TY - JOUR A1 - Sinn, Stefan A1 - Eichler, Mirjam A1 - Müller, Lothar A1 - Bünger, Daniel A1 - Groll, Jüergen A1 - Ziemer, Gerhard A1 - Rupp, Frank A1 - Northoff, Hinnak A1 - Geis-Gerstorfer, Jürgen A1 - Gehring, Frank K. A1 - Wendel, Hans P. T1 - NCO-sP(EO-stat-PO) Coatings on Gold Sensors-a QCM Study of Hemocompatibility JF - Sensors N2 - The reliability of implantable blood sensors is often hampered by unspecific adsorption of plasma proteins and blood cells. This not only leads to a loss of sensor signal over time, but can also result in undesired host vs. graft reactions. Within this study we evaluated the hemocompatibility of isocyanate conjugated star shaped polytheylene oxide-polypropylene oxide co-polymers NCO-sP(EO-stat-PO) when applied to gold surfaces as an auspicious coating material for gold sputtered blood contacting sensors. Quartz crystal microbalance (QCM) sensors were coated with ultrathin NCO-sP(EO-stat-PO) films and compared with uncoated gold sensors. Protein resistance was assessed by QCM measurements with fibrinogen solution and platelet poor plasma (PPP), followed by quantification of fibrinogen adsorption. Hemocompatibility was tested by incubation with human platelet rich plasma (PRP). Thrombin antithrombin-III complex (TAT), beta-thromboglobulin (beta-TG) and platelet factor 4 (PF4) were used as coagulation activation markers. Furthermore, scanning electron microscopy (SEM) was used to visualize platelet adhesion to the sensor surfaces. Compared to uncoated gold sensors, NCO-sP(EO-stat-PO) coated sensors revealed significant better resistance against protein adsorption, lower TAT generation and a lower amount of adherent platelets. Moreover, coating with ultrathin NCO-sP(EO-stat-PO) films creates a cell resistant hemocompatible surface on gold that increases the chance of prolonged sensor functionality and can easily be modified with specific receptor molecules. KW - self-assembled monolayers KW - 316L stainless-steel KW - protein adsorption KW - poly(ethylene glycol) KW - platelet-adhesion KW - blood-plasma KW - surfaces KW - biosensor KW - cell self-assembled monolayers KW - cell coagulation KW - surface coating KW - biosensors KW - hemocompatibility KW - QCM Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-141110 VL - 11 IS - 5 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 - Tony, Hans-Peter A1 - Burmester, Gerd A1 - Schulze-Koops, Hendrik A1 - Grunke, Mathias A1 - Henes, Joerg A1 - Kötter, Ina A1 - Haas, Judith A1 - Unger, Leonore A1 - Lovric, Svjetlana A1 - Haubitz, Marion A1 - Fischer-Betz, Rebecca A1 - Chehab, Gamal A1 - Rubbert-Roth, Andrea A1 - Specker, Christof A1 - Weinerth, Jutta A1 - Holle, Julia A1 - Müller-Ladner, Ulf A1 - König, Ramona A1 - Fiehn, Christoph A1 - Burgwinkel, Philip A1 - Budde, Klemens A1 - Sörensen, Helmut A1 - Meurer, Michael A1 - Aringer, Martin A1 - Kieseier, Bernd A1 - Erfurt-Berge, Cornelia A1 - Sticherling, Michael A1 - Veelken, Roland A1 - Ziemann, Ulf A1 - Strutz, Frank A1 - von Wussow, Praxis A1 - Meier, Florian MP A1 - Hunzelmann, Nico A1 - Schmidt, Enno A1 - Bergner, Raoul A1 - Schwarting, Andreas A1 - Eming, Rüdiger A1 - Schwarz-Eywill, Michael A1 - Wassenberg, Siegfried A1 - Fleck, Martin A1 - Metzler, Claudia A1 - Zettl, Uwe A1 - Westphal, Jens A1 - Heitmann, Stefan A1 - Herzog, Anna L. A1 - Wiendl, Heinz A1 - Jakob, Waltraud A1 - Schmidt, Elvira A1 - Freivogel, Klaus A1 - Dörner, Thomas A1 - Hertl, Michael A1 - Stadler, Rudolf T1 - Safety and clinical outcomes of rituximab therapy in patients with different autoimmune diseases: experience from a national registry (GRAID) JF - Arthritis Research & Therapy N2 - Introduction: Evidence from a number of open-label, uncontrolled studies has suggested that rituximab may benefit patients with autoimmune diseases who are refractory to standard-of-care. The objective of this study was to evaluate the safety and clinical outcomes of rituximab in several standard-of-care-refractory autoimmune diseases (within rheumatology, nephrology, dermatology and neurology) other than rheumatoid arthritis or