@article{ElHelouBiegnerBodeetal.2019,
  author    = {El-Helou, Sabine M. and Biegner, Anika-Kerstin and Bode, Sebastian and Ehl, Stephan R. and Heeg, Maximilian and Maccari, Maria E. and Ritterbusch, Henrike and Speckmann, Carsten and Rusch, Stephan and Scheible, Raphael and Warnatz, Klaus and Atschekzei, Faranaz and Beider, Renata and Ernst, Diana and Gerschmann, Stev and Jablonka, Alexandra and Mielke, Gudrun and Schmidt, Reinhold E. and Sch{\"u}rmann, Gesine and Sogkas, Georgios and Baumann, Ulrich H. and Klemann, Christian and Viemann, Dorothee and Bernuth, Horst von and Kr{\"u}ger, Renate and Hanitsch, Leif G. and Scheibenbogen, Carmen M. and Wittke, Kirsten and Albert, Michael H. and Eichinger, Anna and Hauck, Fabian and Klein, Christoph and Rack-Hoch, Anita and Sollinger, Franz M. and Avila, Anne and Borte, Michael and Borte, Stephan and Fasshauer, Maria and Hauenherm, Anja and Kellner, Nils and M{\"u}ller, Anna H. and {\"U}lzen, Anett and Bader, Peter and Bakhtiar, Shahrzad and Lee, Jae-Yun and Heß, Ursula and Schubert, Ralf and W{\"o}lke, Sandra and Zielen, Stefan and Ghosh, Sujal and Laws, Hans-Juergen and Neubert, Jennifer and Oommen, Prasad T. and H{\"o}nig, Manfred and Schulz, Ansgar and Steinmann, Sandra and Klaus, Schwarz and D{\"u}ckers, Gregor and Lamers, Beate and Langemeyer, Vanessa and Niehues, Tim and Shai, Sonu and Graf, Dagmar and M{\"u}glich, Carmen and Schmalzing, Marc T. and Schwaneck, Eva C. and Tony, Hans-Peter and Dirks, Johannes and Haase, Gabriele and Liese, Johannes G. and Morbach, Henner and Foell, Dirk and Hellige, Antje and Wittkowski, Helmut and Masjosthusmann, Katja and Mohr, Michael and Geberzahn, Linda and Hedrich, Christian M. and M{\"u}ller, Christiane and R{\"o}sen-Wolff, Angela and Roesler, Joachim and Zimmermann, Antje and Behrends, Uta and Rieber, Nikolaus and Schauer, Uwe and Handgretinger, Rupert and Holzer, Ursula and Henes, J{\"o}rg and Kanz, Lothar and Boesecke, Christoph and Rockstroh, J{\"u}rgen K. and Schwarze-Zander, Carolynne and Wasmuth, Jan-Christian and Dilloo, Dagmar and H{\"u}lsmann, Brigitte and Sch{\"o}nberger, Stefan and Schreiber, Stefan and Zeuner, Rainald and Ankermann, Tobias and Bismarck, Philipp von and Huppertz, Hans-Iko and Kaiser-Labusch, Petra and Greil, Johann and Jakoby, Donate and Kulozik, Andreas E. and Metzler, Markus and Naumann-Bartsch, Nora and Sobik, Bettina and Graf, Norbert and Heine, Sabine and Kobbe, Robin and Lehmberg, Kai and M{\"u}ller, Ingo and Herrmann, Friedrich and Horneff, Gerd and Klein, Ariane and Peitz, Joachim and Schmidt, Nadine and Bielack, Stefan and Groß-Wieltsch, Ute and Classen, Carl F. and Klasen, Jessica and Deutz, Peter and Kamitz, Dirk and Lassy, Lisa and Tenbrock, Klaus and Wagner, Norbert and Bernbeck, Benedikt and Brummel, Bastian and Lara-Villacanas, Eusebia and M{\"u}nstermann, Esther and Schneider, Dominik T. and Tietsch, Nadine and Westkemper, Marco and Weiß, Michael and Kramm, Christof and K{\"u}hnle, Ingrid and Kullmann, Silke and Girschick, Hermann and Specker, Christof and Vinnemeier-Laubenthal, Elisabeth and Haenicke, Henriette and Schulz, Claudia and Schweigerer, Lothar and M{\"u}ller, Thomas G. and Stiefel, Martina and Belohradsky, Bernd H. and Soetedjo, Veronika and Kindle, Gerhard and Grimbacher, Bodo},
  title     = {The German national registry of primary immunodeficiencies (2012-2017)},
  series = {Frontiers in Immunology},
  volume    = {10},
  journal   = {Frontiers in Immunology},
  doi       = {10.3389/fimmu.2019.01272},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-226629},
  year      = {2019},
  abstract  = {Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57\% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36\% of patients. Familial cases were observed in 21\% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74\%) and immune dysregulation (22\%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49\% of all patients received immunoglobulin G (IgG) substitution (70\%-subcutaneous; 29\%-intravenous; 1\%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.},
  language  = {en}
}
@article{LopezKleinheinzAukemaetal.2019,
