TY - JOUR A1 - Ferreira, Manuel A. A1 - Gamazon, Eric R. A1 - Al-Ejeh, Fares A1 - Aittomäki, Kristiina A1 - Andrulis, Irene L. A1 - Anton-Culver, Hoda A1 - Arason, Adalgeir A1 - Arndt, Volker A1 - Aronson, Kristan J. A1 - Arun, Banu K. A1 - Asseryanis, Ella A1 - Azzollini, Jacopo A1 - Balmaña, Judith A1 - Barnes, Daniel R. A1 - Barrowdale, Daniel A1 - Beckmann, Matthias W. A1 - Behrens, Sabine A1 - Benitez, Javier A1 - Bermisheva, Marina A1 - Bialkowska, Katarzyna A1 - Blomqvist, Carl A1 - Bogdanova, Natalia V. A1 - Bojesen, Stig E. A1 - Bolla, Manjeet K. A1 - Borg, Ake A1 - Brauch, Hiltrud A1 - Brenner, Hermann A1 - Broeks, Annegien A1 - Burwinkel, Barbara A1 - Caldés, Trinidad A1 - Caligo, Maria A. A1 - Campa, Daniele A1 - Campbell, Ian A1 - Canzian, Federico A1 - Carter, Jonathan A1 - Carter, Brian D. A1 - Castelao, Jose E. A1 - Chang-Claude, Jenny A1 - Chanock, Stephen J. A1 - Christiansen, Hans A1 - Chung, Wendy K. A1 - Claes, Kathleen B. M. A1 - Clarke, Christine L. A1 - Couch, Fergus J. A1 - Cox, Angela A1 - Cross, Simon S. A1 - Czene, Kamila A1 - Daly, Mary B. A1 - de la Hoya, Miguel A1 - Dennis, Joe A1 - Devilee, Peter A1 - Diez, Orland A1 - Dörk, Thilo A1 - Dunning, Alison M. A1 - Dwek, Miriam A1 - Eccles, Diana M. A1 - Ejlertsen, Bent A1 - Ellberg, Carolina A1 - Engel, Christoph A1 - Eriksson, Mikael A1 - Fasching, Peter A. A1 - Fletcher, Olivia A1 - Flyger, Henrik A1 - Friedman, Eitan A1 - Frost, Debra A1 - Gabrielson, Marike A1 - Gago-Dominguez, Manuela A1 - Ganz, Patricia A. A1 - Gapstur, Susan M. A1 - Garber, Judy A1 - García-Closas, Montserrat A1 - García-Sáenz, José A. A1 - Gaudet, Mia M. A1 - Giles, Graham G. A1 - Glendon, Gord A1 - Godwin, Andrew K. A1 - Goldberg, Mark S. A1 - Goldgar, David E. A1 - González-Neira, Anna A1 - Greene, Mark H. A1 - Gronwald, Jacek A1 - Guenél, Pascal A1 - Haimann, Christopher A. A1 - Hall, Per A1 - Hamann, Ute A1 - He, Wei A1 - Heyworth, Jane A1 - Hogervorst, Frans B. L. A1 - Hollestelle, Antoinette A1 - Hoover, Robert N. A1 - Hopper, John L. A1 - Hulick, Peter J. A1 - Humphreys, Keith A1 - Imyanitov, Evgeny N. A1 - Isaacs, Claudine A1 - Jakimovska, Milena A1 - Jakubowska, Anna A1 - James, Paul A. A1 - Janavicius, Ramunas A1 - Jankowitz, Rachel C. A1 - John, Esther M. A1 - Johnson, Nichola A1 - Joseph, Vijai A1 - Karlan, Beth Y. A1 - Khusnutdinova, Elza A1 - Kiiski, Johanna I. A1 - Ko, Yon-Dschun A1 - Jones, Michael E. A1 - Konstantopoulou, Irene A1 - Kristensen, Vessela N. A1 - Laitman, Yael A1 - Lambrechts, Diether A1 - Lazaro, Conxi A1 - Leslie, Goska A1 - Lester, Jenny A1 - Lesueur, Fabienne A1 - Lindström, Sara A1 - Long, Jirong A1 - Loud, Jennifer T. A1 - Lubiński, Jan A1 - Makalic, Enes A1 - Mannermaa, Arto A1 - Manoochehri, Mehdi A1 - Margolin, Sara A1 - Maurer, Tabea A1 - Mavroudis, Dimitrios A1 - McGuffog, Lesley A1 - Meindl, Alfons A1 - Menon, Usha A1 - Michailidou, Kyriaki A1 - Miller, Austin A1 - Montagna, Marco A1 - Moreno, Fernando A1 - Moserle, Lidia A1 - Mulligan, Anna Marie A1 - Nathanson, Katherine L. A1 - Neuhausen, Susan L. A1 - Nevanlinna, Heli A1 - Nevelsteen, Ines A1 - Nielsen, Finn C. A1 - Nikitina-Zake, Liene A1 - Nussbaum, Robert L. A1 - Offit, Kenneth A1 - Olah, Edith A1 - Olopade, Olufunmilayo I. A1 - Olsson, Håkan A1 - Osorio, Ana A1 - Papp, Janos A1 - Park-Simon, Tjoung-Won A1 - Parsons, Michael T. A1 - Pedersen, Inge Sokilde A1 - Peixoto, Ana A1 - Peterlongo, Paolo A1 - Pharaoh, Paul D. P. A1 - Plaseska-Karanfilska, Dijana A1 - Poppe, Bruce A1 - Presneau, Nadege A1 - Radice, Paolo A1 - Rantala, Johanna A1 - Rennert, Gad A1 - Risch, Harvey A. A1 - Saloustros, Emmanouil A1 - Sanden, Kristin A1 - Sawyer, Elinor J. A1 - Schmidt, Marjanka K. A1 - Schmutzler, Rita K. A1 - Sharma, Priyanka A1 - Shu, Xiao-Ou A1 - Simard, Jaques A1 - Singer, Christian F. A1 - Soucy, Penny A1 - Southey, Melissa C. A1 - Spinelli, John J. A1 - Spurdle, Amanda B. A1 - Stone, Jennifer A1 - Swerdlow, Anthony J. A1 - Tapper, William J. A1 - Taylor, Jack A. A1 - Teixeira, Manuel R. A1 - Terry, Mary Beth A1 - Teulé, Alex A1 - Thomassen, Mads A1 - Thöne, Kathrin A1 - Thull, Darcy L. A1 - Tischkowitz, Marc A1 - Toland, Amanda E. A1 - Torres, Diana A1 - Truong, Thérèse A1 - Tung, Nadine A1 - Vachon, Celine M. A1 - van Asperen, Christi J. A1 - van den Ouweland, Ans M. W. A1 - van Rensburg, Elizabeth J. A1 - Vega, Ana A1 - Viel, Alexandra A1 - Wang, Qin A1 - Wappenschmidt, Barbara A1 - Weitzel, Jeffrey N. A1 - Wendt, Camilla A1 - Winqvist, Robert A1 - Yang, Xiaohong R. A1 - Yannoukakos, Drakoulis A1 - Ziogas, Argyrios A1 - Kraft, Peter A1 - Antoniou, Antonis C. A1 - Zheng, Wei A1 - Easton, Douglas F. A1 - Milne, Roger L. A1 - Beesley, Jonathan A1 - Chenevix-Trench, Georgia T1 - Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer JF - Nature Communications N2 - Genome-wide association studies (GWAS) have identified more than 170 breast cancer susceptibility loci. Here we hypothesize that some risk-associated variants might act in non-breast tissues, specifically adipose tissue and immune cells from blood and spleen. Using expression quantitative trait loci (eQTL) reported in these tissues, we identify 26 previously unreported, likely target genes of overall breast cancer risk variants, and 17 for estrogen receptor (ER)-negative breast cancer, several with a known immune function. We determine the directional effect of gene expression on disease risk measured based on single and multiple eQTL. In addition, using a gene-based test of association that considers eQTL from multiple tissues, we identify seven (and four) regions with variants associated with overall (and ER-negative) breast cancer risk, which were not reported in previous GWAS. Further investigation of the function of the implicated genes in breast and immune cells may provide insights into the etiology of breast cancer. KW - cancer KW - genetics Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-228024 VL - 10 ER - TY - JOUR A1 - Dörk, Thilo A1 - Peterlongo, Peter A1 - Mannermaa, Arto A1 - Bolla, Manjeet K. A1 - Wang, Qin A1 - Dennis, Joe A1 - Ahearn, Thomas A1 - Andrulis, Irene L. A1 - Anton-Culver, Hoda A1 - Arndt, Volker A1 - Aronson, Kristan J. A1 - Augustinsson, Annelie A1 - Beane Freeman, Laura E. A1 - Beckmann, Matthias