TY  - JOUR
A1  - Couch, Fergus J.
A1  - Wang, Xianshu
A1  - McGuffog, Lesley
A1  - Lee, Andrew
A1  - Olswold, Curtis
A1  - Kuchenbaecker, Karoline B.
A1  - Soucy, Penny
A1  - Fredericksen, Zachary
A1  - Barrowdale, Daniel
A1  - Dennis, Joe
A1  - Gaudet, Mia M.
A1  - Dicks, Ed
A1  - Kosel, Matthew
A1  - Healey, Sue
A1  - Sinilnikova, Olga M.
A1  - Lee, Adam
A1  - Bacot, Françios
A1  - Vincent, Daniel
A1  - Hogervorst, Frans B. L.
A1  - Peock, Susan
A1  - Stoppa-Lyonnet, Dominique
A1  - Jakubowska, Anna
A1  - Radice, Paolo
A1  - Schmutzler, Rita Katharina
A1  - Domchek, Susan M.
A1  - Piedmonte, Marion
A1  - Singer, Christian F.
A1  - Friedman, Eitan
A1  - Thomassen, Mads
A1  - Hansen, Thomas V. O.
A1  - Neuhausen, Susan L.
A1  - Szabo, Csilla I.
A1  - Blanco, Ingnacio
A1  - Greene, Mark H.
A1  - Karlan, Beth Y.
A1  - Garber, Judy
A1  - Phelan, Catherine M.
A1  - Weitzel, Jeffrey N.
A1  - Montagna, Marco
A1  - Olah, Edith
A1  - Andrulis, Irene L.
A1  - Godwin, Andrew K.
A1  - Yannoukakos, Drakoulis
A1  - Goldgar, David E.
A1  - Caldes, Trinidad
A1  - Nevanlinna, Heli
A1  - Osorio, Ana
A1  - Terry, Mary Beth
A1  - Daly, Mary B.
A1  - van Rensburg, Elisabeth J.
A1  - Hamann, Ute
A1  - Ramus, Susan J.
A1  - Toland, Amanda Ewart
A1  - Caligo, Maria A.
A1  - Olopade, Olufunmilayo I.
A1  - Tung, Nadine
A1  - Claes, Kathleen
A1  - Beattie, Mary S.
A1  - Southey, Melissa C.
A1  - Imyanitov, Evgeny N.
A1  - Tischkowitz, Marc
A1  - Janavicius, Ramunas
A1  - John, Esther M.
A1  - Kwong, Ava
A1  - Diez, Orland
A1  - Kwong, Ava
A1  - Balmaña, Judith
A1  - Barkardottir, Rosa B.
A1  - Arun, Banu K.
A1  - Rennert, Gad
A1  - Teo, Soo-Hwang
A1  - Ganz, Patricia A.
A1  - Campbell, Ian
A1  - van der Hout, Annemarie H.
A1  - van Deurzen, Carolien H. M.
A1  - Seynaeve, Caroline
A1  - Garcia, Encarna B. Gómez
A1  - van Leeuwen, Flora E.
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Gille, Johannes J. P.
A1  - Ausems, Magreet G. E. M.
A1  - Blok, Marinus J.
A1  - Ligtenberg, Marjolinjin J. L.
A1  - Rookus, Matti A.
A1  - Devilee, Peter
A1  - Verhoef, Senno
A1  - van Os, Theo A. M.
A1  - Wijnen, Juul T.
A1  - Frost, Debra
A1  - Ellis, Steve
A1  - Fineberg, Elena
A1  - Platte, Radke
A1  - Evans, D. Gareth
A1  - Izatt, Luise
A1  - Eeles, Rosalind A.
A1  - Adlard, Julian
A1  - Eccles, Diana M.
A1  - Cook, Jackie
A1  - Brewer, Carole
A1  - Douglas, Fiona
A1  - Hodgson, Shirley
A1  - Morrison, Patrick J.
A1  - Side, Lucy E.
A1  - Donaldson, Alan
A1  - Houghton, Catherine
A1  - Rogers, Mark T.
A1  - Dorkins, Huw
A1  - Eason, Jacqueline
A1  - Gregory, Helen
A1  - McCann, Emma
A1  - Murray, Alex
A1  - Calender, Alain
A1  - Hardouin, Agnès
A1  - Berthet, Pascaline
A1  - Delnatte, Capucine
A1  - Nogues, Catherine
A1  - Lasset, Christine
A1  - Houdayer, Claude
A1  - Leroux,, Dominique
A1  - Rouleau, Etienne
A1  - Prieur, Fabienne
A1  - Damiola, Francesca
A1  - Sobol, Hagay
A1  - Coupier, Isabelle
A1  - Venat-Bouvet, Laurence
A1  - Castera, Laurent
A1  - Gauthier-Villars, Marion
A1  - Léoné, Mélanie
A1  - Pujol, Pascal
A1  - Mazoyer, Sylvie
A1  - Bignon, Yves-Jean
A1  - Zlowocka-Perlowska, Elzbieta
A1  - Gronwald, Jacek
A1  - Lubinski,, Jan
A1  - Durda, Katarzyna
A1  - Jaworska, Katarzyna
A1  - Huzarski, Tomasz
A1  - Spurdle, Amanda B.
A1  - Viel, Alessandra
A1  - Peissel, Bernhard
A1  - Bonanni, Bernardo
A1  - Melloni, Guilia
A1  - Ottini, Laura
A1  - Papi, Laura
A1  - Varesco, Liliana
A1  - Tibiletti, Maria Grazia
A1  - Peterlongo, Paolo
A1  - Volorio, Sara
A1  - Manoukian, Siranoush
A1  - Pensotti, Valeria
A1  - Arnold, Norbert
A1  - Engel, Christoph
A1  - Deissler, Helmut
A1  - Gadzicki, Dorothea
A1  - Gehrig, Andrea
A1  - Kast, Karin
A1  - Rhiem, Kerstin
A1  - Meindl, Alfons
A1  - Niederacher, Dieter
A1  - Ditsch, Nina
A1  - Plendl, Hansjoerg
A1  - Preisler-Adams, Sabine
A1  - Engert, Stefanie
A1  - Sutter, Christian
A1  - Varon-Mateeva, Raymenda
A1  - Wappenschmidt, Barbara
A1  - Weber, Bernhard H. F.
A1  - Arver, Brita
A1  - Stenmark-Askmalm, Marie
A1  - Loman, Niklas
A1  - Rosenquist, Richard
A1  - Einbeigi, Zakaria
A1  - Nathanson, Katherine L.
A1  - Rebbeck, Timothy R.
A1  - Blank, Stephanie V.
A1  - Cohn, David E.
A1  - Rodriguez, Gustavo C.
A1  - Small, Laurie
A1  - Friedlander, Michael
A1  - Bae-Jump, Victoria L.
A1  - Fink-Retter, Anneliese
A1  - Rappaport, Christine
A1  - Gschwantler-Kaulich, Daphne
A1  - Pfeiler, Georg
A1  - Tea, Muy-Kheng
A1  - Lindor, Noralane M.
A1  - Kaufman, Bella
A1  - Paluch, Shani Shimon
A1  - Laitman, Yael
A1  - Skytte, Anne-Bine
A1  - Gerdes, Anne-Marie
A1  - Pedersen, Inge Sokilde
A1  - Moeller, Sanne Traasdahl
A1  - Kruse, Torben A.
A1  - Jensen, Uffe Birk
A1  - Vijai, Joseph
A1  - Sarrel, Kara
A1  - Robson, Mark
A1  - Kauff, Noah
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Ozcelik, Hilmi
A1  - Ejlertsen, Bent
A1  - Nielsen, Finn C.
A1  - Jønson, Lars
A1  - Andersen, Mette K.
A1  - Ding, Yuan Chun
A1  - Steele, Linda
A1  - Foretova, Lenka
A1  - Teulé, Alex
A1  - Lazaro, Conxi
A1  - Brunet, Joan
A1  - Pujana, Miquel Angel
A1  - Mai, Phuong L.
A1  - Loud, Jennifer T.
A1  - Walsh, Christine
A1  - Lester, Jenny
A1  - Orsulic, Sandra
A1  - Narod, Steven A.
A1  - Herzog, Josef
A1  - Sand, Sharon R.
A1  - Tognazzo, Silvia
A1  - Agata, Simona
A1  - Vaszko, Tibor
A1  - Weaver, Joellen
A1  - Stravropoulou, Alexandra V.
A1  - Buys, Saundra S.
A1  - Romero, Atocha
A1  - de la Hoya, Miguel
A1  - Aittomäki, Kristiina
A1  - Muranen, Taru A.
A1  - Duran, Mercedes
A1  - Chung, Wendy K.
A1  - Lasa, Adriana
A1  - Dorfling, Cecilia M.
A1  - Miron, Alexander
A1  - Benitez, Javier
A1  - Senter, Leigha
A1  - Huo, Dezheng
A1  - Chan, Salina B.
A1  - Sokolenko, Anna P.
A1  - Chiquette, Jocelyne
A1  - Tihomirova, Laima
A1  - Friebel, Tara M.
A1  - Agnarsson, Bjarne A.
A1  - Lu, Karen H.
A1  - Lejbkowicz, Flavio
A1  - James, Paul A.
A1  - Hall, Per
A1  - Dunning, Alison M.
A1  - Tessier, Daniel
A1  - Cunningham, Julie
A1  - Slager, Susan L.
A1  - Chen, Wang
A1  - Hart, Steven
A1  - Stevens, Kristen
A1  - Simard, Jacques
A1  - Pastinen, Tomi
A1  - Pankratz, Vernon S.
A1  - Offit, Kenneth
A1  - Easton, Douglas F.
A1  - Chenevix-Trench, Georgia
A1  - Antoniou, Antonis C.
T1  - Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk
JF  - PLOS Genetics
N2  - BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7 x 10(-8), HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4 x 10(-8), HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4 x 10(-8), HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific association. The 17q21.31 locus was also associated with ovarian cancer risk in 8,211 BRCA2 carriers (P = 2 x 10(-4)). These loci may lead to an improved understanding of the etiology of breast and ovarian tumors in BRCA1 carriers. Based on the joint distribution of the known BRCA1 breast cancer risk-modifying loci, we estimated that the breast cancer lifetime risks for the 5% of BRCA1 carriers at lowest risk are 28%-50% compared to 81%-100% for the 5% at highest risk. Similarly, based on the known ovarian cancer risk-modifying loci, the 5% of BRCA1 carriers at lowest risk have an estimated lifetime risk of developing ovarian cancer of 28% or lower, whereas the 5% at highest risk will have a risk of 63% or higher. Such differences in risk may have important implications for risk prediction and clinical management for BRCA1 carriers.
