalb der Unterstreichung mit OCR transkribiert werden und auch andere Artefakte wie handschriftliche Notizen in alten Drucken erkannt werden.},
  language  = {de}
}
@article{GassenmaierPetritschKunzetal.2015,
  author    = {Gassenmaier, Tobias and Petritsch, Bernhard and Kunz, Andreas S. and Gkaniatsas, Spyridon and Gaudron, Philipp D. and Weidemann, Frank and Nordbeck, Peter and Beer, Meinrad},
  title     = {Long term evolution of MRI characteristics in a case of atypical left lateral wall hypertrophic cardiomyopathy},
  series = {World Journal of Cardiology},
  volume    = {7},
  journal   = {World Journal of Cardiology},
  number    = {6},
  doi       = {10.4330/wjc.v7.i6.357},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124934},
  pages     = {357-360},
  year      = {2015},
  abstract  = {We are reporting a long-time magnetic resonance imaging (MRI) follow-up in a rare case of cardiac left lateral wall hypertrophy. Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiovascular disorder and a significant cause of sudden cardiac death. Cardiac magnetic resonance (CMR) imaging can be a valuable tool for assessment of detailed information on size, localization, and tissue characteristics of hypertrophied myocardium. However, there is still little knowledge of long-term evolution of HCM as visualized by magnetic resonance imaging. Recently, our group reported a case of left lateral wall HCM as a rare variant of the more common forms, such as septal HCM, or apical HCM. As we now retrieved an old cardiac MRI acquired in this patient more than 20 years ago, we are able to provide the thrilling experience of an ultra-long MRI follow-up presentation in this rare case of left lateral wall hypertrophy. Furthermore, this case outlines the tremendous improvements in imaging quality within the last two decades of CMR imaging.},
  language  = {en}
}
@article{GuptaKupperRatzkaetal.2015,
  author    = {Gupta, Shishir K. and Kupper, Maria and Ratzka, Carolin and Feldhaar, Heike and Vilcinskas, Andreas and Gross, Roy and Dandekar, Thomas and F{\"o}rster, Frank},
  title     = {Scrutinizing the immune defence inventory of Camponotus floridanus applying total transcriptome sequencing},
  series = {BMC Genomics},
  volume    = {16},
  journal   = {BMC Genomics},
  number    = {540},
  doi       = {10.1186/s12864-015-1748-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125279},
  year      = {2015},
  abstract  = {Background Defence mechanisms of organisms are shaped by their lifestyle, environment and pathogen pressure. Carpenter ants are social insects which live in huge colonies comprising genetically closely related individuals in high densities within nests. This lifestyle potentially facilitates the rapid spread of pathogens between individuals. In concert with their innate immune system, social insects may apply external immune defences to manipulate the microbial community among individuals and within nests. Additionally, carpenter ants carry a mutualistic intracellular and obligate endosymbiotic bacterium, possibly maintained and regulated by the innate immune system. Thus, different selective forces could shape internal immune defences of Camponotus floridanus. Results The immune gene repertoire of C. floridanus was investigated by re-evaluating its genome sequence combined with a full transcriptome analysis of immune challenged and control animals using Illumina sequencing. The genome was re-annotated by mapping transcriptome reads and masking repeats. A total of 978 protein sequences were characterised further by annotating functional domains, leading to a change in their original annotation regarding function and domain composition in about 8 \% of all proteins. Based on homology analysis with key components of major immune pathways of insects, the C. floridanus immune-related genes were compared to those of Drosophila melanogaster, Apis mellifera, and other hymenoptera. This analysis revealed that overall the immune system of carpenter ants comprises many components found in these insects. In addition, several C. floridanus specific genes of yet unknown functions but which are strongly induced after immune challenge were discovered. In contrast to solitary insects like Drosophila or the hymenopteran Nasonia vitripennis, the number of genes encoding pattern recognition receptors specific for bacterial peptidoglycan (PGN) and a variety of known antimicrobial peptide (AMP) genes is lower in C. floridanus. The comparative analysis of gene expression post immune-challenge in different developmental stages of C. floridanus suggests a stronger induction of immune gene expression in larvae in comparison to adults. Conclusions The comparison of the immune system of C. floridanus with that of other insects revealed the presence of a broad immune repertoire. However, the relatively low number of PGN recognition proteins and AMPs, the identification of Camponotus specific putative immune genes, and stage specific differences in immune gene regulation reflects Camponotus specific evolution including adaptations to its lifestyle.},
  language  = {en}
}
@article{KreisslBockischDietleinetal.2014,
  author    = {Kreissl, Michael C. and Bockisch, Andreas and Dietlein, Markus and Gr{\"u}nwald, Frank and Luster, Markus},
  title     = {Inconsistencies},
  series = {Deutsches {\"A}rzteblatt International},
  volume    = {111},
  journal   = {Deutsches {\"A}rzteblatt International},
  number    = {16},
  doi       = {10.3238/arztebl.2014.0288a},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-119770},
  pages     = {288},
  year      = {2014},
  abstract  = {No abstract available.},
  language  = {en}
}
@phdthesis{Frank2009,
  author    = {Frank, Andreas},
  title     = {Untersuchungen zur Anwendbarkeit und Validit{\"a}t von In-vitro-Methoden bez{\"u}glich der Inhibition von Cytochrom-P450-Enzymen durch Arzneipflanzenextrakte},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-36236},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2009},
  abstract  = {Um Arzneimittelwechselwirkungen von Arzneistoffen sowie neuen Arzneistoffkandidaten zu vermeiden, werden zur Absch{\"a}tzung des Interaktionsrisikos so genannte In-vitro-Interaktionsstudien durchgef{\"u}hrt. Hierf{\"u}r werden vor allem Mikrotiterplatten-basierte Fluoreszenz- und LC/MS-Methoden verwendet. Das Ziel dieser Arbeit war die Untersuchung der Anwendbarkeit und Validit{\"a}t dieser In-vitro-Methoden bez{\"u}glich der Inhibition von CYP-Enzymen durch Arzneipflanzenextrakte. Die in dieser Arbeit erhaltenen Daten belegen, dass die verwendeten Fluoreszenz-Assays f{\"u}r Pflanzenextrakte keine validen Ergebnisse liefern und f{\"u}r die Bestimmung der inhibitorischen Aktivit{\"a}t von Pflanzenextrakten nur in wenigen F{\"a}llen geeignet sind. Bei einigen untersuchten Pflanzenextrakten wurden sehr starke inhibitorische Aktivit{\"a}ten gefunden, da durch Quenching des Fluoreszenzsignals falsch positive Ergebnisse vorget{\"a}uscht wurden. Ebenso war die Inhibition bei einigen Pflanzenextrakten aufgrund einer starken Eigenfluoreszenz sehr schwach oder konnte {\"u}berhaupt nicht bestimmt werden. Des Weiteren wurden als Referenzmethoden f{\"u}r die Bestimmung der Inhibition von CYP-Enzymen LC/MS-basierte Methoden mit Online-Festphasenextraktion verwendet, die speziell f{\"u}r Pflanzenextrakte entwickelt und validiert wurden. Die Ergebnisse der LC/MS-basierten CYP-Assays wurden