TY  - JOUR
A1  - Lüke, Florian
A1  - Haller, Florian
A1  - Utpatel, Kirsten
A1  - Krebs, Markus
A1  - Meidenbauer, Norbert
A1  - Scheiter, Alexander
A1  - Spoerl, Silvia
A1  - Heudobler, Daniel
A1  - Sparrer, Daniela
A1  - Kaiser, Ulrich
A1  - Keil, Felix
A1  - Schubart, Christoph
A1  - Tögel, Lars
A1  - Einhell, Sabine
A1  - Dietmaier, Wolfgang
A1  - Huss, Ralf
A1  - Dintner, Sebastian
A1  - Sommer, Sebastian
A1  - Jordan, Frank
A1  - Goebeler, Maria-Elisabeth
A1  - Metz, Michaela
A1  - Haake, Diana
A1  - Scheytt, Mithun
A1  - Gerhard-Hartmann, Elena
A1  - Maurus, Katja
A1  - Brändlein, Stephanie
A1  - Rosenwald, Andreas
A1  - Hartmann, Arndt
A1  - Märkl, Bruno
A1  - Einsele, Hermann
A1  - Mackensen, Andreas
A1  - Herr, Wolfgang
A1  - Kunzmann, Volker
A1  - Bargou, Ralf
A1  - Beckmann, Matthias W.
A1  - Pukrop, Tobias
A1  - Trepel, Martin
A1  - Evert, Matthias
A1  - Claus, Rainer
A1  - Kerscher, Alexander
T1  - Identification of disparities in personalized cancer care — a joint approach of the German WERA consortium
JF  - Cancers
N2  - (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 Würzburg, 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.
KW  - precision oncology
KW  - MTB
KW  - patient access
KW  - cancer care
KW  - outreach
KW  - real world data
KW  - outcomes research
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290311
SN  - 2072-6694
VL  - 14
IS  - 20
ER  - 
TY  - JOUR
A1  - Arndt, Andreas
A1  - Hoffacker, Peter
A1  - Zellmer, Konstantin
A1  - Goecer, Oktay
A1  - Recks, Mascha S.
A1  - Kuerten, Stefanie
T1  - Conventional Housing Conditions Attenuate the Development of Experimental Autoimmune Encephalomyelitis
JF  - PLoS ONE
N2  - BACKGROUND:
The etiology of multiple sclerosis (MS) has remained unclear, but a causative contribution of factors outside the central nervous system (CNS) is conceivable. It was recently suggested that gut bacteria trigger the activation of CNS-reactive T cells and the development of demyelinative disease.
METHODS:
C57BL/6 (B6) mice were kept either under specific pathogen free or conventional housing conditions, immunized with the myelin basic protein (MBP)-proteolipid protein (PLP) fusion protein MP4 and the development of EAE was clinically monitored. The germinal center size of the Peyer's patches was determined by immunohistochemistry in addition to the level of total IgG secretion which was assessed by ELISPOT. ELISPOT assays were also used to measure MP4-specific T cell and B cell responses in the Peyer's patches and the spleen. Ear swelling assays were performed to determine the extent of delayed-type hypersensitivity reactions in specific pathogen free and conventionally housed mice.
RESULTS:
In B6 mice that were actively immunized with MP4 and kept under conventional housing conditions clinical disease was significantly attenuated compared to specific pathogen free mice. Conventionally housed mice displayed increased levels of IgG secretion in the Peyer's patches, while the germinal center formation in the gut and the MP4-specific TH17 response in the spleen were diminished after immunization. Accordingly, these mice displayed an attenuated delayed type hypersensitivity (DTH) reaction in ear swelling assays.
CONCLUSIONS:
The data corroborate the notion that housing conditions play a substantial role in the induction of murine EAE and suggest that the presence of gut bacteria might be associated with a decreased immune response to antigens of lower affinity. This concept could be of importance for MS and calls for caution when considering the therapeutic approach to treat patients with antibiotics."