KW  - common variants
KW  - susceptibility alleles
KW  - genetic variants
KW  - modifiers
KW  - ZNF365
KW  - investigators
KW  - population
KW  - consortium
KW  - selection
KW  - subtypes
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-127947
SN  - 1553-7404
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Blanco, Ignacio
A1  - Kuchenbaecker, Karoline
A1  - Cuadras, Daniel
A1  - Wang, Xianshu
A1  - Barrowdale, Daniel
A1  - Ruiz de Garibay, Gorka
A1  - Librado, Pablo
A1  - Sanchez-Gracia, Alejandro
A1  - Rozas, Julio
A1  - Bonifaci, Núria
A1  - McGuffog, Lesley
A1  - Pankratz, Vernon S.
A1  - Islam, Abul
A1  - Mateo, Francesca
A1  - Berenguer, Antoni
A1  - Petit, Anna
A1  - Català, Isabel
A1  - Brunet, Joan
A1  - Feliubadaló, Lidia
A1  - Tornero, Eva
A1  - Benítez, Javier
A1  - Osorio, Ana
A1  - Ramón y Cajal, Teresa
A1  - Nevanlinna, Heli
A1  - Aittomäki, Kristina
A1  - Arun, Banu K.
A1  - Toland, Amanda E.
A1  - Karlan, Beth Y.
A1  - Walsh, Christine
A1  - Lester, Jenny
A1  - Greene, Mark H.
A1  - Mai, Phuong L.
A1  - Nussbaum, Robert L.
A1  - Andrulis, Irene L.
A1  - Domchek, Susan M.
A1  - Nathanson, Katherine L.
A1  - Rebbeck, Timothy R.
A1  - Barkardottir, Rosa B.
A1  - Jakubowska, Anna
A1  - Lubinski, Jan
A1  - Durda, Katarzyna
A1  - Jaworska-Bieniek, Katarzyna
A1  - Claes, Kathleen
A1  - Van Maerken, Tom
A1  - Díez, Orland
A1  - Hansen, Thomas V.
A1  - Jønson, Lars
A1  - Gerdes, Anne-Marie
A1  - Ejlertsen, Bent
A1  - De la Hoya, Miguel
A1  - Caldés, Trinidad
A1  - Dunning, Alison M.
A1  - Oliver, Clare
A1  - Fineberg, Elena
A1  - Cook, Margaret
A1  - Peock, Susan
A1  - McCann, Emma
A1  - Murray, Alex
A1  - Jacobs, Chris
A1  - Pichert, Gabriella
A1  - Lalloo, Fiona
A1  - Chu, Carol
A1  - Dorkins, Huw
A1  - Paterson, Joan
A1  - Ong, Kai-Ren
A1  - Teixeira, Manuel R.
A1  - Hogervorst, Frans B. L.
A1  - Van der Hout, Annemarie H.
A1  - Seynaeve, Caroline
A1  - Van der Luijt, Rob B.
A1  - Ligtenberg, Marjolijn J. L.
A1  - Devilee, Peter
A1  - Wijnen, Juul T.
A1  - Rookus, Matti A.
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Blok, Marinus J.
A1  - Van den Ouweland, Ans M. W.
A1  - Aalfs, Cora M.
A1  - Rodriguez, Gustavo C.
A1  - Phillips, Kelly-Anne A.
A1  - Piedmonte, Marion
A1  - Nerenstone, Stacy R.
A1  - Bae-Jump, Victoria L.
A1  - O'Malley, David M.
A1  - Schmutzler, Rita K.
A1  - Wappenschmidt, Barbara
A1  - Rhiem, Kerstin
A1  - Engel, Christoph
A1  - Meindl, Alfons
A1  - Ditsch, Nina
A1  - Arnold, Norbert
A1  - Plendl, Hansjoerg J.
A1  - Niederacher, Dieter
A1  - Sutter, Christian
A1  - Wang-Gohrke, Shan
A1  - Steinemann, Doris
A1  - Preisler-Adams, Sabine
A1  - Kast, Karin
A1  - Varon-Mateeva, Raymonda
A1  - Gehrig, Andrea
A1  - Bojesen, Anders
A1  - Pedersen, Inge Sokilde
A1  - Sunde, Lone
A1  - Birk Jensen, Uffe
A1  - Thomassen, Mads
A1  - Kruse, Torben A.
A1  - Foretova, Lenka
A1  - Peterlongo, Paolo
A1  - Bernard, Loris
A1  - Peissel, Bernard
A1  - Scuvera, Giulietta
A1  - Manoukian, Siranoush
A1  - Radice, Paolo
A1  - Ottini, Laura
A1  - Montagna, Marco
A1  - Agata, Simona
A1  - Maugard, Christine
A1  - Simard, Jacques
A1  - Soucy, Penny
A1  - Berger, Andreas
A1  - Fink-Retter, Anneliese
A1  - Singer, Christian F.
A1  - Rappaport, Christine
A1  - Geschwantler-Kaulich, Daphne
A1  - Tea, Muy-Kheng
A1  - Pfeiler, Georg
A1  - John, Esther M.
A1  - Miron, Alex
A1  - Neuhausen, Susan L.
A1  - Terry, Mary Beth
A1  - Chung, Wendy K.
A1  - Daly, Mary B.
A1  - Goldgar, David E.
A1  - Janavicius, Ramunas
A1  - Dorfling, Cecilia M.
A1  - Van Rensburg, Elisabeth J.
A1  - Fostira, Florentia
A1  - Konstantopoulou, Irene
A1  - Garber, Judy
A1  - Godwin, Andrew K.
A1  - Olah, Edith
A1  - Narod, Steven A.
A1  - Rennert, Gad
A1  - Paluch, Shani Shimon
A1  - Laitman, Yael
A1  - Friedman, Eitan
A1  - Liljegren, Annelie
A1  - Rantala, Johanna
A1  - Stenmark-Askmalm, Marie
A1  - Loman, Niklas
A1  - Imyanitov, Evgeny N.
A1  - Hamann, Ute
A1  - Spurdle, Amanda B.
A1  - Healey, Sue
A1  - Weitzel, Jeffrey N.
A1  - Herzog, Josef
A1  - Margileth, David
A1  - Gorrini, Chiara
A1  - Esteller, Manel
A1  - Gómez, Antonio
A1  - Sayols, Sergi
A1  - Vidal, Enrique
A1  - Heyn, Holger
A1  - Stoppa-Lyonnet, Dominique
A1  - Léoné, Melanie
A1  - Barjhoux, Laure
A1  - Fassy-Colcombet, Marion
A1  - Pauw, Antoine de
A1  - Lasset, Christine
A1  - Fert Ferrer, Sandra
A1  - Castera, Laurent
A1  - Berthet, Pascaline
A1  - Cornelis, François
A1  - Bignon, Yves-Jean
A1  - Damiola, Francesca
A1  - Mazoyer, Sylvie
A1  - Sinilnikova, Olga M.
A1  - Maxwell, Christopher A.
A1  - Vijai, Joseph
A1  - Robson, Mark
A1  - Kauff, Noah
A1  - Corines, Marina J.
A1  - Villano, Danylko
A1  - Cunningham, Julie
A1  - Lee, Adam
A1  - Lindor, Noralane
A1  - Lázaro, Conxi
A1  - Easton, Douglas F.
A1  - Offit, Kenneth
A1  - Chenevix-Trench, Georgia
A1  - Couch, Fergus J.
A1  - Antoniou, Antonis C.
A1  - Pujana, Miguel Angel
T1  - Assessing associations between the AURKA-HMMR-TPX2-TUBG1 functional module and breast cancer risk in BRCA1/2 mutation carriers
JF  - PLoS ONE
N2  - While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10\(^{-4}\) (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted p\(_{interaction}\) values > 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
KW  - genetic interaction networks
KW  - genome-wide association
KW  - expression signature
KW  - susceptibility loci
KW  - survival
KW  - modifiers
KW  - polymorphism
KW  - cell
KW  - chip-seq
KW  - elements
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-143469
VL  - 10
IS  - 4
ER  - 
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  - Müntze, Jonas
A1  - Gensler, Daniel
A1  - Maniuc, Octavian
A1  - Liu, Dan
A1  - Cairns, Tereza
A1  - Oder, Daniel
A1  - Hu, Kai
A1  - Lorenz, Kristina
A1  - Frantz, Stefan
A1  - Wanner, Christoph
A1  - Nordbeck, Peter
T1  - Oral Chaperone Therapy Migalastat for Treating Fabry Disease: Enzymatic Response and Serum Biomarker Changes After 1 Year
JF  - Clinical Pharmacology & Therapeutics
N2  - Long-term effects of migalastat therapy in clinical practice are currently unknown. We evaluated migalastat efficacy and biomarker changes in a prospective, single-center study on 14 patients with Fabry disease (55 ± 14 years; 11 men). After 1 year of open-label migalastat therapy, patients showed significant changes in alpha-galactosidase-A activity (0.06–0.2 nmol/minute/mg protein; P = 0.001), left ventricular myocardial mass index (137–130 g/m2; P = 0.037), and serum creatinine (0.94–1.0 mg/dL; P = 0.021), accounting for deterioration in estimated glomerular filtration rate (87–78 mL/minute/1.73 m2; P = 0.012). The enzymatic increase correlated with myocardial mass reduction (r = −0.546; P = 0.044) but not with renal function (r = −0.086; P = 0.770). Plasma globotriaosylsphingosine was reduced in therapy-naive patients (10.9–6.0 ng/mL; P = 0.021) and stable (9.6–12.1 ng/mL; P = 0.607) in patients switched from prior enzyme-replacement therapy. These first real-world data show that migalastat substantially increases alpha-galactosidase-A activity, stabilizes related serum biomarkers, and improves cardiac integrity in male and female patients with amenable Fabry disease mutations.
