TY - JOUR A1 - Schoffer, Olaf A1 - Schülein, Stefanie A1 - Arand, Gerlinde A1 - Arnholdt, Hans A1 - Baaske, Dieter A1 - Bargou, Ralf C. A1 - Becker, Nikolaus A1 - Beckmann, Matthias W. A1 - Bodack, Yves A1 - Böhme, Beatrix A1 - Bozkurt, Tayfun A1 - Breitsprecher, Regine A1 - Buchali, Andre A1 - Burger, Elke A1 - Burger, Ulrike A1 - Dommisch, Klaus A1 - Elsner, Gudrun A1 - Fernschild, Karin A1 - Flintzer, Ulrike A1 - Funke, Uwe A1 - Gerken, Michael A1 - Göbel, Hubert A1 - Grobe, Norbert A1 - Gumpp, Vera A1 - Heinzerling, Lucie A1 - Kempfer, Lana Raffaela A1 - Kiani, Alexander A1 - Klinkhammer-Schalke, Monika A1 - Klöcking, Sabine A1 - Kreibich, Ute A1 - Knabner, Katrin A1 - Kuhn, Peter A1 - Lutze, Stine A1 - Mäder, Uwe A1 - Maisel, Tanja A1 - Maschke, Jan A1 - Middeke, Martin A1 - Neubauer, Andreas A1 - Niedostatek, Antje A1 - Opazo-Saez, Anabelle A1 - Peters, Christoph A1 - Schell, Beatrice A1 - Schenkirsch, Gerhard A1 - Schmalenberg, Harald A1 - Schmidt, Peter A1 - Schneider, Constanze A1 - Schubotz, Birgit A1 - Seide, Anika A1 - Strecker, Paul A1 - Taubenheim, Sabine A1 - Wackes, Matthias A1 - Weiß, Steffen A1 - Welke, Claudia A1 - Werner, Carmen A1 - Wittekind, Christian A1 - Wulff, Jörg A1 - Zettl, Heike A1 - Klug, Stefanie J. T1 - Tumour stage distribution and survival of malignant melanoma in Germany 2002-2011 JF - BMC Cancer N2 - Background Over the past two decades, there has been a rising trend in malignant melanoma incidence worldwide. In 2008, Germany introduced a nationwide skin cancer screening program starting at age 35. The aims of this study were to analyse the distribution of malignant melanoma tumour stages over time, as well as demographic and regional differences in stage distribution and survival of melanoma patients. Methods Pooled data from 61 895 malignant melanoma patients diagnosed between 2002 and 2011 and documented in 28 German population-based and hospital-based clinical cancer registries were analysed using descriptive methods, joinpoint regression, logistic regression and relative survival. Results The number of annually documented cases increased by 53.2% between 2002 (N = 4 779) and 2011 (N = 7 320). There was a statistically significant continuous positive trend in the proportion of stage UICC I cases diagnosed between 2002 and 2011, compared to a negative trend for stage UICC II. No trends were found for stages UICC III and IV respectively. Age (OR 0.97, 95% CI 0.97–0.97), sex (OR 1.18, 95% CI 1.11–1.25), date of diagnosis (OR 1.05, 95% CI 1.04–1.06), ‘diagnosis during screening’ (OR 3.24, 95% CI 2.50–4.19) and place of residence (OR 1.23, 95% CI 1.16–1.30) had a statistically significant influence on the tumour stage at diagnosis. The overall 5-year relative survival for invasive cases was 83.4% (95% CI 82.8–83.9%). Conclusions No distinct changes in the distribution of malignant melanoma tumour stages among those aged 35 and older were seen that could be directly attributed to the introduction of skin cancer screening in 2008. " KW - Malignant melanoma KW - TNM staging KW - Survival analysis KW - Skin cancer screening KW - Stage distribution Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164544 VL - 16 IS - 936 ER - TY - JOUR A1 - Jobs, Alexander A1 - Vonthein, Reinhard A1 - König, Inke R. A1 - Schäfer, Jane A1 - Nauck, Matthias A1 - Haag, Svenja A1 - Fichera, Carlo Federico A1 - Stiermaier, Thomas A1 - Ledwoch, Jakob A1 - Schneider, Alisa A1 - Valentova, Miroslava A1 - von Haehling, Stephan A1 - Störk, Stefan A1 - Westermann, Dirk A1 - Lenz, Tobias A1 - Arnold, Natalie A1 - Edelmann, Frank A1 - Seppelt, Philipp A1 - Felix, Stephan A1 - Lutz, Matthias A1 - Hedwig, Felix A1 - Borggrefe, Martin A1 - Scherer, Clemens A1 - Desch, Steffen A1 - Thiele, Holger T1 - Inferior vena cava ultrasound in acute decompensated heart failure: design rationale of the CAVA‐ADHF‐DZHK10 trial JF - ESC Heart Failure N2 - Aims Treating patients with acute decompensated heart failure (ADHF) presenting with volume overload is a common task. However, optimal guidance of decongesting therapy and treatment targets are not well defined. The inferior vena cava (IVC) diameter and its collapsibility can be used to estimate right atrial pressure, which is a measure of right‐sided haemodynamic congestion. The CAVA‐ADHF‐DZHK10 trial is designed to test the hypothesis that ultrasound assessment of the IVC in addition to clinical assessment improves decongestion as compared with clinical assessment alone. Methods and results CAVA‐ADHF‐DZHK10 is a randomized, controlled, patient‐blinded, multicentre, parallel‐group trial randomly assigning 388 patients with ADHF to either decongesting therapy guided by ultrasound assessment of the IVC in addition to clinical assessment or clinical assessment alone. IVC ultrasound will be performed daily between baseline and hospital discharge in all patients. However, ultrasound results will only be reported to treating physicians in the intervention group. Treatment target is relief of congestion‐related signs and symptoms in both groups with the additional goal to reduce the IVC diameter ≤21 mm and increase IVC collapsibility >50% in the intervention group. The primary endpoint is change in N‐terminal pro‐brain natriuretic peptide from baseline to hospital discharge. Secondary endpoints evaluate feasibility, efficacy of decongestion on other scales, and the impact of the intervention on clinical endpoints. Conclusions CAVA‐ADHF‐DZHK10 will investigate whether IVC ultrasound supplementing clinical assessment improves decongestion in patients admitted for ADHF. KW - acute decompensated heart failure KW - inferior vena cava KW - congestion KW - NT‐proBNP KW - ultrasound Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212692 VL - 7 IS - 3 SP - 973 EP - 983 ER - TY - JOUR A1 - Schulmeyer, Carla E. A1 - Fasching, Peter A. A1 - Häberle, Lothar A1 - Meyer, Julia A1 - Schneider, Michael A1 - Wachter, David A1 - Ruebner, Matthias A1 - Pöschke, Patrik A1 - Beckmann, Matthias W. A1 - Hartmann, Arndt A1 - Erber, Ramona A1 - Gass, Paul T1 - Expression of the immunohistochemical markers CK5, CD117, and EGFR in molecular subtypes of breast cancer correlated with prognosis JF - Diagnostics N2 - Molecular-based subclassifications of breast cancer are important for identifying treatment options and stratifying the prognosis in breast cancer. This study aimed to assess the prognosis relative to disease-free survival (DFS) and overall survival (OS) in patients with triple-negative breast cancer (TNBC) and other subtypes, using a biomarker panel including cytokeratin 5 (CK5), cluster of differentiation 117 (CD117), and epidermal growth factor receptor (EGFR). This cohort–case study included histologically confirmed breast carcinomas as cohort arm. From a total of 894 patients, 572 patients with early breast cancer, sufficient clinical data, and archived tumor tissue were included. Using the immunohistochemical markers CK5, CD117, and EGFR, two subgroups were formed: one with all three biomarkers negative (TBN) and one with at least one of those three biomarkers positive (non-TBN). There were significant differences between the two biomarker subgroups (TBN versus non-TBN) in TNBC for DFS (p = 0.04) and OS (p = 0.02), with higher survival rates (DFS and OS) in the non-TBN subgroup. In this study, we found the non-TBN subgroup of TNBC lesions with at least one positive biomarker of CK5, CD117, and/or EGFR, to be associated with longer DFS and OS. KW - early breast cancer KW - therapy KW - prognosis KW - CK5 KW - CD117 KW - EGFR KW - triple-negative breast cancer Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-304987 SN - 2075-4418 VL - 13 IS - 3 ER - TY - THES A1 - Schneider, Matthias T1 - Characterisation of