durch die Pflanzenmatrix nicht beeinflusst, so dass diese Assays hervorragend als Referenzmethoden f{\"u}r die Bestimmung der inhibitorischen Aktivit{\"a}t von Pflanzenextrakten geeignet sind. Bei sehr hohen Extraktkonzentrationen zeigten einige Pflanzenextrakte sehr starke Abweichungen der mittels LC/MS und Fluorimetrie in Mikrotiterplatten erhaltenen inhibitorischen Aktivit{\"a}t. Die Verwendung von niedrigen Extraktkonzentrationen f{\"u}hrte zu einer besseren {\"U}bereinstimmung der erhaltenen Ergebnisse. D.h. vor allem bei hohen Extraktkonzentrationen sind starke Quenching- und Eigenfluoreszenz-Effekte zu erwarten. Dennoch sind auch bei niedrigen Extraktkonzentrationen diese Effekte nicht auszuschließen. In den meisten Ver{\"o}ffentlichungen wurden sehr hohe Testkonzentrationen f{\"u}r die Bestimmung der inhibitorischen Aktivit{\"a}t von Pflanzenextrakten verwendet, so dass mit hoher Wahrscheinlichkeit aufgrund von Quenching- und Eigenfluoreszenz-Effekten falsch positive bzw. negative Ergebnisse erhalten wurden. Untersuchungen zum Quenching haben gezeigt, dass die meisten Extrakte in den {\"u}blicherweise verwendeten Konzentrationen (ca. 10-1000 µg/ml) die Fluoreszenzintensit{\"a}t der Metabolite sehr stark reduzierten. Die Quenching-Effekte der Pflanzenextrakte beeinflussten das Fluoreszenzsignal aller enzymatisch gebildeten Metabolite (Cumarin-Derivate, Resorufin, Fluorescein), wobei die Quenching-Effekte bei Resorufin und Fluorescein in ihrer St{\"a}rke und H{\"a}ufigkeit geringer ausfielen. Bei CYP2B6, CYP2C9 und CYP2D6 wurden in Verbindung mit Fluoreszenzsubstraten, die eine Cumarinstruktur aufweisen, sehr oft falsch negative oder gar keine Ergebnisse erhalten, weil die Eigenfluoreszenz der Extrakte die Metabolitenfluoreszenz {\"u}berlagerte. Quenching-Effekte traten bei den untersuchten Pflanzenextrakten weitaus h{\"a}ufiger auf als eine Eigenfluoreszenz. Aufgrund dieser Tatsachen k{\"o}nnen die Mikrotiterplatten-basierten Fluoreszenz-Methoden nur eingesetzt werden, wenn vorher gezeigt wurde, dass die Pflanzenextrakte bei allen Testkonzentrationen sowie bei verschiedenen Metabolitenkonzentrationen weder Quenching- noch Eigenfluoreszenz-Effekte zeigen. Ebenso wurde in dieser Arbeit gezeigt, dass die bisher in Ver{\"o}ffentlichungen durchgef{\"u}hrten Kontrollinkubationen nur bedingt zur Kompensation von Quenching- und Eigenfluoreszenz-Effekten geeignet sind. Das Auftreten und Ausmaß der Quenching- und Eigenfluoreszenz-Effekte sind abh{\"a}ngig vom Inhibitor (Pflanzenextrakt), der Inhibitorkonzentration, dem Metaboliten und dessen Anregungs- und Emissionswellenl{\"a}nge sowie der Metabolitenkonzentration, die durch die enzymatische Umsetzung des Substrats und der inhibitorischen Aktivit{\"a}t des Inhibitors bestimmt wird. W{\"a}hrend der Inhibitor, die zu testenden Inhibitorkonzentrationen, der Metabolit sowie dessen Anregungs- und Emissionswellenl{\"a}nge eine feste Gr{\"o}ße darstellen, ist die Metabolitenkonzentration je nach inhibitorischer Aktivit{\"a}t des Inhibitors sehr unterschiedlich. D. h. letztendlich h{\"a}ngt das genaue Ausmaß der Eigenfluoreszenz- und Quenching-Effekte von der inhibitorischen Aktivit{\"a}t der Pflanzenextrakte ab. Es konnte gezeigt werden, dass je geringer die Metabolitenkonzentration ist, desto st{\"a}rker wird das Fluoreszenzsignal reduziert (Quenching) bzw. erh{\"o}ht (Eigenfluoreszenz). Eine sinnvolle Kontrollinkubation zur Kompensation von Quenching- und Eigenfluoreszenz-Effekten kann also gar nicht durchgef{\"u}hrt werden. Bei In-vitro-Untersuchungen zur Bestimmung der inhibitorischen Aktivit{\"a}t ist die Metabolitenkonzentration nicht bekannt und somit der Einfluss der Effekte nicht bestimmbar.},
  subject      = {In vitro},
  language  = {de}
}
@article{RascheDuellMorgneretal.2013,
  author    = {Rasche, Leo and Duell, Johannes and Morgner, Charlotte and Chatterjee, Manik and Hensel, Frank and Rosenwald, Andreas and Einsele, Hermann and Topp, Max S. and Br{\"a}ndlein, Stephanie},
  title     = {The Natural Human IgM Antibody PAT-SM6 Induces Apoptosis in Primary Human Multiple Myeloma Cells by Targeting Heat Shock Protein GRP78},
  series = {PLoS ONE},
  volume    = {8},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/journal.pone.0063414},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130125},
  pages     = {e63414},
  year      = {2013},
  abstract  = {In contrast to other haematological malignancies, targeted immunotherapy has not entered standard treatment regimens for de novo or relapsed multiple myeloma (MM) yet. While a number of IgG-formatted monoclonal antibodies are currently being evaluated in clinical trials in MM, our study aimed to investigate whether the fully human IgM monoclonal antibody PAT-SM6 that targets a tumour-specific variant of the heat shock protein GRP78 might be an attractive candidate for future immunotherapeutic approaches. We here show that GRP78 is stably and consistently expressed on the surface on tumour cells from patients with de novo, but also relapsed MM and that binding of PAT-SM6 to MM cells can specifically exert cytotoxic effects on malignant plasma cells, whereas non-malignant cells are not targeted. We demonstrate that the induction of apoptosis and, to a lesser extent, complement dependent cytotoxicity is the main mode of action of PAT-SM6, whereas antibody dependent cellular cytotoxicity does not appear to contribute to the cytotoxic properties of this antibody. Given the favourable safety profile of PAT-SM6 in monkeys, but also in a recent phase I trial in patients with malignant melanoma, our results form the basis for a planned phase I study in patients with relapsed MM.},
  language  = {en}
}
@article{SchmittKellerNourkamiTutdibietal.2011,
  author    = {Schmitt, Jana and Keller, Andreas and Nourkami-Tutdibi, Nasenien and Heisel, Sabrina and Habel, Nunja and Leidinger, Petra and Ludwig, Nicole and Gessler, Manfred and Graf, Norbert and Berthold, Frank and Lenhof, Hans-Peter and Meese, Eckart},
  title     = {Autoantibody Signature Differentiates Wilms Tumor Patients from Neuroblastoma Patients},
  series = {PLoS ONE},
  volume    = {6},
  journal   = {PLoS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0028951},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-133794},
  pages     = {e28951},
  year      = {2011},
  abstract  = {Several studies report autoantibody signatures in cancer. The majority of these studies analyzed adult tumors and compared the seroreactivity pattern of tumor patients with the pattern in healthy controls. Here, we compared the autoimmune response in patients with neuroblastoma and patients with Wilms tumor representing two different childhood tumors. We were able to differentiate untreated neuroblastoma patients from untreated Wilms tumor patients with an accuracy of 86.8\%, a sensitivity of 87.0\% and a specificity of 86.7\%. The separation of treated neuroblastoma patients from treated Wilms tumor patients' yielded comparable results with an accuracy of 83.8\%. We furthermore identified the antigens that contribute most to the differentiation between both tumor types. The analysis of these antigens revealed that neuroblastoma was considerably more immunogenic than Wilms tumor. The reported antigens have not been found to be relevant for comparative analyses between other tumors and controls. In summary, neuroblastoma appears as a highly immunogenic tumor as demonstrated by the extended number of antigens that separate this tumor from Wilms tumor.},