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231626
VL  - 105
ER  - 
TY  - JOUR
A1  - Dornelas, Maria
A1  - Antão, Laura H.
A1  - Moyes, Faye
A1  - Bates, Amanda E.
A1  - Magurran, Anne E.
A1  - Adam, Dušan
A1  - Akhmetzhanova, Asem A.
A1  - Appeltans, Ward
A1  - Arcos, José Manuel
A1  - Arnold, Haley
A1  - Ayyappan, Narayanan
A1  - Badihi, Gal
A1  - Baird, Andrew H.
A1  - Barbosa, Miguel
A1  - Barreto, Tiago Egydio
A1  - Bässler, Claus
A1  - Bellgrove, Alecia
A1  - Belmaker, Jonathan
A1  - Benedetti-Cecchi, Lisandro
A1  - Bett, Brian J.
A1  - Bjorkman, Anne D.
A1  - Błażewicz, Magdalena
A1  - Blowes, Shane A.
A1  - Bloch, Christopher P. Bloch
A1  - Bonebrake, Timothy C.
A1  - Boyd, Susan
A1  - Bradford, Matt
A1  - Brooks, Andrew J.
A1  - Brown, James H.
A1  - Bruelheide, Helge
A1  - Budy, Phaedra
A1  - Carvalho, Fernando
A1  - Castañeda-Moya, Edward
A1  - Chen, Chaolun Allen
A1  - Chamblee, John F.
A1  - Chase, Tory J.
A1  - Siegwart Collier, Laura
A1  - Collinge, Sharon K.
A1  - Condit, Richard
A1  - Cooper, Elisabeth J.
A1  - Cornelissen, J. Hans C.
A1  - Cotano, Unai
A1  - Crow, Shannan Kyle
A1  - Damasceno, Gabriella
A1  - Davies, Claire H.
A1  - Davis, Robert A.
A1  - Day, Frank P.
A1  - Degraer, Steven
A1  - Doherty, Tim S.
A1  - Dunn, Timothy E.
A1  - Durigan, Giselda
A1  - Duffy, J. Emmett
A1  - Edelist, Dor
A1  - Edgar, Graham J.
A1  - Elahi, Robin
A1  - Elmendorf, Sarah C.
A1  - Enemar, Anders
A1  - Ernest, S. K. Morgan
A1  - Escribano, Rubén
A1  - Estiarte, Marc
A1  - Evans, Brian S.
A1  - Fan, Tung-Yung
A1  - Turini Farah, Fabiano
A1  - Loureiro Fernandes, Luiz
A1  - Farneda, Fábio Z.
A1  - Fidelis, Alessandra
A1  - Fitt, Robert
A1  - Fosaa, Anna Maria
A1  - Franco, Geraldo Antonio Daher Correa
A1  - Frank, Grace E.
A1  - Fraser, William R.
A1  - García, Hernando
A1  - Cazzolla Gatti, Roberto
A1  - Givan, Or
A1  - Gorgone-Barbosa, Elizabeth
A1  - Gould, William A.
A1  - Gries, Corinna
A1  - Grossman, Gary D.
A1  - Gutierréz, Julio R.
A1  - Hale, Stephen
A1  - Harmon, Mark E.
A1  - Harte, John
A1  - Haskins, Gary
A1  - Henshaw, Donald L.
A1  - Hermanutz, Luise
A1  - Hidalgo, Pamela
A1  - Higuchi, Pedro
A1  - Hoey, Andrew
A1  - Van Hoey, Gert
A1  - Hofgaard, Annika
A1  - Holeck, Kristen
A1  - Hollister, Robert D.
A1  - Holmes, Richard
A1  - Hoogenboom, Mia
A1  - Hsieh, Chih-hao
A1  - Hubbell, Stephen P.
A1  - Huettmann, Falk
A1  - Huffard, Christine L.
A1  - Hurlbert, Allen H.
A1  - Ivanauskas, Natália Macedo
A1  - Janík, David
A1  - Jandt, Ute
A1  - Jażdżewska, Anna
A1  - Johannessen, Tore
A1  - Johnstone, Jill
A1  - Jones, Julia
A1  - Jones, Faith A. M.
A1  - Kang, Jungwon
A1  - Kartawijaya, Tasrif
A1  - Keeley, Erin C.
A1  - Kelt, Douglas A.
A1  - Kinnear, Rebecca
A1  - Klanderud, Kari
A1  - Knutsen, Halvor
A1  - Koenig, Christopher C.
A1  - Kortz, Alessandra R.
A1  - Král, Kamil
A1  - Kuhnz, Linda A.
A1  - Kuo, Chao-Yang
A1  - Kushner, David J.
A1  - Laguionie-Marchais, Claire
A1  - Lancaster, Lesley T.
A1  - Lee, Cheol Min
A1  - Lefcheck, Jonathan S.
A1  - Lévesque, Esther
A1  - Lightfoot, David
A1  - Lloret, Francisco
A1  - Lloyd, John D.
A1  - López-Baucells, Adrià
A1  - Louzao, Maite
A1  - Madin, Joshua S.
A1  - Magnússon, Borgþór
A1  - Malamud, Shahar
A1  - Matthews, Iain
A1  - McFarland, Kent P.
A1  - McGill, Brian
A1  - McKnight, Diane
A1  - McLarney, William O.
A1  - Meador, Jason
A1  - Meserve, Peter L.
A1  - Metcalfe, Daniel J.
A1  - Meyer, Christoph F. J.
A1  - Michelsen, Anders
A1  - Milchakova, Nataliya
A1  - Moens, Tom
A1  - Moland, Even
A1  - Moore, Jon
A1  - Moreira, Carolina Mathias
A1  - Müller, Jörg
A1  - Murphy, Grace
A1  - Myers-Smith, Isla H.
A1  - Myster, Randall W.
A1  - Naumov, Andrew
A1  - Neat, Francis
A1  - Nelson, James A.
A1  - Nelson, Michael Paul
A1  - Newton, Stephen F.
A1  - Norden, Natalia
A1  - Oliver, Jeffrey C.
A1  - Olsen, Esben M.
A1  - Onipchenko, Vladimir G.
A1  - Pabis, Krzysztof
A1  - Pabst, Robert J.
A1  - Paquette, Alain
A1  - Pardede, Sinta
A1  - Paterson, David M.
A1  - Pélissier, Raphaël
A1  - Peñuelas, Josep
A1  - Pérez-Matus, Alejandro
A1  - Pizarro, Oscar
A1  - Pomati, Francesco
A1  - Post, Eric
A1  - Prins, Herbert H. T.
A1  - Priscu, John C.
A1  - Provoost, Pieter
A1  - Prudic, Kathleen L.
A1  - Pulliainen, Erkki
A1  - Ramesh, B. R.
A1  - Ramos, Olivia Mendivil
A1  - Rassweiler, Andrew
A1  - Rebelo, Jose Eduardo
A1  - Reed, Daniel C.
A1  - Reich, Peter B.
A1  - Remillard, Suzanne M.
A1  - Richardson, Anthony J.
A1  - Richardson, J. Paul
A1  - van Rijn, Itai
A1  - Rocha, Ricardo
A1  - Rivera-Monroy, Victor H.
A1  - Rixen, Christian
A1  - Robinson, Kevin P.
A1  - Rodrigues, Ricardo Ribeiro
A1  - de Cerqueira Rossa-Feres, Denise
A1  - Rudstam, Lars
A1  - Ruhl, Henry
A1  - Ruz, Catalina S.
A1  - Sampaio, Erica M.
A1  - Rybicki, Nancy
A1  - Rypel, Andrew
A1  - Sal, Sofia
A1  - Salgado, Beatriz
A1  - Santos, Flavio A. M.
A1  - Savassi-Coutinho, Ana Paula
A1  - Scanga, Sara
A1  - Schmidt, Jochen
A1  - Schooley, Robert
A1  - Setiawan, Fakhrizal
A1  - Shao, Kwang-Tsao
A1  - Shaver, Gaius R.
A1  - Sherman, Sally
A1  - Sherry, Thomas W.
A1  - Siciński, Jacek
A1  - Sievers, Caya
A1  - da Silva, Ana Carolina
A1  - da Silva, Fernando Rodrigues
A1  - Silveira, Fabio L.
A1  - Slingsby, Jasper
A1  - Smart, Tracey
A1  - Snell, Sara J.
A1  - Soudzilovskaia, Nadejda A.
A1  - Souza, Gabriel B. G.
A1  - Souza, Flaviana Maluf
A1  - Souza, Vinícius Castro
A1  - Stallings, Christopher D.
A1  - Stanforth, Rowan
A1  - Stanley, Emily H.
A1  - Sterza, José Mauro
A1  - Stevens, Maarten
A1  - Stuart-Smith, Rick
A1  - Suarez, Yzel Rondon
A1  - Supp, Sarah
A1  - Tamashiro, Jorge Yoshio
A1  - Tarigan, Sukmaraharja
A1  - Thiede, Gary P.
A1  - Thorn, Simon
A1  - Tolvanen, Anne
A1  - Toniato, Maria Teresa Zugliani
A1  - Totland, Ørjan
A1  - Twilley, Robert R.
A1  - Vaitkus, Gediminas
A1  - Valdivia, Nelson
A1  - Vallejo, Martha Isabel
A1  - Valone, Thomas J.
A1  - Van Colen, Carl
A1  - Vanaverbeke, Jan
A1  - Venturoli, Fabio
A1  - Verheye, Hans M.
A1  - Vianna, Marcelo
A1  - Vieira, Rui P.
A1  - Vrška, Tomáš
A1  - Vu, Con Quang
A1  - Vu, Lien Van
A1  - Waide, Robert B.
A1  - Waldock, Conor
A1  - Watts, Dave
A1  - Webb, Sara
A1  - Wesołowski, Tomasz
A1  - White, Ethan P.
A1  - Widdicombe, Claire E.
A1  - Wilgers, Dustin
A1  - Williams, Richard
A1  - Williams, Stefan B.
A1  - Williamson, Mark
A1  - Willig, Michael R.
A1  - Willis, Trevor J.
A1  - Wipf, Sonja
A1  - Woods, Kerry D.
A1  - Woehler, Eric J.
A1  - Zawada, Kyle
A1  - Zettler, Michael L.
T1  - BioTIME: A database of biodiversity time series for the Anthropocene
JF  - Global Ecology and Biogeography
N2  - Motivation
The BioTIME database contains raw data on species identities and abundances in ecological assemblages through time. These data enable users to calculate temporal trends in biodiversity within and amongst assemblages using a broad range of metrics. BioTIME is being developed as a community-led open-source database of biodiversity time series. Our goal is to accelerate and facilitate quantitative analysis of temporal patterns of biodiversity in the Anthropocene.

