@article{BousquetAntoBachertetal.2021, author = {Bousquet, Jean and Anto, Josep M. and Bachert, Claus and Haahtela, Tari and Zuberbier, Torsten and Czarlewski, Wienczyslawa and Bedbrook, Anna and Bosnic-Anticevich, Sinthia and Walter Canonica, G. and Cardona, Victoria and Costa, Elisio and Cruz, Alvaro A. and Erhola, Marina and Fokkens, Wytske J. and Fonseca, Joao A. and Illario, Maddalena and Ivancevich, Juan-Carlos and Jutel, Marek and Klimek, Ludger and Kuna, Piotr and Kvedariene, Violeta and Le, LTT and Larenas-Linnemann, D{\´e}sir{\´e}e E. and Laune, Daniel and Louren{\c{c}}o, Olga M. and Mel{\´e}n, Erik and Mullol, Joaquim and Niedoszytko, Marek and Odemyr, Mika{\"e}la and Okamoto, Yoshitaka and Papadopoulos, Nikos G. and Patella, Vincenzo and Pfaar, Oliver and Pham-Thi, Nh{\^a}n and Rolland, Christine and Samolinski, Boleslaw and Sheikh, Aziz and Sofiev, Mikhail and Suppli Ulrik, Charlotte and Todo-Bom, Ana and Tomazic, Peter-Valentin and Toppila-Salmi, Sanna and Tsiligianni, Ioanna and Valiulis, Arunas and Valovirta, Erkka and Ventura, Maria-Teresa and Walker, Samantha and Williams, Sian and Yorgancioglu, Arzu and Agache, Ioana and Akdis, Cezmi A. and Almeida, Rute and Ansotegui, Ignacio J. and Annesi-Maesano, Isabella and Arnavielhe, Sylvie and Basaga{\~n}a, Xavier and D. Bateman, Eric and B{\´e}dard, Annabelle and Bedolla-Barajas, Martin and Becker, Sven and Bennoor, Kazi S. and Benveniste, Samuel and Bergmann, Karl C. and Bewick, Michael and Bialek, Slawomir and E. Billo, Nils and Bindslev-Jensen, Carsten and Bjermer, Leif and Blain, Hubert and Bonini, Matteo and Bonniaud, Philippe and Bosse, Isabelle and Bouchard, Jacques and Boulet, Louis-Philippe and Bourret, Rodolphe and Boussery, Koen and Braido, Fluvio and Briedis, Vitalis and Briggs, Andrew and Brightling, Christopher E. and Brozek, Jan and Brusselle, Guy and Brussino, Luisa and Buhl, Roland and Buonaiuto, Roland and Calderon, Moises A. and Camargos, Paulo and Camuzat, Thierry and Caraballo, Luis and Carriazo, Ana-Maria and Carr, Warner and Cartier, Christine and Casale, Thomas and Cecchi, Lorenzo and Cepeda Sarabia, Alfonso M. and H. Chavannes, Niels and Chkhartishvili, Ekaterine and Chu, Derek K. and Cingi, Cemal and Correia de Sousa, Jaime and Costa, David J. and Courbis, Anne-Lise and Custovic, Adnan and Cvetkosvki, Biljana and D'Amato, Gennaro and da Silva, Jane and Dantas, Carina and Dokic, Dejan and Dauvilliers, Yves and De Feo, Giulia and De Vries, Govert and Devillier, Philippe and Di Capua, Stefania and Dray, Gerard and Dubakiene, Ruta and Durham, Stephen R. and Dykewicz, Mark and Ebisawa, Motohiro and Gaga, Mina and El-Gamal, Yehia and Heffler, Enrico and Emuzyte, Regina and Farrell, John and Fauquert, Jean-Luc and Fiocchi, Alessandro and Fink-Wagner, Antje and Fontaine, Jean-Fran{\c{c}}ois and Fuentes Perez, Jos{\´e} M. and Gemicioğlu, Bilun and Gamkrelidze, Amiran and Garcia-Aymerich, Judith and Gevaert, Philippe and Gomez, Ren{\´e} Maximiliano and Gonz{\´a}lez Diaz, Sandra and Gotua, Maia and Guldemond, Nick A. and Guzm{\´a}n, Maria-Antonieta and Hajjam, Jawad and Huerta Villalobos, Yunuen R. and Humbert, Marc and Iaccarino, Guido and Ierodiakonou, Despo and Iinuma, Tomohisa and Jassem, Ewa and Joos, Guy and Jung, Ki-Suck and Kaidashev, Igor and Kalayci, Omer and Kardas, Przemyslaw and Keil, Thomas and Khaitov, Musa and Khaltaev, Nikolai and Kleine-Tebbe, Jorg and Kouznetsov, Rostislav and Kowalski, Marek L. and Kritikos, Vicky and Kull, Inger and La Grutta, Stefania and Leonardini, Lisa and Ljungberg, Henrik and Lieberman, Philip and Lipworth, Brian and Lodrup Carlsen, Karin C. and Lopes-Pereira, Catarina and Loureiro, Claudia C. and Louis, Renaud and Mair, Alpana and Mahboub, Bassam and Makris, Micha{\"e}l and Malva, Joao and Manning, Patrick and Marshall, Gailen D. and Masjedi, Mohamed