KW  - B cells
KW  - secretion
KW  - multiple sclerosis
KW  - enzyme-linked immunoassays
KW  - Peyer's patches
KW  - gut bacteria
KW  - T cells
KW  - immune response
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-119603
VL  - 9
IS  - 6
ER  - 
TY  - JOUR
A1  - Opolka, Alexander
A1  - Müller, Dominik
A1  - Fella, Christian
A1  - Balles, Andreas
A1  - Mohr, Jürgen
A1  - Last, Arndt
T1  - Multi-lens array full-field X-ray microscopy
JF  - Applied Sciences
N2  - X-ray full-field microscopy at laboratory sources for photon energies above 10 keV suffers from either long exposure times or low resolution. The photon flux is mainly limited by the objectives used, having a limited numerical aperture NA. We show that this can be overcome by making use of the cone-beam illumination of laboratory sources by imaging the same field of view (FoV) several times under slightly different angles using an array of X-ray lenses. Using this technique, the exposure time can be reduced drastically without any loss in terms of resolution. A proof-of-principle is given using an existing laboratory metal-jet source at the 9.25 keV Ga K\(_α\)-line and compared to a ray-tracing simulation of the setup.
KW  - X-ray microscopy
KW  - full-field microscopy
KW  - compound refractive X-ray lenses
KW  - CRLs
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-244974
SN  - 2076-3417
VL  - 11
IS  - 16
ER  - 
TY  - JOUR
A1  - Gröbner, Susanne N.
A1  - Worst, Barbara C.
A1  - Weischenfeldt, Joachim
A1  - Buchhalter, Ivo
A1  - Kleinheinz, Kortine
A1  - Rudneva, Vasilisa A.
A1  - Johann, Pascal D.
A1  - Balasubramanian, Gnana Prakash
A1  - Segura-Wang, Maia
A1  - Brabetz, Sebastian
A1  - Bender, Sebastian
A1  - Hutter, Barbara
A1  - Sturm, Dominik
A1  - Pfaff, Elke
A1  - Hübschmann, Daniel
A1  - Zipprich, Gideon
A1  - Heinold, Michael
A1  - Eils, Jürgen
A1  - Lawerenz, Christian
A1  - Erkek, Serap
A1  - Lambo, Sander
A1  - Waszak, Sebastian
A1  - Blattmann, Claudia
A1  - Borkhardt, Arndt
A1  - Kuhlen, Michaela
A1  - Eggert, Angelika
A1  - Fulda, Simone
A1  - Gessler, Manfred
A1  - Wegert, Jenny
A1  - Kappler, Roland
A1  - Baumhoer, Daniel
A1  - Stefan, Burdach
A1  - Kirschner-Schwabe, Renate
A1  - Kontny, Udo
A1  - Kulozik, Andreas E.
A1  - Lohmann, Dietmar
A1  - Hettmer, Simone
A1  - Eckert, Cornelia
A1  - Bielack, Stefan
A1  - Nathrath, Michaela
A1  - Niemeyer, Charlotte
A1  - Richter, Günther H.
A1  - Schulte, Johannes
A1  - Siebert, Reiner
A1  - Westermann, Frank
A1  - Molenaar, Jan J.
A1  - Vassal, Gilles
A1  - Witt, Hendrik
A1  - Burkhardt, Birgit
A1  - Kratz, Christian P.
A1  - Witt, Olaf
A1  - van Tilburg, Cornelis M.
A1  - Kramm, Christof M.
A1  - Fleischhack, Gudrun
A1  - Dirksen, Uta
A1  - Rutkowski, Stefan
A1  - Frühwald, Michael
A1  - Hoff, Katja von
A1  - Wolf, Stephan
A1  - Klingebeil, Thomas
A1  - Koscielniak, Ewa
A1  - Landgraf, Pablo
A1  - Koster, Jan
A1  - Resnick, Adam C.
A1  - Zhang, Jinghui
A1  - Liu, Yanling
A1  - Zhou, Xin
A1  - Waanders, Angela J.
A1  - Zwijnenburg, Danny A.
A1  - Raman, Pichai
A1  - Brors, Benedikt
A1  - Weber, Ursula D.
A1  - Northcott, Paul A.
A1  - Pajtler, Kristian W.
A1  - Kool, Marcel
A1  - Piro, Rosario M.
A1  - Korbel, Jan O.
A1  - Schlesner, Matthias
A1  - Eils, Roland
A1  - Jones, David T. W.
A1  - Lichter, Peter
A1  - Chavez, Lukas
A1  - Zapatka, Marc
A1  - Pfister, Stefan M.
T1  - The landscape of genomic alterations across childhood cancers
JF  - Nature
N2  - 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.
KW  - cancer genomics
KW  - oncogenesis
KW  - paediatric cancer
KW  - predictive markers
KW  - translational research
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229579
VL  - 555
ER  -