Main types of variables included
The database contains 8,777,413 species abundance records, from assemblages consistently sampled for a minimum of 2 years, which need not necessarily be consecutive. In addition, the database contains metadata relating to sampling methodology and contextual information about each record.

Spatial location and grain
BioTIME is a global database of 547,161 unique sampling locations spanning the marine, freshwater and terrestrial realms. Grain size varies across datasets from 0.0000000158 km2 (158 cm2) to 100 km2 (1,000,000,000,000 cm2).

Time period and grain
BioTIME records span from 1874 to 2016. The minimal temporal grain across all datasets in BioTIME is a year.

Major taxa and level of measurement
BioTIME includes data from 44,440 species across the plant and animal kingdoms, ranging from plants, plankton and terrestrial invertebrates to small and large vertebrates.

Software format
.csv and .SQL.
KW  - biodiversity
KW  - global
KW  - spatial
KW  - species richness
KW  - temporal
KW  - turnover
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-222846
VL  - 27
ER  - 
TY  - JOUR
A1  - Boltze, Johannes
A1  - Kleinschnitz, Christoph
A1  - Reymann, Klaus G.
A1  - Reiser, Georg
A1  - Wagner, Daniel-Christoph
A1  - Kranz, Alexander
A1  - Michalski, Dominik
T1  - Neurovascular pathophysiology in cerebral ischemia, dementia and the ageing brain – current trends in basic, translational and clinical research
JF  - Experimental & Translational Stroke Medicine
N2  - The 7th International Symposium on Neuroprotection and Neurorepair was held from May 2nd to May 5th, 2012 in Potsdam, Germany. The symposium, which directly continues the successful Magdeburg meeting series, attracted over 330 colleagues from 29 countries to discuss recent findings and advances in the field. The focus of the 2012 symposium was widened from stroke and traumatic brain injury to neurodegenerative diseases, notably dementia, and more generally the ageing brain. Thereby, emphasis was given on neurovascular aspects of neurodegeneration and stroke including the blood–brain barrier, recent findings regarding the pathomechanism of Alzheimer’s disease, and brain imaging approaches. In addition, neurobiochemical aspects of neuroprotection, the role of astrogliosis, the clinical progress of cell-based approaches as well as translational hurdles and opportunities were discussed in-depth. This review summarizes some of the most stimulating discussions and reports from the meeting.
KW  - translational research
KW  - small vessel disease
KW  - Alzheimer’s disease
KW  - cerebral ischemia
KW  - neurorepair
KW  - neuroprotection
KW  - vascular dementia
KW  - mitochondria
KW  - astrogliosis
KW  - in vivo imaging
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-126679
VL  - 4
IS  - 14
ER  - 
TY  - JOUR
A1  - Meier, Johannes P.
A1  - Möbus, Selina
A1  - Heigl, Florian
A1  - Asbach-Nitzsche, Alexandra
A1  - Niller, Hans Helmut
A1  - Plentz, Annelie
A1  - Avsar, Korkut
A1  - Heiß-Neumann, Marion
A1  - Schaaf, Bernhard
A1  - Cassens, Uwe
A1  - Seese, Bernd
A1  - Teschner, Daniel
A1  - Handzhiev, Sabin
A1  - Graf, Uwe
A1  - Lübbert, Christoph
A1  - Steinmaurer, Monika
A1  - Kontogianni, Konstantina
A1  - Berg, Christoph
A1  - Maieron, Andreas
A1  - Blaas, Stefan H.
A1  - Wagner, Ralf
A1  - Deml, Ludwig
A1  - Barabas, Sascha
T1  - Performance of T-Track\(^®\) TB, a novel dual marker RT-qPCR-based whole-blood test for improved detection of active tuberculosis
JF  - Diagnostics
N2  - Tuberculosis (TB) is one of the leading causes of death by an infectious disease. It remains a major health burden worldwide, in part due to misdiagnosis. Therefore, improved diagnostic tests allowing the faster and more reliable diagnosis of patients with active TB are urgently needed. This prospective study examined the performance of the new molecular whole-blood test T-Track\(^®\) TB, which relies on the combined evaluation of IFNG and CXCL10 mRNA levels, and compared it to that of the QuantiFERON\(^®\)-TB Gold Plus (QFT-Plus) enzyme-linked immunosorbent assay (ELISA). Diagnostic accuracy and agreement analyses were conducted on the whole blood of 181 active TB patients and 163 non-TB controls. T-Track\(^®\) TB presented sensitivity of 94.9% and specificity of 93.8% for the detection of active TB vs. non-TB controls. In comparison, the QFT-Plus ELISA showed sensitivity of 84.3%. The sensitivity of T-Track\(^®\) TB was significantly higher (p < 0.001) than that of QFT-Plus. The overall agreement of T-Track\(^®\) TB with QFT-Plus to diagnose active TB was 87.9%. Out of 21 samples with discordant results, 19 were correctly classified by T-Track\(^®\) TB while misclassified by QFT-Plus (T-Track\(^®\) TB-positive/QFT-Plus-negative), and two samples were misclassified by T-Track\(^®\) TB while correctly classified by QFT-Plus (T-Track\(^®\) TB-negative/QFT-Plus-positive). Our results demonstrate the excellent performance of the T-Track\(^®\) TB molecular assay and its suitability to accurately detect TB infection and discriminate active TB patients from non-infected controls.
KW  - tuberculosis
KW  - TB
KW  - active TB
KW  - infection detection
KW  - T-Track\(^®\) TB
KW  - QuantiFERON\(^®\)-TB Gold Plus
KW  - mRNA
KW  - RT-qPCR
KW  - CXCL10
KW  - IFNG
Y1  - 2023
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304113
SN  - 2075-4418
VL  - 13
IS  - 4
ER  - 
TY  - JOUR
A1  - Koch, Oliver
A1  - Cappel, Daniel
A1  - Nocker, Monika
A1  - Jaeger, Timo
A1  - Flohé, Leopold
A1  - Sotriffer, Christoph
A1  - Selzer, Paul
T1  - Virtual screening using structure-based consensus pharmacophore models and ensemble docking based on MD-generated conformations : [From 6th German Conference on Chemoinformatics, GCC 2010, Goslar, Germany. 7-9 November 2010]
JF  - Journal of Cheminformatics
N2  - No abstract available.
KW  - chemistry
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142830
VL  - 3
IS  - Suppl. 1
ER  - 
TY  - JOUR
A1  - Oder, Daniel
A1  - Vergho, Dorothee
A1  - Ertl, Georg
A1  - Wanner, Christoph
A1  - Nordbeck, Peter
T1  - Case report of a 45-year old female Fabry disease patient carrying two alpha-galactosidase A gene mutation alleles
JF  - BMC Medical Genetics
N2  - Background
X-chromosomal inheritance patterns and generally rare occurrence of Fabry disease (FD) account for mono-mutational hemizygous male and heterozygous female patients. Female mutation carriers are usually clinically much less severely affected, which has been explained by a suggested mosaicism in cell phenotype due to random allele shutdown. However, clinical evidence is scarce and potential additional effects in female gene carriers, which might account for specific clinical characteristics such as less severe chronic kidney disease, are yet unknown.

Case presentation
This article reports on a 45 year old female patient carrying the two alpha-galactosidase A gene mutations c.416A > G, p.N139S in exon 3 and c.708G > C, p.W236C in exon 5, but still showing only mild organ manifestations.