  author    = {L{\´o}pez, Cristina and Kleinheinz, Kortine and Aukema, Sietse M. and Rohde, Marius and Bernhart, Stephan H. and H{\"u}bschmann, Daniel and Wagener, Rabea and Toprak, Umut H. and Raimondi, Francesco and Kreuz, Markus and Waszak, Sebastian M. and Huang, Zhiqin and Sieverling, Lina and Paramasivam, Nagarajan and Seufert, Julian and Sungalee, Stephanie and Russell, Robert B. and Bausinger, Julia and Kretzmer, Helene and Ammerpohl, Ole and Bergmann, Anke K. and Binder, Hans and Borkhardt, Arndt and Brors, Benedikt and Claviez, Alexander and Doose, Gero and Feuerbach, Lars and Haake, Andrea and Hansmann, Martin-Leo and Hoell, Jessica and Hummel, Michael and Korbel, Jan O. and Lawerenz, Chris and Lenze, Dido and Radlwimmer, Bernhard and Richter, Julia and Rosenstiel, Philip and Rosenwald, Andreas and Schilhabel, Markus B. and Stein, Harald and Stilgenbauer, Stephan and Stadler, Peter F. and Szczepanowski, Monika and Weniger, Marc A. and Zapatka, Marc and Eils, Roland and Lichter, Peter and Loeffler, Markus and M{\"o}ller, Peter and Tr{\"u}mper, Lorenz and Klapper, Wolfram and Hoffmann, Steve and K{\"u}ppers, Ralf and Burkhardt, Birgit and Schlesner, Matthias and Siebert, Reiner},
  title     = {Genomic and transcriptomic changes complement each other in the pathogenesis of sporadic Burkitt lymphoma},
  series = {Nature Communications},
  volume    = {10},
  journal   = {Nature Communications},
  organization    = {ICGC MMML-Seq Consortium},
  doi       = {10.1038/s41467-019-08578-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-237281},
  year      = {2019},
  abstract  = {Burkitt lymphoma (BL) is the most common B-cell lymphoma in children. Within the International Cancer Genome Consortium (ICGC), we performed whole genome and transcriptome sequencing of 39 sporadic BL. Here, we unravel interaction of structural, mutational, and transcriptional changes, which contribute to MYC oncogene dysregulation together with the pathognomonic IG-MYC translocation. Moreover, by mapping IGH translocation breakpoints, we provide evidence that the precursor of at least a subset of BL is a B-cell poised to express IGHA. We describe the landscape of mutations, structural variants, and mutational processes, and identified a series of driver genes in the pathogenesis of BL, which can be targeted by various mechanisms, including IG-non MYC translocations, germline and somatic mutations, fusion transcripts, and alternative splicing.},
  language  = {en}
}
@article{DumontWeberLassalleJolyBeauparlantetal.2022,
  author    = {Dumont, Martine and Weber-Lassalle, Nana and Joly-Beauparlant, Charles and Ernst, Corinna and Droit, Arnaud and Feng, Bing-Jian and Dubois, St{\´e}phane and Collin-Deschesnes, Annie-Claude and Soucy, Penny and Vall{\´e}e, Maxime and Fournier, Fr{\´e}d{\´e}ric and Lema{\c{c}}on, Audrey and Adank, Muriel A. and Allen, Jamie and Altm{\"u}ller, Janine and Arnold, Norbert and Ausems, Margreet G. E. M. and Berutti, Riccardo and Bolla, Manjeet K. and Bull, Shelley and Carvalho, Sara and Cornelissen, Sten and Dufault, Michael R. and Dunning, Alison M. and Engel, Christoph and Gehrig, Andrea and Geurts-Giele, Willemina R. R. and Gieger, Christian and Green, Jessica and Hackmann, Karl and Helmy, Mohamed and Hentschel, Julia and Hogervorst, Frans B. L. and Hollestelle, Antoinette and Hooning, Maartje J. and Horv{\´a}th, Judit and Ikram, M. Arfan and Kaulfuß, Silke and Keeman, Renske and Kuang, Da and Luccarini, Craig and Maier, Wolfgang and Martens, John W. M. and Niederacher, Dieter and N{\"u}rnberg, Peter and Ott, Claus-Eric and Peters, Annette and Pharoah, Paul D. P. and Ramirez, Alfredo and Ramser, Juliane and Riedel-Heller, Steffi and Schmidt, Gunnar and Shah, Mitul and Scherer, Martin and St{\"a}bler, Antje and Strom, Tim M. and Sutter, Christian and Thiele, Holger and van Asperen, Christi J. and van der Kolk, Lizet and van der Luijt, Rob B. and Volk, Alexander E. and Wagner, Michael and Waisfisz, Quinten and Wang, Qin and Wang-Gohrke, Shan and Weber, Bernhard H. F. and Devilee, Peter and Tavtigian, Sean and Bader, Gary D. and Meindl, Alfons and Goldgar, David E. and Andrulis, Irene L. and Schmutzler, Rita K. and Easton, Douglas F. and Schmidt, Marjanka K. and Hahnen, Eric and Simard, Jacques},
  title     = {Uncovering the contribution of moderate-penetrance susceptibility genes to breast cancer by whole-exome sequencing and targeted enrichment sequencing of candidate genes in women of European ancestry},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {14},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14143363},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-281768},
  year      = {2022},
