TY  - JOUR
A1  - Manchia, Mirko
A1  - Adli, Mazda
A1  - Akula, Nirmala
A1  - Arda, Raffaella
A1  - Aubry, Jean-Michel
A1  - Backlund, Lena
A1  - Banzato, Claudio E. M.
A1  - Baune, Bernhard T.
A1  - Bellivier, Frank
A1  - Bengesser, Susanne
A1  - Biernacka, Joanna M.
A1  - Brichant-Petitjean, Clara
A1  - Bui, Elise
A1  - Calkin, Cynthia V.
A1  - Cheng, Andrew Tai Ann
A1  - Chillotti, Caterina
A1  - Cichon, Sven
A1  - Clark, Scott
A1  - Czerski, Piotr M.
A1  - Dantas, Clarissa
A1  - Del Zompo, Maria
A1  - DePaulo, J. Raymond
A1  - Detera-Wadleigh, Sevilla D.
A1  - Etain, Bruno
A1  - Falkai, Peter
A1  - Frisén, Louise
A1  - Frye, Mark A.
A1  - Fullerton, Jan
A1  - Gard, Sébastien
A1  - Garnham, Julie
A1  - Goes, Fernando S.
A1  - Grof, Paul
A1  - Gruber, Oliver
A1  - Hashimoto, Ryota
A1  - Hauser, Joanna
A1  - Heilbronner, Urs
A1  - Hoban, Rebecca
A1  - Hou, Liping
A1  - Jamain, Stéphane
A1  - Kahn, Jean-Pierre
A1  - Kassem, Layla
A1  - Kato, Tadafumi
A1  - Kelsoe, John R.
A1  - Kittel-Schneider, Sarah
A1  - Kliwicki, Sebastian
A1  - Kuo, Po-Hsiu
A1  - Kusumi, Ichiro
A1  - Laje, Gonzalo
A1  - Lavebratt, Catharina
A1  - Leboyer, Marion
A1  - Leckband, Susan G.
A1  - López Jaramillo, Carlos A.
A1  - Maj, Mario
A1  - Malafosse, Alain
A1  - Martinsson, Lina
A1  - Masui, Takuya
A1  - Mitchell, Philip B.
A1  - Mondimore, Frank
A1  - Monteleone, Palmiero
A1  - Nallet, Audrey
A1  - Neuner, Maria
A1  - Novák, Tomás
A1  - O'Donovan, Claire
A1  - Ösby, Urban
A1  - Ozaki, Norio
A1  - Perlis, Roy H.
A1  - Pfennig, Andrea
A1  - Potash, James B.
A1  - Reich-Erkelenz, Daniela
A1  - Reif, Andreas
A1  - Reininghaus, Eva
A1  - Richardson, Sara
A1  - Rouleau, Guy A.
A1  - Rybakowski, Janusz K.
A1  - Schalling, Martin
A1  - Schofield, Peter R.
A1  - Schubert, Oliver K.
A1  - Schweizer, Barbara
A1  - Seemüller, Florian
A1  - Grigoroiu-Serbanescu, Maria
A1  - Severino, Giovanni
A1  - Seymour, Lisa R.
A1  - Slaney, Claire
A1  - Smoller, Jordan W.
A1  - Squassina, Alessio
A1  - Stamm, Thomas
A1  - Steele, Jo
A1  - Stopkova, Pavla
A1  - Tighe, Sarah K.
A1  - Tortorella, Alfonso
A1  - Turecki, Gustavo
A1  - Wray, Naomi R.
A1  - Wright, Adam
A1  - Zandi, Peter P.
A1  - Zilles, David
A1  - Bauer, Michael
A1  - Rietschel, Marcella
A1  - McMahon, Francis J.
A1  - Schulze, Thomas G.