Conclusion
This current case highlights the importance of careful clinical characterization in patients with Fabry disease, who may show additional rare constellations and, therefore, are in need of personalized medicine. The impact of potential additional protective effects exceeding the presence of a non-pathogenic GLA allele in female gene carriers requires further investigation.
KW  - Fabry disease
KW  - cryptogenic stroke
KW  - Pain
KW  - hypertrophic cardiomyopathy
KW  - chronic kidney disease
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-146617
VL  - 17
IS  - 46
ER  - 
TY  - BOOK
A1  - Falk, Michael
A1  - Marohn, Frank
A1  - Michel, René
A1  - Hofmann, Daniel
A1  - Macke, Maria
A1  - Spachmann, Christoph
A1  - Englert, Stefan
T1  - A First Course on Time Series Analysis : Examples with SAS [Version 2012.August.01]
N2  - The analysis of real data by means of statistical methods with the aid of a software package common in industry and administration usually is not an integral part of mathematics studies, but it will certainly be part of a future professional work. The present book links up elements from time series analysis with a selection of statistical procedures used in general practice including the statistical software package SAS. Consequently this book addresses students of statistics as well as students of other branches such as economics, demography and engineering, where lectures on statistics belong to their academic training. But it is also intended for the practician who, beyond the use of statistical tools, is interested in their mathematical background. Numerous problems illustrate the applicability of the presented statistical procedures, where SAS gives the solutions. The programs used are explicitly listed and explained. No previous experience is expected neither in SAS nor in a special computer system so that a short training period is guaranteed. This book is meant for a two semester course (lecture, seminar or practical training) where the first three chapters can be dealt within the first semester. They provide the principal components of the analysis of a time series in the time domain. Chapters 4, 5 and 6 deal with its analysis in the frequency domain and can be worked through in the second term. In order to understand the mathematical background some terms are useful such as convergence in distribution, stochastic convergence, maximum likelihood estimator as well as a basic knowledge of the test theory, so that work on the book can start after an introductory lecture on stochastics. Each chapter includes exercises. An exhaustive treatment is recommended. Chapter 7 (case study) deals with a practical case and demonstrates the presented methods. It is possible to use this chapter independent in a seminar or practical training course, if the concepts of time series analysis are already well understood. This book is consecutively subdivided in a statistical part and an SAS-specific part. For better clearness the SAS-specific parts are highlighted. This book is an open source project under the GNU Free Documentation License.
KW  - Zeitreihenanalyse
KW  - Box-Jenkins-Verfahren
KW  - SAS <Programm>
KW  - Zustandsraummodelle
KW  - Time Series Analysis
KW  - State-Space Models
KW  - Frequency Domain
KW  - Box–Jenkins Program
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-72617
N1  - Version: 2012-August-01
ER  - 
TY  - BOOK
A1  - Falk, Michael
A1  - Marohn, Frank
A1  - Michel, René
A1  - Hofmann, Daniel
A1  - Macke, Maria
A1  - Tewes, Bernward
A1  - Dinges, Peter
A1  - Spachmann, Christoph
A1  - Englert, Stefan
T1  - A First Course on Time Series Analysis : Examples with SAS
N2  - The analysis of real data by means of statistical methods with the aid of a software package common in industry and administration usually is not an integral part of mathematics studies, but it will certainly be part of a future professional work. The present book links up elements from time series analysis with a selection of statistical procedures used in general practice including the statistical software package SAS. Consequently this book addresses students of statistics as well as students of other branches such as economics, demography and engineering, where lectures on statistics belong to their academic training. But it is also intended for the practician who, beyond the use of statistical tools, is interested in their mathematical background. Numerous problems illustrate the applicability of the presented statistical procedures, where SAS gives the solutions. The programs used are explicitly listed and explained. No previous experience is expected neither in SAS nor in a special computer system so that a short training period is guaranteed. This book is meant for a two semester course (lecture, seminar or practical training) where the first three chapters can be dealt within the first semester. They provide the principal components of the analysis of a time series in the time domain. Chapters 4, 5 and 6 deal with its analysis in the frequency domain and can be worked through in the second term. In order to understand the mathematical background some terms are useful such as convergence in distribution, stochastic convergence, maximum likelihood estimator as well as a basic knowledge of the test theory, so that work on the book can start after an introductory lecture on stochastics. Each chapter includes exercises. An exhaustive treatment is recommended. Chapter 7 (case study) deals with a practical case and demonstrates the presented methods. It is possible to use this chapter independent in a seminar or practical training course, if the concepts of time series analysis are already well understood. This book is consecutively subdivided in a statistical part and an SAS-specific part. For better clearness the SAS-specific parts are highlighted. This book is an open source project under the GNU Free Documentation License.
KW  - Zeitreihenanalyse
KW  - Box-Jenkins-Verfahren
KW  - SAS <Programm>
KW  - Zustandsraummodelle
KW  - Time Series Analysis
KW  - State-Space Models
KW  - Frequency Domain
KW  - Box–Jenkins Program
Y1  - 2011
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-56489
N1  - Version: 2011-March-01
ER  - 
TY  - JOUR
A1  - Drechsler, Christiane
A1  - Schmiedeke, Benjamin
A1  - Niemann, Markus
A1  - Schmiedeke, Daniel
A1  - Krämer, Johannes
A1  - Turkin, Irina
A1  - Blouin, Katja
A1  - Emmert, Andrea
A1  - Pilz, Stefan
A1  - Obermayer-Pietsch, Barbara
A1  - Wiedemann, Frank
A1  - Breunig, Frank
A1  - Wanner, Christoph
T1  - Potential role of vitamin D deficiency on Fabry cardiomyopathy
JF  - Journal of Inherited Metabolic Disease
N2  - Patients with Fabry disease frequently develop left ventricular (LV) hypertrophy and renal fibrosis. Due to heat intolerance and an inability to sweat, patients tend to avoid exposure to sunlight. We hypothesized that subsequent vitamin D deficiency may contribute to Fabry cardiomyopathy. This study investigated the vitamin D status and its association with LV mass and adverse clinical symptoms in patients with Fabry disease. 25-hydroxyvitamin D (25[OH]D) was measured in 111 patients who were genetically proven to have Fabry disease. LV mass and cardiomyopathy were assessed by magnetic resonance imaging and echocardiography. In cross-sectional analyses, associations with adverse clinical outcomes were determined by linear and binary logistic regression analyses, respectively, and were adjusted for age, sex, BMI and season. Patients had a mean age of 40 ± 13 years (42 % males), and a mean 25(OH)D of 23.5 ± 11.4 ng/ml. Those with overt vitamin D deficiency (25[OH]D ≤ 15 ng/ml) had an adjusted six fold higher risk of cardiomyopathy, compared to those with sufficient 25(OH)D levels >30 ng/ml (p = 0.04). The mean LV mass was distinctively different with 170 ± 75 g in deficient, 154 ± 60 g in moderately deficient and 128 ± 58 g in vitamin D sufficient patients (p = 0.01). With increasing severity of vitamin D deficiency, the median levels of proteinuria increased, as well as the prevalences of depression, edema, cornea verticillata and the need for medical pain therapy. In conclusion, vitamin D deficiency was strongly associated with cardiomyopathy and adverse clinical symptoms in patients with Fabry disease. Whether vitamin D supplementation improves complications of Fabry disease, requires a randomized controlled trial.
KW  - Fabry patient
KW  - urinary protein excretion
KW  - hypertrophic cardiomyopathy
KW  - renal fibrosis
KW  - left ventricular mass
KW  - LV mass
KW  - diabetic mouse
KW  - septal hypertrophy
KW  - Fabry nephropathy
KW  - cardiac hypertrophy
KW  - cornea verticillata
KW  - enzyme replacement therapy
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-132102
VL  - 37
IS  - 2
ER  - 
TY  - JOUR
A1  - Antoniou, Antonis C.
A1  - Kuchenbaecker, Karoline B.
A1  - Soucy, Penny
A1  - Beesley, Jonathan
A1  - Chen, Xiaoqing
A1  - McGuffog, Lesley
A1  - Lee, Andrew
A1  - Barrowdale, Daniel
A1  - Healey, Sue
A1  - Sinilnikova, Olga M.
A1  - Caligo, Maria A.
A1  - Loman, Niklas
A1  - Harbst, Katja
A1  - Lindblom, Annika
A1  - Arver, Brita
A1  - Rosenquist, Richard
A1  - Karlsson, Per
A1  - Nathanson, Kate
A1  - Domchek, Susan
A1  - Rebbeck, Tim
A1  - Jakubowska, Anna
A1  - Lubinski, Jan
A1  - Jaworska, Katarzyna
A1  - Durda, Katarzyna
A1  - Zlowowcka-Perłowska, Elżbieta
A1  - Osorio, Ana
A1  - Durán, Mercedes
A1  - Andrés, Raquel
A1  - Benítez, Javier