  language  = {en}
}
@article{WernerIlhanLehneretal.2018,
  author    = {Werner, Rudolf A. and Ilhan, Harun and Lehner, Sebastian and Papp, L{\´a}szl{\´o} and Zs{\´o}t{\´e}r, Norbert and Schatka, Imke and Muegge, Dirk O. and Javadi, Mehrbod S. and Higuchi, Takahiro and Buck, Andreas K. and Bartenstein, Peter and Bengel, Frank and Essler, Markus and Lapa, Constantin and Bundschuh, Ralph A.},
  title     = {Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy},
  series = {Molecular Imaging and Biology},
  journal   = {Molecular Imaging and Biology},
  issn      = {1536-1632},
  doi       = {10.1007/s11307-018-1252-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167168},
  year      = {2018},
  abstract  = {Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed. Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated. Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{TrudzinskiMinkoRappetal.2016,
  author    = {Trudzinski, Franziska C. and Minko, Peter and Rapp, Daniel and F{\"a}hndrich, Sebastian and Haake, Hendrik and Haab, Myriam and Bohle, Rainer M. and Flaig, Monika and Kaestner, Franziska and Bals, Robert and Wilkens, Heinrike and Muellenbach, Ralf M. and Link, Andreas and Groesdonk, Heinrich V. and Lensch, Christian and Langer, Frank and Lepper, Philipp M.},
  title     = {Runtime and aPTT predict venous thrombosis and thromboembolism in patients on extracorporeal membrane oxygenation: a retrospective analysis},
  series = {Annals of Intensive Care},
  volume    = {6},
  journal   = {Annals of Intensive Care},
  doi       = {10.1186/s13613-016-0172-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164455},
  pages     = {66},
  year      = {2016},
  abstract  = {Background Even though bleeding and thromboembolic events are major complications of extracorporeal membrane oxygenation (ECMO), data on the incidence of venous thrombosis (VT) and thromboembolism (VTE) under ECMO are scarce. This study analyzes the incidence and predictors of VTE in patients treated with ECMO due to respiratory failure. Methods Retrospective analysis of patients treated on ECMO in our center from 04/2010 to 11/2015. Patients with thromboembolic events prior to admission were excluded. Diagnosis was made by imaging in survivors and postmortem examination in deceased patients. Results Out of 102 screened cases, 42 survivors and 21 autopsy cases [mean age 46.0 ± 14.4 years; 37 (58.7 \%) males] fulfilling the above-mentioned criteria were included. Thirty-four patients (54.0 \%) underwent ECMO therapy due to ARDS, and 29 patients (46.0 \%) with chronic organ failure were bridged to lung transplantation. Despite systemic anticoagulation at a mean PTT of 50.6 ± 12.8 s, [VT/VTE 47.0 ± 12.3 s and no VT/VTE 53.63 ± 12.51 s (p = 0.037)], VT and/or VTE was observed in 29 cases (46.1 \%). The rate of V. cava thrombosis was 15/29 (51.7 \%). Diagnosis of pulmonary embolism prevailed in deceased patients [5/21 (23.8 \%) vs. 2/42 (4.8 \%) (p = 0.036)]. In a multivariable analysis, only aPTT and time on ECMO predicted VT/VTE. There was no difference in the incidence of clinically diagnosed VT in ECMO survivors and autopsy findings. Conclusions Venous thrombosis and thromboembolism following ECMO therapy are frequent. Quality of anticoagulation and ECMO runtime predicted thromboembolic events. "},
  language  = {en}
}
@article{WildeLiebLeichtetal.2021,
  author    = {Wilde, Anne-Christin Beatrice and Lieb, Charlotte and Leicht, Elise and Greverath, Lena Maria and Steinhagen, Lara Marleen and Wald de Chamorro, Nina and Petersen, J{\"o}rg and Hofmann, Wolf Peter and Hinrichsen, Holger and Heyne, Renate and Berg, Thomas and Naumann, Uwe and Schwenzer, Jeannette and Vermehren, Johannes and Geier, Andreas and Tacke, Frank and M{\"u}ller, Tobias},
  title     = {Real-world clinical management of patients with primary biliary cholangitis — a retrospective multicenter study from Germany},
  series = {Journal of Clinical Medicine},
  volume    = {10},
  journal   = {Journal of Clinical Medicine},
  number    = {5},
  issn      = {2077-0383},
  doi       = {10.3390/jcm10051061},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234003},
  year      = {2021},
  abstract  = {Background: Clinical practice guidelines for patients with primary biliary cholangitis (PBC) have been recently revised and implemented for well-established response criteria to standard first-line ursodeoxycholic acid (UDCA) therapy at 12 months after treatment initiation for the early identification of high-risk patients with inadequate treatment responses who may require treatment modification. However, there are only very limited data concerning the real-world clinical management of patients with PBC in Germany. Objective: The aim of this retrospective multicenter study was to evaluate response rates to standard first-line UDCA therapy and subsequent Second-line treatment regimens in a large cohort of well-characterized patients with PBC from 10 independent hepatological referral centers in Germany prior to the introduction of obeticholic acid as a licensed second-line treatment option. Methods: Diagnostic confirmation of PBC, standard first-line UDCA treatment regimens and response rates at 12 months according to Paris-I, Paris-II, and Barcelona criteria, the follow-up cut-off alkaline phosphatase (ALP) ≤ 1.67 × upper limit of normal (ULN) and the normalization of bilirubin (bilirubin ≤ 1 × ULN) were retrospectively examined between June 1986 and March 2017. The management and hitherto applied second-line treatment regimens in patients with an inadequate response to UDCA and subsequent response rates at 12 months were also evaluated. Results: Overall, 480 PBC patients were included in this study. The median UDCA dosage was 13.2 mg UDCA/kg bodyweight (BW)/d. Adequate UDCA treatment response rates according to Paris-I, Paris-II, and Barcelona criteria were observed in 91, 71.3, and 61.3\% of patients, respectively. In 83.8\% of patients, ALP ≤ 1.67 × ULN were achieved. A total of 116 patients (24.2\%) showed an inadequate response to UDCA according to at least one criterion. The diverse second-line treatment regimens applied led to significantly higher response rates according to Paris-II (35 vs. 60\%, p = 0.005), Barcelona (13 vs. 34\%, p = 0.0005), ALP ≤ 1.67 × ULN and bilirubin ≤ 1 × ULN (52.1 vs. 75\%, p = 0.002). The addition of bezafibrates appeared to induce the strongest beneficial effect in this cohort (Paris II: 24 vs. 74\%, p = 0.004; Barcelona: 50 vs. 84\%, p = 0.046; ALP < 1.67 × ULN and bilirubin ≤ 1 × ULN: 33 vs. 86\%, p = 0.001). Conclusion: Our large retrospective multicenter study confirms high response rates following UDCA first-line standard treatment in patients with PBC and highlights the need for close monitoring and early treatment modification in high-risk patients with an insufficient response to UDCA since early treatment modification significantly increases subsequent response rates of these patients.},
  language  = {en}
}
@article{GhazaryanRienowOldenburgetal.2021,
  author    = {Ghazaryan, Gohar and Rienow, Andreas and Oldenburg, Carsten and Thonfeld, Frank and Trampnau, Birte and Sticksel, Sarah and J{\"u}rgens, Carsten},
  title     = {Monitoring of urban sprawl and densification processes in Western Germany in the light of SDG indicator 11.3.1 based on an automated retrospective classification approach},
