@article{HoffmannPfeilAlfonsoetal.2016,
  author    = {Hoffmann, Angelika and Pfeil, Johannes and Alfonso, Julieta and Kurz, Felix T. and Sahm, Felix and Heiland, Sabine and Monyer, Hannah and Bendszus, Martin and Mueller, Ann-Kristin and Helluy, Xavier and Pham, Mirko},
  title     = {Experimental Cerebral Malaria Spreads along the Rostral Migratory Stream},
  series = {PLoS Pathogens},
  volume    = {12},
  journal   = {PLoS Pathogens},
  number    = {3},
  doi       = {10.1371/journal.ppat.1005470},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167434},
  pages     = {e1005470},
  year      = {2016},
  abstract  = {It is poorly understood how progressive brain swelling in experimental cerebral malaria (ECM) evolves in space and over time, and whether mechanisms of inflammation or microvascular sequestration/obstruction dominate the underlying pathophysiology. We therefore monitored in the Plasmodium berghei ANKA-C57BL/6 murine ECM model, disease manifestation and progression clinically, assessed by the Rapid-Murine-Coma-and-Behavioral-Scale (RMCBS), and by high-resolution in vivo MRI, including sensitive assessment of early blood-brain-barrier-disruption (BBBD), brain edema and microvascular pathology. For histological correlation HE and immunohistochemical staining for microglia and neuroblasts were obtained. Our results demonstrate that BBBD and edema initiated in the olfactory bulb (OB) and spread along the rostral-migratory-stream (RMS) to the subventricular zone of the lateral ventricles, the dorsal-migratory-stream (DMS), and finally to the external capsule (EC) and brainstem (BS). Before clinical symptoms (mean RMCBS = 18.5±1) became evident, a slight, non-significant increase of quantitative T2 and ADC values was observed in OB+RMS. With clinical manifestation (mean RMCBS = 14.2±0.4), T2 and ADC values significantly increased along the OB+RMS (p = 0.049/p = 0.01). Severe ECM (mean RMCBS = 5±2.9) was defined by further spread into more posterior and deeper brain structures until reaching the BS (significant T2 elevation in DMS+EC+BS (p = 0.034)). Quantitative automated histological analyses confirmed microglial activation in areas of BBBD and edema. Activated microglia were closely associated with the RMS and neuroblasts within the RMS were severely misaligned with respect to their physiological linear migration pattern. Microvascular pathology and ischemic brain injury occurred only secondarily, after vasogenic edema formation and were both associated less with clinical severity and the temporal course of ECM. Altogether, we identified a distinct spatiotemporal pattern of microglial activation in ECM involving primarily the OB+RMS axis, a distinct pathway utilized by neuroblasts and immune cells. Our data suggest significant crosstalk between these two cell populations to be operative in deeper brain infiltration and further imply that the manifestation and progression of cerebral malaria may depend on brain areas otherwise serving neurogenesis.},
  language  = {en}
}
@article{GabrielJirůHillmannKraftetal.2020,
  author    = {Gabriel, Katharina M. A. and J{\´i}rů-Hillmann, Steffi and Kraft, Peter and Selig, Udo and R{\"u}cker, Victoria and M{\"u}hler, Johannes and D{\"o}tter, Klaus and Keidel, Matthias and Soda, Hassan and Rascher, Alexandra and Schneider, Rolf and Pfau, Mathias and Hoffmann, Roy and Stenzel, Joachim and Benghebrid, Mohamed and Goebel, Tobias and Doerck, Sebastian and Kramer, Daniela and Haeusler, Karl Georg and Volkmann, Jens and Heuschmann, Peter U. and Fluri, Felix},
  title     = {Two years' experience of implementing a comprehensive telemedical stroke network comprising in mainly rural region: the Transregional Network for Stroke Intervention with Telemedicine (TRANSIT-Stroke)},
  series = {BMC Neurology},
  volume    = {20},
  journal   = {BMC Neurology},