Metalloprotease-mediated EGFR Signal Transactivation after GPCR Stimulation T1 - Charakterisierung der EGFR Signaltransaktivierung nach GPCR Stimulation N2 - In the context of metalloprotease-mediated transactivation of the epidermal growth factor receptor, different monoclonal antibodies against ADAM17 / TACE were characterized for their ability to block the sheddase. Activity of some of them was observed at doses between 2µg/mL and 10µg/mL. Kinetic analyses showed their activity starting at around 30 minutes. In cellular assays performed with the antibodies, especially upon treatment of cells with sphingosine-1-phosphate a reduction in proliferation was observed with some candidates. Moreover this study provides potential new roles for ß-Arrestins. Their involvement in the triple membrane-passing signal pathway of EGFR transactivation was shown. Furthermore, in overexpressing cellular model systems, an interaction between ADAM17 and ß-Arrestin1 could be observed. Detailed analysis discovered that phosphorylation of ß-Arrestin1 is crucial for this interaction. Additionally, the novel mechanism of UV-induced EGFR transactivation was extended to squamous cell carcinoma. The mechanism happens in a dose dependent manner and requires a metalloprotease to shed the proligand Amphiregulin. The involvement of both ADAM9 and ADAM17, being the metalloproteases responsible for this cleavage, was shown for SCC9 cells. N2 - Im Rahmen dieser Arbeit wurden verschiedene monoklonale Antikörper gegen ADAM17 / TACE im Kontext der Metalloprotease-vermittelten Transaktivierung des Epidermalen Wachstumsfaktors auf ihre Fähigkeit hin untersucht, die Proteaseaktivität zu unterdrücken. Einige von Ihnen zeigten inhibitorische Aktivität bei Konzentrationen zwischen 2µg/ml und 10µg/ml. Die Untersuchung der Zeitabhängigkeit ihrer Wirkungsweise ergab eine Aktivität ab 30 Minuten Vorinkubation. In zellulären Versuchen konnte eine Verminderung der Proliferation besonders nach Stimulation mit Sphingosin-1-Phosphat gezeigt werden. Darüber hinaus konnten möglich neue Funktionen von ß-Arrestinen gezeigt werden. Eine Beteiligung am „triple membrane-passing“ Signalwegs der Transaktivierung des Epidermalen Wachstumsfaktors wurde dargestellt. Zudem wurde eine Interaktion von ß-Arrestin1 und ADAM17 in überexprimierenden Zellsystemen gezeigt. Detaillierte Analysen belegten, dass die Phosphorylierung von ß-Arrestin1 eine notwendige Voraussetzung dafür ist. Weiterhin wurde der neue Mechanismus der UV-vermittelten Aktivierung des epidermalen Wachstumsfaktors auf Plattenephithelkarzinom-Zellen ausgeweitet. Er findet in einer dosisabhängigen Form statt und bedarf einer Metalloprotease zum Aktivieren des Liganden Amphiregulin. Sowohl ADAM9 als auch ADAM17 wurden als die verantwortlichen Metalloproteasen in den untersuchten SCC9 Zellen ermittelt. KW - Epidermaler Wachstumsfaktor-Rezeptor KW - G-Protein gekoppelte Rezeptoren KW - Metalloprotease KW - Krebs KW - EGF Rezeptor KW - Transaktivierung KW - GPCR KW - UV KW - EGFR Transactivation KW - Metalloprotease KW - GPCR KW - Cancer KW - UV Y1 - 2011 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-65105 ER - TY - JOUR A1 - Amthor, Matthias A1 - Weißenseel, Sebastian A1 - Fischer, Julian A1 - Kamp, Martin A1 - Schneider, Christian A1 - Höfling, Sven T1 - Electro-optical switching between polariton and cavity lasing in an InGaAs quantum well microcavity N2 - We report on the condensation of microcavity exciton polaritons under optical excitation in a microcavity with four embedded InGaAs quantum wells. The polariton laser is characterized by a distinct nonlinearity in the input-output-characteristics, which is accompanied by a drop of the emission linewidth indicating temporal coherence and a characteristic persisting emission blueshift with increased particle density. The temporal coherence of the device at threshold is underlined by a characteristic drop of the second order coherence function to a value close to 1. Furthermore an external electric field is used to switch between polariton regime, polariton condensate and photon lasing. KW - Quantum-well, -wire and -dot devices KW - Scattering KW - stimulated KW - Resonators KW - Microcavity devices Y1 - 2014 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-111130 ER - TY - JOUR A1 - Winkler, Karol A1 - Fischer, Julian A1 - Schade, Anne A1 - Amthor, Matthias A1 - Dall, Robert A1 - Geßler, Jonas A1 - Emmerling, Monika A1 - Ostrovskaya, Elena A. A1 - Kamp, Martin A1 - Schneider, Christian A1 - Höfling, Sven T1 - A polariton condensate in a photonic crystal potential landscape JF - New Journal of Physics N2 - The possibility of investigating macroscopic coherent quantum states in polariton condensates and of engineering polariton landscapes in semiconductors has triggered interest in using polaritonic systems to simulate complex many-body phenomena. However, advanced experiments require superior trapping techniques that allow for the engineering of periodic and arbitrary potentials with strong on-site localization, clean condensate formation, and nearest-neighbor coupling. Here we establish a technology that meets these demands and enables strong, potentially tunable trapping without affecting the favorable polariton characteristics. The traps are based on a locally elongated microcavity which can be formed by standard lithography. We observe polariton condensation with non-resonant pumping in single traps and photonic crystal square lattice arrays. In the latter structures, we observe pronounced energy bands, complete band gaps, and spontaneous condensation at the M-point of the Brillouin zone. Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125050 VL - 17 ER - TY - JOUR A1 - Marenholz, Ingo A1 - Esparza-Gordillo, Jorge A1 - Rüschendorf, Franz A1 - Bauerfeind, Anja A1 - Strachan, David P. A1 - Spycher, Ben D. A1 - Baurecht, Hansjörg A1 - Magaritte-Jeannin, Patricia A1 - Sääf, Annika A1 - Kerkhof, Marjan A1 - Ege, Markus A1 - Baltic, Svetlana A1 - Matheson, Melanie C. A1 - Li, Jin A1 - Michel, Sven A1 - Ang, Wei Q. A1 - McArdle, Wendy A1 - Arnold, Andreas A1 - Homuth, Georg A1 - Demenais, Florence A1 - Bouzigon, Emmanuelle A1 - Söderhäll, Cilla A1 - Pershagen, Göran A1 - de Jongste, Johan C. A1 - Postma, Dirkje S. A1 - Braun-Fahrländer, Charlotte A1 - Horak, Elisabeth A1 - Ogorodova, Ludmila M. A1 - Puzyrev, Valery P. A1 - Bragina, Elena Yu A1 - Hudson, Thomas J. A1 - Morin, Charles A1 - Duffy, David L. A1 - Marks, Guy B. A1 - Robertson, Colin F. A1 - Montgomery, Grant W. A1 - Musk, Bill A1 - Thompson, Philip J. A1 - Martin, Nicholas G. A1 - James, Alan A1 - Sleiman, Patrick A1 - Toskala, Elina A1 - Rodriguez, Elke A1 - Fölster-Holst, Regina A1 - Franke, Andre A1 - Lieb, Wolfgang A1 - Gieger, Christian A1 - Heinzmann, Andrea A1 - Rietschel, Ernst A1 - Keil, Thomas A1 - Cichon, Sven A1 - Nöthen, Markus M. A1 - Pennel, Craig E. A1 - Sly, Peter D. A1 - Schmidt, Carsten O. A1 - Matanovic, Anja A1 - Schneider, Valentin A1 - Heinig, Matthias A1 - Hübner, Norbert A1 - Holt, Patrick G. A1 - Lau, Susanne A1 - Kabesch, Michael A1 - Weidinger, Stefan A1 - Hakonarson, Hakon A1 - Ferreira, Manuel A. R. A1 - Laprise, Catherine A1 - Freidin, Maxim B. A1 - Genuneit, Jon A1 - Koppelman, Gerard H. A1 - Melén, Erik A1 - Dizier, Marie-Hélène A1 - Henderson, A. John A1 - Lee, Young Ae T1 - Meta-analysis identifies seven susceptibility loci involved in the atopic march JF - Nature Communications N2 - Eczema often precedes the development of asthma in a disease course called the 'atopic march'. To unravel the genes underlying this characteristic pattern of allergic disease, we conduct a multi-stage genome-wide association study on infantile eczema followed by childhood asthma in 12 populations