W. A1 - Beeghly-Fadiel, Alicia A1 - Behrens, Sabine A1 - Bermisheva, Marina A1 - Blomqvist, Carl A1 - Bogdanova, Natalia V. A1 - Bojesen, Stig E. A1 - Brauch, Hiltrud A1 - Brenner, Hermann A1 - Burwinkel, Barbara A1 - Canzian, Federico A1 - Chan, Tsun L. A1 - Chang-Claude, Jenny A1 - Chanock, Stephen J. A1 - Choi, Ji-Yeob A1 - Christiansen, Hans A1 - Clarke, Christine L. A1 - Couch, Fergus J. A1 - Czene, Kamila A1 - Daly, Mary B. A1 - dos-Santos-Silva, Isabel A1 - Dwek, Miriam A1 - Eccles, Diana M. A1 - Ekici, Arif B. A1 - Eriksson, Mikael A1 - Evans, D. Gareth A1 - Fasching, Peter A. A1 - Figueroa, Jonine A1 - Flyger, Henrik A1 - Fritschi, Lin A1 - Gabrielson, Marike A1 - Gago-Dominguez, Manuela A1 - Gao, Chi A1 - Gapstur, Susan M. A1 - García-Closas, Montserrat A1 - García-Sáenz, José A. A1 - Gaudet, Mia M. A1 - Giles, Graham G. A1 - Goldberg, Mark S. A1 - Goldgar, David E. A1 - Guenél, Pascal A1 - Haeberle, Lothar A1 - Haimann, Christopher A. A1 - Håkansson, Niclas A1 - Hall, Per A1 - Hamann, Ute A1 - Hartman, Mikael A1 - Hauke, Jan A1 - Hein, Alexander A1 - Hillemanns, Peter A1 - Hogervorst, Frans B. L. A1 - Hooning, Maartje J. A1 - Hopper, John L. A1 - Howell, Tony A1 - Huo, Dezheng A1 - Ito, Hidemi A1 - Iwasaki, Motoki A1 - Jakubowska, Anna A1 - Janni, Wolfgang A1 - John, Esther M. A1 - Jung, Audrey A1 - Kaaks, Rudolf A1 - Kang, Daehee A1 - Kapoor, Pooja Middha A1 - Khusnutdinova, Elza A1 - Kim, Sung-Won A1 - Kitahara, Cari M. A1 - Koutros, Stella A1 - Kraft, Peter A1 - Kristensen, Vessela N. A1 - Kwong, Ava A1 - Lambrechts, Diether A1 - Le Marchand, Loic A1 - Li, Jingmei A1 - Lindström, Sara A1 - Linet, Martha A1 - Lo, Wing-Yee A1 - Long, Jirong A1 - Lophatananon, Artitaya A1 - Lubiński, Jan A1 - Manoochehri, Mehdi A1 - Manoukian, Siranoush A1 - Margolin, Sara A1 - Martinez, Elena A1 - Matsuo, Keitaro A1 - Mavroudis, Dimitris A1 - Meindl, Alfons A1 - Menon, Usha A1 - Milne, Roger L. A1 - Mohd Taib, Nur Aishah A1 - Muir, Kenneth A1 - Mulligan, Anna Marie A1 - Neuhausen, Susan L. A1 - Nevanlinna, Heli A1 - Neven, Patrick A1 - Newman, William G. A1 - Offit, Kenneth A1 - Olopade, Olufunmilayo I. A1 - Olshan, Andrew F. A1 - Olson, Janet E. A1 - Olsson, Håkan A1 - Park, Sue K. A1 - Park-Simon, Tjoung-Won A1 - Peto, Julian A1 - Plaseska-Karanfilska, Dijana A1 - Pohl-Rescigno, Esther A1 - Presneau, Nadege A1 - Rack, Brigitte A1 - Radice, Paolo A1 - Rashid, Muhammad U. A1 - Rennert, Gad A1 - Rennert, Hedy S. A1 - Romero, Atocha A1 - Ruebner, Matthias A1 - Saloustros, Emmanouil A1 - Schmidt, Marjanka K. A1 - Schmutzler, Rita K. A1 - Schneider, Michael O. A1 - Schoemaker, Minouk J. A1 - Scott, Christopher A1 - Shen, Chen-Yang A1 - Shu, Xiao-Ou A1 - Simard, Jaques A1 - Slager, Susan A1 - Smichkoska, Snezhana A1 - Southey, Melissa C. A1 - Spinelli, John J. A1 - Stone, Jennifer A1 - Surowy, Harald A1 - Swerdlow, Anthony J. A1 - Tamimi, Rulla M. A1 - Tapper, William J. A1 - Teo, Soo H. A1 - Terry, Mary Beth A1 - Toland, Amanda E. A1 - Tollenaar, Rob A. E. M. A1 - Torres, Diana A1 - Torres-Mejía, Gabriela A1 - Troester, Melissa A. A1 - Truong, Thérèse A1 - Tsugane, Shoichiro A1 - Untch, Michael A1 - Vachon, Celine M. A1 - van den Ouweland, Ans M. W. A1 - van Veen, Elke M. A1 - Vijai, Joseph A1 - Wendt, Camilla A1 - Wolk, Alicja A1 - Yu, Jyh-Cherng A1 - Zheng, Wei A1 - Ziogas, Argyrios A1 - Ziv, Elad A1 - Dunnig, Alison A1 - Pharaoh, Paul D. P. A1 - Schindler, Detlev A1 - Devilee, Peter A1 - Easton, Douglas F. T1 - Two truncating variants in FANCC and breast cancer risk JF - Scientific Reports N2 - Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44–1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants. KW - oncology KW - risk factors Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222838 VL - 9 ER - TY - JOUR A1 - Jungwirth, Gerhard A1 - Yu, Tao A1 - Moustafa, Mahmoud A1 - Rapp, Carmen A1 - Warta, Rolf A1 - Jungk, Christine A1 - Sahm, Felix A1 - Dettling, Steffen A1 - Zweckberger, Klaus A1 - Lamszus, Katrin A1 - Senft, Christian A1 - Loehr, Mario A1 - Keßler, Almuth F. A1 - Ketter, Ralf A1 - Westphal, Manfred A1 - Debus, Juergen A1 - von Deimling, Andreas A1 - Simon, Matthias A1 - Unterberg, Andreas A1 - Abdollahi, Amir A1 - Herold-Mende, Christel T1 - Identification of KIF11 as a Novel Target in Meningioma JF - Cancers N2 - Kinesins play an important role in many physiological functions including intracellular vesicle transport and mitosis. The emerging role of kinesins in different cancers led us to investigate the expression and functional role of kinesins in meningioma. Therefore, we re-analyzed our previous microarray dataset of benign, atypical, and anaplastic meningiomas (n = 62) and got evidence for differential expression of five kinesins (KIFC1, KIF4A, KIF11, KIF14 and KIF20A). Further validation in an extended study sample (n = 208) revealed a significant upregulation of these genes in WHO°I to °III meningiomas (WHO°I n = 61, WHO°II n = 88, and WHO°III n = 59), which was most pronounced in clinically more aggressive tumors of the same WHO grade. Immunohistochemical staining confirmed a WHO grade-associated upregulated protein expression in meningioma tissues. Furthermore, high mRNA expression levels of KIFC1, KIF11, KIF14 and KIF20A were associated with shorter progression-free survival. On a functional level, knockdown of kinesins in Ben-Men-1 cells and in the newly established anaplastic meningioma cell line NCH93 resulted in a significantly inhibited tumor cell proliferation upon siRNA-mediated downregulation of KIF11 in both cell lines by up to 95% and 71%, respectively. Taken together, in this study we were able to identify the prognostic and functional role of several kinesin family members of which KIF11 exhibits the most promising properties as a novel prognostic marker and therapeutic target, which may offer new treatment options for aggressive meningiomas. KW - meningioma KW - KIF KW - kinesin KW - KIF11 KW - NCH93 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197402 SN - 2072-6694 VL - 11 IS - 4 ER - TY - JOUR A1 - Wittmann, Katharina A1 - Sieber, Cornel A1 - von Stengel, Simon A1 - Kohl, Matthias A1 - Freiberger, Ellen A1 - Jakob, Franz A1 - Lell, Michael A1 - Engelke, Klaus A1 - Kemmler, Wolfgang