  doi       = {10.1186/s12883-020-01676-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229214},
  year      = {2020},
  abstract  = {Background Telemedicine improves the quality of acute stroke care in rural regions with limited access to specialized stroke care. We report the first 2 years' experience of implementing a comprehensive telemedical stroke network comprising all levels of stroke care in a defined region. Methods The TRANSIT-Stroke network covers a mainly rural region in north-western Bavaria (Germany). All hospitals providing acute stroke care in this region participate in TRANSIT-Stroke, including four hospitals with a supra-regional certified stroke unit (SU) care (level III), three of those providing teleconsultation to two hospitals with a regional certified SU (level II) and five hospitals without specialized SU care (level I). For a two-year-period (01/2015 to 12/2016), data of eight of these hospitals were available; 13 evidence-based quality indicators (QIs) related to processes during hospitalisation were evaluated quarterly and compared according to predefined target values between level-I- and level-II/III-hospitals. Results Overall, 7881 patients were included (mean age 74.6 years +/- 12.8; 48.4\% female). In level-II/III-hospitals adherence of all QIs to predefined targets was high ab initio. In level-I-hospitals, three patterns of QI-development were observed: a) high adherence ab initio (31\%), mainly in secondary stroke prevention; b) improvement over time (44\%), predominantly related to stroke specific diagnosis and in-hospital organization; c) no clear time trends (25\%). Overall, 10 out of 13 QIs reached predefined target values of quality of care at the end of the observation period. Conclusion The implementation of the comprehensive TRANSIT-Stroke network resulted in an improvement of quality of care in level-I-hospitals.},
  language  = {en}
}
@masterthesis{Hoffmann2018,
  type      = {Bachelor Thesis},
  author    = {Hoffmann, Felix},
  title     = {Volksgesetzgebung und politischer Entscheidungsprozess},
  issn      = {2193-9179},
  doi       = {10.25972/OPUS-16191},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-161919},
  school      = {Universit{\"a}t W{\"u}rzburg},
  pages     = {1-61},
  year      = {2018},
  abstract  = {Seit den 1990er-Jahren kommt direktdemokratischen Verfahren in der Bundesrepublik Deutschland auf Landes- wie auch auf kommunaler Ebene eine wachsende Bedeutung zu. Mit einer sukzessiven institutionellen {\"O}ffnung ging eine kontinuierlich ansteigende Anwendung dieser Beteiligungskan{\"a}le einher. Dabei l{\"a}sst sich auf subnationaler Ebene eine Vielzahl an Verfahrenskonstruktionen vorfinden, denen sich die vergleichende Direktdemokratieforschung in breiter Weise angenommen hat. Studien, die an Effekten und Wirkungen auf den politischen Entscheidungsprozess ansetzen, lassen sich bisher nur vereinzelt ausmachen. Die vorliegende Arbeit st{\"o}ßt in diese Forschungsl{\"u}cke und untersucht die Effekte von Volksgesetzgebungsverfahren auf den politischen Entscheidungsprozess in den Bundesl{\"a}ndern Brandenburg und Schleswig-Holstein. Auf zentralen konzeptionellen Modellierungen aufbauend, wird ein Analyseraster entwickelt, um policy-Effekte wie auch Modi der politischen Entscheidungsfindung zu identifizieren. Diese werden in Zusammenhang zur Zielrichtung der jeweiligen Verfahren gebracht (Agenda-Setting/Veto), um eine prozessuale Determination von policy-Effekten und eine inhaltliche Determination des Modus der politischen Entscheidungsfindung zu {\"u}berpr{\"u}fen.},
  subject      = {Direkte Demokratie},
  language  = {de}
}
@article{ButtStempfleListeretal.2020,
  author    = {Butt, Elke and Stempfle, Katrin and Lister, Lorenz and Wolf, Felix and Kraft, Marcella and Herrmann, Andreas B. and Viciano, Cristina Perpina and Weber, Christian and Hochhaus, Andreas and Ernst, Thomas and Hoffmann, Carsten and Zernecke, Alma and Frietsch, Jochen J.},