including 2,428 cases and 17,034 controls. Here we report two novel loci specific for the combined eczema plus asthma phenotype, which are associated with allergic disease for the first time; rs9357733 located in EFHC1 on chromosome 6p12.3 (OR 1.27; P = 2.1 x 10(-8)) and rs993226 between TMTC2 and SLC6A15 on chromosome 12q21.3 (OR 1.58; P = 5.3 x 10(-9)). Additional susceptibility loci identified at genome-wide significance are FLG (1q21.3), IL4/KIF3A (5q31.1), AP5B1/OVOL1 (11q13.1), C11orf30/LRRC32 (11q13.5) and IKZF3 (17q21). We show that predominantly eczema loci increase the risk for the atopic march. Our findings suggest that eczema may play an important role in the development of asthma after eczema. KW - chromosome 11Q13 KW - risk KW - genomewide association KW - hay fever KW - birth cohort KW - filaggrin mutations KW - food allergy KW - juvenile myoclonic epilepsy KW - childhood asthma KW - dermatitis Y1 - 2015 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-139835 VL - 6 IS - 8804 ER - TY - THES A1 - Schneider, Matthias T1 - Computerunterstützte Auswertung in der automatisierten zweidimensionalen Dünnschichtchromatographie T1 - Computer-aided evaluation in automated two-dimensional thin-layer chromatography N2 - Die vorliegende Arbeit beschäftigt sich mit der zweidimensionalen Dünnschichtchromatographie (DC) und deren quantitativer Auswertung. Es wird auf die Grundlagen der DC eingegangen. Darüberhinaus werden die Vorgehensweisen der quantitativen Auswertung gegenübergestellt und bewertet. Besonders behandelt werden die nichtlinearen Regressionsmethoden. Die in dieser Arbeit verwendete Entwicklungstechnik wird erklärt und die Vorteile beschrieben. Der im Rahmen dieser Arbeit entwickelte Scanner und die dazugehörige Software werden vorgestellt. Als Lichtquelle dient eine 30 W Deuteriumlampe, die ohne Sperrfilter betrieben wird. Dies ermöglicht die Verwendung von Licht auch im Bereich von 198-210 nm. Auf einen Betrieb der Lichtquelle im Vakuum wurde verzichtet. Die Einblendtechnik der Lichtstrahlen in den Lichtwellenleiter wurde nicht verändert. Der bewegliche Teil des Scanners besteht aus einem Kreuztisch, dessen Vorschubeinheiten um 90° versetzt angebracht wurden, um die Platte in x- und in y-Richtung bewegen zu können. Die Wahl der Spindelsteigung ermöglicht eine Schrittweite von 0.1 mm im Bedarfsfall. Jede Vorschubeinheit wird durch eine eigene Steuerkarte angesprochen. Damit kann in beide Richtungen unabhängig voneinander verfahren werden. Die Vorschubgeschwindigkeit ist in zwei Stufen wählbar. Um den Intensitätsverlust bei der Lichtübertragung gering zu halten und einen modularen Aufbau realisieren zu können, wurde als Übertragungsmedium zwischen Lampe und Platte ein Lichtleiter gewählt. Dieser ist in der Lage, sowohl eine als auch mehrere Wellenlängen zu übertragen. Durch den Einsatz eines optimierten Faserbündels, das mit Wasserstoff begast wurde, um die Bildung von Farbzentren zu verhindern, kann die Alterung stark verlangsamt werden. Die Dämpfung der Lichtintensität innerhalb der Faser spielt durch die Verwendung kurzer Fasern nur eine untergeordnete Rolle. Als Detektionseinheit werden Photodiodenarrays verwendet, die 256 bzw. 512 Dioden besitzen. Eingebaut wird jeweils nur das vorjustierte Array, das auf eine Platine aufgebracht ist, die die Elektronik zum Auslesen sowie die Möglichkeit zur Ansteuerung des Auslesevorganges bereits enthält. Die Minimalkonfiguration erlaubt das Verwenden eigener, für den Einsatzzweck optimierter Bauteile. Die erstellte Software verarbeitet die registrierten Daten und ordnet die Signale den entsprechenden Wellenlängen zu. Die Rohdaten werden nach der bekannten Gleichung von Kubelka und Munk in Remissionswerte umgerechnet. Ein neues Verfahren zur Glättung von zweidimensional verrauschten Daten wird eingeführt, mit Hilfe dessen die Signale in eine verwertbare Form übergeführt werden. Hierzu wird eine Regressionsrechnung in zwei Dimensionen mittels eines Polynoms durchgeführt. Die Glättungsbreite kann variabel für beide Dimensionen bestimmt werden. Die Faltungsoperation kann im Gegensatz zu bisher bekannten Verfahren auch während der Auswertung durchgeführt werden. Statische Faltungsoperatoren werden nicht mehr benötigt. Peaks werden gesucht und ihre Lage mit Hilfe einer Basisfläche korrigiert. Diese Fläche berücksichtigt Matrixeinflüsse der Platte, Schwankungen im Lichtstrom der Lampe und Änderungen der mobilen Phase während der Entwicklung. Die transformierten und geglätteten Daten werden in zwei Dateien geschrieben, die sich nur in der Art der Speicherung unterscheiden, um sie mit Fremdprogrammen weiterverarbeiten zu können. Es wird die Möglichkeit untersucht, Remissionsspektren unterschiedlicher Herkunft und UV-Spektren miteinander zu vergleichen. Um auf umfangreiche existierende UV- Spektrenkataloge zurückgreifen zu können, wird eine Möglichkeit gesucht, mit deren Hilfe die Remissionsspektren UV-Spektren zugeordnet werden können. Ein automatisiertes Vorgehen alleine reicht nicht aus, der Eingriff des Benutzers ist unerläßlich. Bei Remissionsdaten findet eine nicht reproduzierbare Verschiebung der Wellenlängen statt, die ein direktes Inbezugsetzen verhindert. Es wird ein Auftrageschema vorgestellt, das auch für quantitative Analysen 2D- entwickelter Platten anwendbar ist. Zusätzlich zu dem zu untersuchenden Gemisch werden 3 Standardgemische bekannter Konzentration und Zusammensetzung aufgetragen. Die erste Entwicklung erfolgt von gegenüberliegenden Seiten bis zur Mitte der Platte, nach Trocknen und Drehen um 90° wird die zweite Entwicklung ebenfalls beidseitig durchgeführt. So wird die Plattenoberfläche optimal ausgenutzt und die Kriterien zur quantitativen Auswertung werden erfüllt. Die Leistungsfähigkeit des neu eingeführten Glättungsalgorithmus wird gezeigt. Auf die Besonderheiten einer Auswertung anhand des Peakvolumen und nicht wie bisher anhand der Peakfläche wird eingegangen. Ein Datensatz von aufgenommenen Spektren wird nach der Verarbeitung gezeigt. Das entwickelte System aus Hard- und Software ist in der Lage, jeden Punkt auf der Platte anzusteuern und Daten zur weiteren Auswertung in genügend hoher Genauigkeit zu liefern. N2 - The presented thesis deals with quantitative two-dimensional thin-layercchromatography. The basics of thin-layer chromatography are covered. Known quantitation methods are compared and evaluated with respect to non-linear regression methods. These play a prominent role in thin-layer chromatography. The developing method used in this work is described and the advantages are shown. The scanner and software developed in this thesis are described. As a light emitting source a deuterium lamp was used that is operated without a limiting filter, allowing usage of light below 210 nm down to 198 nm. The operation of the lamp in vacuum is rejected. The connection of the lamp to the used optic fibre is not altered. The movable parts of the scanner consist of two motor-driven plates that run perpendicular to each other making movement in both x- and y- direction possible. The created system allows single steps down to 0.1 mm if necessary. Each moving plate is adressed by its own controller making independent movement in both directions possible. The speed of the moving plates is switchable in two steps, one of those being fast enough to bridge long distances, the other being precisely enough to position in a least oscillating way. In order to minimize the loss of intensity while transmitting the UV light and to realize a modular construction, fibre optics were used between TLC-plate and lamp. The fibre is capable of transmitting single or multiple wavelengths, respectivly. Optimization is done by treating the fibre in a hydrogen-atmosphere. This leads to the