  abstract  = {Rare variants in at least 10 genes, including BRCA1, BRCA2, PALB2, ATM, and CHEK2, are associated with increased risk of breast cancer; however, these variants, in combination with common variants identified through genome-wide association studies, explain only a fraction of the familial aggregation of the disease. To identify further susceptibility genes, we performed a two-stage whole-exome sequencing study. In the discovery stage, samples from 1528 breast cancer cases enriched for breast cancer susceptibility and 3733 geographically matched unaffected controls were sequenced. Using five different filtering and gene prioritization strategies, 198 genes were selected for further validation. These genes, and a panel of 32 known or suspected breast cancer susceptibility genes, were assessed in a validation set of 6211 cases and 6019 controls for their association with risk of breast cancer overall, and by estrogen receptor (ER) disease subtypes, using gene burden tests applied to loss-of-function and rare missense variants. Twenty genes showed nominal evidence of association (p-value < 0.05) with either overall or subtype-specific breast cancer. Our study had the statistical power to detect susceptibility genes with effect sizes similar to ATM, CHEK2, and PALB2, however, it was underpowered to identify genes in which susceptibility variants are rarer or confer smaller effect sizes. Larger sample sizes would be required in order to identify such genes.},
  language  = {en}
}
@article{KochPetzoldWesselyetal.2021,
  author    = {Koch, Elias A. T. and Petzold, Anne and Wessely, Anja and Dippel, Edgar and Gesierich, Anja and Gutzmer, Ralf and Hassel, Jessica C. and Haferkamp, Sebastian and Hohberger, Bettina and K{\"a}hler, Katharina C. and Knorr, Harald and Kreuzberg, Nicole and Leiter, Ulrike and Loquai, Carmen and Meier, Friedegund and Meissner, Markus and Mohr, Peter and Pf{\"o}hler, Claudia and Rahimi, Farnaz and Schadendorf, Dirk and Schell, Beatrice and Schlaak, Max and Terheyden, Patrick and Thoms, Kai-Martin and Schuler-Thurner, Beatrice and Ugurel, Selma and Ulrich, Jens and Utikal, Jochen and Weichenthal, Michael and Ziller, Fabian and Berking, Carola and Heppt, Markus},
  title     = {Immune checkpoint blockade for metastatic uveal melanoma: patterns of response and survival according to the presence of hepatic and extrahepatic metastasis},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {13},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13133359},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-242603},
  year      = {2021},
  abstract  = {Background: Since there is no standardized and effective treatment for advanced uveal melanoma (UM), the prognosis is dismal once metastases develop. Due to the availability of immune checkpoint blockade (ICB) in the real-world setting, the prognosis of metastatic UM has improved. However, it is unclear how the presence of hepatic and extrahepatic metastasis impacts the response and survival after ICB. Methods: A total of 178 patients with metastatic UM treated with ICB were included in this analysis. Patients were recruited from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of hepatic metastasis, two cohorts were compared: patients with liver metastasis only (cohort A, n = 55) versus those with both liver and extra-hepatic metastasis (cohort B, n = 123). Data were analyzed in both cohorts for response to treatment, progression-free survival (PFS), and overall survival (OS). The survival and progression probabilities were calculated with the Kaplan-Meier method. Log-rank tests, χ\(^2\) tests, and t-tests were performed to detect significant differences between both cohorts. Results: The median OS of the overall population was 16 months (95\% CI 13.4-23.7) and the median PFS, 2.8 months (95\% CI 2.5-3.0). The median OS was longer in cohort B than in cohort A (18.2 vs. 6.1 months; p = 0.071). The best objective response rate to dual ICB was 13.8\% and to anti-PD-1 monotherapy 8.9\% in the entire population. Patients with liver metastases only had a lower response to dual ICB, yet without significance (cohort A 8.7\% vs. cohort B 16.7\%; p = 0.45). Adverse events (AE) occurred in 41.6\%. Severe AE were observed in 26.3\% and evenly distributed between both cohorts. Conclusion: The survival of this large cohort of patients with advanced UM was more favorable than reported in previous benchmark studies. Patients with both hepatic and extrahepatic metastasis showed more favorable survival and higher response to dual ICB than those with hepatic metastasis only.},
  language  = {en}
}
@article{LoddeForschnerHasseletal.2021,