non-Hodgkin’s lymphoma in a real-life clinical setting. Methods: Patients who received rituximab having shown an inadequate response to standard-of-care had their safety and clinical outcomes data retrospectively analysed as part of the German Registry of Autoimmune Diseases. The main outcome measures were safety and clinical response, as judged at the discretion of the investigators. Results: A total of 370 patients (299 patient-years) with various autoimmune diseases (23.0% with systemic lupus erythematosus, 15.7% antineutrophil cytoplasmic antibody-associated granulomatous vasculitides, 15.1% multiple sclerosis and 10.0% pemphigus) from 42 centres received a mean dose of 2,440 mg of rituximab over a median (range) of 194 (180 to 1,407) days. The overall rate of serious infections was 5.3 per 100 patient-years during rituximab therapy. Opportunistic infections were infrequent across the whole study population, and mostly occurred in patients with systemic lupus erythematosus. There were 11 deaths (3.0% of patients) after rituximab treatment (mean 11.6 months after first infusion, range 0.8 to 31.3 months), with most of the deaths caused by infections. Overall (n = 293), 13.3% of patients showed no response, 45.1% showed a partial response and 41.6% showed a complete response. Responses were also reflected by reduced use of glucocorticoids and various immunosuppressives during rituximab therapy and follow-up compared with before rituximab. Rituximab generally had a positive effect on patient well-being (physician’s visual analogue scale; mean improvement from baseline of 12.1 mm) KW - GRAID Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-142856 VL - 13 IS - R75 ER - TY - JOUR A1 - Merget, Benjamin A1 - Koetschan, Christian A1 - Hackl, Thomas A1 - Förster, Frank A1 - Dandekar, Thomas A1 - Müller, Tobias A1 - Schultz, Jörg A1 - Wolf, Matthias T1 - The ITS2 Database JF - Journal of Visual Expression N2 - The internal transcribed spacer 2 (ITS2) has been used as a phylogenetic marker for more than two decades. As ITS2 research mainly focused on the very variable ITS2 sequence, it confined this marker to low-level phylogenetics only. However, the combination of the ITS2 sequence and its highly conserved secondary structure improves the phylogenetic resolution1 and allows phylogenetic inference at multiple taxonomic ranks, including species delimitation. The ITS2 Database presents an exhaustive dataset of internal transcribed spacer 2 sequences from NCBI GenBank accurately reannotated. Following an annotation by profile Hidden Markov Models (HMMs), the secondary structure of each sequence is predicted. First, it is tested whether a minimum energy based fold (direct fold) results in a correct, four helix conformation. If this is not the case, the structure is predicted by homology modeling. In homology modeling, an already known secondary structure is transferred to another ITS2 sequence, whose secondary structure was not able to fold correctly in a direct fold. The ITS2 Database is not only a database for storage and retrieval of ITS2 sequence-structures. It also provides several tools to process your own ITS2 sequences, including annotation, structural prediction, motif detection and BLAST search on the combined sequence-structure information. Moreover, it integrates trimmed versions of 4SALE and ProfDistS for multiple sequence-structure alignment calculation and Neighbor Joining tree reconstruction. Together they form a coherent analysis pipeline from an initial set of sequences to a phylogeny based on sequence and secondary structure. In a nutshell, this workbench simplifies first phylogenetic analyses to only a few mouse-clicks, while additionally providing tools and data for comprehensive large-scale analyses. KW - homology modeling KW - molecular systematics KW - internal transcribed spacer 2 KW - alignment KW - genetics KW - secondary structure KW - ribosomal RNA KW - phylogenetic tree KW - phylogeny Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-124600 VL - 61 IS - e3806 ER - TY - JOUR A1 - Förster, Frank A1 - Beisser, Daniela A1 - Grohme, Markus A. A1 - Liang, Chunguang A1 - Mali, Brahim A1 - Siegl, Alexander Matthias A1 - Engelmann, Julia C. A1 - Shkumatov, Alexander V. A1 - Schokraie, Elham A1 - Müller, Tobias A1 - Schnölzer, Martina A1 - Schill, Ralph O. A1 - Frohme, Marcus A1 - Dandekar, Thomas T1 - Transcriptome analysis in tardigrade species reveals specific molecular pathways for stress adaptations JF - Bioinformatics and biology insights N2 - Tardigrades have unique stress-adaptations that allow them to survive extremes of cold, heat, radiation and vacuum. To study this, encoded protein clusters and pathways from an ongoing transcriptome study on the tardigrade \(Milnesium\) \(tardigradum\) were analyzed using bioinformatics tools and compared to expressed sequence tags (ESTs) from \(Hypsibius\) \(dujardini\), revealing major pathways involved in resistance against extreme environmental conditions. ESTs are available on the Tardigrade Workbench along with software and databank updates. Our analysis reveals that RNA stability motifs for \(M.\) \(tardigradum\) are different from typical motifs known from higher animals. \(M.\) \(tardigradum\) and \(H.\) \(dujardini\) protein clusters and conserved domains imply metabolic storage pathways for glycogen, glycolipids and specific secondary metabolism as well as stress response pathways (including heat shock proteins, bmh2, and specific repair pathways). Redox-, DNA-, stress- and protein protection pathways complement specific repair capabilities to achieve the strong robustness of \(M.\) \(tardigradum\). These pathways are partly conserved in other animals and their manipulation could boost stress adaptation even in human cells. However, the unique combination of resistance and repair pathways make tardigrades and \(M.\) \(tardigradum\) in particular so highly stress resistant. KW - RNA KW - expressed sequence tag KW - cluster KW - protein familiy KW - adaption KW - tardigrada KW - transcriptome Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-123089 N1 - This is an open access article. Unrestricted non-commercial use is permitted provided the original work is properly cited. VL - 6 ER - TY - JOUR A1 - Steinmann, Diana A1 - Paelecke-Habermann, Yvonne A1 - Geinitz, Hans A1 - Aschoff, Raimund A1 - Bayerl, Anja A1 - Bölling, Tobias A1 - Bosch, Elisabeth A1 - Bruns, Frank A1 - Eichenseder-Seiss, Ute A1 - Gerstein, Johanna A1 - Gharbi, Nadine A1 - Hagg, Juliane A1 - Hipp, Matthias A1 - Kleff, Irmgard A1 - Müller, Axel A1 - Schäfer, Christof A1 - Schleicher, Ursula A1 - Sehlen, Susanne A1 - Theodorou, Marilena A1 - Wypior, Hans-Joachim A1 - Zehentmayr, Franz A1 - van Oorschot, Birgitt A1 - Vordermark, Dirk T1 - Prospective evaluation of quality of life effects in patients undergoing palliative radiotherapy for brain metastases JF - BMC Cancer N2 - Background: Recently published results of quality of life (QoL) studies indicated different outcomes of palliative radiotherapy for brain metastases. This prospective multi-center QoL study of patients with brain metastases was designed to investigate which QoL domains improve or worsen after palliative radiotherapy and which might provide prognostic information. Methods: From 01/2007-01/2009, n=151 patients with previously untreated brain metastases were recruited at 14 centers in Germany and Austria. Most patients (82 %) received whole-brain radiotherapy. QoL was measured with the EORTC-QLQ-C15-PAL and brain module BN20 before the start of radiotherapy and after 3 months. Results: At 3 months, 88/142 (62 %) survived. Nine patients were not able to be followed up. 62 patients (70.5 % of 3-month survivors) completed the second set of questionnaires. Three months after the start of radiotherapy QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. Although the use of corticosteroid at 3 months could be reduced compared to pre-treatment (63 % vs. 37 %), the score for headaches remained stable. Initial QoL at the start of treatment was better in those alive than in those deceased at 3 months, significantly for physical function, motor