T1 - Impact of whole body electromyostimulation on cardiometabolic risk factors in older women with sarcopenic obesity: the randomized controlled FORMOsA-sarcopenic obesity study JF - Clinical Interventions in Aging N2 - Background: Sarcopenic obesity (SO) is characterized by a combination of low muscle and high fat mass with an additive negative effect of both conditions on cardiometabolic risk. The aim of the study was to determine the effect of whole-body electromyostimulation (WB-EMS) on the metabolic syndrome (MetS) in community-dwelling women aged ≥70 years with SO. Methods: The study was conducted in an ambulatory university setting. Seventy-five community-dwelling women aged ≥70 years with SO living in Northern Bavaria, Germany, were randomly allocated to either 6 months of WB-EMS application with (WB-EMS&P) or without (WB-EMS) dietary supplementation (150 kcal/day, 56% protein) or a non-training control group (CG). WB-EMS included one session of 20 min (85 Hz, 350 µs, 4 s of strain–4 s of rest) per week with moderate-to-high intensity. The primary study endpoint was the MetS Z-score with the components waist circumference (WC), mean arterial pressure (MAP), triglycerides, fasting plasma glucose, and high-density lipoprotein cholesterol (HDL-C); secondary study endpoints were changes in these determining variables. Results: MetS Z-score decreased in both groups; however, changes compared with the CG were significant (P=0.001) in the WB-EMS&P group only. On analyzing the components of the MetS, significant positive effects for both WB-EMS groups (P≤0.038) were identified for MAP, while the WB-EMS group significantly differed for WC (P=0.036), and the WB-EMS&P group significantly differed for HDL-C (P=0.006) from the CG. No significant differences were observed between the WB-EMS groups. Conclusion: The study clearly confirms the favorable effect of WB-EMS application on the MetS in community-dwelling women aged ≥70 years with SO. However, protein-enriched supplements did not increase effects of WB-EMS alone. In summary, we considered this novel technology an effective and safe method to prevent cardiometabolic risk factors and diseases in older women unable or unwilling to exercise conventionally. KW - sarcopenia KW - obesity KW - whole-body electromyostimulation KW - cardiovascular KW - metabolic risk KW - metabolic syndrome KW - community-dwelling KW - older people Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164930 VL - 11 ER - TY - INPR A1 - Müller, Stefan A1 - Draeger, Simon A1 - Ma, Kiaonan A1 - Hensen, Matthias A1 - Kenneweg, Tristan A1 - Pfeiffer, Walter A1 - Brixner, Tobias T1 - Fluorescence-Detected Two-Quantum and One-Quantum-Two-Quantum 2D Electronic Spectroscopy T2 - Journal of Physical Chemistry Letters N2 - We demonstrate two-quantum (2Q) coherent two-dimensional (2D)electronic spectroscopy using a shot-to-shot-modulated pulse shaper and fluorescence detection. Broadband collinear excitation is realized with the supercontinuum output of an argon-filled hollow-core fiber, enabling us to excite multiple transitions simultaneously in the visible range. The 2Q contribution is extracted via a three-pulse sequence with 16-fold phase cycling and simulated employing cresyl violet as a model system. Furthermore, we report the first experimental realization of one-quantum−two-quantum (1Q-2Q) 2D spectroscopy, offering less congested spectra as compared with the 2Q implementation. We avoid scattering artifacts and nonresonant solvent contributions by using fluorescence as the observable. This allows us to extract quantitative information about doubly excited states that agree with literature expectations. The high sensitivity and background-free nature of fluorescence detection allow for a general applicability of this method to many other systems. KW - Zweidimensionale Spektroskopie KW - elektronisch angeregte Zustände KW - Doppelquantenkohärenz KW - Fluoreszenz KW - Optische Spektroskopie KW - Molekülzustand Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-173468 UR - https://pubs.acs.org/doi/10.1021/acs.jpclett.8b00541 ER - TY - RPRT A1 - Hochrein, Simon A1 - Muther, Matthias A1 - Bogaschewsky, Ronald T1 - The Performance Impact of Strategy Alignment in Purchasing and Supply Management: Systematic Review, Construct Analysis and Development of a New Overall Alignment Index N2 - Das vorliegende Working Paper untersucht die Performancewirkung eines multi-dimensionalen Strategie-Alignments in der Beschaffung. Hierfür wird zunächst ein Systematischer Literatur Review durchgeführt und der Wissenstand im Forschungsfeld erhoben. Die systematische Klassifikation, Analyse, Bewertung und Synthese der identifizierten 29 empirischen Studien erfolgt dabei auf der Grundlage eines konzeptionellen Frameworks und zugehöriger Inhaltskategorien sowie weiterer methodischer Vergleichsgrößen. Die Ergebnisse dieser Untersuchung zeigen nachdrücklich auf, dass eine Abstimmung, Harmonisierung und Verbindung von Beschaffungsstrategien (1) mit den übergeordneten Unternehmenszielen und -strategien, (2) anderen funktionalen Teilbereichen, sowie (3) der Lieferantenbasis (unter Berücksichtigung der kontextbezogenen Anforderungen und Gegebenheiten) zu signifikant positiven Performance-Effekten beiträgt. Insofern sollten die Empfehlungen dieser Untersuchung für ein holistisches Strategie-Alignment im Einkauf herangezogen werden. Neben der Ableitung von Implikationen für die Unternehmenspraxis wird eine Forschungsagenda für interessierte Wissenschaftler erarbeitet, indem inhaltliche Wissenslücken und methodische Verbesserungspotenziale auf Basis des Bezugsrahmens und einschlägiger Referenztexte definiert sowie zukünftige Forschungsbedarfe aufgezeigt werden. Darauf aufbauend wird die zentrale (bis dato unbeantwortete) Forschungsfrage eines integrativen Strategie-Alignment-Index durch die Operationalisierung der zugehörigen Konstrukte sowie der Formulierung entsprechender Hypothesen als Grundlage für die Durchführung einer empirischen Studie adressiert. T3 - Working Paper Series of the Institute of Business Management - 3 KW - Beschaffung KW - Einkauf KW - Empirische Forschung KW - Alignment KW - Effizienz KW - Outcomes KW - Procurement KW - Sourcing KW - Purchasing KW - Literature Review KW - State-of-the-Art KW - Systematischer Überblick KW - Supply Management Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-103649 SN - ISSN: 2199-0328 ER - TY - JOUR A1 - Dech, Stefan A1 - Holzwarth, Stefanie A1 - Asam, Sarah A1 - Andresen, Thorsten A1 - Bachmann, Martin A1 - Boettcher, Martin A1 - Dietz, Andreas A1 - Eisfelder, Christina A1 - Frey, Corinne A1 - Gesell, Gerhard A1 - Gessner, Ursula A1 - Hirner, Andreas A1 - Hofmann, Matthias A1 - Kirches, Grit A1 - Klein, Doris A1 - Klein, Igor A1 - Kraus, Tanja A1 - Krause, Detmar A1 - Plank, Simon A1 - Popp, Thomas A1 - Reinermann, Sophie A1 - Reiners, Philipp A1 - Roessler, Sebastian A1 - Ruppert, Thomas A1 - Scherbachenko, Alexander A1 - Vignesh, Ranjitha A1 - Wolfmueller, Meinhard A1 - Zwenzner, Hendrik A1 - Kuenzer, Claudia T1 - Potential and challenges of harmonizing 40 years of AVHRR data: the TIMELINE experience JF - Remote Sensing N2 - Earth Observation satellite data allows for the monitoring of the surface of our planet at predefined intervals covering large areas. However, there is only one medium resolution sensor family in orbit that enables an observation time span of 40 and more years at a daily repeat interval. This is the AVHRR sensor family. If we want to investigate the long-term impacts of climate change on our environment, we can only do so based on data that remains available for several decades. If we then want to investigate processes with respect to climate change, we need very high temporal resolution enabling the generation of long-term time series and the derivation of related statistical parameters such as mean, variability, anomalies, and trends. The challenges to generating a well calibrated and harmonized 40-year-long time series based on AVHRR sensor data flown on 14 different platforms are enormous. However, only extremely thorough pre-processing and harmonization ensures that trends found in the data are real trends and not sensor-related (or other) artefacts. The generation of European-wide time series as a basis for the derivation of a multitude of parameters is therefore an extremely challenging task, the details of which are presented in this paper. KW - AVHRR KW - Earth Observation KW - harmonization KW - time series analysis KW - climate related trends KW - automatic processing KW - Europe KW - TIMELINE Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-246134 SN - 2072-4292 VL - 13 IS - 18 ER - TY - JOUR A1 - Ramachandran, Sarada Devi A1 - Schirmer, Katharina A1 - Münst, Bernhard A1 - Heinz, Stefan A1 - Ghafoory, Shahrouz A1 - Wölfl, Stefan A1 - Simon-Keller, Katja A1 - Marx, Alexander A1 - Øie, Cristina Ionica A1 - Ebert, Matthias P. A1 - Walles, Heike A1 - Braspenning, Joris A1 - Breitkopf-Heinlein, Katja T1 - In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells JF - PLoS One N2 - In this study we used differentiated adult human upcyte (R) cells for the in vitro generation of liver organoids. Upcyte (R) cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte (R) process). Proliferating upcyte (R) cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte (R) cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel\(^{TM}\), they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions. KW - adults KW - enzyme metabolism KW - albumins KW - primary cells KW - induction KW - expression KW - human heptocytes KW - mesenchymal stem cells KW - oragnoids KW - heptaocytes KW - drug metabolism Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139552 VL - 10 IS - 10 ER - TY - JOUR A1 - Harter, Patrick N. A1 - Bernatz, Simon A1 - Scholz, Alexander A1 - Zeiner, Pia S. A1 - Zinke, Jenny A1 - Kiyose, Makoto A1 - Blasel, Stella A1 - Beschorner, Rudi A1 - Senft, Christian A1 - Bender, Benjamin A1 - Ronellenfitsch, Michael W. A1 - Wikman, Harriet A1 - Glatzel, Markus A1 - Meinhardt, Matthias A1 - Juratli, Tareq A. A1 - Steinbach, Joachim P. A1 - Plate, Karl H. A1 - Wischhusen, Jörg A1 - Weide, Benjamin A1 - Mittelbronn, Michel T1 - Distribution and prognostic relevance of tumor-infiltrating lymphocytes (TILs) and PD-1/PD-L1 immune checkpoints in human brain metastases JF - Oncotarget N2 - The activation of immune cells by targeting checkpoint inhibitors showed promising results with increased patient survival in distinct primary cancers. Since only limited data exist for human brain metastases, we aimed at characterizing tumor infiltrating lymphocytes (TILs) and expression of immune checkpoints in the respective tumors. Two brain metastases cohorts, a mixed entity cohort (n = 252) and a breast carcinoma validation cohort (n = 96) were analyzed for CD3+, CD8+, FOXP3+, PD-1+ lymphocytes and PD-L1+ tumor cells by immunohistochemistry. Analyses for association with clinico-epidemiological and neuroradiological parameters such as patient survival or tumor size were performed. TILs infiltrated brain metastases in three different patterns (stromal, peritumoral, diffuse). While carcinomas often show a strong stromal infiltration, TILs in melanomas often diffusely infiltrate the tumors. Highest levels of CD3+ and CD8+ lymphocytes were seen in renal cell carcinomas (RCC) and strongest PD-1 levels on RCCs and melanomas. High amounts of TILs, high ratios of PD-1+/CD8+ cells and high levels of PD-L1 were negatively correlated with brain metastases size, indicating that in smaller brain metastases CD8+ immune response might get blocked. PD-L1 expression strongly correlated with TILs and FOXP3 expression. No significant association of patient survival with TILs was observed, while high levels of PD-L1 showed a strong trend towards better survival in melanoma brain metastases (Log-Rank p = 0.0537). In summary, melanomas and RCCs seem to be the most immunogenic entities. Differences in immunotherapeutic response between tumor entities regarding brain metastases might be attributable to this finding and need further investigation in larger patient cohorts. KW - B7-H1 KW - PD-L1 KW - immunoresistance KW - immunosurveillance KW - safety KW - survival KW - expression KW - melanoma KW - breast cancer KW - PC-1 blockade KW - cell lung cancer KW - tumor-infiltrating lymphocytes KW - brain metastases KW - PD-1 Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137107 VL - 6 IS - 38 SP - 40836 EP - 40849 ER - TY - JOUR A1 - Ueberschaar, Simon A1 - Goebeler, Matthias A1 - Kneitz, Hermann T1 - CD10-Positive Cutaneous PEComa: An Extremely Rare Skin Tumour JF - Case Reports in Dermatology N2 - We here present the case of a 67-year-old woman with a history of a slowly progressive, polypous nodule on her left wrist. The lesion was excised, and the histological analysis revealed a clear cell tumour that was relatively sharply demarked from the surrounding tissue extending into the subcutaneous tissue. The tumour showed a characteristic trabecular pattern in which the tumour cells were arranged around numerous vessels. The neoplastic cells had a predominantly epithelioid shape, granular eosinophilic to clear cytoplasm and prominent centrally located nucleoli. The histological differential diagnosis included a metastatic clear-cell renal cell carcinoma and a primary cutaneous perivascular epithelioid cell tumour (PEComa). Immunohistochemically, the tumour cells revealed homogenous expression of HMB-45, MiTF and CD10, whereas MART-1 and S100 were negative. Antibodies against actin marked the trabecularly arranged vessels, and the neoplastic cells yielded a patchy positivity against actin and desmin. Additional immunohistochemical stains against pan-cytokeratin, CAIX, PAX-8 and EMA were negative. Based on the morphologic and immunophenotypic findings, the histological diagnosis of a CD10-positive cutaneous PEComa was made. KW - PEComa KW - cutaneous PEComa KW - Skin KW - CD10 KW - perivascular epitheloid cell tumour Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236151 VL - 12 ER - TY - RPRT A1 - Hochrein, Simon A1 - Bogaschewsky, Ronald A1 - Heider, Matthias T1 - Supply Chain Management Reviews N2 - Diese Arbeit untersucht Literatur Reviews (LRs) im Forschungsfeld des Supply Chain Managements (SCM). Hierfür werden zunächst die methodischen und terminologischen Grundlagen der Analyse erarbeitet sowie taxonomische und thematische Klassifikati-onsschemata vergleichend gegenübergestellt. Anschließend werden der LR-Prozess dieser Untersuchung und ausgewählte Evaluationsdimensionen definiert. Auf diesen grundlegenden Vorarbeiten aufbauend werden LRs des SCM identifiziert, klassifiziert und umfassend bewertet. Die Forschungsergebnisse zeigen, dass es narrativen LRs teil-weise an methodischer Genauigkeit mangelt und infolgedessen die Technik des syste-matischen LR zunehmend an Bedeutung gewinnt. Darüber hinaus dient diese Arbeit als Bewertungsraster zur Evaluation der methodischen Güte von LRs, als Leitlinie zur Er-stellung von systematischen LRs und als State-of-the-Art der Sekundärforschung im SCM. T3 - Working Paper Series of the Institute of Business Management - 2 KW - Supply chain management KW - Supply Chain KW - Literatur Review KW - Systematischer (Literatur) Review KW - Meta-Analyse KW - State-of-the-Art KW - Systematischer Überblick KW - Tertiärstudie Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-95577 SN - 2199-0328 ER - TY - JOUR A1 - Kemmler, Wolfgang A1 - Kohl, Matthias A1 - Jakob, Franz A1 - Engelke, Klaus A1 - Stengel, Simon von T1 - Effects of high intensity dynamic resistance exercise and whey protein supplements on osteosarcopenia in older men with low bone and muscle mass. Final results of the randomized controlled FrOST study JF - Nutrients N2 - The present study aimed to evaluate the effect of high intensity dynamic resistance exercise (HIT-DRT) and whey protein supplementation (WPS) on bone mineral density (BMD) and sarcopenia parameters in osteosarcopenic men. Men ≥ 72 years with osteosarcopenia (n = 43) were randomly assigned to a HIT-RT (HIT-RT: n = 21) or a non-training control group (n = 22). Supervised HIT-RT twice/week was applied for 18 months, while the control group maintained their habitual lifestyle. Supplying WPS, total protein intake amounted to 1.5–1.6 (HIT-RT) and 1.2 g/kg/body mass/d (control). Both groups were supplied with calcium and vitamin D. Primary study outcomes were BMD and the sarcopenia Z-score. After adjusting for multiplicity, we observed significant positive effects for sarcopenia Z-score (standardized mean difference (SMD): 1.40), BMD at lumbar spine (SMD: 0.72) and total hip (SMD: 0.72). In detail, effect sizes for skeletal muscle mass changes were very pronounced (1.97, p < 0.001), while effects for functional sarcopenia parameters were moderate (0.87, p = 0.008; handgrip strength) or low (0.39, p = 0.209; gait velocity). Apart from one man who reported short periods of temporary worsening of existing joint pain, no HIT-RT/WPS-related adverse effects or injuries were reported. We consider HIT-RT supported by whey protein supplementation as a feasible, attractive, safe and highly effective option to fight osteosarcopenia in older men. KW - resistance exercise KW - osteopenia KW - sarcopenia KW - bone mineral density Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-211108 SN - 2072-6643 VL - 12 IS - 8 ER - TY - JOUR A1 - Ullherr, Maximilian A1 - Diez, Matthias A1 - Zabler, Simon T1 - Robust image reconstruction strategy for multiscalar holotomography JF - Journal of Imaging N2 - Holotomography is an extension of computed tomography where samples with low X-ray absorption can be investigated with higher contrast. In order to achieve this, the imaging system must yield an optical resolution of a few micrometers or less, which reduces the measurement area (field of view = FOV) to a few mm at most. If the sample size, however, exceeds the field of view (called local tomography or region of interest = ROI CT), filter problems arise during the CT reconstruction and phase retrieval in holotomography. In this paper, we will first investigate the practical impact of these filter problems and discuss approximate solutions. Secondly, we will investigate the effectiveness of a technique we call “multiscalar holotomography”, where, in addition to the ROI CT, a lower resolution non-ROI CT measurement is recorded. This is used to avoid the filter problems while simultaneously reconstructing a larger part of the sample, albeit with a lower resolution in the additional area. KW - reconstruction KW - region