  author    = {Lodde, Georg and Forschner, Andrea and Hassel, Jessica and Wulfken, Lena M. and Meier, Friedegund and Mohr, Peter and K{\"a}hler, Katharina and Schilling, Bastian and Loquai, Carmen and Berking, Carola and H{\"u}ning, Svea and Schatton, Kerstin and Gebhardt, Christoffer and Eckardt, Julia and Gutzmer, Ralf and Reinhardt, Lydia and Glutsch, Valerie and Nikfarjam, Ulrike and Erdmann, Michael and Stang, Andreas and Kowall, Bernd and Roesch, Alexander and Ugurel, Selma and Zimmer, Lisa and Schadendorf, Dirk and Livingstone, Elisabeth},
  title     = {Factors influencing the adjuvant therapy decision: results of a real-world multicenter data analysis of 904 melanoma patients},
  series = {Cancers},
  volume    = {13},
  journal   = {Cancers},
  number    = {10},
  issn      = {2072-6694},
  doi       = {10.3390/cancers13102319},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-239583},
  year      = {2021},
  abstract  = {Adjuvant treatment of melanoma patients with immune-checkpoint inhibition (ICI) and targeted therapy (TT) significantly improved recurrence-free survival. This study investigates the real-world situation of 904 patients from 13 German skin cancer centers with an indication for adjuvant treatment since the approval of adjuvant ICI and TT. From adjusted log-binomial regression models, we estimated relative risks for associations between various influence factors and treatment decisions (adjuvant therapy yes/no, TT vs. ICI in BRAF mutant patients). Of these patients, 76.9\% (95\% CI 74-80) opted for a systemic adjuvant treatment. The probability of starting an adjuvant treatment was 26\% lower in patients >65 years (RR 0.74, 95\% CI 68-80). The most common reasons against adjuvant treatment given by patients were age (29.4\%, 95\% CI 24-38), and fear of adverse events (21.1\%, 95\% CI 16-28) and impaired quality of life (11.9\%, 95\% CI 7-16). Of all BRAF-mutated patients who opted for adjuvant treatment, 52.9\% (95\% CI 47-59) decided for ICI. Treatment decision for TT or ICI was barely associated with age, gender and tumor stage, but with comorbidities and affiliated center. Shortly after their approval, adjuvant treatments have been well accepted by physicians and patients. Age plays a decisive role in the decision for adjuvant treatment, while pre-existing autoimmune disease and regional differences influence the choice between TT or ICI.},
  language  = {en}
}
@article{LoebLinsmeierHerbertetal.2023,
  author    = {L{\"o}b, Sanja and Linsmeier, Eva and Herbert, Saskia-Laureen and Schlaiß, Tanja and Kiesel, Matthias and Wischhusen, J{\"o}rg and Salmen, Jessica and Kranke, Peter and Quenzer, Anne and Kurz, Florian and Weiss, Claire and Gerhard-Hartmann, Elena and W{\"o}ckel, Achim and Diessner, Joachim},
  title     = {Prognostic effect of HER2 evolution from primary breast cancer to breast cancer metastases},
  series = {Journal of Cancer Research and Clinical Oncology},
  volume    = {149},
  journal   = {Journal of Cancer Research and Clinical Oncology},
  number    = {8},
  doi       = {10.1007/s00432-022-04486-0},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324068},
  pages     = {5417-5428},
  year      = {2023},
  abstract  = {Purpose Therapeutic options for breast cancer (BC) treatment are constantly evolving. The Human Epidermal Growth Factor 2 (HER2)-low BC entity is a new subgroup, representing about 55\% of all BC patients. New antibody-drug conjugates demonstrated promising results for this BC subgroup. Currently, there is limited information about the conversion of HER2 subtypes between primary tumor and recurrent disease. Methods This retrospective study included women with BC at the University Medical Centre Wuerzburg from 1998 to 2021. Data were retrieved from patients' records. HER2 evolution from primary diagnosis to the first relapse and the development of secondary metastases was investigated. Results In the HR-positive subgroup without HER2 overexpression, HER2-low expression in primary BC was 56.7 vs. 14.6\% in the triple-negative subgroup (p < 0.000). In the cohort of the first relapse, HER2-low represented 64.1\% of HR-positive vs. 48.2\% of the triple-negative cohort (p = 0.03). In patients with secondary metastases, HER2-low was 75.6\% vs. 50\% in the triple negative subgroup (p = 0.10). The subgroup of HER2-positive breast cancer patients numerically increased in the course of disease; the HER2-negative overall cohort decreased. A loss of HER2 expression from primary BC to the first relapse correlated with a better OS (p = 0.018). No clinicopathological or therapeutic features could be identified as potential risk factors for HER2 conversion. Conclusion HER2 expression is rising during the progression of BC disease. In view of upcoming therapeutical options, the re-analysis of newly developed metastasis will become increasingly important.},