  series = {Remote Sensing},
  volume    = {13},
  journal   = {Remote Sensing},
  number    = {9},
  issn      = {2072-4292},
  doi       = {10.3390/rs13091694},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236671},
  year      = {2021},
  abstract  = {By 2050, two-third of the world's population will live in cities. In this study, we develop a framework for analyzing urban growth-related imperviousness in North Rhine-Westphalia (NRW) from the 1980s to date using Landsat data. For the baseline 2017-time step, official geodata was extracted to generate labelled data for ten classes, including three classes representing low, middle, and high level of imperviousness. We used the output of the 2017 classification and information based on radiometric bi-temporal change detection for retrospective classification. Besides spectral bands, we calculated several indices and various temporal composites, which were used as an input for Random Forest classification. The results provide information on three imperviousness classes with accuracies exceeding 75\%. According to our results, the imperviousness areas grew continuously from 1985 to 2017, with a high imperviousness area growth of more than 167,000 ha, comprising around 30\% increase. The information on the expansion of urban areas was integrated with population dynamics data to estimate the progress towards SDG 11. With the intensity analysis and the integration of population data, the spatial heterogeneity of urban expansion and population growth was analysed, showing that the urban expansion rates considerably excelled population growth rates in some regions in NRW. The study highlights the applicability of earth observation data for accurately quantifying spatio-temporal urban dynamics for sustainable urbanization and targeted planning.},
  language  = {en}
}
@article{BerntRangrezEdenetal.2016,
  author    = {Bernt, Alexander and Rangrez, Ashraf Y. and Eden, Matthias and Jungmann, Andreas and Katz, Sylvia and Rohr, Claudia and M{\"u}ller, Oliver J. and Katus, Hugo A. and Sossalla, Samuel T. and Williams, Tatjana and Ritter, Oliver and Frank, Derk and Frey, Norbert},
  title     = {Sumoylation-independent activation of Calcineurin-NFAT-signaling via SUMO2 mediates cardiomyocyte hypertrophy},
  series = {Scientific Reports},
  volume    = {6},
  journal   = {Scientific Reports},
  number    = {35758},
  doi       = {10.1038/srep35758},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167525},
  year      = {2016},
  abstract  = {The objective of this study was to identify unknown modulators of Calcineurin (Cn)-NFAT signaling. Measurement of NFAT reporter driven luciferase activity was therefore utilized to screen a human cardiac cDNA-library (~10\(^{7}\) primary clones) in C2C12 cells through serial dilutions until single clones could be identified. This extensive screening strategy culminated in the identification of SUMO2 as a most efficient Cn-NFAT activator. SUMO2-mediated activation of Cn-NFAT signaling in cardiomyocytes translated into a hypertrophic phenotype. Prohypertrophic effects were also observed in mice expressing SUMO2 in the heart using AAV9 (Adeno-associated virus), complementing the in vitro findings. In addition, increased SUMO2-mediated sumoylation in human cardiomyopathy patients and in mouse models of cardiomyopathy were observed. To decipher the underlying mechanism, we generated a sumoylation-deficient SUMO2 mutant (ΔGG). Surprisingly, ΔGG replicated Cn-NFAT-activation and the prohypertrophic effects of native SUMO2, both in vitro and in vivo, suggesting a sumoylation-independent mechanism. Finally, we discerned a direct interaction between SUMO2 and CnA, which promotes CnA nuclear localization. In conclusion, we identified SUMO2 as a novel activator of Cn-NFAT signaling in cardiomyocytes. In broader terms, these findings reveal an unexpected role for SUMO2 in cardiac hypertrophy and cardiomyopathy, which may open the possibility for therapeutic manipulation of this pathway.},
  language  = {en}
}
@article{HeinemannSiegmannThonfeldetal.2020,
  author    = {Heinemann, Sascha and Siegmann, Bastian and Thonfeld, Frank and Muro, Javier and Jedmowski, Christoph and Kemna, Andreas and Kraska, Thorsten and Muller, Onno and Schultz, Johannes and Udelhoven, Thomas and Wilke, Norman and Rascher, Uwe},
  title     = {Land surface temperature retrieval for agricultural areas using a novel UAV platform equipped with a thermal infrared and multispectral sensor},
  series = {Remote Sensing},
  volume    = {12},
  journal   = {Remote Sensing},
  number    = {7},
  issn      = {2072-4292},
  doi       = {10.3390/rs12071075},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-203557},
  year      = {2020},
  abstract  = {Land surface temperature (LST) is a fundamental parameter within the system of the Earth's surface and atmosphere, which can be used to describe the inherent physical processes of energy and water exchange. The need for LST has been increasingly recognised in agriculture, as it affects the growth phases of crops and crop yields. However, challenges in overcoming the large discrepancies between the retrieved LST and ground truth data still exist. Precise LST measurement depends mainly on accurately deriving the surface emissivity, which is very dynamic due to changing states of land cover and plant development. In this study, we present an LST retrieval algorithm for the combined use of multispectral optical and thermal UAV images, which has been optimised for operational applications in agriculture to map the heterogeneous and diverse agricultural crop systems of a research campus in Germany (April 2018). We constrain the emissivity using certain NDVI thresholds to distinguish different land surface types. The algorithm includes atmospheric corrections and environmental thermal emissions to minimise the uncertainties. In the analysis, we emphasise that the omission of crucial meteorological parameters and inaccurately determined emissivities can lead to a considerably underestimated LST; however, if the emissivity is underestimated, the LST can be overestimated. The retrieved LST is validated by reference temperatures from nearby ponds and weather stations. The validation of the thermal measurements indicates a mean absolute error of about 0.5 K. The novelty of the dual sensor system is that it simultaneously captures highly spatially resolved optical and thermal images, in order to construct the precise LST ortho-mosaics required to monitor plant diseases and drought stress and validate airborne and satellite data.},
  language  = {en}
}
@article{WernerDerlinLapaetal.2020,
  author    = {Werner, Rudolf A. and Derlin, Thorsten and Lapa, Constantin and Sheikbahaei, Sara and Higuchi, Takahiro and Giesel, Frederik L. and Behr, Spencer and Drzezga, Alexander and Kimura, Hiroyuki and Buck, Andreas K. and Bengel, Frank M. and Pomper, Martin G. and Gorin, Michael A. and Rowe, Steven P.},
  title     = {\(^{18}\)F-labeled, PSMA-targeted radiotracers: leveraging the advantages of radiofluorination for prostate cancer molecular imaging},
  series = {Theranostics},
  volume    = {10},
  journal   = {Theranostics},
  number    = {1},
  issn      = {1838-7640},
  doi       = {10.7150/thno.37894},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202559},
  pages     = {1-16},
  year      = {2020},