A1  - Alda, Martin
T1  - Assessment of Response to Lithium Maintenance Treatment in Bipolar Disorder: A Consortium on Lithium Genetics (ConLiGen) Report
JF  - PLoS ONE
N2  - Objective: The assessment of response to lithium maintenance treatment in bipolar disorder (BD) is complicated by variable length of treatment, unpredictable clinical course, and often inconsistent compliance. Prospective and retrospective methods of assessment of lithium response have been proposed in the literature. In this study we report the key phenotypic measures of the "Retrospective Criteria of Long-Term Treatment Response in Research Subjects with Bipolar Disorder" scale currently used in the Consortium on Lithium Genetics (ConLiGen) study. 
Materials and Methods: Twenty-nine ConLiGen sites took part in a two-stage case-vignette rating procedure to examine inter-rater agreement [Kappa (\(\kappa\))] and reliability [intra-class correlation coefficient (ICC)] of lithium response. Annotated first-round vignettes and rating guidelines were circulated to expert research clinicians for training purposes between the two stages. Further, we analyzed the distributional properties of the treatment response scores available for 1,308 patients using mixture modeling. 
Results: Substantial and moderate agreement was shown across sites in the first and second sets of vignettes (\(\kappa\) = 0.66 and \(\kappa\) = 0.54, respectively), without significant improvement from training. However, definition of response using the A score as a quantitative trait and selecting cases with B criteria of 4 or less showed an improvement between the two stages (\(ICC_1 = 0.71\) and \(ICC_2 = 0.75\), respectively). Mixture modeling of score distribution indicated three subpopulations (full responders, partial responders, non responders). 
Conclusions: We identified two definitions of lithium response, one dichotomous and the other continuous, with moderate to substantial inter-rater agreement and reliability. Accurate phenotypic measurement of lithium response is crucial for the ongoing ConLiGen pharmacogenomic study.
KW  - age
KW  - observer agreement
KW  - prophylactic lithium
KW  - mapping susceptibility genes
KW  - mood disorders
KW  - onset
KW  - association
KW  - reliability
KW  - morality
KW  - illness
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130938
VL  - 8
IS  - 6
ER  - 
TY  - JOUR
A1  - El-Helou, Sabine M.
A1  - Biegner, Anika-Kerstin
A1  - Bode, Sebastian
A1  - Ehl, Stephan R.
A1  - Heeg, Maximilian
A1  - Maccari, Maria E.
A1  - Ritterbusch, Henrike
A1  - Speckmann, Carsten
A1  - Rusch, Stephan
A1  - Scheible, Raphael
A1  - Warnatz, Klaus
A1  - Atschekzei, Faranaz
A1  - Beider, Renata
A1  - Ernst, Diana
A1  - Gerschmann, Stev
A1  - Jablonka, Alexandra
A1  - Mielke, Gudrun
A1  - Schmidt, Reinhold E.
A1  - Schürmann, Gesine
A1  - Sogkas, Georgios
A1  - Baumann, Ulrich H.
A1  - Klemann, Christian
A1  - Viemann, Dorothee
A1  - Bernuth, Horst von
A1  - Krüger, Renate
A1  - Hanitsch, Leif G.
A1  - Scheibenbogen, Carmen M.
A1  - Wittke, Kirsten
A1  - Albert, Michael H.
A1  - Eichinger, Anna
A1  - Hauck, Fabian
A1  - Klein, Christoph
A1  - Rack-Hoch, Anita
A1  - Sollinger, Franz M.
A1  - Avila, Anne
A1  - Borte, Michael
A1  - Borte, Stephan
A1  - Fasshauer, Maria
A1  - Hauenherm, Anja
A1  - Kellner, Nils
A1  - Müller, Anna H.
A1  - Ülzen, Anett
A1  - Bader, Peter
A1  - Bakhtiar, Shahrzad
A1  - Lee, Jae-Yun
A1  - Heß, Ursula
A1  - Schubert, Ralf
A1  - Wölke, Sandra
A1  - Zielen, Stefan
A1  - Ghosh, Sujal
A1  - Laws, Hans-Juergen
A1  - Neubert, Jennifer
A1  - Oommen, Prasad T.