  language  = {en}
}
@article{BeyerJadaszSamperAgreloetal.2020,
  author    = {Beyer, Felix and Jadasz, Janusz and Samper Agrelo, Iria and Schira-Heinen, Jessica and Groh, Janos and Manousi, Anastasia and B{\"u}termann, Christine and Estrada, Veronica and Reiche, Laura and Cantone, Martina and Vera, Julio and Vigan{\`o}, Francesca and Dimou, Leda and M{\"u}ller, Hans Werner and Hartung, Hans-Peter and K{\"u}ry, Patrick},
  title     = {Heterogeneous fate choice of genetically modulated adult neural stem cells in gray and white matter of the central nervous system},
  series = {Glia},
  volume    = {68},
  journal   = {Glia},
  number    = {2},
  doi       = {10.1002/glia.23724},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218566},
  pages     = {393 -- 406},
  year      = {2020},
  abstract  = {Apart from dedicated oligodendroglial progenitor cells, adult neural stem cells (aNSCs) can also give rise to new oligodendrocytes in the adult central nervous system (CNS). This process mainly confers myelinating glial cell replacement in pathological situations and can hence contribute to glial heterogeneity. Our previous studies demonstrated that the p57kip2 gene encodes an intrinsic regulator of glial fate acquisition and we here investigated to what degree its modulation can affect stem cell-dependent oligodendrogenesis in different CNS environments. We therefore transplanted p57kip2 knockdown aNSCs into white and gray matter (WM and GM) regions of the mouse brain, into uninjured spinal cords as well as in the vicinity of spinal cord injuries and evaluated integration and differentiation in vivo. Our experiments revealed that under healthy conditions intrinsic suppression of p57kip2 as well as WM localization promote differentiation toward myelinating oligodendrocytes at the expense of astrocyte generation. Moreover, p57kip2 knockdown conferred a strong benefit on cell survival augmenting net oligodendrocyte generation. In the vicinity of hemisectioned spinal cords, the gene knockdown led to a similar induction of oligodendroglial features; however, newly generated oligodendrocytes appeared to suffer more from the hostile environment. This study contributes to our understanding of mechanisms of adult oligodendrogenesis and glial heterogeneity and further reveals critical factors when considering aNSC mediated cell replacement in injury and disease.},
  language  = {en}
}
@article{RohmannHuoSperberetal.2020,
  author    = {Rohmann, Jessica L. and Huo, Shufan and Sperber, Pia S. and Piper, Sophie K. and Rosendaal, Frits R. and Heuschmann, Peter U. and Endres, Matthias and Liman, Thomas G. and Siegerink, Bob},
  title     = {Coagulation factor XII, XI, and VIII activity levels and secondary events after first ischemic stroke},
  series = {Journal of Thrombosis and Haemostasis},
  volume    = {18},
  journal   = {Journal of Thrombosis and Haemostasis},
  number    = {12},
  doi       = {10.1111/jth.15092},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-217877},
  pages     = {3316 -- 3324},
  year      = {2020},
  abstract  = {Background Though risk for recurrent vascular events is high following ischemic stroke, little knowledge about risk factors for secondary events post-stroke exists. Objectives Coagulation factors XII, XI, and VIII (FXII, FXI, and FVIII) have been implicated in first thrombotic events, and our aim was to estimate their effects on vascular outcomes within 3 years after first stroke. Patients/Methods In the Prospective Cohort with Incident Stroke Berlin (PROSCIS-B) study, we followed participants aged 18 and older for 3 years after first mild to moderate ischemic stroke event or until occurrence of recurrent stroke, myocardial infarction, or all-cause mortality. We compared high coagulation factor activity levels to normal and low levels and also analyzed activities as continuous variables. We used Cox proportional hazards models adjusted for age, sex, and cardiovascular risk factors to estimate hazard ratios (HRs) for the combined endpoint. Results In total, 94 events occurred in 576 included participants, resulting in an absolute rate of 6.6 events per 100 person-years. After confounding adjustment, high FVIII activity showed the strongest relationship with the combined endpoint (HR = 2.05, 95\% confidence interval [CI] 1.28-3.29). High FXI activity was also associated with a higher hazard (HR = 1.80, 95\% CI 1.09-2.98), though high FXII activity was not (HR = 0.86, 95\% CI 0.49-1.51). Continuous analyses yielded similar results. Conclusions In our study of mild to moderate ischemic stroke patients, high activity levels of FXI and FVIII but not FXII were associated with worse vascular outcomes in the 3-year period after first ischemic stroke.},