  abstract  = {Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with \(^{68}\)Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from \(^{68}\)Ga- to \(^{18}\)F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite \(^{68}\)Ge/\(^{68}\)Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, \(^{18}\)F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, \(^{18}\)F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging \(^{18}\)F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available \(^{18}\)F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.},
  language  = {en}
}
@article{ReulChristHarteltetal.2019,
  author    = {Reul, Christian and Christ, Dennis and Hartelt, Alexander and Balbach, Nico and Wehner, Maximilian and Springmann, Uwe and Wick, Christoph and Grundig, Christine and B{\"u}ttner, Andreas and Puppe, Frank},
  title     = {OCR4all—An open-source tool providing a (semi-)automatic OCR workflow for historical printings},
  series = {Applied Sciences},
  volume    = {9},
  journal   = {Applied Sciences},
  number    = {22},
  issn      = {2076-3417},
  doi       = {10.3390/app9224853},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-193103},
  pages     = {4853},
  year      = {2019},
  abstract  = {Optical Character Recognition (OCR) on historical printings is a challenging task mainly due to the complexity of the layout and the highly variant typography. Nevertheless, in the last few years, great progress has been made in the area of historical OCR, resulting in several powerful open-source tools for preprocessing, layout analysis and segmentation, character recognition, and post-processing. The drawback of these tools often is their limited applicability by non-technical users like humanist scholars and in particular the combined use of several tools in a workflow. In this paper, we present an open-source OCR software called OCR4all, which combines state-of-the-art OCR components and continuous model training into a comprehensive workflow. While a variety of materials can already be processed fully automatically, books with more complex layouts require manual intervention by the users. This is mostly due to the fact that the required ground truth for training stronger mixed models (for segmentation, as well as text recognition) is not available, yet, neither in the desired quantity nor quality. To deal with this issue in the short run, OCR4all offers a comfortable GUI that allows error corrections not only in the final output, but already in early stages to minimize error propagations. In the long run, this constant manual correction produces large quantities of valuable, high quality training material, which can be used to improve fully automatic approaches. Further on, extensive configuration capabilities are provided to set the degree of automation of the workflow and to make adaptations to the carefully selected default parameters for specific printings, if necessary. During experiments, the fully automated application on 19th Century novels showed that OCR4all can considerably outperform the commercial state-of-the-art tool ABBYY Finereader on moderate layouts if suitably pretrained mixed OCR models are available. Furthermore, on very complex early printed books, even users with minimal or no experience were able to capture the text with manageable effort and great quality, achieving excellent Character Error Rates (CERs) below 0.5\%. The architecture of OCR4all allows the easy integration (or substitution) of newly developed tools for its main components by standardized interfaces like PageXML, thus aiming at continual higher automation for historical printings.},
  language  = {en}
}
@article{ScognamiglioCabezasWallscheidThieretal.2016,
  author    = {Scognamiglio, Roberta and Cabezas-Wallscheid, Nina and Thier, Marc Christian and Altamura, Sandro and Reyes, Alejandro and Prendergast, {\´A}ine M. and Baumg{\"a}rtner, Daniel and Carnevalli, Larissa S. and Atzberger, Ann and Haas, Simon and von Paleske, Lisa and Boroviak, Thorsten and W{\"o}rsd{\"o}rfer, Philipp and Essers, Marieke A. G. and Kloz, Ulrich and Eisenman, Robert N. and Edenhofer, Frank and Bertone, Paul and Huber, Wolfgang and van der Hoeven, Franciscus and Smith, Austin and Trumpp, Andreas},
  title     = {Myc depletion induces a pluripotent dormant state mimicking diapause},
  series = {Cell},
  volume    = {164},
  journal   = {Cell},
  number    = {4},
  doi       = {10.1016/j.cell.2015.12.033},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-190868},
  pages     = {668-680},
  year      = {2016},
  abstract  = {Mouse embryonic stem cells (ESCs) are maintained in a naive ground state of pluripotency in the presence of MEK and GSK3 inhibitors. Here, we show that ground-state ESCs express low Myc levels. Deletion of both c-myc and N-myc (dKO) or pharmacological inhibition of Myc activity strongly decreases transcription, splicing, and protein synthesis, leading to proliferation arrest. This process is reversible and occurs without affecting pluripotency, suggesting that Myc-depleted stem cells enter a state of dormancy similar to embryonic diapause. Indeed, c-Myc is depleted in diapaused blastocysts, and the differential expression signatures of dKO ESCs and diapaused epiblasts are remarkably similar. Following Myc inhibition, pre-implantation blastocysts enter biosynthetic dormancy but can progress through their normal developmental program after transfer into pseudo-pregnant recipients. Our study shows that Myc controls the biosynthetic machinery of stem cells without affecting their potency, thus regulating their entry and exit from the dormant state.},
  language  = {en}
}
@article{KaireitSorrentinoRenneetal.2017,
  author    = {Kaireit, Till F. and Sorrentino, Sajoscha A. and Renne, Julius and Schoenfeld, Christian and Voskrebenzev, Andreas and Gutberlet, Marcel and Schulz, Angela and Jakob, Peter M. and Hansen, Gesine and Wacker, Frank and Welte, Tobias and T{\"u}mmler, Burkhard and Vogel-Claussen, Jens},
  title     = {Functional lung MRI for regional monitoring of patients with cystic fibrosis},
  series = {PLoS ONE},
  volume    = {12},
  journal   = {PLoS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0187483},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-172457},
  year      = {2017},
  abstract  = {Purpose To test quantitative functional lung MRI techniques in young adults with cystic fibrosis (CF) compared to healthy volunteers and to monitor immediate treatment effects of a single inhalation of hypertonic saline in comparison to clinical routine pulmonary function tests. Materials and methods Sixteen clinically stable CF patients and 12 healthy volunteers prospectively underwent two functional lung MRI scans and pulmonary function tests before and 2h after a single treatment of inhaled hypertonic saline or without any treatment. MRI-derived oxygen enhanced T1 relaxation measurements, fractional ventilation, first-pass perfusion parameters and a morpho-functional CF-MRI score were acquired. Results Compared to healthy controls functional lung MRI detected and quantified significantly increased ventilation heterogeneity in CF patients. Regional functional lung MRI measures of ventilation and perfusion as well as the CF-MRI score and pulmonary function tests could not detect a significant treatment effect two hours after a single treatment with hypertonic saline in young adults with CF (p>0.05). Conclusion This study shows the feasibility of functional lung MRI as a non-invasive, radiation-free tool for monitoring patients with CF.},