A1  - Hönig, Manfred
A1  - Schulz, Ansgar
A1  - Steinmann, Sandra
A1  - Klaus, Schwarz
A1  - Dückers, Gregor
A1  - Lamers, Beate
A1  - Langemeyer, Vanessa
A1  - Niehues, Tim
A1  - Shai, Sonu
A1  - Graf, Dagmar
A1  - Müglich, Carmen
A1  - Schmalzing, Marc T.
A1  - Schwaneck, Eva C.
A1  - Tony, Hans-Peter
A1  - Dirks, Johannes
A1  - Haase, Gabriele
A1  - Liese, Johannes G.
A1  - Morbach, Henner
A1  - Foell, Dirk
A1  - Hellige, Antje
A1  - Wittkowski, Helmut
A1  - Masjosthusmann, Katja
A1  - Mohr, Michael
A1  - Geberzahn, Linda
A1  - Hedrich, Christian M.
A1  - Müller, Christiane
A1  - Rösen-Wolff, Angela
A1  - Roesler, Joachim
A1  - Zimmermann, Antje
A1  - Behrends, Uta
A1  - Rieber, Nikolaus
A1  - Schauer, Uwe
A1  - Handgretinger, Rupert
A1  - Holzer, Ursula
A1  - Henes, Jörg
A1  - Kanz, Lothar
A1  - Boesecke, Christoph
A1  - Rockstroh, Jürgen K.
A1  - Schwarze-Zander, Carolynne
A1  - Wasmuth, Jan-Christian
A1  - Dilloo, Dagmar
A1  - Hülsmann, Brigitte
A1  - Schönberger, Stefan
A1  - Schreiber, Stefan
A1  - Zeuner, Rainald
A1  - Ankermann, Tobias
A1  - Bismarck, Philipp von
A1  - Huppertz, Hans-Iko
A1  - Kaiser-Labusch, Petra
A1  - Greil, Johann
A1  - Jakoby, Donate
A1  - Kulozik, Andreas E.
A1  - Metzler, Markus
A1  - Naumann-Bartsch, Nora
A1  - Sobik, Bettina
A1  - Graf, Norbert
A1  - Heine, Sabine
A1  - Kobbe, Robin
A1  - Lehmberg, Kai
A1  - Müller, Ingo
A1  - Herrmann, Friedrich
A1  - Horneff, Gerd
A1  - Klein, Ariane
A1  - Peitz, Joachim
A1  - Schmidt, Nadine
A1  - Bielack, Stefan
A1  - Groß-Wieltsch, Ute
A1  - Classen, Carl F.
A1  - Klasen, Jessica
A1  - Deutz, Peter
A1  - Kamitz, Dirk
A1  - Lassy, Lisa
A1  - Tenbrock, Klaus
A1  - Wagner, Norbert
A1  - Bernbeck, Benedikt
A1  - Brummel, Bastian
A1  - Lara-Villacanas, Eusebia
A1  - Münstermann, Esther
A1  - Schneider, Dominik T.
A1  - Tietsch, Nadine
A1  - Westkemper, Marco
A1  - Weiß, Michael
A1  - Kramm, Christof
A1  - Kühnle, Ingrid
A1  - Kullmann, Silke
A1  - Girschick, Hermann
A1  - Specker, Christof
A1  - Vinnemeier-Laubenthal, Elisabeth
A1  - Haenicke, Henriette
A1  - Schulz, Claudia
A1  - Schweigerer, Lothar
A1  - Müller, Thomas G.
A1  - Stiefel, Martina
A1  - Belohradsky, Bernd H.
A1  - Soetedjo, Veronika
A1  - Kindle, Gerhard
A1  - Grimbacher, Bodo
T1  - The German national registry of primary immunodeficiencies (2012-2017)
JF  - Frontiers in Immunology
N2  - Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. 

Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. 

Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE-syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. 

Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
KW  - registry for primary immunodeficiency
KW  - primary immunodeficiency (PID)
KW  - German PID-NET registry
KW  - PID prevalence
KW  - European Society for Immunodeficiencies (ESID)
KW  - IgG substitution therapy
KW  - CVID
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226629
VL  - 10
ER  - 
TY  - JOUR
A1  - Wächtler, Maria
A1  - Kübel, Joachim
A1  - Barthelmes, Kevin
A1  - Winter, Andreas
A1  - Schmiedel, Alexander
A1  - Pascher, Torbjörn
A1  - Lambert, Christoph
A1  - Schubert, Ulrich S.
A1  - Dietzek, Benjamin
T1  - Energy transfer and formation of long-lived \(^3\)MLCT states in multimetallic complexes with extended highly conjugated bis-terpyridyl ligands
JF  - Physical Chemistry Chemical Physics
N2  - Multimetallic complexes with extended and highly conjugated bis-2,2':6',2''-terpyridyl bridging ligands, which present building blocks for coordination polymers, are investigated with respect to their ability to act as light-harvesting antennae. The investigated species combine Ru(II)- with Os(II)- and Fe(II)-terpyridyl chromophores, the latter acting as energy sinks. Due to the extended conjugated system the ligands are able to prolong the lifetime of the \(^3\)MLCT states compared to unsubstituted terpyridyl species by delocalization and energetic stabilization of the \(^3\)MLCT states. This concept is applied for the first time to Fe(II) terpyridyl species and results in an exceptionally long lifetime of 23 ps for the Fe(II) \(^3\)MLCT state. While partial energy (>80%) transfer is observed between the Ru(II) and Fe(II) centers with a time-constant of 15 ps, excitation energy is transferred completely from the Ru(II) to the Os(II) center within the first 200 fs after excitation.
KW  - polypyridyl complexes
KW  - bis-terpyridyl ligands
KW  - multimetallic complexes
KW  - metal-to-ligand charge transfer (MLCT)
KW  - RU-(II) complexes
KW  - Ru(II)–Fe(II)–Ru(II) complex
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-191041
VL  - 18
IS  - 4
ER  - 
TY  - JOUR
A1  - Schubert, Maria
A1  - Joniau, Steven
A1  - Gontero, Paolo
A1  - Kneitz, Susanne
A1  - Scholz, Claus-Jürgen
A1  - Kneitz, Burkhard
A1  - Briganti, Alberto
A1  - Karnes, R. Jeffery
A1  - Tombal, Bertrand
A1  - Walz, Jochen
A1  - Hsu, Chao-Yu
A1  - Marchioro, Giansilvio
A1  - Bader, Pia
A1  - Bangma, Chris
A1  - Frohneberg, Detlef
A1  - Graefen, Markus
A1  - Schröder, Fritz
A1  - van Cangh, Paul
A1  - van Poppel, Hein
A1  - Spahn, Martin
T1  - The Role of Adjuvant Hormonal Treatment after Surgery for Localized High-Risk Prostate Cancer: Results of a Matched Multiinstitutional Analysis
JF  - Advances in Urology
N2  - Introduction. To assess the role of adjuvant androgen deprivation therapy (ADT) in high-risk prostate cancer patients (PCa) after surgery. Materials and Methods. The analysis case matched 172 high-risk PCa patients with positive section margins or non-organ confined disease and negative lymph nodes to receive adjuvant ADT (group 1, n=86 ) or no adjuvant ADT (group 2, n=86). Results. Only 11.6% of the patients died, 2.3% PCa related. Estimated 5–10-year clinical progression-free survival was 96.9% (94.3%) for group 1 and 73.7% (67.0%) for group 2, respectively. Subgroup analysis identified men with T2/T3a tumors at low-risk and T3b margins positive disease at higher risk for progression. Conclusion. Patients with T2/T3a tumors are at low-risk for metastatic disease and cancer-related death and do not need adjuvant ADT. We identified men with T3b margin positive disease at highest risk for clinical progression. These patients benefit from immediate adjuvant ADT.