reduction of E'-centers and improvement of the lifetime-stability of the fibre optics. Normal attenuation plays a minor role because of the limited lenghts of the optics. A photodiodearray consisting of 256 and 512 diodes, respectivly, is used as a detection unit. Implemented is only the readily adjusted array fixed to a small controller. The controller offers the electronics for reading the array and for synchronizing the reading cycles. This minimum configuration allows the further usage of parts that are specialized for the required scanning process. The programmed software evaluates the registered data and sorts the signals to the corresponding wavelengths. Raw data is transformed to remission data by using the known equation of Kubelka and Munk. A new method of smoothing two-dimensional scattered data is introduced. It is done by a regression in two dimensions using a polynom. The smoothing width can be varied for each direction independently. This convolution can be carried out during evaluating the data whereas known methods have to determine the convolution integers in advance. Static convolution integers are not needed any more. Peaks are searched and their shape is stripped by using not only baseline but a basearea correction. This is done for correcting influences of the matrix, disturbances in the lightstream, and change of the mobile phase due to decomposition of the eluent mixture. Transformed and smoothed data are written in two files differing only by ways of storing data. A plain-text file is produced for importing the data into commercially available software. It is examined whether remission spectra of different sources and UV-spectra are comparable. In order to use existing UV-databases, a way of pairing remission and corresponding UV data is searched. An automatic approach is not sufficient, correction by the user is mandatory. In recording remission data, a non-reproducible shift of wavelengths is observed that prevents the direct comparing. A spotting scheme is presented that is usable for quantitative analysis of two-dimensional developped chromatograms. In addition to the examined mixture, three standards of known compounds and concentrations are transferred to the plate as well. The first development is carried out from opposing sides to the middle of the plate. After drying and switching 90° the second development is done from opposing sides also. This is done for using the surface optimally and meeting the requirements for quantitative evaluation. The power of the presented smoothing algorithm is shown. The specialities of evaluating the peak-volume instead of only the peak-area are dealt with. A dataset of recorded spectra is shown after evaluating. The developed system consisting of hard- and software is capable of moving to every point of the plate-surface and recording data for further evaluation in sufficient precision. KW - Dünnschichtchromatographie KW - Datenauswertung KW - Dünnschichtchromatographie KW - zweidimensional KW - Scanner KW - Quantifizierung KW - Zuordnung KW - Thin-layer chromatography KW - two-dimensional KW - scanner KW - quantification KW - relation Y1 - 2002 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-5654 ER - TY - JOUR A1 - Freitag‐Wolf, Sandra A1 - Munz, Matthias A1 - Junge, Olaf A1 - Graetz, Christian A1 - Jockel‐Schneider, Yvonne A1 - Staufenbiel, Ingmar A1 - Bruckmann, Corinna A1 - Lieb, Wolfgang A1 - Franke, Andre A1 - Loos, Bruno G. A1 - Jepsen, Søren A1 - Dommisch, Henrik A1 - Schaefer, Arne S. T1 - Sex‐specific genetic factors affect the risk of early‐onset periodontitis in Europeans JF - Journal of Clinical Periodontology N2 - Aims Various studies have reported that young European women are more likely to develop early‐onset periodontitis compared to men. A potential explanation for the observed variations in sex and age of disease onset is the natural genetic variation within the autosomal genomes. We hypothesized that genotype‐by‐sex (G × S) interactions contribute to the increased prevalence and severity. Materials and methods Using the case‐only design, we tested for differences in genetic effects between men and women in 896 North‐West European early‐onset cases, using imputed genotypes from the OmniExpress genotyping array. Population‐representative 6823 controls were used to verify that the interacting variables G and S were uncorrelated in the general population. Results In total, 20 loci indicated G × S associations (P < 0.0005), 3 of which were previously suggested as risk genes for periodontitis (ABLIM2, CDH13, and NELL1). We also found independent G × S interactions of the related gene paralogs MACROD1/FLRT1 (chr11) and MACROD2/FLRT3 (chr20). G × S‐associated SNPs at CPEB4, CDH13, MACROD1, and MECOM were genome‐wide‐associated with heel bone mineral density (CPEB4, MECOM), waist‐to‐hip ratio (CPEB4, MACROD1), and blood pressure (CPEB4, CDH13). Conclusions Our results indicate that natural genetic variation affects the different heritability of periodontitis among sexes and suggest genes that contribute to inter‐sex phenotypic variation in early‐onset periodontitis. KW - alveolar bone loss KW - gene × sex interaction KW - genetic risk KW - heritability KW - inflammation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262445 VL - 48 IS - 11 SP - 1404 EP - 1413 ER - TY - JOUR A1 - Lombardi, Jolina A1 - Mayer, Benjamin A1 - Semler, Elisa A1 - Anderl‐Straub, Sarah A1 - Uttner, Ingo A1 - Kassubek, Jan A1 - Diehl‐Schmid, Janine A1 - Danek, Adrian A1 - Levin, Johannes A1 - Fassbender, Klaus A1 - Fliessbach, Klaus A1 - Schneider, Anja A1 - Huppertz, Hans‐Jürgen A1 - Jahn, Holger A1 - Volk, Alexander A1 - Kornhuber, Johannes A1 - Landwehrmeyer, Bernhard A1 - Lauer, Martin A1 - Prudlo, Johannes A1 - Wiltfang, Jens A1 - Schroeter, Matthias L. A1 - Ludolph, Albert A1 - Otto, Markus T1 - Quantifying progression in primary progressive aphasia with structural neuroimaging JF - Alzheimer's & Dementia N2 - Introduction The term primary progressive aphasia (PPA) sums up the non‐fluent (nfv), the semantic (sv), and the logopenic (lv) variant. Up to now, there is only limited data available concerning magnetic resonance imaging volumetry to monitor disease progression. Methods Structural brain imaging and an extensive assessment were applied at baseline and up to 4‐year(s) follow‐up in 269 participants. With automated atlas‐based volumetry 56 brain regions were assessed. Atrophy progression served to calculate sample sizes for therapeutic trials. Results At baseline highest atrophy appeared in parts of the left frontal lobe for nfvPPA (–17%) and of the left temporal lobe for svPPA (–34%) and lvPPA (–24%). Severest progression within 1‐year follow‐up occurred in the basal ganglia in nfvPPA (–7%), in the hippocampus/amygdala in svPPA (–9%), and in (medial) temporal regions in lvPPA (–6%). Conclusion PPA presents as a left‐dominant, mostly gray matter sensitive disease with considerable atrophy at baseline that proceeds variant‐specific. KW - atlas‐based volumetry KW - disease progression KW - frontotemporal dementia KW - longitudinal magnetic resonance imaging KW - primary progressive aphasia KW - sample size calculation Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262605 VL - 17 IS - 10 SP - 1595 EP - 1609 ER - TY - JOUR A1 - Gabriel, Katharina M. A. A1 - Jírů-Hillmann, Steffi A1 - Kraft, Peter A1 - Selig, Udo A1 - Rücker, Victoria A1 - Mühler, Johannes A1 - Dötter, Klaus A1 - Keidel, Matthias A1 - Soda, Hassan A1 - Rascher, Alexandra A1 - Schneider, Rolf A1 - Pfau, Mathias A1 - Hoffmann, Roy A1 - Stenzel, Joachim A1 - Benghebrid, Mohamed A1 - Goebel, Tobias A1 - Doerck, Sebastian A1 - Kramer, Daniela A1 - Haeusler, Karl Georg A1 - Volkmann, Jens A1 - Heuschmann, Peter