  language  = {en}
}
@article{MechauFrankBakircietal.2021,
  author    = {Mechau, Jannik and Frank, Andreas and Bakirci, Ezgi and Gumbel, Simon and Jungst, Tomasz and Giesa, Reiner and Groll, J{\"u}rgen and Dalton, Paul D. and Schmidt, Hans-Werner},
  title     = {Hydrophilic (AB)\(_{n}\) Segmented Copolymers for Melt Extrusion-Based Additive Manufacturing},
  series = {Macromolecular Chemistry and Physics},
  volume    = {222},
  journal   = {Macromolecular Chemistry and Physics},
  number    = {1},
  doi       = {10.1002/macp.202000265},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-224513},
  year      = {2021},
  abstract  = {Several manufacturing technologies beneficially involve processing from the melt, including extrusion-based printing, electrospinning, and electrohydrodynamic jetting. In this study, (AB)\(_{n}\) segmented copolymers are tailored for melt-processing to form physically crosslinked hydrogels after swelling. The copolymers are composed of hydrophilic poly(ethylene glycol)-based segments and hydrophobic bisurea segments, which form physical crosslinks via hydrogen bonds. The degree of polymerization was adjusted to match the melt viscosity to the different melt-processing techniques. Using extrusion-based printing, a width of approximately 260 µm is printed into 3D constructs, with excellent interlayer bonding at fiber junctions, due to hydrogen bonding between the layers. For melt electrospinning, much thinner fibers in the range of about 1-15 µm are obtained and produced in a typical nonwoven morphology. With melt electrowriting, fibers are deposited in a controlled way to well-defined 3D constructs. In this case, multiple fiber layers fuse together enabling constructs with line width in the range of 70 to 160 µm. If exposed to water the printed constructs swell and form physically crosslinked hydrogels that slowly disintegrate, which is a feature for soluble inks within biofabrication strategies. In this context, cytotoxicity tests confirm the viability of cells and thus demonstrating biocompatibility of this class of copolymers.},
  language  = {en}
}
@article{SchmidtStolteSuessetal.2019,
  author    = {Schmidt, David and Stolte, Matthias and S{\"u}ß, Jasmin and Liess, Dr. Andreas and Stepanenko, Vladimir and W{\"u}rthner, Frank},
  title     = {Protein-like enwrapped perylene bisimide chromophore as bright microcrystalline emitter material},
  series = {Angewandte Chemie International Edition},
  volume    = {58},
  journal   = {Angewandte Chemie International Edition},
  number    = {38},
  doi       = {10.1002/ange.201907618},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204809},
  pages     = {13385-13389},
  year      = {2019},
  abstract  = {Strongly emissive solid-state materials are mandatory components for many emerging optoelectronic technologies, but fluorescence is often quenched in the solid state owing to strong intermolecular interactions. The design of new organic pigments, which retain their optical properties despite their high tendency to crystallize, could overcome such limitations. Herein, we show a new material with monomer-like absorption and emission profiles as well as fluorescence quantum yields over 90 \% in its crystalline solid state. The material was synthesized by attaching two bulky tris(4-tert-butylphenyl)phenoxy substituents at the perylene bisimide bay positions. These substituents direct a packing arrangement with full enwrapping of the chromophore and unidirectional chromophore alignment within the crystal lattice to afford optical properties that resemble those of their natural pigment counterparts, in which chromophores are rigidly embedded in protein environments.},
  language  = {en}
}
@article{BiegstraatenArngrimssonBarbeyetal.2015,
  author    = {Biegstraaten, Marieke and Arngr{\´i}msson, Reynir and Barbey, Frederic and Boks, Lut and Cecchi, Franco and Deegan, Patrick B and Feldt-Rasmussen, Ulla and Geberhiwot, Tarekegn and Germain, Dominique P and Hendriksz, Chris and Hughes, Derralynn A and Kantola, Ilkka and Karabul, Nesrin and Lavery, Christine and Linthorst, Gabor E and Mehta, Atul and van de Mheen, Erica and Oliveira, Jo{\~a}o P and Parini, Rossella and Ramaswami, Uma and Rudnicki, Michael and Serra, Andreas and Sommer, Claudia and Sunder-Plassmann, Gere and Svarstad, Einar and Sweeb, Annelies and Terryn, Wim and Tylki-Szymanska, Anna and T{\o}ndel, Camilla and Vujkovac, Bojan and Weidemann, Frank and Wijburg, Frits A and Woolfson, Peter and Hollak, Carla EM},
  title     = {Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry disease: the European Fabry Working Group consensus document},
  series = {Orphanet Journal of Rare Diseases},
  volume    = {10},
  journal   = {Orphanet Journal of Rare Diseases},
  number    = {36},
  doi       = {10.1186/s13023-015-0253-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175374},
  year      = {2015},
  abstract  = {Introduction: Fabry disease (FD) is a lysosomal storage disorder resulting in progressive nervous system, kidney and heart disease. Enzyme replacement therapy (ERT) may halt or attenuate disease progression. Since administration is burdensome and expensive, appropriate use is mandatory. We aimed to define European consensus recommendations for the initiation and cessation of ERT in patients with FD. Methods: A Delphi procedure was conducted with an online survey (n = 28) and a meeting (n = 15). Patient organization representatives were present at the meeting to give their views. Recommendations were accepted with ≥75\% agreement and no disagreement. Results: For classically affected males, consensus was achieved that ERT is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients of ≥16 years in the absence of clinical signs or symptoms of organ involvement. Classically affected females and males with non-classical FD should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD. Consensus was achieved that treatment should not be withheld from patients with severe renal insufficiency (GFR < 45 ml/min/1.73 m\(^{2}\)) and from those on dialysis or with cognitive decline, but carefully considered on an individual basis. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered. ERT in patients who are non-compliant or fail to attend regularly at visits should be stopped. Conclusion: The recommendations can be used as a benchmark for initiation and cessation of ERT, although final decisions should be made on an individual basis. Future collaborative efforts are needed for optimization of these recommendations.},
  language  = {en}
}
@article{WeidemannMaierStoerketal.2016,
  author    = {Weidemann, Frank and Maier, Sebastian K. G. and St{\"o}rk, Stefan and Brunner, Thomas and Liu, Dan and Hu, Kai and Seydelmann, Nora and Schneider, Andreas and Becher, Jan and Canan-K{\"u}hl, Sima and Blaschke, Daniela and Bijnens, Bart and Ertl, Georg and Wanner, Christoph and Nordbeck, Peter},
  title     = {Usefulness of an implantable loop recorder to detect clinically relevant arrhythmias in patients with advanced fabry cardiomyopathy},
  series = {The American Journal of Cardiology},
  volume    = {118},
  journal   = {The American Journal of Cardiology},
  number    = {2},
  doi       = {10.1016/j.amjcard.2016.04.033},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-188093},