A1  - Hamann, Ute
A1  - Hogervorst, Frans B.
A1  - van Os, Theo A.
A1  - Verhoef, Senno
A1  - Meijers-Heijboer, Hanne E. J.
A1  - Wijnen, Juul
A1  - Garcia, Encarna B. Gómez
A1  - Ligtenberg, Marjolijn J.
A1  - Kriege, Mieke
A1  - Collée, Margriet
A1  - Ausems, Margreet G. E. M.
A1  - Oosterwijk, Jan C.
A1  - Peock, Susan
A1  - Frost, Debra
A1  - Ellis, Steve D.
A1  - Platte, Radka
A1  - Fineberg, Elena
A1  - Evans, D. Gareth
A1  - Lalloo, Fiona
A1  - Jacobs, Chris
A1  - Eeles, Ros
A1  - Adlard, Julian
A1  - Davidson, Rosemarie
A1  - Cole, Trevor
A1  - Cook, Jackie
A1  - Paterson, Joan
A1  - Douglas, Fiona
A1  - Brewer, Carole
A1  - Hodgson, Shirley
A1  - Morrison, Patrick J.
A1  - Walker, Lisa
A1  - Rogers, Mark T.
A1  - Donaldson, Alan
A1  - Dorkins, Huw
A1  - Godwin, Andrew K.
A1  - Bove, Betsy
A1  - Stoppa-Lyonnet, Dominique
A1  - Houdayer, Claude
A1  - Buecher, Bruno
A1  - de Pauw, Antoine
A1  - Mazoyer, Sylvie
A1  - Calender, Alain
A1  - Léoné, Mélanie
A1  - Bressac-de Paillerets, Brigitte
A1  - Caron, Olivier
A1  - Sobol, Hagay
A1  - Frenay, Marc
A1  - Prieur, Fabienne
A1  - Ferrer, Sandra Fert
A1  - Mortemousque, Isabelle
A1  - Buys, Saundra
A1  - Daly, Mary
A1  - Miron, Alexander
A1  - Terry, Mary Beth
A1  - Hopper, John L.
A1  - John, Esther M.
A1  - Southey, Melissa
A1  - Goldgar, David
A1  - Singer, Christian F.
A1  - Fink-Retter, Anneliese
A1  - Muy-Kheng, Tea
A1  - Geschwantler Kaulich, Daphne
A1  - Hansen, Thomas V. O.
A1  - Nielsen, Finn C.
A1  - Barkardottir, Rosa B.
A1  - Gaudet, Mia
A1  - Kirchhoff, Tomas
A1  - Joseph, Vijai
A1  - Dutra-Clarke, Ana
A1  - Offit, Kenneth
A1  - Piedmonte, Marion
A1  - Kirk, Judy
A1  - Cohn, David
A1  - Hurteau, Jean
A1  - Byron, John
A1  - Fiorica, James
A1  - Toland, Amanda E.
A1  - Montagna, Marco
A1  - Oliani, Cristina
A1  - Imyanitov, Evgeny
A1  - Isaacs, Claudine
A1  - Tihomirova, Laima
A1  - Blanco, Ignacio
A1  - Lazaro, Conxi
A1  - Teulé, Alex
A1  - Del Valle, J.
A1  - Gayther, Simon A.
A1  - Odunsi, Kunle
A1  - Gross, Jenny
A1  - Karlan, Beth Y.
A1  - Olah, Edith
A1  - Teo, Soo-Hwang
A1  - Ganz, Patricia A.
A1  - Beattie, Mary S.
A1  - Dorfling, Cecelia M.
A1  - Jansen van Rensburg, Elizabeth
A1  - Diez, Orland
A1  - Kwong, Ava
A1  - Schmutzler, Rita K.
A1  - Wappenschmidt, Barbara
A1  - Engel, Christoph
A1  - Meindl, Alfons
A1  - Ditsch, Nina
A1  - Arnold, Norbert
A1  - Heidemann, Simone
A1  - Niederacher, Dieter
A1  - Preisler-Adams, Sabine
A1  - Gadzicki, Dorothea
A1  - Varon-Mateeva, Raymonda
A1  - Deissler, Helmut
A1  - Gehrig, Andrea
A1  - Sutter, Christian
A1  - Kast, Karin
A1  - Fiebig, Britta
A1  - Schäfer, Dieter
A1  - Caldes, Trinidad
A1  - de la Hoya, Miguel
A1  - Nevanlinna, Heli
A1  - Muranen, Taru A.
A1  - Lespérance, Bernard
A1  - Spurdle, Amanda B.
A1  - Neuhausen, Susan L.
A1  - Ding, Yuan C.
A1  - Wang, Xianshu
A1  - Fredericksen, Zachary
A1  - Pankratz, Vernon S.
A1  - Lindor, Noralane M.
A1  - Peterlongo, Paulo
A1  - Manoukian, Siranoush
A1  - Peissel, Bernard
A1  - Zaffaroni, Daniela
A1  - Bonanni, Bernardo
A1  - Bernard, Loris
A1  - Dolcetti, Riccardo
A1  - Papi, Laura
A1  - Ottini, Laura
A1  - Radice, Paolo
A1  - Greene, Mark H.
A1  - Loud, Jennifer T.
A1  - Andrulis, Irene L.
A1  - Ozcelik, Hilmi
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Thomassen, Mads
A1  - Gerdes, Anne-Marie
A1  - Jensen, Uffe B.
A1  - Skytte, Anne-Bine
A1  - Kruse, Torben A.
A1  - Chenevix-Trench, Georgia
A1  - Couch, Fergus J.
A1  - Simard, Jacques
A1  - Easton, Douglas F.
T1  - Common variants at 12p11, 12q24, 9p21, 9q31.2 and in ZNF365 are associated with breast cancer risk for BRCA1 and/or BRCA2 mutation carriers
JF  - Breast Cancer Research
N2  - Introduction: Several common alleles have been shown to be associated with breast and/or ovarian cancer risk for BRCA1 and BRCA2 mutation carriers. Recent genome-wide association studies of breast cancer have identified eight additional breast cancer susceptibility loci: rs1011970 (9p21, CDKN2A/B), rs10995190 (ZNF365), rs704010 (ZMIZ1), rs2380205 (10p15), rs614367 (11q13), rs1292011 (12q24), rs10771399 (12p11 near PTHLH) and rs865686 (9q31.2). 
Methods: To evaluate whether these single nucleotide polymorphisms (SNPs) are associated with breast cancer risk for BRCA1 and BRCA2 carriers, we genotyped these SNPs in 12,599 BRCA1 and 7,132 BRCA2 mutation carriers and analysed the associations with breast cancer risk within a retrospective likelihood framework. 
Results: Only SNP rs10771399 near PTHLH was associated with breast cancer risk for BRCA1 mutation carriers (per-allele hazard ratio (HR) = 0.87, 95% CI: 0.81 to 0.94, P-trend = 3 x 10\(^{-4}\)). The association was restricted to mutations proven or predicted to lead to absence of protein expression (HR = 0.82, 95% CI: 0.74 to 0.90, P-trend = 3.1 x 10\(^{-5}\), P-difference = 0.03). Four SNPs were associated with the risk of breast cancer for BRCA2 mutation carriers: rs10995190, P-trend = 0.015; rs1011970, P-trend = 0.048; rs865686, 2df P = 0.007; rs1292011 2df P = 0.03. rs10771399 (PTHLH) was predominantly associated with estrogen receptor (ER)-negative breast cancer for BRCA1 mutation carriers (HR = 0.81, 95% CI: 0.74 to 0.90, P-trend = 4 x 10\(^{-5}\)) and there was marginal evidence of association with ER- negative breast cancer for BRCA2 mutation carriers (HR = 0.78, 95% CI: 0.62 to 1.00, P-trend = 0.049). 
Conclusions: The present findings, in combination with previously identified modifiers of risk, will ultimately lead to more accurate risk prediction and an improved understanding of the disease etiology in BRCA1 and BRCA2 mutation carriers.
KW  - investigators
KW  - genetic modifiers
KW  - mammographic density
KW  - susceptibility loci
KW  - ovarian cancer
KW  - hormone-related protein
KW  - genome-wide association
KW  - tumor subtypes
KW  - alleles
KW  - consortium
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130449
VL  - 14
IS  - R33
ER  - 
TY  - JOUR
A1  - Koch, Oliver
A1  - Cappel, Daniel
A1  - Nocker, Monika
A1  - Jäger, Timo
A1  - Flohé, Leopold
A1  - Sotriffer, Christoph A.
A1  - Selzer, Paul M.
T1  - Molecular Dynamics Reveal Binding Mode of Glutathionylspermidine by Trypanothione Synthetase
JF  - PLoS ONE
N2  - The trypanothione synthetase (TryS) catalyses the two-step biosynthesis of trypanothione from spermidine and glutathione and is an attractive new drug target for the development of trypanocidal and antileishmanial drugs, especially since the structural information of TryS from Leishmania major has become available. Unfortunately, the TryS structure was solved without any of the substrates and lacks loop regions that are mechanistically important. This contribution describes docking and molecular dynamics simulations that led to further insights into trypanothione biosynthesis and, in particular, explains the binding modes of substrates for the second catalytic step. The structural model essentially confirm previously proposed binding sites for glutathione, ATP and two \(Mg^{2+}\) ions, which appear identical for both catalytic steps. The analysis of an unsolved loop region near the proposed spermidine binding site revealed a new pocket that was demonstrated to bind glutathionylspermidine in an inverted orientation. For the second step of trypanothione synthesis glutathionylspermidine is bound in a way that preferentially allows \(N^1\)-glutathionylation of \(N^8\)-glutathionylspermidine, classifying \(N^8\)-glutathionylspermidine as the favoured substrate. By inhibitor docking, the binding site for \(N^8\)-glutathionylspermidine was characterised as druggable.
KW  - purification
KW  - crithidia fasciulata
KW  - trypanosoma cruzi
KW  - RESP model
KW  - biosynthesis
KW  - chemotherapy
KW  - metabolism
KW  - brucei
KW  - system
KW  - leishmaniasis
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-131070
VL  - 8
IS  - 2
ER  - 
TY  - JOUR
A1  - Oostinga, Jeroen B.
A1  - Maier, Luis
A1  - Schüffelgen, Peter
A1  - Knott, Daniel
A1  - Ames, Christopher
A1  - Brüne, Christoph
A1  - Tkachov, Grigory
A1  - Buhmann, Hartmut
A1  - Molenkamp, Laurens W.
T1  - Josephson Supercurrent through the Topological Surface States of Strained Bulk HgTe
JF  - Physical Review X
N2  - Strained bulk HgTe is a three-dimensional topological insulator, whose surface electrons have a high mobility (~ 30 000 cm\(^2\)=Vs), while its bulk is effectively free of mobile charge carriers. These properties enable a study of transport through its unconventional surface states without being hindered by a parallel bulk conductance. Here, we show transport experiments on HgTe-based Josephson junctions to investigate the appearance of the predicted Majorana states at the interface between a topological insulator and a superconductor. Interestingly, we observe a dissipationless supercurrent flow through the topological surface states of HgTe. The current-voltage characteristics are hysteretic at temperatures below 1 K, with critical supercurrents of several microamperes. Moreover, we observe a magnetic-field-induced Fraunhofer pattern of the critical supercurrent, indicating a dominant \(2\pi\)-periodic Josephson effect in the unconventional surface states. Our results show that strained bulk HgTe is a promising material system to get a better understanding of the Josephson effect in topological surface states, and to search for the manifestation of zero-energy Majorana states in transport experiments.
KW  - topological insulators
KW  - mesoscopics