U. A1 - Fluri, Felix T1 - Two years' experience of implementing a comprehensive telemedical stroke network comprising in mainly rural region: the Transregional Network for Stroke Intervention with Telemedicine (TRANSIT-Stroke) JF - BMC Neurology N2 - Background Telemedicine improves the quality of acute stroke care in rural regions with limited access to specialized stroke care. We report the first 2 years' experience of implementing a comprehensive telemedical stroke network comprising all levels of stroke care in a defined region. Methods The TRANSIT-Stroke network covers a mainly rural region in north-western Bavaria (Germany). All hospitals providing acute stroke care in this region participate in TRANSIT-Stroke, including four hospitals with a supra-regional certified stroke unit (SU) care (level III), three of those providing teleconsultation to two hospitals with a regional certified SU (level II) and five hospitals without specialized SU care (level I). For a two-year-period (01/2015 to 12/2016), data of eight of these hospitals were available; 13 evidence-based quality indicators (QIs) related to processes during hospitalisation were evaluated quarterly and compared according to predefined target values between level-I- and level-II/III-hospitals. Results Overall, 7881 patients were included (mean age 74.6 years +/- 12.8; 48.4% female). In level-II/III-hospitals adherence of all QIs to predefined targets was high ab initio. In level-I-hospitals, three patterns of QI-development were observed: a) high adherence ab initio (31%), mainly in secondary stroke prevention; b) improvement over time (44%), predominantly related to stroke specific diagnosis and in-hospital organization; c) no clear time trends (25%). Overall, 10 out of 13 QIs reached predefined target values of quality of care at the end of the observation period. Conclusion The implementation of the comprehensive TRANSIT-Stroke network resulted in an improvement of quality of care in level-I-hospitals. KW - pilot project KW - care tempis KW - ischemic stroke KW - thrombolysis KW - areas KW - time KW - hospitals KW - mortality KW - outcomes KW - quality Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229214 VL - 20 ER - TY - JOUR A1 - Schwinn, Stefanie A1 - Mokhtari, Zeinab A1 - Thusek, Sina A1 - Schneider, Theresa A1 - Sirén, Anna-Leena A1 - Tiemeyer, Nicola A1 - Caruana, Ignazio A1 - Miele, Evelina A1 - Schlegel, Paul G. A1 - Beilhack, Andreas A1 - Wölfl, Matthias T1 - Cytotoxic effects and tolerability of gemcitabine and axitinib in a xenograft model for c-myc amplified medulloblastoma JF - Scientific Reports N2 - Medulloblastoma is the most common high-grade brain tumor in childhood. Medulloblastomas with c-myc amplification, classified as group 3, are the most aggressive among the four disease subtypes resulting in a 5-year overall survival of just above 50%. Despite current intensive therapy regimens, patients suffering from group 3 medulloblastoma urgently require new therapeutic options. Using a recently established c-myc amplified human medulloblastoma cell line, we performed an in-vitro-drug screen with single and combinatorial drugs that are either already clinically approved or agents in the advanced stage of clinical development. Candidate drugs were identified in vitro and then evaluated in vivo. Tumor growth was closely monitored by BLI. Vessel development was assessed by 3D light-sheet-fluorescence-microscopy. We identified the combination of gemcitabine and axitinib to be highly cytotoxic, requiring only low picomolar concentrations when used in combination. In the orthotopic model, gemcitabine and axitinib showed efficacy in terms of tumor control and survival. In both models, gemcitabine and axitinib were better tolerated than the standard regimen comprising of cisplatin and etoposide phosphate. 3D light-sheet-fluorescence-microscopy of intact tumors revealed thinning and rarefication of tumor vessels, providing one explanation for reduced tumor growth. Thus, the combination of the two drugs gemcitabine and axitinib has favorable effects on preventing tumor progression in an orthotopic group 3 medulloblastoma xenograft model while exhibiting a favorable toxicity profile. The combination merits further exploration as a new approach to treat high-risk group 3 medulloblastoma. KW - cancer KW - CNS cancer KW - paediatric cancer Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-261476 VL - 11 IS - 1 ER - TY - JOUR A1 - Kochereshko, Vladimir P. A1 - Durnev, Mikhail V. A1 - Besombes, Lucien A1 - Mariette, Henri A1 - Sapega, Victor F. A1 - Askitopoulos, Alexis A1 - Savenko, Ivan G. A1 - Liew, Timothy C. H. A1 - Shelykh, Ivan A. A1 - Platonov, Alexey V. A1 - Tsintzos, Simeon I. A1 - Hatzopoulos, Z. A1 - Savvidis, Pavlos G. A1 - Kalevich, Vladimir K. A1 - Afanasiev, Mikhail M. A1 - Lukoshkin, Vladimir A. A1 - Schneider, Christian A1 - Amthor, Matthias A1 - Metzger, Christian A1 - Kamp, Martin A1 - Hoefling, Sven A1 - Lagoudakis, Pavlos A1 - Kavokin, Alexey T1 - Lasing in Bose-Fermi mixtures JF - Scientific Reports N2 - Light amplification by stimulated emission of radiation, well-known for revolutionising photonic science, has been realised primarily in fermionic systems including widely applied diode lasers. The prerequisite for fermionic lasing is the inversion of electronic population, which governs the lasing threshold. More recently, bosonic lasers have also been developed based on Bose-Einstein condensates of exciton-polaritons in semiconductor microcavities. These electrically neutral bosons coexist with charged electrons and holes. In the presence of magnetic fields, the charged particles are bound to their cyclotron orbits, while the neutral exciton-polaritons move freely. We demonstrate how magnetic fields affect dramatically the phase diagram of mixed Bose-Fermi systems, switching between fermionic lasing, incoherent emission and bosonic lasing regimes in planar and pillar microcavities with optical and electrical pumping. We collected and analyzed the data taken on pillar and planar microcavity structures at continuous wave and pulsed optical excitation as well as injecting electrons and holes electronically. Our results evidence the transition from a Bose gas to a Fermi liquid mediated by magnetic fields and light-matter coupling. KW - Bose-Fermi KW - magnetic fields KW - Bose gas KW - Fermi liquid KW - light-matter coupling Y1 - 2016 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168152 VL - 6 IS - 20091 ER - TY - JOUR A1 - Schischlevskij, Pavel A1 - Cordts, Isabell A1 - Günther, René A1 - Stolte, Benjamin A1 - Zeller, Daniel A1 - Schröter, Carsten A1 - Weyen, Ute A1 - Regensburger, Martin A1 - Wolf, Joachim A1 - Schneider, Ilka A1 - Hermann, Andreas A1 - Metelmann, Moritz A1 - Kohl, Zacharias A1 - Linker, Ralf A. A1 - Koch, Jan Christoph A1 - Stendel, Claudia A1 - Müschen, Lars H. A1 - Osmanovic, Alma A1 - Binz, Camilla A1 - Klopstock, Thomas A1 - Dorst, Johannes A1 - Ludolph, Albert C. A1 - Boentert, Matthias A1 - Hagenacker, Tim A1 - Deschauer, Marcus A1 - Lingor, Paul A1 - Petri, Susanne A1 - Schreiber-Katz, Olivia T1 - Informal caregiving in amyotrophic lateral sclerosis (ALS): a high caregiver burden and drastic consequences on caregivers' lives JF - Brain Sciences N2 - Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that causes progressive autonomy loss and need for care. This does not only affect patients themselves, but also the patients’ informal caregivers (CGs) in their health, personal and professional lives. The big efforts of this multi-center study were not only to evaluate the caregivers' burden and to identify its predictors, but it also should provide a specific understanding of the needs of ALS patients' CGs