  language  = {en}
}
@article{SchleicherPaduchDebusetal.2016,
  author    = {Schleicher, Ulrike and Paduch, Katrin and Debus, Andrea and Obermeyer, Stephanie and K{\"o}nig, Till and Kling, Jessica C. and Ribechini, Eliana and Dudziak, Diana and Mougiakakos, Dimitrios and Murray, Peter J. and Ostuni, Renato and K{\"o}rner, Heinrich and Bogdan, Christian},
  title     = {TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection},
  series = {Cell Reports},
  volume    = {15},
  journal   = {Cell Reports},
  number    = {5},
  doi       = {10.1016/j.celrep.2016.04.001},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164897},
  pages     = {1062-1075},
  year      = {2016},
  abstract  = {Neutralization or deletion of tumor necrosis factor (TNF) causes loss of control of intracellular pathogens in mice and humans, but the underlying mechanisms are incompletely understood. Here, we found that TNF antagonized alternative activation of macrophages and dendritic cells by IL-4. TNF inhibited IL-4-induced arginase 1 (Arg1) expression by decreasing histone acetylation, without affecting STAT6 phosphorylation and nuclear translocation. In Leishmania major-infected C57BL/6 wild-type mice, type 2 nitric oxide (NO) synthase (NOS2) was detected in inflammatory dendritic cells or macrophages, some of which co-expressed Arg1. In TNF-deficient mice, Arg1 was hyperexpressed, causing an impaired production of NO in situ. A similar phenotype was seen in L. major-infected BALB/c mice. Arg1 deletion in hematopoietic cells protected these mice from an otherwise lethal disease, although their disease-mediating T cell response (Th2, Treg) was maintained. Thus, deletion or TNF-mediated restriction of Arg1 unleashes the production of NO by NOS2, which is critical for pathogen control.},
  language  = {en}
}
@article{KochPetzoldWesselyetal.2022,
  author    = {Koch, Elias A. T. and Petzold, Anne and Wessely, Anja and Dippel, Edgar and Gesierich, Anja and Gutzmer, Ralf and Hassel, Jessica C. and Haferkamp, Sebastian and K{\"a}hler, Katharina C. and Knorr, Harald and Kreuzberg, Nicole and Leiter, Ulrike and Loquai, Carmen and Meier, Friedegund and Meissner, Markus and Mohr, Peter and Pf{\"o}hler, Claudia and Rahimi, Farnaz and Schadendorf, Dirk and Schell, Beatrice and Schlaak, Max and Terheyden, Patrick and Thoms, Kai-Martin and Schuler-Thurner, Beatrice and Ugurel, Selma and Ulrich, Jens and Utikal, Jochen and Weichenthal, Michael and Ziller, Fabian and Berking, Carola and Heppt, Markus V.},
  title     = {Immune checkpoint blockade for metastatic uveal melanoma: re-induction following resistance or toxicity},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {3},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14030518},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-254814},
  year      = {2022},
  abstract  = {Re-induction with immune checkpoint blockade (ICB) needs to be considered in many patients with uveal melanoma (UM) due to limited systemic treatment options. Here, we provide hitherto the first analysis of ICB re-induction in UM. A total of 177 patients with metastatic UM treated with ICB were included from German skin cancer centers and the German national skin cancer registry (ADOReg). To investigate the impact of ICB re-induction, two cohorts were compared: patients who received at least one ICB re-induction (cohort A, n = 52) versus those who received only one treatment line of ICB (cohort B, n = 125). In cohort A, a transient benefit of overall survival (OS) was observed at 6 and 12 months after the treatment start of ICB. There was no significant difference in OS between both groups (p = 0.1) with a median OS of 16.2 months (cohort A, 95\% CI: 11.1-23.8) versus 9.4 months (cohort B, 95\% CI: 6.1-14.9). Patients receiving re-induction of ICB (cohort A) had similar response rates compared to those receiving ICB once. Re-induction of ICB may yield a clinical benefit for a small subgroup of patients even after resistance or development of toxicities.},
  language  = {en}
}
@article{VollmuthMuljukovAbuMugheisibetal.2021,