KW  - superconductivity
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-129834
VL  - 3
IS  - 021007
ER  - 
TY  - JOUR
A1  - Osorio, Ana
A1  - Milne, Roger L.
A1  - Kuchenbaecker, Karoline
A1  - Vaclová, Tereza
A1  - Pita, Guillermo
A1  - Alonso, Rosario
A1  - Peterlongo, Paolo
A1  - Blanco, Ignacio
A1  - de la Hoya, Miguel
A1  - Duran, Mercedes
A1  - Diez, Orland
A1  - Ramón y Cajal, Teresa
A1  - Konstantopoulou, Irene
A1  - Martínez-Bouzas, Christina
A1  - Conejero, Raquel Andrés
A1  - Soucy, Penny
A1  - McGuffog, Lesley
A1  - Barrowdale, Daniel
A1  - Lee, Andrew
A1  - Arver, Brita
A1  - Rantala, Johanna
A1  - Loman, Niklas
A1  - Ehrencrona, Hans
A1  - Olopade, Olufunmilayo I.
A1  - Beattie, Mary S.
A1  - Domchek, Susan M.
A1  - Nathanson, Katherine
A1  - Rebbeck, Timothy R.
A1  - Arun, Banu K.
A1  - Karlan, Beth Y.
A1  - Walsh, Christine
A1  - Lester, Jenny
A1  - John, Esther M.
A1  - Whittemore, Alice S.
A1  - Daly, Mary B.
A1  - Southey, Melissa
A1  - Hopper, John
A1  - Terry, Mary B.
A1  - Buys, Saundra S.
A1  - Janavicius, Ramunas
A1  - Dorfling, Cecilia M.
A1  - van Rensburg, Elizabeth J.
A1  - Steele, Linda
A1  - Neuhausen, Susan L.
A1  - Ding, Yuan Chun
A1  - Hansen, Thomas V. O.
A1  - Jønson, Lars
A1  - Ejlertsen, Bent
A1  - Gerdes, Anne-Marie
A1  - Infante, Mar
A1  - Herráez, Belén
A1  - Moreno, Leticia Thais
A1  - Weitzel, Jeffrey N.
A1  - Herzog, Josef
A1  - Weeman, Kisa
A1  - Manoukian, Siranoush
A1  - Peissel, Bernard
A1  - Zaffaroni, Daniela
A1  - Scuvera, Guilietta
A1  - Bonanni, Bernardo
A1  - Mariette, Frederique
A1  - Volorio, Sara
A1  - Viel, Alessandra
A1  - Varesco, Liliana
A1  - Papi, Laura
A1  - Ottini, Laura
A1  - Tibiletti, Maria Grazia
A1  - Radice, Paolo
A1  - Yannoukakos, Drakoulis
A1  - Garber, Judy
A1  - Ellis, Steve
A1  - Frost, Debra
A1  - Platte, Radka
A1  - Fineberg, Elena
A1  - Evans, Gareth
A1  - Lalloo, Fiona
A1  - Izatt, Louise
A1  - Eeles, Ros
A1  - Adlard, Julian
A1  - Davidson, Rosemarie
A1  - Cole, Trevor
A1  - Eccles, Diana
A1  - Cook, Jackie
A1  - Hodgson, Shirley
A1  - Brewer, Carole
A1  - Tischkowitz, Marc
A1  - Douglas, Fiona
A1  - Porteous, Mary
A1  - Side, Lucy
A1  - Walker, Lisa
A1  - Morrison, Patrick
A1  - Donaldson, Alan
A1  - Kennedy, John
A1  - Foo, Claire
A1  - Godwin, Andrew K.
A1  - Schmutzler, Rita Katharina
A1  - Wappenschmidt, Barbara
A1  - Rhiem, Kerstin
A1  - Engel, Christoph
A1  - Meindl, Alftons
A1  - Ditsch, Nina
A1  - Arnold, Norbert
A1  - Plendl, Hans Jörg
A1  - Niederacher, Dieter
A1  - Sutter, Christian
A1  - Wang-Gohrke, Shan
A1  - Steinemann, Doris
A1  - Preisler-Adams, Sabine
A1  - Kast, Karin
A1  - Varon-Mateeva, Raymonda
A1  - Gehrig, Andrea
A1  - Stoppa-Lyonnet, Dominique
A1  - Sinilnikova, Olga M.
A1  - Mazoyer, Sylvie
A1  - Damiola, Francesca
A1  - Poppe, Bruce
A1  - Claes, Kathleen
A1  - Piedmonte, Marion
A1  - Tucker, Kathy
A1  - Backes, Floor
A1  - Rodríguez, Gustavo
A1  - Brewster, Wendy
A1  - Wakeley, Katie
A1  - Rutherford, Thomas
A1  - Caldés, Trinidad
A1  - Nevanlinna, Heli
A1  - Aittomäki, Kristiina
A1  - Rookus, Matti A.
A1  - van Os, Theo A. M.
A1  - van der Kolk, Lizet
A1  - de Lange, J. L.
A1  - Meijers-Heijboer, Hanne E. J.
A1  - van der Hout, A. H.
A1  - van Asperen, Christi J.
A1  - Goméz Garcia, Encarna B.
A1  - Encarna, B.
A1  - Hoogerbrugge, Nicoline
A1  - Collée, J. Margriet
A1  - van Deurzen, Carolien H. M.
A1  - van der Luijt, Rob B.
A1  - Devilee, Peter
A1  - Olah, Edith
A1  - Lázaro, Conxi
A1  - Teulé, Alex
A1  - Menéndez, Mireia
A1  - Jakubowska, Anna
A1  - Cybulski, Cezary
A1  - Gronwald, Jecek
A1  - Lubinski, Jan
A1  - Durda, Katarzyna
A1  - Jaworska-Bieniek, Katarzyna
A1  - Johannsson, Oskar Th.
A1  - Maugard, Christine
A1  - Montagna, Marco
A1  - Tognazzo, Silvia
A1  - Teixeira, Manuel R.
A1  - Healey, Sue
A1  - Olswold, Curtis
A1  - Guidugli, Lucia
A1  - Lindor, Noralane
A1  - Slager, Susan
A1  - Szabo, Csilla I.
A1  - Vijai, Joseph
A1  - Robson, Mark
A1  - Kauff, Noah
A1  - Zhang, Liying
A1  - Rau-Murthy, Rohini
A1  - Fink-Retter, Anneliese
A1  - Singer, Christine F.
A1  - Rappaport, Christine
A1  - Kaulich, Daphne Geschwantler
A1  - Pfeiler, Georg
A1  - Tea, Muy-Kheng
A1  - Berger, Andreas
A1  - Phelan, Catherine M.
A1  - Greene, Mark H.
A1  - Mai, Phuong L.
A1  - Lejbkowicz, Flavio
A1  - Andrulis, Irene
A1  - Mulligan, Anna Marie
A1  - Glendon, Gord
A1  - Toland, Amanda Ewart
A1  - Bojesen, Anders
A1  - Pedersen, Inge Sokilde
A1  - Sunde, Lone
A1  - Thomassen, Mads
A1  - Kruse, Torben A.
A1  - Jensen, Uffe Birk
A1  - Friedman, Eitan
A1  - Laitman, Yeal
A1  - Shimon, Shanie Paluch
A1  - Simard, Jaques
A1  - Easton, Douglas F.
A1  - Offit, Kenneth
A1  - Couch, Fergus J.
A1  - Chenevix-Trench, Georgia
A1  - Antoniou, Antonis C.
A1  - Benitez, Javier
T1  - DNA Glycosylases Involved in Base Excision Repair May Be Associated with Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
JF  - PLOS Genetics
N2  - Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7x10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95% CI: 1.03-1.21, p = 4.8x10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
KW  - single-nucleotide polymorphisms
KW  - breast cancer
KW  - ovarian cancer
KW  - genetic modifiers
KW  - common variants
KW  - NEIL2
KW  - OGG1
KW  - investigators
KW  - consortium
KW  - damage
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-116820
SN  - 1553-7404
VL  - 4
IS  - e1004256
ER  - 
TY  - JOUR
A1  - Fruchart, Jean-Charles
A1  - Davignon, Jean
A1  - Hermans, Michael P.
A1  - Al-Rubeaan, Khalid
A1  - Amarenco, Pierre
A1  - Assmann, Gerd
A1  - Barter, Philip
A1  - Betteridge, John
A1  - Bruckert, Eric
A1  - Cuevas, Ada
A1  - Farnier, Michel
A1  - Ferrannini, Ele
A1  - Fioretto, Paola
A1  - Genest, Jacques
A1  - Ginsberg, Henry N.
A1  - Gotto Jr., Antonio M.
A1  - Hu, Dayi
A1  - Kadowaki, Takashi
A1  - Kodama, Tatsuhiko
A1  - Krempf, Michel
A1  - Matsuzawa, Yuji
A1  - Núñez-Cortés, Jesús Millán
A1  - Monfil, Calos Calvo
A1  - Ogawa, Hisao
A1  - Plutzky, Jorge
A1  - Rader, Daniel J.
A1  - Sadikot, Shaukat
A1  - Santos, Raul D.
A1  - Shlyakhto, Evgeny
A1  - Sritara, Piyamitr
A1  - Sy, Rody
A1  - Tall, Alan
A1  - Tan, Chee Eng
A1  - Tokgözoğlu, Lale
A1  - Toth, Peter P.
A1  - Valensi, Paul
A1  - Wanner, Christoph
A1  - Zambon, Albertro
A1  - Zhu, Junren
A1  - Zimmet, Paul
T1  - Residual macrovascular risk in 2013: what have we learned?
JF  - Cardiovascual Diabetology
N2  - Cardiovascular disease poses a major challenge for the 21st century, exacerbated by the pandemics of obesity, metabolic syndrome and type 2 diabetes. While best standards of care, including high-dose statins, can ameliorate the risk of vascular complications, patients remain at high risk of cardiovascular events. The Residual Risk Reduction Initiative (R(3)i) has previously highlighted atherogenic dyslipidaemia, defined as the imbalance between proatherogenic triglyceride-rich apolipoprotein B-containing-lipoproteins and antiatherogenic apolipoprotein A-I-lipoproteins (as in high-density lipoprotein, HDL), as an important modifiable contributor to lipid-related residual cardiovascular risk, especially in insulin-resistant conditions. As part of its mission to improve awareness and clinical management of atherogenic dyslipidaemia, the R(3)i has identified three key priorities for action: i) to improve recognition of atherogenic dyslipidaemia in patients at high cardiometabolic risk with or without diabetes; ii) to improve implementation and adherence to guideline-based therapies; and iii) to improve therapeutic strategies for managing atherogenic dyslipidaemia. The R(3)i believes that monitoring of non-HDL cholesterol provides a simple, practical tool for treatment decisions regarding the management of lipid-related residual cardiovascular risk. Addition of a fibrate, niacin (North and South America), omega-3 fatty acids or ezetimibe are all options for combination with a statin to further reduce non-HDL cholesterol, although lacking in hard evidence for cardiovascular outcome benefits. Several emerging treatments may offer promise. These include the next generation peroxisome proliferator-activated receptor alpha agonists, cholesteryl ester transfer protein inhibitors and monoclonal antibody therapy targeting proprotein convertase subtilisin/kexin type 9. However, long-term outcomes and safety data are clearly needed. In conclusion, the R(3)i believes that ongoing trials with these novel treatments may help to define the optimal management of atherogenic dyslipidaemia to reduce the clinical and socioeconomic burden of residual cardiovascular risk.
KW  - phospholipid fatty acids
KW  - term fenofibrate therapy
KW  - cardiovascular munster procam
KW  - residual cardiovascular risk
KW  - atherogenic dyslipidaemia
KW  - type 2 diabetes
KW  - therapeutic options
KW  - high denisty lipoprotein
KW  - randomized controlled-trial
KW  - coronary artery disease
KW  - type-2 diabetes mellitus
KW  - triglyceride-rich lipoproteins
KW  - alpha/delta agonist GFT505
KW  - placebo-controlled trial
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117546
SN  - 1475-2840
VL  - 13
IS  - 26
ER  - 
TY  - JOUR
A1  - Üçeyler, Nurcan
A1  - Kahn, Ann-Kathrin
A1  - Kramer, Daniela
A1  - Zeller, Daniel
A1  - Casanova-Molla, Jordi
A1  - Wanner, Christoph
A1  - Weidemann, Frank
A1  - Katsarava, Zaza
A1  - Sommer, Claudia
T1  - Impaired small fiber conduction in patients with Fabry disease: a neurophysiological case–control study
JF  - BMC Neurology
N2  - Background