and fill the gap of knowledge on their personal and work lives. Using standardized questionnaires, primary data from patients and their main informal CGs (n = 249) were collected. Patients' functional status and disease severity were evaluated using the Barthel Index, the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and the King’s Stages for ALS. The caregivers' burden was recorded by the Zarit Burden Interview (ZBI). Comorbid anxiety and depression of caregivers were assessed by the Hospital Anxiety and Depression Scale. Additionally, the EuroQol Five Dimension Five Level Scale evaluated their health-related quality of life. The caregivers' burden was high (mean ZBI = 26/88, 0 = no burden, ≥24 = highly burdened) and correlated with patients' functional status (r\(_p\) = −0.555, p < 0.001, n = 242). It was influenced by the CGs' own mental health issues due to caregiving (+11.36, 95% CI [6.84; 15.87], p < 0.001), patients' wheelchair dependency (+9.30, 95% CI [5.94; 12.66], p < 0.001) and was interrelated with the CGs' depression (r\(_p\) = 0.627, p < 0.001, n = 234), anxiety (r\(_p\) = 0.550, p < 0.001, n = 234), and poorer physical condition (r\(_p\) = −0.362, p < 0.001, n = 237). Moreover, female CGs showed symptoms of anxiety more often, which also correlated with the patients' impairment in daily routine (r\(_s\) = −0.280, p < 0.001, n = 169). As increasing disease severity, along with decreasing autonomy, was the main predictor of caregiver burden and showed to create relevant (negative) implications on CGs' lives, patient care and supportive therapies should address this issue. Moreover, in order to preserve the mental and physical health of the CGs, new concepts of care have to focus on both, on not only patients but also their CGs and gender-associated specific issues. As caregiving in ALS also significantly influences the socioeconomic status by restrictions in CGs' work lives and income, and the main reported needs being lack of psychological support and a high bureaucracy, the situation of CGs needs more attention. Apart from their own multi-disciplinary medical and psychological care, more support in care and patient management issues is required. KW - amyotrophic lateral sclerosis (ALS) KW - informal caregiving KW - caregiver burden KW - functional status KW - decreasing autonomy KW - depression KW - anxiety KW - health-related quality of life KW - socioeconomic status KW - psychological support Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-240981 SN - 2076-3425 VL - 11 IS - 6 ER - TY - JOUR A1 - Peseschkian, Tara A1 - Cordts, Isabell A1 - Günther, René A1 - Stolte, Benjamin A1 - Zeller, Daniel A1 - Schröter, Carsten A1 - Weyen, Ute A1 - Regensburger, Martin A1 - Wolf, Joachim A1 - Schneider, Ilka A1 - Hermann, Andreas A1 - Metelmann, Moritz A1 - Kohl, Zacharias A1 - Linker, Ralf A. A1 - Koch, Jan Christoph A1 - Büchner, Boriana A1 - Weiland, Ulrike A1 - Schönfelder, Erik A1 - Heinrich, Felix A1 - Osmanovic, Alma A1 - Klopstock, Thomas A1 - Dorst, Johannes A1 - Ludolph, Albert C. A1 - Boentert, Matthias A1 - Hagenacker, Tim A1 - Deschauer, Marcus A1 - Lingor, Paul A1 - Petri, Susanne A1 - Schreiber-Katz, Olivia T1 - A nation-wide, multi-center study on the quality of life of ALS patients in Germany JF - Brain Sciences N2 - Improving quality of life (QoL) is central to amyotrophic lateral sclerosis (ALS) treatment. This Germany-wide, multicenter cross-sectional study analyses the impact of different symptom-specific treatments and ALS variants on QoL. Health-related QoL (HRQoL) in 325 ALS patients was assessed using the Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) and EuroQol Five Dimension Five Level Scale (EQ-5D-5L), together with disease severity (captured by the revised ALS Functional Rating Scale (ALSFRS-R)) and the current care and therapies used by our cohort. At inclusion, the mean ALSAQ-5 total score was 56.93 (max. 100, best = 0) with a better QoL associated with a less severe disease status (β = −1.96 per increase of one point in the ALSFRS-R score, p < 0.001). “Limb-onset” ALS (lALS) was associated with a better QoL than “bulbar-onset” ALS (bALS) (mean ALSAQ-5 total score 55.46 versus 60.99, p = 0.040). Moreover, with the ALSFRS-R as a covariate, using a mobility aid (β = −7.60, p = 0.001), being tracheostomized (β = −14.80, p = 0.004) and using non-invasive ventilation (β = −5.71, p = 0.030) were associated with an improved QoL, compared to those at the same disease stage who did not use these aids. In contrast, antidepressant intake (β = 5.95, p = 0.007), and increasing age (β = 0.18, p = 0.023) were predictors of worse QoL. Our results showed that the ALSAQ-5 was better-suited for ALS patients than the EQ-5D-5L. Further, the early and symptom-specific clinical management and supply of assistive devices can significantly improve the individual HRQoL of ALS patients. Appropriate QoL questionnaires are needed to monitor the impact of treatment to provide the best possible and individualized care. KW - Amyotrophic Lateral Sclerosis (ALS) KW - Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 (ALSAQ-5) KW - ALS treatment KW - “bulbar-onset” ALS (bALS) KW - “limb-onset” ALS (lALS) KW - EuroQol Five Dimension Five Level Scale (EQ-5D-5L) KW - health-related quality of life (HRQoL) KW - quality of life (QoL) KW - symptom-specific treatment KW - assistive devices Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-234147 SN - 2076-3425 VL - 11 IS - 3 ER - TY - JOUR A1 - Schneider, Michael A1 - Tschöpe, André A1 - Hanselmann, Doris A1 - Ballweg, Thomas A1 - Gellermann, Carsten A1 - Franzreb, Matthias A1 - Mandel, Karl T1 - Adsorber Particles with Magnetically‐Supported Improved Electrochemical Conversion Behavior for Waste Water Treatment Processes JF - Particle & Particle Systems Characterization N2 - Micron‐sized supraparticles, consisting of a plurality of discrete nano‐ and microscale functional units, are assembled and fused by means of a droplet extrusion process. By combining nano magnetite, activated carbon, and conductive carbon with a polymeric binder matrix, particles are obtained which unite good magnetic properties, electrical conductivity, and adsorber activity through the high accessible surface area of the incorporated activated carbon of about 570 m\(^{2}\) g\(^{-1}\), thereby enabling a new approach toward sustainable water treatment processes. Due to the interplay of the components, it is possible to adsorb target substances, dissolved in the water which is demonstrated by the adsorption of the model dye methylene blue. A very fast adsorption kinetic and an adsorption capacity of about 400 mg g\(^{-1}\) is determined. By using the developed composite particles, it is also possible to electrochemically alter substances flowing through a magnetically‐stabilized fluidized‐bed reactor by electrochemically charging/discharging, significantly supported by the magnetic field enabling alternatingly optimum mobility/adsorption phases with contact/charging intervals. The electrochemical conversion can be increased up to 151% depending on the applied flow‐rate and electrical voltage. By applying an external magnetic field, a further increase of electrochemical conversion of up to 70% can be observed. KW - composite supraparticles KW - dye adsorption KW - electrochemical conversion KW - magnetic particles KW - water purification Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214738 VL - 37 IS - 2 ER - TY - JOUR A1 - Sommer, Kim K. A1 - Amr, Ali A1 - Bavendiek, Udo A1 - Beierle, Felix A1 - Brunecker, Peter A1 - Dathe, Henning A1 - Eils, Jürgen A1 - Ertl, Maximilian A1 - Fette, Georg A1 - Gietzelt, Matthias A1 - Heidecker, Bettina A1 - Hellenkamp, Kristian A1 - Heuschmann, Peter