R. and Maspero, Jorge F. and Carreiro-Martins, Pedro and Makela, Mika and Mathieu-Dupas, Eve and Maurer, Marcus and De Manuel Keenoy, Esteban and Melo-Gomes, Elisabete and Meltzer, Eli O. and Menditto, Enrica and Mercier, Jacques and Micheli, Yann and Miculinic, Neven and Mihaltan, Florin and Milenkovic, Branislava and Mitsias, Dimitirios I. and Moda, Giuliana and Mogica-Martinez, Maria-Dolores and Mohammad, Yousser and Montefort, Steve and Monti, Ricardo and Morais-Almeida, Mario and M{\"o}sges, Ralph and M{\"u}nter, Lars and Muraro, Antonella and Murray, Ruth and Naclerio, Robert and Napoli, Luigi and Namazova-Baranova, Leyla and Neffen, Hugo and Nekam, Kristoff and Neou, Angelo and Nordlund, Bj{\"o}rn and Novellino, Ettore and Nyembue, Dieudonn{\´e} and O'Hehir, Robyn and Ohta, Ken and Okubo, Kimi and Onorato, Gabrielle L. and Orlando, Valentina and Ouedraogo, Solange and Palamarchuk, Julia and Pali-Sch{\"o}ll, Isabella and Panzner, Peter and Park, Hae-Sim and Passalacqua, Gianni and P{\´e}pin, Jean-Louis and Paulino, Ema and Pawankar, Ruby and Phillips, Jim and Picard, Robert and Pinnock, Hilary and Plavec, Davor and Popov, Todor A. and Portejoie, Fabienne and Price, David and Prokopakis, Emmanuel P. and Psarros, Fotis and Pugin, Benoit and Puggioni, Francesca and Quinones-Delgado, Pablo and Raciborski, Filip and Rajabian-S{\"o}derlund, Rojin and Regateiro, Frederico S. and Reitsma, Sietze and Rivero-Yeverino, Daniela and Roberts, Graham and Roche, Nicolas and Rodriguez-Zagal, Erendira and Rolland, Christine and Roller-Wirnsberger, Regina E. and Rosario, Nelson and Romano, Antonino and Rottem, Menachem and Ryan, Dermot and Salim{\"a}ki, Johanna and Sanchez-Borges, Mario M. and Sastre, Joaquin and Scadding, Glenis K. and Scheire, Sophie and Schmid-Grendelmeier, Peter and Sch{\"u}nemann, Holger J. and Sarquis Serpa, Faradiba and Shamji, Mohamed and Sisul, Juan-Carlos and Sofiev, Mikhail and Sol{\´e}, Dirceu and Somekh, David and Sooronbaev, Talant and Sova, Milan and Spertini, Fran{\c{c}}ois and Spranger, Otto and Stellato, Cristiana and Stelmach, Rafael and Thibaudon, Michel and To, Teresa and Toumi, Mondher and Usmani, Omar and Valero, Antonio A. and Valenta, Rudolph and Valentin-Rostan, Marylin and Pereira, Marilyn Urrutia and van der Kleij, Rianne and Van Eerd, Michiel and Vandenplas, Olivier and Vasankari, Tuula and Vaz Carneiro, Antonio and Vezzani, Giorgio and Viart, Fr{\´e}d{\´e}ric and Viegi, Giovanni and Wallace, Dana and Wagenmann, Martin and Wang, De Yun and Waserman, Susan and Wickman, Magnus and Williams, Dennis M. and Wong, Gary and Wroczynski, Piotr and Yiallouros, Panayiotis K. and Yusuf, Osman M. and Zar, Heather J. and Zeng, St{\´e}phane and Zernotti, Mario E. and Zhang, Luo and Shan Zhong, Nan and Zidarn, Mihaela}, title = {ARIA digital anamorphosis: Digital transformation of health and care in airway diseases from research to practice}, series = {Allergy}, volume = {76}, journal = {Allergy}, number = {1}, doi = {10.1111/all.14422}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-228339}, pages = {168 -- 190}, year = {2021}, abstract = {Digital anamorphosis is used to define a distorted image of health and care that may be viewed correctly using digital tools and strategies. MASK digital anamorphosis represents the process used by MASK to develop the digital transformation of health and care in rhinitis. It strengthens the ARIA change management strategy in the prevention and management of airway disease. The MASK strategy is based on validated digital tools. Using the MASK digital tool and the CARAT online enhanced clinical framework, solutions for practical steps of digital enhancement of care are proposed.}, language = {en} } @article{OttoSchmidtKastneretal.2019, author = {Otto, C. and Schmidt, S. and Kastner, C. and Denk, S. and Kettler, J. and M{\"u}ller, N. and Germer, C.T. and Wolf, E. and Gallant, P. and Wiegering, A.