Fabry disease is an inborn lysosomal storage disorder which is associated with small fiber neuropathy. We set out to investigate small fiber conduction in Fabry patients using pain-related evoked potentials (PREP).

Methods

In this case–control study we prospectively studied 76 consecutive Fabry patients for electrical small fiber conduction in correlation with small fiber function and morphology. Data were compared with healthy controls using non-parametric statistical tests. All patients underwent neurological examination and were investigated with pain and depression questionnaires. Small fiber function (quantitative sensory testing, QST), morphology (skin punch biopsy), and electrical conduction (PREP) were assessed and correlated. Patients were stratified for gender and disease severity as reflected by renal function.

Results

All Fabry patients (31 men, 45 women) had small fiber neuropathy. Men with Fabry disease showed impaired cold (p < 0.01) and warm perception (p < 0.05), while women did not differ from controls. Intraepidermal nerve fiber density (IENFD) was reduced at the lower leg (p < 0.001) and the back (p < 0.05) mainly of men with impaired renal function. When investigating A-delta fiber conduction with PREP, men but not women with Fabry disease had lower amplitudes upon stimulation at face (p < 0.01), hands (p < 0.05), and feet (p < 0.01) compared to controls. PREP amplitudes further decreased with advance in disease severity. PREP amplitudes and warm (p < 0.05) and cold detection thresholds (p < 0.01) at the feet correlated positively in male patients.

Conclusion

Small fiber conduction is impaired in men with Fabry disease and worsens with advanced disease severity. PREP are well-suited to measure A-delta fiber conduction.
KW  - Fabry disease
KW  - Pain-related evoked potentials
KW  - Small fiber neuropathy
KW  - A-delta fibers
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96527
UR  - http://www.biomedcentral.com/1471-2377/13/47
ER  - 
TY  - JOUR
A1  - Kraft, Peter
A1  - Fleischer, Anna
A1  - Wiedmann, Silke
A1  - Rücker, Viktoria
A1  - Mackenrodt, Daniel
A1  - Morbach, Caroline
A1  - Malzahn, Uwe
A1  - Kleinschnitz, Christoph
A1  - Störk, Stefan
A1  - Heuschmann, Peter U.
T1  - Feasibility and diagnostic accuracy of point-of-care handheld echocardiography in acute ischemic stroke patients - a pilot study
JF  - BMC Neurology
N2  - Background:
Standard echocardiography (SE) is an essential part of the routine diagnostic work-up after ischemic stroke (IS) and also serves for research purposes. However, access to SE is often limited. We aimed to assess feasibility and accuracy of point-of-care (POC) echocardiography in a stroke unit (SU) setting.

Methods:
IS patients were recruited on the SU of the University Hospital Würzburg, Germany. Two SU team members were trained in POC echocardiography for a three-month period to assess a set of predefined cardiac parameters including left ventricular ejection fraction (LVEF). Diagnostic agreement was assessed by comparing POC with SE executed by an expert sonographer, and intraclass correlation coefficient (ICC) or kappa (κ) with 95% confidence intervals (95% CI) were calculated.

Results:
In the 78 patients receiving both POC and SE agreement for cardiac parameters was good, with ICC varying from 0.82 (95% CI 0.71–0.89) to 0.93 (95% CI 0.87–0.96), and κ from 0.39 (−95% CI 0.14–0.92) to 0.79 (95% CI 0.67–0.91). Detection of systolic dysfunction with POC echocardiography compared to SE was very good, with an area under the curve of 0.99 (0.96–1.00). Interrater agreement for LVEF measured by POC echocardiography was good with κ 0.63 (95% CI 0.40–0.85).

Conclusions:
POC echocardiography in a SU setting is feasible enabling reliable quantification of LVEF and preliminary assessment of selected cardiac parameters that might be used for research purposes. Its potential clinical utility in triaging stroke patients who should undergo or do not necessarily require SE needs to be investigated in larger prospective diagnostic studies.
KW  - ischemic stroke
KW  - systolic dysfunction
KW  - point-of-care echocardiography
KW  - ejection fraction
KW  - stroke unit
KW  - feasibility
KW  - accuracy
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-158081
VL  - 17
IS  - 159
ER  - 
TY  - JOUR
A1  - Lenschow, Christina
A1  - Fuss, Carmina Teresa
A1  - Kircher, Stefan
A1  - Buck, Andreas
A1  - Kickuth, Ralph
A1  - Reibetanz, Joachim
A1  - Wiegering, Armin
A1  - Stenzinger, Albrecht
A1  - Hübschmann, Daniel
A1  - Germer, Christoph Thomas
A1  - Fassnacht, Martin
A1  - Fröhling, Stefan
A1  - Schlegel, Nicolas
A1  - Kroiss, Matthias
T1  - Case Report: Abdominal Lymph Node Metastases of Parathyroid Carcinoma: Diagnostic Workup, Molecular Diagnosis, and Clinical Management
JF  - Frontiers in Endocrinology
N2  - Parathyroid carcinoma (PC) is an orphan malignancy accounting for only ~1% of all cases with primary hyperparathyroidism. The localization of recurrent PC is of critical importance and can be exceedingly difficult to diagnose and sometimes futile when common sites of recurrence in the neck and chest cannot be confirmed. Here, we present the diagnostic workup, molecular analysis and multimodal therapy of a 46-year old woman with the extraordinary manifestation of abdominal lymph node metastases 12 years after primary diagnosis of PC. The patient was referred to our endocrine tumor center in 2016 with the aim to localize the tumor causative of symptomatic biochemical recurrence. In view of the extensive previous workup we decided to perform [18F]FDG-PET-CT. A pathological lymph node in the liver hilus showed slightly increased FDG-uptake and hence was suspected as site of recurrence. Selective venous sampling confirmed increased parathyroid hormone concentration in liver veins. Abdominal lymph node metastasis was resected and histopathological examination confirmed PC. Within four months, the patient experienced biochemical recurrence and based on high tumor mutational burden detected in the surgical specimen by whole exome sequencing the patient received immunotherapy with pembrolizumab that led to a biochemical response. Subsequent to disease progression repeated abdominal lymph node resection was performed in 10/2018, 01/2019 and in 01/2020. Up to now (12/2020) the patient is biochemically free of disease. In conclusion, a multimodal diagnostic approach and therapy in an interdisciplinary setting is needed for patients with rare endocrine tumors. Molecular analyses may inform additional treatment options including checkpoint inhibitors such as pembrolizumab.
KW  - parathyroid carcinoma
KW  - abdominal lymph node metastases
KW  - molecular diagnostics
KW  - repeated surgery
KW  - [18F]FDG-PET-CT
KW  - immune check inhibitor
KW  - pembrolizumab
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-233362
SN  - 1664-2392
VL  - 12
ER  -