A1 - Hoos, Jennifer D. E. A1 - Kesztyüs, Tibor A1 - Kerwagen, Fabian A1 - Kindermann, Aljoscha A1 - Krefting, Dagmar A1 - Landmesser, Ulf A1 - Marschollek, Michael A1 - Meder, Benjamin A1 - Merzweiler, Angela A1 - Prasser, Fabian A1 - Pryss, Rüdiger A1 - Richter, Jendrik A1 - Schneider, Philipp A1 - Störk, Stefan A1 - Dieterich, Christoph T1 - Structured, harmonized, and interoperable integration of clinical routine data to compute heart failure risk scores JF - Life N2 - Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled clinical studies can be used to calculate the risk of mortality and HF hospitalizations. However, these scores are poorly implemented into routine care, predominantly because their calculation requires considerable efforts in practice and necessary data often are not available in an interoperable format. In this work, we demonstrate the feasibility of a multi-site solution to derive and calculate two exemplary HF scores from clinical routine data (MAGGIC score with six continuous and eight categorical variables; Barcelona Bio-HF score with five continuous and six categorical variables). Within HiGHmed, a German Medical Informatics Initiative consortium, we implemented an interoperable solution, collecting a harmonized HF-phenotypic core data set (CDS) within the openEHR framework. Our approach minimizes the need for manual data entry by automatically retrieving data from primary systems. We show, across five participating medical centers, that the implemented structures to execute dedicated data queries, followed by harmonized data processing and score calculation, work well in practice. In summary, we demonstrated the feasibility of clinical routine data usage across multiple partner sites to compute HF risk scores. This solution can be extended to a large spectrum of applications in clinical care. KW - medical informatics initiative KW - HiGHmed KW - medical data integration center KW - clinical routine data KW - heart failure KW - risk prediction scores KW - semantic interoperability KW - openEHR Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-275239 SN - 2075-1729 VL - 12 IS - 5 ER - TY - JOUR A1 - Richter, Gesa M. A1 - Kruppa, Jochen A1 - Munz, Matthias A1 - Wiehe, Ricarda A1 - Häsler, Robert A1 - Franke, Andre A1 - Martins, Orlando A1 - Jockel-Schneider, Yvonne A1 - Bruckmann, Corinna A1 - Dommisch, Henrik A1 - Schaefer, Arne S. T1 - A combined epigenome- and transcriptome-wide association study of the oral masticatory mucosa assigns CYP1B1 a central role for epithelial health in smokers JF - Clinical Epigenetics N2 - Background The oral mucosa has an important role in maintaining barrier integrity at the gateway to the gastrointestinal and respiratory tracts. Smoking is a strong environmental risk factor for the common oral inflammatory disease periodontitis and oral cancer. Cigarette smoke affects gene methylation and expression in various tissues. This is the first epigenome-wide association study (EWAS) that aimed to identify biologically active methylation marks of the oral masticatory mucosa that are associated with smoking. Results Ex vivo biopsies of 18 current smokers and 21 never smokers were analysed with the Infinium Methylation EPICBeadChip and combined with whole transcriptome RNA sequencing (RNA-Seq; 16 mio reads per sample) of the same samples. We analysed the associations of CpG methylation values with cigarette smoking and smoke pack year (SPY) levels in an analysis of covariance (ANCOVA). Nine CpGs were significantly associated with smoking status, with three CpGs mapping to the genetic region of CYP1B1 (cytochrome P450 family 1 subfamily B member 1;best p=5.5x10(-8)) and two mapping to AHRR (aryl-hydrocarbon receptor repressor; best p=5.9x10(-9)). In the SPY analysis, 61 CpG sites at 52 loci showed significant associations of the quantity of smoking with changes in methylation values. Here, the most significant association located to the gene CYP1B1, with p=4.0x10(-10). RNA-Seq data showed significantly increased expression of CYP1B1 in smokers compared to non-smokers (p=2.2x10(-14)), together with 13 significantly upregulated transcripts. Six transcripts were significantly downregulated. No differential expression was observed for AHRR. In vitro studies with gingival fibroblasts showed that cigarette smoke extract directly upregulated the expression of CYP1B1. Conclusion This study validated the established role of CYP1B1 and AHRR in xenobiotic metabolism of tobacco smoke and highlights the importance of epigenetic regulation for these genes. For the first time, we give evidence of this role for the oral masticatory mucosa. KW - EWAS KW - Methylation KW - Expression KW - Masticatory mucosa KW - CYP1B1 KW - AHRR KW - Cytochrome P 450 pathway KW - OSCC KW - Smoking Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-226175 VL - 11 ER - TY - JOUR A1 - Wurdack, Matthias A1 - Lundt, Nils A1 - Klaas, Martin A1 - Baumann, Vasilij A1 - Kavokin, Alexey V. A1 - Höfling, Sven A1 - Schneider, Christian T1 - Observation of hybrid Tamm-plasmon exciton-polaritons with GaAs quantum wells and a MoSe\(_{2}\) monolayer JF - Nature Communications N2 - Strong light matter coupling between excitons and microcavity photons, as described in the framework of cavity quantum electrodynamics, leads to the hybridization of light and matter excitations. The regime of collective strong coupling arises, when various excitations from different host media are strongly coupled to the same optical resonance. This leads to a well-controllable admixture of various matter components in three hybrid polariton modes. Here, we study a cavity device with four embedded GaAs quantum wells hosting excitons that are spectrally matched to the A-valley exciton resonance of a MoSe\(_{2}\) monolayer. The formation of hybrid polariton modes is evidenced in momentum resolved photoluminescence and reflectivity studies. We describe the energy and k-vector distribution of exciton-polaritons along the hybrid modes by a thermodynamic model, which yields a very good agreement with the experiment. KW - two-dimensional materials KW - microresonators KW - nanophotonics and plasmonics KW - cavity device KW - strong coupling Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-170480 VL - 8 IS - 259 ER - TY - JOUR A1 - McNeill, Rhiannon V. A1 - Ziegler, Georg C. A1 - Radtke, Franziska A1 - Nieberler, Matthias A1 - Lesch, Klaus‑Peter A1 - Kittel‑Schneider, Sarah T1 - Mental health dished up — the use of iPSC models in neuropsychiatric research JF - Journal of Neural Transmission N2 - Genetic and molecular mechanisms that play a causal role in mental illnesses are challenging to elucidate, particularly as there is a lack of relevant in vitro and in vivo models. However, the advent of induced pluripotent stem cell (iPSC) technology has provided researchers with a novel toolbox. We conducted a systematic review using the PRISMA statement. A PubMed and Web of Science online search was performed (studies published between 2006–2020) using the following search strategy: hiPSC OR iPSC OR iPS OR stem cells AND schizophrenia disorder OR personality disorder OR antisocial personality disorder OR psychopathy OR bipolar disorder OR major depressive disorder OR obsessive compulsive disorder OR anxiety disorder OR substance use disorder OR alcohol use disorder OR nicotine use disorder OR opioid use disorder OR eating disorder OR anorexia nervosa OR attention-deficit/hyperactivity disorder OR gaming disorder. Using the above search criteria, a total of 3515 studies were found. After screening, a final total of 56 studies were deemed eligible for inclusion in our study. Using iPSC technology, psychiatric disease can be studied in the context of a patient’s