of interest KW - ROI KW - multiscalar holotomography KW - holotomography KW - computed tomography KW - CT KW - X-ray Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262112 SN - 2313-433X VL - 8 IS - 2 ER - TY - JOUR A1 - Vogel, Patrick A1 - Markert, Jonathan A1 - Rückert, Martin A. A1 - Herz, Stefan A1 - Keßler, Benedikt A1 - Dremel, Kilian A1 - Althoff, Daniel A1 - Weber, Matthias A1 - Buzug, Thorsten M. A1 - Bley, Thorsten A. A1 - Kullmann, Walter H. A1 - Hanke, Randolf A1 - Zabler, Simon A1 - Behr, Volker C. T1 - Magnetic Particle Imaging meets computed tomography: first simultaneous imaging JF - Scientific Reports N2 - Magnetic Particle Imaging (MPI) is a promising new tomographic modality for fast as well as three-dimensional visualization of magnetic material. For anatomical or structural information an additional imaging modality such as computed tomography (CT) is required. In this paper, the first hybrid MPI-CT scanner for multimodal imaging providing simultaneous data acquisition is presented. KW - Applied physics KW - Biomedical engineering KW - Imaging techniques Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202501 VL - 9 ER - TY - JOUR A1 - Kusan, Simon A1 - Surat, Güzin A1 - Kelm, Matthias A1 - Anger, Friedrich A1 - Kim, Mia A1 - Germer, Christoph-Thomas A1 - Schlegel, Nicolas A1 - Flemming, Sven T1 - Microbial spectrum and antibiotic resistance in patients suffering from penetrating Crohn's disease JF - Journal of Clinical Medicine N2 - Intraabdominal abscess formation occurs in up to 30% of patients suffering from Crohn's disease (CD). While international guidelines recommend a step-up approach with a combination of empiric antibiotic therapy and percutaneous drainage to delay or even avoid surgery, evidence about microbial spectrum in penetrating ileitis is sparse. We retrospectively assessed outcomes of 46 patients with terminal penetrating Ileitis where microbial diagnostics have been performed and compared microbial spectrum and antibiotic resistance profile of CD patients with patients suffering from diverticulitis with intraabdominal abscess formation. In both groups, the most frequently isolated pathogen was the gram-negative bacterium E. coli belonging to the family of Enterobacterales. However, overall Enterobacterales were significantly more often verifiable in the control group than in CD patients. Furthermore, microbial analysis showed significant differences regarding isolation of anaerobic pathogens with decreased frequency in patients with CD. Subgroup analysis of CD patients to evaluate a potential influence of immunosuppressive therapy on microbial spectrum only revealed that Enterobacterales was less frequently detected in patients treated with steroids. Immunosuppressive therapy did not show any impact on all other groups of pathogens and did not change antibiotic resistance profile of CD patients. In conclusion, we were able to demonstrate that the microbial spectrum of CD patients does differ only for some pathogen species without increased rate of antibiotic resistance. However, the empiric antibiotic therapy for CD-associated intra-abdominal abscess remains challenging since different points such as local epidemiological and microbiological data, individual patient risk factors, severity of infection, and therapy algorithm including non-surgical and surgical therapy options should be considered before therapeutical decisions are made. KW - Crohn's disease KW - intraabdominal abscess KW - penetrating ileitis KW - microbial spectrum KW - antibiotic resistance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-281835 SN - 2077-0383 VL - 11 IS - 15 ER - TY - JOUR A1 - Kemmler, Wolfgang A1 - Kohl, Matthias A1 - Fröhlich, Michael A1 - Jakob, Franz A1 - Engelke, Klaus A1 - von Stengel, Simon A1 - Schoene, Daniel T1 - Effects of High‐Intensity Resistance Training on Osteopenia and Sarcopenia Parameters in Older Men with Osteosarcopenia—One‐Year Results of the Randomized Controlled Franconian Osteopenia and Sarcopenia Trial (FrOST) JF - Journal of Bone and Mineral Research N2 - Dynamic resistance exercise (DRT) might be the most promising agent for fighting sarcopenia in older people. However, the positive effect of DRT on osteopenia/osteoporosis in men has still to be confirmed. To evaluate the effect of low‐volume/high‐intensity (HIT)‐DRT on bone mineral density (BMD) and skeletal muscle mass index (SMI) in men with osteosarcopenia, we initiated the Franconian Osteopenia and Sarcopenia Trial (FrOST). Forty‐three sedentary community‐dwelling older men (aged 73 to 91 years) with osteopenia/osteoporosis and SMI‐based sarcopenia were randomly assigned to a HIT‐RT exercise group (EG; n = 21) or a control group (CG; n = 22). HIT‐RT provided a progressive, periodized single‐set DRT on machines with high intensity, effort, and velocity twice a week, while CG maintained their lifestyle. Both groups were adequately supplemented with whey protein, vitamin D, and calcium. Primary study endpoint was integral lumbar spine (LS) BMD as determined by quantitative computed tomography. Core secondary study endpoint was SMI as determined by dual‐energy X‐ray absorptiometry. Additional study endpoints were BMD at the total hip and maximum isokinetic hip−/leg‐extensor strength (leg press). After 12 months of exercise, LS‐BMD was maintained in the EG and decreased significantly in the CG, resulting in significant between‐group differences (p < 0.001; standardized mean difference [SMD] = 0.90). In parallel, SMI increased significantly in the EG and decreased significantly in the CG (p < 0.001; SMD = 1.95). Total hip BMD changes did not differ significantly between the groups (p = 0.064; SMD = 0.65), whereas changes in maximum hip−/leg‐extensor strength were much more prominent (p < 0.001; SMD = 1.92) in the EG. Considering dropout (n = 2), attendance rate (95%), and unintended side effects/injuries (n = 0), we believe our HIT‐RT protocol to be feasible, attractive, and safe. In summary, we conclude that our combined low‐threshold HIT‐RT/protein/vitamin D/calcium intervention was feasible, safe, and effective for tackling sarcopenia and osteopenia/osteoporosis in older men with osteosarcopenia. KW - exercise KW - osteoporosis KW - sarcopenia KW - aging KW - bone QCT Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214609 VL - 35 IS - 9 SP - 1634 EP - 1644 ER - TY - JOUR A1 - Ullmann, Tobias A1 - Sauerbrey, Julia A1 - Hoffmeister, Dirk A1 - May, Simon Matthias A1 - Baumhauer, Roland A1 - Bubenzer, Olaf T1 - Assessing Spatiotemporal Variations of Sentinel-1 InSAR Coherence at Different Time Scales over the Atacama Desert (Chile) between 2015 and 2018 JF - Remote Sensing N2 - This study investigates synthetic aperture radar (SAR) time series of the Sentinel-1 mission acquired over the Atacama Desert, Chile, between March 2015 and December 2018. The contribution analyzes temporal and spatial variations of Sentinel-1 interferometric SAR (InSAR) coherence and exemplarily illustrates factors that are responsible for observed signal differences. The analyses are based on long temporal baselines (365–1090 days) and temporally dense time series constructed with short temporal baselines (12–24 days). Results are compared to multispectral data of Sentinel-2, morphometric features of the digital elevation model (DEM) TanDEM-X WorldDEM™, and to a detailed governmental geographic information system (GIS) dataset of the local hydrography. Sentinel-1 datasets are suited for generating extensive, nearly seamless InSAR coherence mosaics covering the entire Atacama Desert (>450 × 1100 km) at a spatial resolution of 20 × 20 meter per pixel. Temporal baselines over several years lead only to very minor decorrelation, indicating a very high signal stability of C-Band in this region, especially in the hyperarid uplands between the Coastal Cordillera and the Central Depression. Signal decorrelation was associated with certain types of surface cover (e.g., water or aeolian deposits) or with actual surface dynamics (e.g., anthropogenic disturbance (mining) or fluvial activity and overland flow). Strong rainfall events and fluvial activity in the periods 2015 to 2016 and 2017 to 2018 caused spatial patterns with significant signal decorrelation; observed linear coherence anomalies matched the reference channel network and indicated actual episodic and sporadic discharge events. In the period 2015–2016, area-wide loss of coherence appeared as strip-like patterns of more than 80 km length that matched the prevailing wind direction. These anomalies, and others observed in that period and in the period 2017–2018, were interpreted to be caused by overland flow of high magnitude, as their spatial location matched well with documented heavy rainfall events that showed cumulative precipitation amounts of more than 20 mm. KW - Chile KW - Atacama KW - Sentinel-1 KW - InSAR KW - coherence KW - geomorphology Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193836 SN - 2072-4292 VL - 11 IS - 24 ER - TY - JOUR A1 - Nemes, Karolina A1 - Johann, Pascal D. A1 - Steinbügl, Mona A1 - Gruhle, Miriam A1 - Bens, Susanne A1 - Kachanov, Denis A1 - Teleshova, Margarita A1 - Hauser, Peter A1 - Simon, Thorsten A1 - Tippelt, Stephan A1 - Eberl, Wolfgang A1 - Chada, Martin A1 - Lopez, Vicente Santa-Maria A1 - Grigull, Lorenz A1 - Hernáiz-Driever, Pablo A1 - Eyrich, Matthias A1 - Pears, Jane A1 - Milde, Till A1 - Reinhard, Harald A1 - Leipold, Alfred A1 - van de Wetering, Marianne A1 - Gil-da-Costa, Maria João A1 - Ebetsberger-Dachs, Georg A1 - Kerl, Kornelius A1 - Lemmer, Andreas A1 - Boztug, Heidrun A1 - Furtwängler, Rhoikos A1 - Kordes, Uwe A1 - Vokuhl, Christian A1 - Hasselblatt, Martin A1 - Bison, Brigitte A1 - Kröncke, Thomas A1 - Melchior, Patrick A1 - Timmermann, Beate A1 - Gerss, Joachim A1 - Siebert, Reiner A1 - Frühwald, Michael C. T1 - Infants and newborns with atypical teratoid rhabdoid tumors (ATRT) and extracranial malignant rhabdoid tumors (eMRT) in the EU-RHAB registry: a unique and challenging population JF - Cancers N2 - Introduction: Malignant rhabdoid tumors (MRT) predominantly affect infants and young children. Patients below six months of age represent a particularly therapeutically challenging group. Toxicity to developing organ sites limits intensity of treatment. Information on prognostic factors, genetics, toxicity of treatment and long-term outcomes is sparse. Methods: Clinical, genetic, and treatment data of 100 patients (aged below 6 months at diagnosis) from 13 European countries were analyzed (2005–2020). Tumors and matching blood samples were examined for SMARCB1 mutations using FISH, MLPA and Sanger sequencing. DNA methylation subgroups (ATRT-TYR, ATRT-SHH, and ATRT-MYC) were determined using 450 k / 850 k-profiling. Results: A total of 45 patients presented with ATRT, 29 with extracranial, extrarenal (eMRT) and 9 with renal rhabdoid tumors (RTK). Seventeen patients demonstrated synchronous tumors (SYN). Metastases (M+) were present in 27% (26/97) at diagnosis. A germline mutation (GLM) was detected in 55% (47/86). DNA methylation subgrouping was available in 50% (31 / 62) with ATRT or SYN; for eMRT, methylation-based subgrouping was not performed. The 5-year overall (OS) and event free survival (EFS) rates were 23.5 ± 4.6% and 19 ± 4.1%, respectively. Male sex (11 ± 5% vs. 35.8 ± 7.4%), M+ stage (6.1 ± 5.4% vs. 36.2 ± 7.4%), presence of SYN (7.1 ± 6.9% vs. 26.6 ± 5.3%) and GLM (7.7 ± 4.2% vs. 45.7 ± 8.6%) were significant prognostic factors for 5-year OS. Molecular subgrouping and survival analyses confirm a previously described survival advantage for ATRT-TYR. In an adjusted multivariate model, clinical factors that favorably influence the prognosis were female sex, localized stage, absence of a GLM and maintenance therapy. Conclusions: In this cohort of homogenously treated infants with MRT, significant predictors of outcome were sex, M-stage, GLM and maintenance therapy. We confirm the need to stratify which patient groups benefit from multimodal treatment, and which need novel therapeutic strategies. Biomarker-driven tailored trials may be a key option. KW - atypical teratoid rhabdoid tumors KW - extracranial malignant rhabdoid tumor KW - RTPS1 KW - RTPS2 KW - germline mutation KW - EU-RHAB registry Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270730 SN - 2072-6694 VL - 14 IS - 9 ER - TY - JOUR A1 - Mages, Michelle A1 - Shojaa, Mahdieh A1 - Kohl, Matthias A1 - Stengel, Simon von A1 - Becker, Clemens A1 - Gosch, Markus A1 - Jakob, Franz A1 - Kerschan-Schindl, Katharina A1 - Kladny, Bernd A1 - Klöckner, Nicole A1 - Lange, Uwe A1 - Middeldorf, Stefan A1 - Peters, Stefan A1 - Schoene, Daniel A1 - Sieber, Cornel C. A1 - Tholen, Reina A1 - Thomasius, Friederike E. A1 - Uder, Michael A1 - Kemmler, Wolfgang T1 - Exercise effects on Bone Mineral Density in men JF - Nutrients N2 - In contrast to postmenopausal women, evidence for a favorable effect of exercise on Bone Mineral Density (BMD) is still limited for men. This might be due to the paucity of studies, but also to the great variety of participants and study characteristics that may dilute study results. The aim of the present systematic review and meta-analysis was to evaluate the effect of exercise on BMD changes with rational eligibility criteria. A comprehensive search of six electronic databases up to 15 March 2021 was conducted. Briefly, controlled trials ≥6 months that determined changes in areal BMD in men >18 years old, with no apparent diseases or pharmacological therapy that relevantly affect bone metabolism, were included. BMD changes (standardized mean differences: SMD) of the lumbar spine (LS) and femoral neck (FN) were considered as outcomes. Twelve studies with 16 exercise and 12 control groups were identified. The pooled estimate of random-effect analysis was SMD = 0.38, 95%-CI: 0.14–0.61 and SMD = 0.25, 95%-CI: 0.00–0.49, for LS and FN, respectively. Heterogeneity between the trials was low–moderate. Funnel plots and rank and regression correlation tests indicate evidence for small study publication bias for LS but not FN-BMD. Subgroup analyses that focus on study length, type of exercise and methodologic quality revealed no significant difference between each of the three categories. In summary, we provided further evidence for a low but significant effect of exercise on BMD in men. However, we are currently unable to give even rough exercise recommendations for male cohorts. KW - Bone Mineral Density KW - exercise KW - men KW - overview Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-250247 SN - 2072-6643 VL - 13 IS - 12 ER - TY - JOUR A1 - Kelm, Matthias A1 - Kusan, Simon A1 - Surat, Güzin A1 - Anger, Friedrich A1 - Reibetanz, Joachim A1 - Germer, Christoph-Thomas A1 - Schlegel, Nicolas A1 - Flemming, Sven T1 - Disease- and medication-specific differences of the microbial spectrum in perianal fistulizing Crohn’s Disease — relevant aspects for antibiotic therapy JF - Biomedicines N2 - Perianal fistulizing Crohn’s Disease (CD) with abscess formation represents an aggressive phenotype in Inflammatory Bowel Disease (IBD) with increased morbidity. Treatment is multidisciplinary and includes antibiotics, but knowledge about the microbial spectrum is rare often resulting in inadequate antimicrobial therapy. In this single center retrospective study, all patients who were operated due to perianal abscess formation were retrospectively analyzed and the microbial spectrum evaluated. Patients were divided into a CD and non-CD group with further subgroup analysis. 138 patients were finally included in the analysis with 62 patients suffering from CD. Relevant differences were detected for the microbial spectrum with anaerobic bacteria being significantly more often isolated from non-CD patients. In a subgroup-analysis of CD patients only, medical therapy had a relevant effect on the microbial spectrum since Streptococcus groups and Enterobacterales were significantly more often isolated in patients treated with steroids compared to those being treated by antibodies. In conclusion, the microbial spectrum of patients suffering from CD varies significantly from non-CD patients and immunosuppressive medication has a relevant effect on isolated pathogens. Based on that, adaption of antibiotic treatment might be discussed in the future. KW - fistulizing Crohn’s Disease KW - microbial spectrum KW - anorectal abscess KW - perianal fistulas Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-290281 SN - 2227-9059 VL - 10 IS - 11 ER - TY - JOUR A1 - Dong, Meng A1 - Böpple, Kathrin A1 - Thiel, Julia A1 - Winkler, Bernd A1 - Liang, Chunguang A1 - Schueler, Julia A1 - Davies, Emma J. A1 - Barry, Simon T. A1 - Metsalu, Tauno A1 - Mürdter, Thomas E. A1 - Sauer, Georg A1 - Ott, German A1 - Schwab, Matthias A1 - Aulitzky, Walter E. T1 - Perfusion air culture of precision-cut tumor slices: an ex vivo system to evaluate individual drug response under controlled culture conditions JF - Cells N2 - Precision-cut tumor slices (PCTS) maintain tissue heterogeneity concerning different cell types and preserve the tumor microenvironment (TME). Typically, PCTS are cultured statically on a filter support at an air–liquid interface, which gives rise to intra-slice gradients during culture. To overcome this problem, we developed a perfusion air culture (PAC) system that can provide a continuous and controlled oxygen medium, and drug supply. This makes it an adaptable ex vivo system for evaluating drug responses in a tissue-specific microenvironment. PCTS from mouse xenografts (MCF-7, H1437) and primary human ovarian tumors (primary OV) cultured in the PAC system maintained the morphology, proliferation, and TME for more than 7 days, and no intra-slice gradients were observed. Cultured PCTS were analyzed for DNA damage, apoptosis, and transcriptional biomarkers for the cellular stress response. For the primary OV slices, cisplatin treatment induced a diverse increase in the cleavage of caspase-3 and PD-L1 expression, indicating a heterogeneous response to drug treatment between patients. Immune cells were preserved throughout the culturing period, indicating that immune therapy can be analyzed. The novel PAC system is suitable for assessing individual drug responses and can thus be used as a preclinical model to predict in vivo therapy responses. KW - precision-cut tumor slices KW - perfusion culture KW - tumor microenvironment KW - ovarian tumor KW - individual drug responses KW - mouse xenografts KW - preclinical model KW - personalized medicine Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-311030 SN - 2073-4409 VL - 12 IS - 5 ER -