  author    = {Vollmuth, Christoph and Muljukov, Olga and Abu-Mugheisib, Mazen and Angermeier, Anselm and Barlinn, Jessica and Busetto, Loraine and Grau, Armin J. and G{\"u}nther, Albrecht and Gumbinger, Christoph and Hubert, Nikolai and H{\"u}ttemann, Katrin and Klingner, Carsten and Naumann, Markus and Palm, Frederick and Remi, Jan and R{\"u}cker, Viktoria and Schessl, Joachim and Schlachetzki, Felix and Schuppner, Ramona and Schwab, Stefan and Schwartz, Andreas and Trommer, Adrian and Urbanek, Christian and Volbers, Bastian and Weber, Joachim and Wojciechowski, Claudia and Worthmann, Hans and Zickler, Philipp and Heuschmann, Peter U. and Haeusler, Karl Georg and Hubert, Gordian Jan},
  title     = {Impact of the coronavirus disease 2019 pandemic on stroke teleconsultations in Germany in the first half of 2020},
  series = {European Journal of Neurology},
  volume    = {28},
  journal   = {European Journal of Neurology},
  number    = {10},
  doi       = {10.1111/ene.14787},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259396},
  pages     = {3267-3278},
  year      = {2021},
  abstract  = {Background and purpose The effects of the coronavirus disease 2019 (COVID-19) pandemic on telemedical care have not been described on a national level. Thus, we investigated the medical stroke treatment situation before, during, and after the first lockdown in Germany. Methods In this nationwide, multicenter study, data from 14 telemedical networks including 31 network centers and 155 spoke hospitals covering large parts of Germany were analyzed regarding patients' characteristics, stroke type/severity, and acute stroke treatment. A survey focusing on potential shortcomings of in-hospital and (telemedical) stroke care during the pandemic was conducted. Results Between January 2018 and June 2020, 67,033 telemedical consultations and 38,895 telemedical stroke consultations were conducted. A significant decline of telemedical (p < 0.001) and telemedical stroke consultations (p < 0.001) during the lockdown in March/April 2020 and a reciprocal increase after relaxation of COVID-19 measures in May/June 2020 were observed. Compared to 2018-2019, neither stroke patients' age (p = 0.38), gender (p = 0.44), nor severity of ischemic stroke (p = 0.32) differed in March/April 2020. Whereas the proportion of ischemic stroke patients for whom endovascular treatment (14.3\% vs. 14.6\%; p = 0.85) was recommended remained stable, there was a nonsignificant trend toward a lower proportion of recommendation of intravenous thrombolysis during the lockdown (19.0\% vs. 22.1\%; p = 0.052). Despite the majority of participating network centers treating patients with COVID-19, there were no relevant shortcomings reported regarding in-hospital stroke treatment or telemedical stroke care. Conclusions Telemedical stroke care in Germany was able to provide full service despite the COVID-19 pandemic, but telemedical consultations declined abruptly during the lockdown period and normalized after relaxation of COVID-19 measures in Germany.},
  language  = {en}
}
@article{ZhouRuckdeschelPeteretal.2022,
  author    = {Zhou, Xiang and Ruckdeschel, Anna and Peter, Jessica and B{\"o}ckle, David and Hornburger, Hannah and Danhof, Sophia and Steinhardt, Maximilian Johannes and Heimeshoff, Larissa and Einsele, Hermann and Kort{\"u}m, Klaus Martin and Rasche, Leo},
  title     = {Salvage therapy with "Dara-KDT-P(A)CE" in heavily pretreated, high-risk, proliferative, relapsed/refractory multiple myeloma},
  series = {Hematological Oncology},
  volume    = {40},
  journal   = {Hematological Oncology},
  number    = {2},
  doi       = {10.1002/hon.2949},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257495},
  pages     = {202-211},
  year      = {2022},
  abstract  = {The multi-agent therapy "VDT-PACE" represents an established regimen in relapsed/refractory multiple myeloma (RRMM). Here, we report on our experience with a "modified VDT-PACE" incorporating new generation anti-MM agents daratumumab and carfilzomib ("Dara-KDT-P(A)CE"). We retrospectively analyzed 38 patients with RRMM treated with "Dara-KDT-P(A)CE". The median age was 62 (range 45-82) years, and the patients were heavily pretreated with a median of 5 (range 2-12) prior lines of therapy. Twenty-one (55\%) patients suffered from penta-refractory MM. High-risk cytogenetics was present in 31 (81\%) patients. The patients received a median of 2 (range 1-10) cycles of this therapy, and the overall response rate (ORR) was 70\%. Patients with penta-refractory MM and high-risk cytogenetics showed similar ORR of 65\% and 79\%, respectively. The median progression-free survival (PFS) and overall survival were 4.1 (95\% CI 2.7-5.4) and 8.4 (95\% CI 6.7-10.0) months, respectively. Patients with lactate dehydrogenase >250 IU/L showed significantly shorter PFS in comparison with others patients (p = 0.006). We used this regimen as bridging therapy prior to chimeric antigen receptor T-cell infusion in four patients. In conclusion, "Dara-KDT-P(A)CE" is an effective salvage therapy for patients with heavily pretreated, multi-refractory, high-risk RRMM lacking alternative options.},