  pages     = {264-274},
  year      = {2016},
  abstract  = {Patients with genetic cardiomyopathy that involves myocardial hypertrophy often develop clinically relevant arrhythmias that increase the risk of sudden death. Consequently, guidelines for medical device therapy were established for hypertrophic cardiomyopathy, but not for conditions with only anecdotal evidence of arrhythmias, like Fabry cardiomyopathy. Patients with Fabry cardiomyopathy progressively develop myocardial fibrosis, and sudden cardiac death occurs regularly. Because 24-hour Holier electrocardiograms (ECGs) might not detect clinically important arrhythmias, we tested an implanted loop recorder for continuous heart rhythm surveillance and determined its impact on therapy. This prospective study included 16 patients (12 men) with advanced Fabry cardiomyopathy, relevant hypertrophy, and replacement fibrosis in "loco typico." No patients previously exhibited clinically relevant arrhythmias on Holier ECGs. Patients received an implantable loop recorder and were prospectively followed with telemedicine for a median of 1.2 years (range 0.3 to 2.0 years). The primary end point was a clinically meaningful event, which required a therapy change, captured with the loop recorder. Patients submitted data regularly (14 +/- 11 times per month). During follow-up, 21 events were detected (including 4 asystole, i.e., ECG pauses >= 3 seconds) and 7 bradycardia events; 5 episodes of intermittent atrial fibrillation (>3 minutes) and 5 episodes of ventricular tachycardia (3 sustained and 2 nonsustained). Subsequently, as defined in the primary end point, 15 events leaded to a change of therapy. These patients required therapy with a pacemaker or cardioverter defibrillator implantation and/or anticoagulation therapy for atrial fibrillation. In conclusion, clinically relevant arrhythmias that require further device and/or medical therapy are often missed with Holier ECGs in patients with advanced stage Fabry cardiomyopathy, but they can be detected by telemonitoring with an implantable loop recorder.},
  language  = {en}
}
@article{BakirciFrankGumbeletal.2021,
  author    = {Bakirci, Ezgi and Frank, Andreas and Gumbel, Simon and Otto, Paul F. and F{\"u}rsattel, Eva and Tessmer, Ingrid and Schmidt, Hans-Werner and Dalton, Paul D.},
  title     = {Melt Electrowriting of Amphiphilic Physically Crosslinked Segmented Copolymers},
  series = {Macromolecular Chemistry and Physics},
  volume    = {222},
  journal   = {Macromolecular Chemistry and Physics},
  number    = {22},
  doi       = {10.1002/macp.202100259},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257572},
  year      = {2021},
  abstract  = {Various (AB)\(_{n}\) and (ABAC)\(_{n}\) segmented copolymers with hydrophilic and hydrophobic segments are processed via melt electrowriting (MEW). Two different (AB)\(_{n}\) segmented copolymers composed of bisurea segments and hydrophobic poly(dimethyl siloxane) (PDMS) or hydrophilic poly(propylene oxide)-poly(ethylene oxide)-poly(propylene oxide) (PPO-PEG-PPO) segments, while the amphiphilic (ABAC)\(_{n}\) segmented copolymers consist of bisurea segments in the combination of hydrophobic PDMS segments and hydrophilic PPO-PEG-PPO segments with different ratios, are explored. All copolymer compositions are processed using the same conditions, including nozzle temperature, applied voltage, and collector distance, while changes in applied pressure and collector speed altered the fiber diameter in the range of 7 and 60 µm. All copolymers showed excellent processability with MEW, well-controlled fiber stacking, and inter-layer bonding. Notably, the surfaces of all four copolymer fibers are very smooth when visualized using scanning electron microscopy. However, the fibers show different roughness demonstrated with atomic force microscopy. The non-cytotoxic copolymers increased L929 fibroblast attachment with increasing PDMS content while the different copolymer compositions result in a spectrum of physical properties.},
  language  = {en}
}
@article{SchembriKimLiessetal.2021,
  author    = {Schembri, Tim and Kim, Jin Hong and Liess, Andreas and Stepanenko, Vladimir and Stolte, Matthias and W{\"u}rthner, Frank},
  title     = {Semitransparent Layers of Social Self-Sorting Merocyanine Dyes for Ultranarrow Bandwidth Organic Photodiodes},
  series = {Advanced Optical Materials},
  volume    = {9},
  journal   = {Advanced Optical Materials},
  number    = {15},
  doi       = {10.1002/adom.202100213},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-244762},
  year      = {2021},
  abstract  = {Two dipolar merocyanines consisting of the same π-conjugated chromophore but different alkyl substituents adopt very different packing arrangements in their respective solid state with either H- or J-type exciton coupling, leading to ultranarrow absorption bands at 477 and 750 nm, respectively, due to exchange narrowing. The social self-sorting behavior of these push-pull chromophores in their mixed thin films is evaluated and the impact on morphology as well as opto-electronical properties is determined. The implementation of this well-tuned two-component material with tailored optical features allows to optimize planar heterojunction organic photodiodes with fullerene ​(C\(_{60}\)) with either dual or single wavelength selectivity in the blue and NIR spectral range with ultranarrow bandwidths of only 11 nm (200 cm\(^{-1}\)) and an external quantum efficiency of up to 18\% at 754 nm under 0 V bias. The application of these photodiodes as low-power consuming heart rate monitors is demonstrated by a reflectance-mode photoplethysmography (PPG) sensor.},
  language  = {en}
}
@article{TuetuencueOlmaKunzeetal.2022,
  author    = {T{\"u}t{\"u}nc{\"u}, Serdar and Olma, Manuel and Kunze, Claudia and Dietzel, Joanna and Schurig, Johannes and Fiessler, Cornelia and Malsch, Carolin and Haas, Tobias Eberhard and Dimitrijeski, Boris and Doehner, Wolfram and Hagemann, Georg and Hamilton, Frank and Honermann, Martin and Jungehulsing, Gerhard Jan and Kauert, Andreas and Koennecke, Hans-Christian and Mackert, Bruno-Marcel and Nabavi, Darius and Nolte, Christian H. and Reis, Joschua Mirko and Schmehl, Ingo and Sparenberg, Paul and Stingele, Robert and V{\"o}lzke, Enrico and Waldschmidt, Carolin and Zeise-Wehry, Daniel and Heuschmann, Peter U. and Endress, Matthias and Haeusler, Karl Georg},
  title     = {Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry},
  series = {Journal of Neurology},
  volume    = {269},
  journal   = {Journal of Neurology},
  number    = {1},
  issn      = {1432-1459},
  doi       = {10.1007/s00415-021-10866-2},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-266969},
  pages     = {470-480},
  year      = {2022},
  abstract  = {Aims We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. Methods The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. Results At stroke onset, an off-label daily dose was prescribed in 61 (25.5\%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8\%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95\% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95\% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2\%) of 61 patients. Overall, 79 (13.7\%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6\%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95\% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95\% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95\% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95\% CI 1.28-2.84, P < 0.01]. Conclusion At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge.},