own unique genetic background. This has allowed great strides to be made into uncovering the etiology of psychiatric disease, as well as providing a unique paradigm for drug testing. However, there is a lack of data for certain psychiatric disorders and several limitations to present iPSC-based studies, leading us to discuss how this field may progress in the next years to increase its utility in the battle to understand psychiatric disease. KW - hiPSC KW - iPSC KW - stem cells KW - mental disorders KW - affective disorders KW - ADHD Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235666 SN - 0300-9564 VL - 127 ER - TY - JOUR A1 - Hoesl, Christine A1 - Fröhlich, Thomas A1 - Posch, Christian A1 - Kneitz, Hermann A1 - Goebeler, Matthias A1 - Schneider, Marlon R. A1 - Dahlhoff, Maik T1 - The transmembrane protein LRIG1 triggers melanocytic tumor development following chemically induced skin carcinogenesis JF - Molecular Oncology N2 - The incidence of melanoma and nonmelanoma skin cancer has increased tremendously in recent years. Although novel treatment options have significantly improved patient outcomes, the prognosis for most patients with an advanced disease remains dismal. It is, thus, imperative to understand the molecular mechanisms involved in skin carcinogenesis in order to develop new targeted treatment strategies. Receptor tyrosine kinases (RTK) like the ERBB receptor family, including EGFR/ERBB1, ERBB2/NEU, ERBB3, and ERBB4, are important regulators of skin homeostasis and their dysregulation often results in cancer, which makes them attractive therapeutic targets. Members of the leucine‐rich repeats and immunoglobulin‐like domains protein family (LRIG1‐3) are ERBB regulators and thus potential therapeutic targets to manipulate ERBB receptors. Here, we analyzed the function of LRIG1 during chemically induced skin carcinogenesis in transgenic mice expressing LRIG1 in the skin under the control of the keratin 5 promoter (LRIG1‐TG mice). We observed a significant induction of melanocytic tumor formation in LRIG1‐TG mice and no difference in papilloma incidence between LRIG1‐TG and control mice. Our findings also revealed that LRIG1 affects ERBB signaling via decreased phosphorylation of EGFR and increased activation of the oncoprotein ERBB2 during skin carcinogenesis. The epidermal proliferation rate was significantly decreased during epidermal tumorigenesis under LRIG1 overexpression, and the apoptosis marker cleaved caspase 3 was significantly activated in the epidermis of transgenic LRIG1 mice. Additionally, we detected LRIG1 expression in human cutaneous squamous cell carcinoma and melanoma samples. Therefore, we depleted LRIG1 in human melanoma cells (A375) by CRISPR/Cas9 technology and found that this caused EGFR and ERBB3 downregulation in A375 LRIG1 knockout cells 6 h following stimulation with EGF. In conclusion, our study demonstrated that LRIG1‐TG mice develop melanocytic skin tumors during chemical skin carcinogenesis and a deletion of LRIG1 in human melanoma cells reduces EGFR and ERBB3 expression after EGF stimulation. KW - ERBB receptors KW - LRIG1 KW - melanoma KW - mouse model KW - skin carcinogenesis Y1 - 2021 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-238925 VL - 15 IS - 8 SP - 2140 EP - 2155 ER - TY - JOUR A1 - Semler, Elisa A1 - Anderl-Straub, Sarah A1 - Uttner, Ingo A1 - Diehl-Schmid, Janine A1 - Danek, Adrian A1 - Einsiedler, Beate A1 - Fassbender, Klaus A1 - Fliessbach, Klaus A1 - Huppertz, Hans-Jürgen A1 - Jahn, Holger A1 - Kornhuber, Johannes A1 - Landwehrmeyer, Bernhard A1 - Lauer, Martin A1 - Muche, Rainer A1 - Prudlo, Johannes A1 - Schneider, Anja A1 - Schroeter, Matthias L. A1 - Ludolph, Albert C. A1 - Otto, Markus T1 - A language-based sum score for the course and therapeutic intervention in primary progressive aphasia JF - Alzheimer's Research & Therapy N2 - Background With upcoming therapeutic interventions for patients with primary progressive aphasia (PPA), instruments for the follow-up of patients are needed to describe disease progression and to evaluate potential therapeutic effects. So far, volumetric brain changes have been proposed as clinical endpoints in the literature, but cognitive scores are still lacking. This study followed disease progression predominantly in language-based performance within 1 year and defined a PPA sum score which can be used in therapeutic interventions. Methods We assessed 28 patients with nonfluent variant PPA, 17 with semantic variant PPA, 13 with logopenic variant PPA, and 28 healthy controls in detail for 1 year. The most informative neuropsychological assessments were combined to a sum score, and associations between brain atrophy were investigated followed by a sample size calculation for clinical trials. Results Significant absolute changes up to 20% in cognitive tests were found after 1 year. Semantic and phonemic word fluency, Boston Naming Test, Digit Span, Token Test, AAT Written language, and Cookie Test were identified as the best markers for disease progression. These tasks provide the basis of a new PPA sum score. Assuming a therapeutic effect of 50% reduction in cognitive decline for sample size calculations, a number of 56 cases is needed to find a significant treatment effect. Correlations between cognitive decline and atrophy showed a correlation up to r = 0.7 between the sum score and frontal structures, namely the superior and inferior frontal gyrus, as well as with left-sided subcortical structures. Conclusion Our findings support the high performance of the proposed sum score in the follow-up of PPA and recommend it as an outcome measure in intervention studies. KW - frontotemporal dementia KW - cognitive neuropsychology in dementia KW - assessment of cognitive disorders/dementia KW - volumetric MRI KW - aphasia Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236277 VL - 10 ER - TY - JOUR A1 - Li, Donghai A1 - Shan, Hangyong A1 - Rupprecht, Christoph A1 - Knopf, Heiko A1 - Watanabe, Kenji A1 - Taniguchi, Takashi A1 - Qin, Ying A1 - Tongay, Sefaattin A1 - Nuß, Matthias A1 - Schröder, Sven A1 - Eilenberger, Falk A1 - Höfling, Sven A1 - Schneider, Christian A1 - Brixner, Tobias T1 - Hybridized exciton-photon-phonon states in a transition-metal-dichalcogenide van-der-Waals heterostructure microcavity JF - Physical Review Letters N2 - Excitons in atomically thin transition-metal dichalcogenides (TMDs) have been established as an attractive platform to explore polaritonic physics, owing to their enormous binding energies and giant oscillator strength. Basic spectral features of exciton polaritons in TMD microcavities, thus far, were conventionally explained via two-coupled-oscillator models. This ignores, however, the impact of phonons on the polariton energy structure. Here we establish and quantify the threefold coupling between excitons, cavity photons, and phonons. For this purpose, we employ energy-momentum-resolved photoluminescence and spatially resolved coherent two-dimensional spectroscopy to investigate the spectral properties of a high-quality-factor microcavity with an embedded WSe\(_2\) van-der-Waals heterostructure at room temperature. Our approach reveals a rich multi-branch structure which thus far has not been captured in previous experiments. Simulation of the data reveals hybridized exciton-photon-phonon states, providing new physical insight into the exciton polariton system based on layered TMDs. KW - strong coupling KW - laser spectroscopy KW - transition metal dichalcogenide KW - coherent multidimensional spectroscopy KW - exciton Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-351303 UR - https://journals.aps.org/prl/abstract/10.1103/PhysRevLett.128.087401 SN - 1079-7114 ET - accepted version ER -