}, title = {Targeting bromodomain-containing protein 4 (BRD4) inhibits MYC expression in colorectal cancer cells}, series = {Neoplasia}, volume = {21}, journal = {Neoplasia}, number = {11}, doi = {10.1016/j.neo.2019.10.003}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202451}, pages = {1110-1120}, year = {2019}, abstract = {The transcriptional regulator BRD4 has been shown to be important for the expression of several oncogenes including MYC. Inhibiting of BRD4 has broad antiproliferative activity in different cancer cell types. The small molecule JQ1 blocks the interaction of BRD4 with acetylated histones leading to transcriptional modulation. Depleting BRD4 via engineered bifunctional small molecules named PROTACs (proteolysis targeting chimeras) represents the next-generation approach to JQ1-mediated BRD4 inhibition. PROTACs trigger BRD4 for proteasomale degradation by recruiting E3 ligases. The aim of this study was therefore to validate the importance of BRD4 as a relevant target in colorectal cancer (CRC) cells and to compare the efficacy of BRD4 inhibition with BRD4 degradation on downregulating MYC expression. JQ1 induced a downregulation of both MYC mRNA and MYC protein associated with an antiproliferative phenotype in CRC cells. dBET1 and MZ1 induced degradation of BRD4 followed by a reduction in MYC expression and CRC cell proliferation. In SW480 cells, where dBET1 failed, we found significantly lower levels of the E3 ligase cereblon, which is essential for dBET1-induced BRD4 degradation. To gain mechanistic insight into the unresponsiveness to dBET1, we generated dBET1-resistant LS174t cells and found a strong downregulation of cereblon protein. These findings suggest that inhibition of BRD4 by JQ1 and degradation of BRD4 by dBET1 and MZ1 are powerful tools for reducing MYC expression and CRC cell proliferation. In addition, downregulation of cereblon may be an important mechanism for developing dBET1 resistance, which can be evaded by incubating dBET1-resistant cells with JQ1 or MZ1.}, language = {en} } @article{OttoRubenwolfBurgeretal.2012, author = {Otto, Wolfgang and Rubenwolf, Peter C. and Burger, Maximilian and Fritsche, Hans-Martin and R{\"o}ßler, Wolfgang and May, Matthias and Hartmann, Arndt and Hofst{\"a}dter, Ferdinand and Wieland, Wolf F. and Denzinger, Stefan}, title = {Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer}, series = {BMC Cancer}, volume = {12}, journal = {BMC Cancer}, number = {459}, doi = {10.1186/1471-2407-12-459}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-135679}, year = {2012}, abstract = {Background: Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. Method: AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guerin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. Results: 59\% of patients were shown to exhibit AQP3-positive tumours, whereas 41\% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20\% vs. 72\%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 - 44.68; p=0.025). Conclusions: Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC.}, language = {en} } @article{DupuisDenglerHenekaetal.2012, author = {Dupuis, Luc and Dengler, Reinhard and Heneka, Michael T. and Meyer, Thomas and Zierz, Stephan and Kassubek, Jan and Fischer, Wilhelm and Steiner, Franziska and Lindauer, Eva and Otto, Markus and Dreyhaupt, Jens and Grehl, Torsten and Hermann, Andreas and Winkler, Andrea S. and Bogdahn, Ulrich and Benecke, Reiner and Schrank, Bertold and Wessig, Carsten and Grosskreutz, Julian and Ludolph, Albert C.