  language  = {en}
}
@article{KaemmererTribiusCohrsetal.2023,
  author    = {K{\"a}mmerer, Peer W. and Tribius, Silke and Cohrs, Lena and Engler, Gabriel and Ettl, Tobias and Freier, Kolja and Frerich, Bernhard and Ghanaati, Shahram and Gosau, Martin and Haim, Dominik and Hartmann, Stefan and Heiland, Max and Herbst, Manuel and Hoefert, Sebastian and Hoffmann, J{\"u}rgen and H{\"o}lzle, Frank and Howaldt, Hans-Peter and Kreutzer, Kilian and Leonhardt, Henry and Lutz, Rainer and Moergel, Maximilian and Modabber, Ali and Neff, Andreas and Pietzka, Sebastian and Rau, Andrea and Reichert, Torsten E. and Smeets, Ralf and Sproll, Christoph and Steller, Daniel and Wiltfang, J{\"o}rg and Wolff, Klaus-Dietrich and Kronfeld, Kai and Al-Nawas, Bilal},
  title     = {Adjuvant radiotherapy in patients with squamous cell carcinoma of the oral cavity or oropharynx and solitary ipsilateral lymph node metastasis (pN1) — a prospective multicentric cohort study},
  series = {Cancers},
  volume    = {15},
  journal   = {Cancers},
  number    = {6},
  issn      = {2072-6694},
  doi       = {10.3390/cancers15061833},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311024},
  year      = {2023},
  abstract  = {(1) Background: Evaluation of impact of adjuvant radiation therapy (RT) in patients with oral squamous cell carcinoma of the oral cavity/oropharynx (OSCC) of up to 4 cm (pT1/pT2) and solitary ipsilateral lymph node metastasis (pN1). A non-irradiated group with clinical follow-up was chosen for control, and survival and quality of life (QL) were compared; (2) Methods: This prospective multicentric comprehensive cohort study included patients with resected OSCC (pT1/pT2, pN1, and cM0) who were allocated into adjuvant radiation therapy (RT) or observation. The primary endpoint was overall survival. Secondary endpoints were progression-free survival and QL after surgery; (3) Results: Out of 27 centers, 209 patients were enrolled with a median follow-up of 3.4 years. An amount of 137 patients were in the observation arm, and 72 received adjuvant irradiation. Overall survival did not differ between groups (hazard ratio (HR) 0.98 [0.55-1.73], p = 0.94). There were fewer neck metastases (HR 0.34 [0.15-0.77]; p = 0.01), as well as fewer local recurrences (HR 0.41 [0.19-0.89]; p = 0.02) under adjuvant RT. For QL, irradiated patients showed higher values for the symptom scale pain after 0.5, two, and three years (all p < 0.05). After six months and three years, irradiated patients reported higher symptom burdens (impaired swallowing, speech, as well as teeth-related problems (all p < 0.05)). Patients in the RT group had significantly more problems with mouth opening after six months, one, and two years (p < 0.05); (4) Conclusions: Adjuvant RT in patients with early SCC of the oral cavity and oropharynx does not seem to influence overall survival, but it positively affects progression-free survival. However, irradiated patients report a significantly decreased QL up to three years after therapy compared to the observation group.},
  language  = {en}
}
@article{GroebnerWorstWeischenfeldtetal.2018,
  author    = {Gr{\"o}bner, Susanne N. and Worst, Barbara C. and Weischenfeldt, Joachim and Buchhalter, Ivo and Kleinheinz, Kortine and Rudneva, Vasilisa A. and Johann, Pascal D. and Balasubramanian, Gnana Prakash and Segura-Wang, Maia and Brabetz, Sebastian and Bender, Sebastian and Hutter, Barbara and Sturm, Dominik and Pfaff, Elke and H{\"u}bschmann, Daniel and Zipprich, Gideon and Heinold, Michael and Eils, J{\"u}rgen and Lawerenz, Christian and Erkek, Serap and Lambo, Sander and Waszak, Sebastian and Blattmann, Claudia and Borkhardt, Arndt and Kuhlen, Michaela and Eggert, Angelika and Fulda, Simone and Gessler, Manfred and Wegert, Jenny and Kappler, Roland and Baumhoer, Daniel and Stefan, Burdach and Kirschner-Schwabe, Renate and Kontny, Udo and Kulozik, Andreas E. and Lohmann, Dietmar and Hettmer, Simone and Eckert, Cornelia and Bielack, Stefan and Nathrath, Michaela and Niemeyer, Charlotte and Richter, G{\"u}nther H. and Schulte, Johannes and Siebert, Reiner and Westermann, Frank and Molenaar, Jan J. and Vassal, Gilles and Witt, Hendrik and Burkhardt, Birgit and Kratz, Christian P. and Witt, Olaf and van Tilburg, Cornelis M. and Kramm, Christof M. and Fleischhack, Gudrun and Dirksen, Uta and Rutkowski, Stefan and Fr{\"u}hwald, Michael and Hoff, Katja von and Wolf, Stephan and Klingebeil, Thomas and Koscielniak, Ewa and Landgraf, Pablo and Koster, Jan and Resnick, Adam C. and Zhang, Jinghui and Liu, Yanling and Zhou, Xin and Waanders, Angela J. and Zwijnenburg, Danny A. and Raman, Pichai and Brors, Benedikt and Weber, Ursula D. and Northcott, Paul A. and Pajtler, Kristian W. and Kool, Marcel and Piro, Rosario M. and Korbel, Jan O. and Schlesner, Matthias and Eils, Roland and Jones, David T. W. and Lichter, Peter and Chavez, Lukas and Zapatka, Marc and Pfister, Stefan M.},
  title     = {The landscape of genomic alterations across childhood cancers},
  series = {Nature},
  volume    = {555},
  journal   = {Nature},
  organization    = {ICGC PedBrain-Seq Project, ICGC MMML-Seq Project,},
  doi       = {10.1038/nature25480},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229579},
  pages     = {321-327},
  year      = {2018},
  abstract  = {Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8\% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50\% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.},
  language  = {en}
}
@article{WenFeilWoltersetal.2018,
  author    = {Wen, Lai and Feil, Susanne and Wolters, Markus and Thunemann, Martin and Regler, Frank and Schmidt, Kjestine and Friebe, Andreas and Olbrich, Marcus and Langer, Harald and Gawaz, Meinrad and de Wit, Cor and Feil, Robert},
  title     = {A shear-dependent NO-cGMP-cGKI cascade in platelets acts as an auto-regulatory brake of thrombosis},
  series = {Nature Communications},
  volume    = {9},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-018-06638-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233616},
  year      = {2018},
  abstract  = {Mechanisms that limit thrombosis are poorly defined. One of the few known endogenous platelet inhibitors is nitric oxide (NO). NO activates NO sensitive guanylyl cyclase (NO-GC) in platelets, resulting in an increase of cyclic guanosine monophosphate (cGMP). Here we show, using cGMP sensor mice to study spatiotemporal dynamics of platelet cGMP, that NO-induced cGMP production in pre-activated platelets is strongly shear-dependent. We delineate a new mode of platelet-inhibitory mechanotransduction via shear-activated NO-GC followed by cGMP synthesis, activation of cGMP-dependent protein kinase I (cGKI), and suppression of Ca2+ signaling. Correlative profiling of cGMP dynamics and thrombus formation in vivo indicates that high cGMP concentrations in shear-exposed platelets at the thrombus periphery limit thrombosis, primarily through facilitation of thrombus dissolution. We propose that an increase in shear stress during thrombus growth activates the NO-cGMP-cGKI pathway, which acts as an auto-regulatory brake to prevent vessel occlusion, while preserving wound closure under low shear.},
  language  = {en}
}