  title     = {Phosphorylation-dependent differences in CXCR4-LASP1-AKT1 interaction between breast cancer and chronic myeloid leukemia},
  series = {Cells},
  volume    = {9},
  journal   = {Cells},
  number    = {2},
  issn      = {2073-4409},
  doi       = {10.3390/cells9020444},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200638},
  year      = {2020},
  abstract  = {The serine/threonine protein kinase AKT1 is a downstream target of the chemokine receptor 4 (CXCR4), and both proteins play a central role in the modulation of diverse cellular processes, including proliferation and cell survival. While in chronic myeloid leukemia (CML) the CXCR4 is downregulated, thereby promoting the mobilization of progenitor cells into blood, the receptor is highly expressed in breast cancer cells, favoring the migratory capacity of these cells. Recently, the LIM and SH3 domain protein 1 (LASP1) has been described as a novel CXCR4 binding partner and as a promoter of the PI3K/AKT pathway. In this study, we uncovered a direct binding of LASP1, phosphorylated at S146, to both CXCR4 and AKT1, as shown by immunoprecipitation assays, pull-down experiments, and immunohistochemistry data. In contrast, phosphorylation of LASP1 at Y171 abrogated these interactions, suggesting that both LASP1 phospho-forms interact. Finally, findings demonstrating different phosphorylation patterns of LASP1 in breast cancer and chronic myeloid leukemia may have implications for CXCR4 function and tyrosine kinase inhibitor treatment.},
  language  = {en}
}
@article{LenzPahlHaucketal.2021,
  author    = {Lenz, Dominic and Pahl, Jens and Hauck, Fabian and Alameer, Seham and Balasubramanian, Meena and Baric, Ivo and Boy, Nikolas and Church, Joseph A. and Crushell, Ellen and Dick, Anke and Distelmaier, Felix and Gujar, Jidnyasa and Indolfi, Giuseppe and Lurz, Eberhard and Peters, Bianca and Schwerd, Tobias and Serranti, Daniele and K{\"o}lker, Stefan and Klein, Christoph and Hoffmann, Georg F. and Prokisch, Holger and Greil, Johann and Cerwenka, Adelheid and Giese, Thomas and Staufner, Christian},
  title     = {NBAS Variants Are Associated with Quantitative and Qualitative NK and B Cell Deficiency},
  series = {Journal of Clinical Immunology},
  volume    = {41},
  journal   = {Journal of Clinical Immunology},
  number    = {8},
  issn      = {0271-9142},
  doi       = {10.1007/s10875-021-01110-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-308362},
  pages     = {1781-1793},
  year      = {2021},
  abstract  = {Purpose Biallelic pathogenic NBAS variants manifest as a multisystem disorder with heterogeneous clinical phenotypes such as recurrent acute liver failure, growth retardation, and susceptibility to infections. This study explores how NBAS-associated disease affects cells of the innate and adaptive immune system. Methods Clinical and laboratory parameters were combined with functional multi-parametric immunophenotyping methods in fifteen NBAS-deficient patients to discover possible alterations in their immune system. Results Our study revealed reduced absolute numbers of mature CD56dim natural killer (NK) cells. Notably, the residual NK cell population in NBAS-deficient patients exerted a lower potential for activation and degranulation in response to K562 target cells, suggesting an NK cell-intrinsic role for NBAS in the release of cytotoxic granules. NBAS-deficient NK cell activation and degranulation was normalized upon pre-activation by IL-2 in vitro, suggesting that functional impairment was reversible. In addition, we observed a reduced number of na{\"i}ve B cells in the peripheral blood associated with hypogammaglobulinemia. Conclusion In summary, we demonstrate that pathogenic biallelic variants in NBAS are associated with dysfunctional NK cells as well as impaired adaptive humoral immunity.},
  language  = {en}
}