dysfunction and the symptom scales fatigue, pain, appetite loss and weakness of legs. In a multivariate model, lower Karnofsky performance score, higher age and higher pain ratings before radiotherapy were prognostic of 3-month survival. Conclusions: Moderate deterioration in several QoL domains was predominantly observed three months after start of palliative radiotherapy for brain metastases. Future studies will need to address the individual subjective benefit or burden from such treatment. Baseline QoL scores before palliative radiotherapy for brain metastases may contain prognostic information. KW - breast cancer KW - brain tumours KW - survival KW - validation KW - symptoms KW - EORTC-QLQ-C15-PAL KW - EORTC-BN20 KW - whole-brain radiotherapy KW - partitioning analysis RPA KW - cancer patients KW - lung cancer KW - prognostic index KW - radiation oncology KW - clinical trials Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135254 VL - 12 IS - 283 ER - TY - JOUR A1 - Hanfstein, Benjamin A1 - Lauseker, Michael A1 - Hehlmann, Rüdiger A1 - Saussele, Susanne A1 - Erben, Philipp A1 - Dietz, Christian A1 - Fabarius, Alice A1 - Proetel, Ulrike A1 - Schnittger, Susanne A1 - Haferlach, Claudia A1 - Krause, Stefan W. A1 - Schubert, Jörg A1 - Einsele, Hermann A1 - Hänel, Mathias A1 - Dengler, Jolanta A1 - Falge, Christiane A1 - Kanz, Lothar A1 - Neubauer, Andreas A1 - Kneba, Michael A1 - Stengelmann, Frank A1 - Pfreundschuh, Michael A1 - Waller, Cornelius F. A1 - Spiekerman, Karsten A1 - Baerlocher, Gabriela M. A1 - Pfirrmann, Markus A1 - Hasford, Joerg A1 - Hofmann, Wolf-Karsten A1 - Hochhaus, Andreas A1 - Müller, Martin C. T1 - Distinct characteristics of e13a2 versus e14a2 BCR-ABL1 driven chronic myeloid leukemia under first-line therapy with imatinib JF - Haematologica N2 - The vast majority of chronic myeloid leukemia patients express a BCR-ABL1 fusion gene mRNA encoding a 210 kDa tyrosine kinase which promotes leukemic transformation. A possible differential impact of the corresponding BCR-ABL1 transcript variants e13a2 ("b2a2") and e14a2 ("b3a2") on disease phenotype and outcome is still a subject of debate. A total of 1105 newly diagnosed imatinib-treated patients were analyzed according to transcript type at diagnosis (e13a2, n=451; e14a2, n=496; e13a2+e14a2, n=158). No differences regarding age, sex, or Euro risk score were observed. A significant difference was found between e13a2 and e14a2 when comparing white blood cells (88 vs. 65 x 10(9)/L, respectively; P<0.001) and platelets (296 vs. 430 x 109/L, respectively; P<0.001) at diagnosis, indicating a distinct disease phenotype. No significant difference was observed regarding other hematologic features, including spleen size and hematologic adverse events, during imatinib-based therapies. Cumulative molecular response was inferior in e13a2 patients (P=0.002 for major molecular response; P<0.001 for MR4). No difference was observed with regard to cytogenetic response and overall survival. In conclusion, e13a2 and e14a2 chronic myeloid leukemia seem to represent distinct biological entities. However, clinical outcome under imatinib treatment was comparable and no risk prediction can be made according to e13a2 versus e14a2 BCR-ABL1 transcript type at diagnosis. (clinicaltrials.gov identifier: 00055874) KW - chronic myelogenous leukemia KW - polymerase-chain-reaktion KW - hybrid messenger RNA KW - chronic phase KW - cytogenetic response KW - no correlation KW - ABL gene KW - transcripts KW - breakpoint KW - survival Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-115476 SN - 1592-8721 VL - 99 IS - 9 ER - TY - JOUR A1 - Hebestreit, Helge A1 - Zeidler, Cornelia A1 - Schippers, Christopher A1 - de Zwaan, Martina A1 - Deckert, Jürgen A1 - Heuschmann, Peter A1 - Krauth, Christian A1 - Bullinger, Monika A1 - Berger, Alexandra A1 - Berneburg, Mark A1 - Brandstetter, Lilly A1 - Deibele, Anna A1 - Dieris-Hirche, Jan A1 - Graessner, Holm A1 - Gündel, Harald A1 - Herpertz, Stephan A1 - Heuft, Gereon A1 - Lapstich, Anne-Marie A1 - Lücke, Thomas A1 - Maisch, Tim A1 - Mundlos, Christine A1 - Petermann-Meyer, Andrea A1 - Müller, Susanne A1 - Ott, Stephan A1 - Pfister, Lisa A1 - Quitmann, Julia A1 - Romanos, Marcel A1 - Rutsch, Frank A1 - Schaubert, Kristina A1 - Schubert, Katharina A1 - Schulz, Jörg B. A1 - Schweiger, Susann A1 - Tüscher, Oliver A1 - Ungethüm, Kathrin A1 - Wagner, Thomas O. F. A1 - Haas, Kirsten T1 - Dual guidance structure for evaluation of patients with unclear diagnosis in centers for rare diseases (ZSE-DUO): study protocol for a controlled multi-center cohort study JF - Orphanet Journal of Rare Diseases N2 - Background In individuals suffering from a rare disease the diagnostic process and the confirmation of a final diagnosis often extends over many years. Factors contributing to delayed diagnosis include health care professionals' limited knowledge of rare diseases and frequent (co-)occurrence of mental disorders that may complicate and delay the diagnostic process. The ZSE-DUO study aims to assess the benefits of a combination of a physician focusing on somatic aspects with a mental health expert working side by side as a tandem in the diagnostic process. Study design This multi-center, prospective controlled study has a two-phase cohort design. Methods Two cohorts of 682 patients each are sequentially recruited from 11 university-based German Centers for Rare Diseases (CRD): the standard care cohort (control, somatic expertise only) and the innovative care cohort (experimental, combined somatic and mental health expertise). Individuals aged 12 years and older presenting with symptoms and signs which are not explained by current diagnoses will be included. Data will be collected prior to the first visit to the CRD’s outpatient clinic (T0), at the first visit (T1) and 12 months thereafter (T2). Outcomes Primary outcome is the percentage of patients with one or more confirmed diagnoses covering the symptomatic spectrum presented. Sample size is calculated to detect a 10 percent increase from 30% in standard care to 40% in the innovative dual expert cohort. Secondary outcomes are (a) time to diagnosis/diagnoses explaining the symptomatology; (b) proportion of patients successfully referred from CRD to standard care; (c) costs of diagnosis including incremental cost effectiveness ratios; (d) predictive value of screening instruments administered at T0 to identify patients with mental disorders; (e) patients’ quality of life and evaluation of care; and f) physicians’ satisfaction with the innovative care approach. Conclusions This is the first multi-center study to investigate the effects of a mental health specialist working in tandem with a somatic expert physician in CRDs. If this innovative approach proves successful, it will be made available on a larger scale nationally and promoted internationally. In the best case, ZSE-DUO can significantly shorten the time to diagnosis for a suspected rare disease. KW - rare diseases KW - multi‑center cohort study KW - dual guidance Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-300440 VL - 17 IS - 1 ER - TY - JOUR A1 - Müller, Ulrich A1 - Spenst, Peter A1 - Kagerer, Philipp A1 - Stolte, Matthias A1 - Würthner, Frank A1 - Pflaum, Jens T1 - Photon‐Correlation Studies on Multichromophore Macrocycles of Perylene Dyes JF - Advanced Optical Materials N2 - Organic dyes offer unique properties for their application as room temperature single photon emitters. By means of photon‐correlation, the emission characteristics of macrocyclic para‐xylylene linked perylene bisimide (PBI) trimers and tetramers dispersed in polymethyl methacrylate matrices are analyzed. The optical data indicate that, despite of the strong emission enhancement of PBI trimers and tetramers according to their larger number of chromophores, the photon‐correlation statistics still obeys that of single photon emitters. Moreover, driving PBI trimers and tetramers at higher excitation powers, saturated emission behavior for monomers is found while macrocycle emission is still far‐off saturation but shows enhanced fluctuations. This observation is attributed to fast