  language  = {en}
}
@article{SamperAgreloSchiraHeinenBeyeretal.2020,
  author    = {Samper Agrelo, Iria and Schira-Heinen, Jessica and Beyer, Felix and Groh, Janos and B{\"u}termann, Christine and Estrada, Veronica and Poschmann, Gereon and Bribian, Ana and Jadasz, Janusz J. and Lopez-Mascaraque, Laura and Kremer, David and Martini, Rudolf and M{\"u}ller, Hans Werner and Hartung, Hans Peter and Adjaye, James and St{\"u}hler, Kai and K{\"u}ry, Patrick},
  title     = {Secretome analysis of mesenchymal stem cell factors fostering oligodendroglial differentiation of neural stem cells in vivo},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {12},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21124350},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285465},
  year      = {2020},
  abstract  = {Mesenchymal stem cell (MSC)-secreted factors have been shown to significantly promote oligodendrogenesis from cultured primary adult neural stem cells (aNSCs) and oligodendroglial precursor cells (OPCs). Revealing underlying mechanisms of how aNSCs can be fostered to differentiate into a specific cell lineage could provide important insights for the establishment of novel neuroregenerative treatment approaches aiming at myelin repair. However, the nature of MSC-derived differentiation and maturation factors acting on the oligodendroglial lineage has not been identified thus far. In addition to missing information on active ingredients, the degree to which MSC-dependent lineage instruction is functional in vivo also remains to be established. We here demonstrate that MSC-derived factors can indeed stimulate oligodendrogenesis and myelin sheath generation of aNSCs transplanted into different rodent central nervous system (CNS) regions, and furthermore, we provide insights into the underlying mechanism on the basis of a comparative mass spectrometry secretome analysis. We identified a number of secreted proteins known to act on oligodendroglia lineage differentiation. Among them, the tissue inhibitor of metalloproteinase type 1 (TIMP-1) was revealed to be an active component of the MSC-conditioned medium, thus validating our chosen secretome approach.},
  language  = {en}
}
@article{BaluapuriHofstetterDudvarskiStankovicetal.2019,
  author    = {Baluapuri, Apoorva and Hofstetter, Julia and Dudvarski Stankovic, Nevenka and Endres, Theresa and Bhandare, Pranjali and Vos, Seychelle Monique and Adhikari, Bikash and Schwarz, Jessica Denise and Narain, Ashwin and Vogt, Markus and Wang, Shuang-Yan and D{\"u}ster, Robert and Jung, Lisa Anna and Vanselow, Jens Thorsten and Wiegering, Armin and Geyer, Matthias and Maric, Hans Michael and Gallant, Peter and Walz, Susanne and Schlosser, Andreas and Cramer, Patrick and Eilers, Martin and Wolf, Elmar},
  title     = {MYC Recruits SPT5 to RNA Polymerase II to Promote Processive Transcription Elongation},
  series = {Molecular Cell},
  volume    = {74},
  journal   = {Molecular Cell},
  doi       = {10.1016/j.molcel.2019.02.031},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221438},
  pages     = {674-687},
  year      = {2019},
  abstract  = {The MYC oncoprotein binds to promoter-proximal regions of virtually all transcribed genes and enhances RNA polymerase II (Pol II) function, but its precise mode of action is poorly understood. Using mass spectrometry of both MYC and Pol II complexes, we show here that MYC controls the assembly of Pol II with a small set of transcription elongation factors that includes SPT5, a subunit of the elongation factor DSIF. MYC directly binds SPT5, recruits SPT5 to promoters, and enables the CDK7-dependent transfer of SPT5 onto Pol II. Consistent with known functions of SPT5, MYC is required for fast and processive transcription elongation. Intriguingly, the high levels of MYC that are expressed in tumors sequester SPT5 into non-functional complexes, thereby decreasing the expression of growth-suppressive genes. Altogether, these results argue that MYC controls the productive assembly of processive Pol II elongation complexes and provide insight into how oncogenic levels of MYC permit uncontrolled cellular growth.},
  language  = {en}
}