KW  - prostate cancer
KW  - adjuvant hormonal treatment
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-137712
VL  - 2012
ER  - 
TY  - JOUR
A1  - Schubert, Maria
A1  - Spahn, Martin
A1  - Kneitz, Susanne
A1  - Scholz, Claus Jürgen
A1  - Joniau, Steven
A1  - Stroebel, Philipp
A1  - Riedmiller, Hubertus
A1  - Kneitz, Burkhard
T1  - Distinct microRNA Expression Profile in Prostate Cancer Patients with Early Clinical Failure and the Impact of let-7 as Prognostic Marker in High-Risk Prostate Cancer
JF  - PLoS ONE
N2  - Background

The identification of additional prognostic markers to improve risk stratification and to avoid overtreatment is one of the most urgent clinical needs in prostate cancer (PCa). MicroRNAs, being important regulators of gene expression, are promising biomarkers in various cancer entities, though the impact as prognostic predictors in PCa is poorly understood. The aim of this study was to identify specific miRNAs as potential prognostic markers in high-risk PCa and to validate their clinical impact.

Methodology and Principal Findings

We performed miRNA-microarray analysis in a high-risk PCa study group selected by their clinical outcome (clinical progression free survival (CPFS) vs. clinical failure (CF)). We identified seven candidate miRNAs (let-7a/b/c, miR-515-3p/5p, -181b, -146b, and -361) that showed differential expression between both groups. Further qRT-PCR analysis revealed down-regulation of members of the let-7 family in the majority of a large, well-characterized high-risk PCa cohort (n = 98). Expression of let-7a/b/and -c was correlated to clinical outcome parameters of this group. While let-7a showed no association or correlation with clinical relevant data, let-7b and let-7c were associated with CF in PCa patients and functioned partially as independent prognostic marker. Validation of the data using an independent high-risk study cohort revealed that let-7b, but not let-7c, has impact as an independent prognostic marker for BCR and CF. Furthermore, we identified HMGA1, a non-histone protein, as a new target of let-7b and found correlation of let-7b down-regulation with HMGA1 over-expression in primary PCa samples.

Conclusion

Our findings define a distinct miRNA expression profile in PCa cases with early CF and identified let-7b as prognostic biomarker in high-risk PCa. This study highlights the importance of let-7b as tumor suppressor miRNA in high-risk PCa and presents a basis to improve individual therapy for high-risk PCa patients.
KW  - biomarkers
KW  - gene expression
KW  - gene targeting
KW  - luciferase
KW  - MircoRNA
KW  - microarrays
KW  - oncogenes
KW  - prostate cancer
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-96825
ER  - 
TY  - JOUR
A1  - Brodehl, Andreas
A1  - Meshkov, Alexey
A1  - Myasnikov, Roman
A1  - Kiseleva, Anna
A1  - Kulikova, Olga
A1  - Klauke, Bärbel
A1  - Sotnikova, Evgeniia
A1  - Stanasiuk, Caroline
A1  - Divashuk, Mikhail
A1  - Pohl, Greta Marie
A1  - Kudryavtseva, Maria
A1  - Klingel, Karin
A1  - Gerull, Brenda
A1  - Zharikova, Anastasia
A1  - Gummert, Jan
A1  - Koretskiy, Sergey
A1  - Schubert, Stephan
A1  - Mershina, Elena
A1  - Gärtner, Anna
A1  - Pilus, Polina
A1  - Laser, Kai Thorsten
A1  - Sinitsyn, Valentin
A1  - Boytsov, Sergey
A1  - Drapkina, Oxana
A1  - Milting, Hendrik
T1  - Hemi- and homozygous loss-of-function mutations in DSG2 (desmoglein-2) cause recessive arrhythmogenic cardiomyopathy with an early onset
JF  - International Journal of Molecular Sciences
N2  - About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.
KW  - desmoglein-2
KW  - desmocollin-2
KW  - DSG2
KW  - DSC2
KW  - ARVC
KW  - ACM
KW  - LVNC
KW  - cardiomyopathy
KW  - desmosomes
KW  - desmin
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285279
SN  - 1422-0067
VL  - 22
IS  - 7
ER  -