}, title = {A Randomized, Double Blind, Placebo-Controlled Trial of Pioglitazone in Combination with Riluzole in Amyotrophic Lateral Sclerosis}, series = {PLoS One}, volume = {7}, journal = {PLoS One}, number = {6}, doi = {10.1371/journal.pone.0037885}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-130255}, pages = {e37885}, year = {2012}, abstract = {Background: Pioglitazone, an oral anti-diabetic that stimulates the PPAR-gamma transcription factor, increased survival of mice with amyotrophic lateral sclerosis (ALS). Methods/Principal Findings: We performed a phase II, double blind, multicentre, placebo controlled trial of pioglitazone in ALS patients under riluzole. 219 patients were randomly assigned to receive 45 mg/day of pioglitazone or placebo (one: one allocation ratio). The primary endpoint was survival. Secondary endpoints included incidence of non-invasive ventilation and tracheotomy, and slopes of ALS-FRS, slow vital capacity, and quality of life as assessed using EUROQoL EQ-5D. The study was conducted under a two-stage group sequential test, allowing to stop for futility or superiority after interim analysis. Shortly after interim analysis, 30 patients under pioglitazone and 24 patients under placebo had died. The trial was stopped for futility; the hazard ratio for primary endpoint was 1.21 (95\% CI: 0.71-2.07, p = 0.48). Secondary endpoints were not modified by pioglitazone treatment. Pioglitazone was well tolerated. Conclusion/Significance: Pioglitazone has no beneficial effects on the survival of ALS patients as add-on therapy to riluzole.}, language = {en} } @article{LeikamHufnagelOttoetal.2015, author = {Leikam, C and Hufnagel, AL and Otto, C and Murphy, DJ and M{\"u}hling, B and Kneitz, S and Nanda, I and Schmid, M and Wagner, TU and Haferkamp, S and Br{\"o}cker, E-B and Schartl, M and Meierjohann, S}, title = {In vitro evidence for senescent multinucleated melanocytes as a source for tumor-initiating cells}, series = {Cell Death and Disease}, volume = {6}, journal = {Cell Death and Disease}, number = {e1711}, doi = {10.1038/cddis.2015.71}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-148718}, year = {2015}, abstract = {Oncogenic signaling in melanocytes results in oncogene-induced senescence (OIS), a stable cell-cycle arrest frequently characterized by a bi-or multinuclear phenotype that is considered as a barrier to cancer progression. However, the long-sustained conviction that senescence is a truly irreversible process has recently been challenged. Still, it is not known whether cells driven into OIS can progress to cancer and thereby pose a potential threat. Here, we show that prolonged expression of the melanoma oncogene N-RAS\(^{61K}\) in pigment cells overcomes OIS by triggering the emergence of tumor-initiating mononucleated stem-like cells from senescent cells. This progeny is dedifferentiated, highly proliferative, anoikis-resistant and induces fast growing, metastatic tumors. Our data describe that differentiated cells, which are driven into senescence by an oncogene, use this senescence state as trigger for tumor transformation, giving rise to highly aggressive tumor-initiating cells. These observations provide the first experimental in vitro evidence for the evasion of OIS on the cellular level and ensuing transformation.}, language = {en} } @article{HerwegHansmeierOttoetal.2015, author = {Herweg, Jo-Ana and Hansmeier, Nicole and Otto, Andreas and Geffken, Anna C. and Subbarayal, Prema and Prusty, Bhupesh K. and Becher, D{\"o}rte and Hensel, Michael and Schaible, Ulrich E. and Rudel, Thomas and Hilbi, Hubert}, title = {Purification and proteomics of pathogen-modified vacuoles and membranes}, series = {Frontiers in Cellular and Infection Microbiology}, volume = {5}, journal = {Frontiers in Cellular and Infection Microbiology}, number = {48}, doi = {10.3389/fcimb.2015.00048}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-151823}, year = {2015}, abstract = {Certain pathogenic bacteria adopt an intracellular lifestyle and