singlet–singlet annihilation, i.e., faster than the radiative lifetime of the excited S1 state, and the enlarged number of conformational arrangements of multichromophores in the polymeric host. Finally, embedding trimeric PBI macrocycles in active organic light‐emitting diode matrices, electrically driven bright fluorescence together with an indication for antibunching at room temperature can be detected. This, so far, has only been observed for phosphorescent emitters that feature much longer lifetimes of the excited states and, thus, smaller radiative recombination rates. The results are discussed in the context of possible effects on the g(2) behavior of molecular emitters. KW - multichromophores KW - organic light emitting diodes KW - perylene dyes KW - photon‐correlation KW - single photon emission Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-287219 VL - 10 IS - 14 ER - TY - JOUR A1 - Kleinert, Evelyn A1 - Müller, Frank A1 - Furaijat, Ghefar A1 - Hillermann, Nele A1 - Jablonka, Alexandra A1 - Happle, Christine A1 - Simmenroth, Anne T1 - Does refugee status matter? Medical needs of newly arrived asylum seekers and resettlement refugees - a retrospective observational study of diagnoses in a primary care setting JF - Conflict and Health N2 - Background Providing adequate healthcare to newly arrived refugees is considered one of the significant challenges for the German healthcare system. These refugees can be classified mainly into two groups: asylum seekers (who have applied for asylum after arrival in Germany and are waiting for the refugee-status decision) and resettlement refugees (who have already been granted asylum status before arriving in Germany). Whereas earlier studies have explored the health status of asylum seekers especially in terms of mental and behavioural disorders and infectious diseases without distinguishing between these two groups, our study aims to evaluate possible relationships of asylum status and medical needs of these two groups with a special focus on mental and behavioural disorders and infectious diseases. Methods In this retrospective observational study, collected data on all asylum-seeker and resettlement-refugee patients (N = 2252) of a German reception centre (August 2017 to August 2018) is analysed by absolute and relative frequencies and medians. Patient data, collected by chart review, include age, gender, country of origin, asylum status, and diagnoses (ICD-10). To describe the relationship between sociodemographic factors (including asylum status) and diagnoses, we used tests of significance and bivariate correlations with Spearman correlation coefficients. All collected data are pseudonymised. Results Of all 2252 patients, 43% were resettlement refugees. In almost all ICD-10 categories, asylum seekers received significantly more diagnoses than resettlement refugees. According to our data, asylum seekers presented with mental and behavioural disorders nine times more often (9%) than resettlement refugees (1%). In the case of infectious diseases, the results are mixed: asylum seekers were twice as frequently (11%) diagnosed with certain infectious and parasitic diseases than resettlement refugees (5%), but resettlement refugees were treated twice as often (22% of the asylum seekers and 41% of the resettlement refugees) for diseases of the respiratory system, of which 84% were acute respiratory infections (in both groups). Conclusion This study indicates that patients with unregulated migration more frequently present symptoms of psychiatric diseases and somatoform symptoms than resettlement refugees. A health policy approach within migration policy should aim to enable persecuted persons to migrate under regulated and safe conditions. Trial registration German Clinical Trials Register: DRKS00013076, retrospectively registered on 29.09.2017. KW - primary healthcare KW - resettlement refugees KW - asylum seekers KW - asylum status KW - common diseases KW - migrant KW - infections KW - mental health Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325869 VL - 13 ER -