proliferate in eukaryotic host cells. The intracellular niche protects the bacteria from cellular and humoral components of the mammalian immune system, and at the same time, allows the bacteria to gain access to otherwise restricted nutrient sources. Yet, intracellular protection and access to nutrients comes with a price, i.e., the bacteria need to overcome cell-autonomous defense mechanisms, such as the bactericidal endocytic pathway. While a few bacteria rupture the early phagosome and escape into the host cytoplasm, most intracellular pathogens form a distinct, degradation-resistant and replication-permissive membranous compartment. Intracellular bacteria that form unique pathogen vacuoles include Legionella, Mycobacterium, Chlamydia, Simkania, and Salmonella species. In order to understand the formation of these pathogen niches on a global scale and in a comprehensive and quantitative manner, an inventory of compartment-associated host factors is required. To this end, the intact pathogen compartments need to be isolated, purified and biochemically characterized. Here, we review recent progress on the isolation and purification of pathogen-modified vacuoles and membranes, as well as their proteomic characterization by mass spectrometry and different validation approaches. These studies provide the basis for further investigations on the specific mechanisms of pathogen-driven compartment formation.}, language = {en} } @article{KadeOttoLuxenhoferetal.2021, author = {Kade, Juliane C. and Otto, Paul F. and Luxenhofer, Robert and Dalton, Paul D.}, title = {Melt electrowriting of poly(vinylidene difluoride) using a heated collector}, series = {Polymers for Advanced Technologies}, volume = {32}, journal = {Polymers for Advanced Technologies}, number = {12}, issn = {1042-7147}, doi = {10.1002/pat.5463}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318493}, pages = {4951 -- 4955}, year = {2021}, abstract = {Previous research on the melt electrowriting (MEW) of poly(vinylidene difluoride) (PVDF) resulted in electroactive fibers, however, printing more than five layers is challenging. Here, we investigate the influence of a heated collector to adjust the solidification rate of the PVDF jet so that it adheres sufficiently to each layer. A collector temperature of 110°C is required to improve fiber processing, resulting in a total of 20 fiber layers. For higher temperatures and higher layers, an interesting phenomenon occurred, where the intersection points of the fibers coalesced into periodic spheres of diameter 206 ± 52 μm (26G, 150°C collector temperature, 2000 mm/min, 10 layers in x- and y-direction).The heated collector is an important component of a MEW printer that allows polymers with a high melting point to be processable with increased layers.}, language = {en} } @article{HussAbdelhakMayeretal.2022, author = {Huss, Andr{\´e} and Abdelhak, Ahmed and Mayer, Benjamin and Tumani, Hayrettin and M{\"u}ller, Hans-Peter and Althaus, Katharina and Kassubek, Jan and Otto, Markus and Ludolph, Albert C. and Yilmazer-Hanke, Deniz and Neugebauer, Hermann}, title = {Association of serum GFAP with functional and neurocognitive outcome in sporadic small vessel disease}, series = {Biomedicines}, volume = {10}, journal = {Biomedicines}, number = {8}, issn = {2227-9059}, doi = {10.3390/biomedicines10081869}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-285973}, year = {2022}, abstract = {Cerebrospinal fluid (CSF) and serum biomarkers are critical for clinical decision making in neurological diseases. In cerebral small vessel disease (CSVD), white matter hyperintensities (WMH) are an important neuroimaging biomarker, but more blood-based biomarkers capturing different aspects of CSVD pathology are needed. In 42 sporadic CSVD patients, we prospectively analysed WMH on magnetic resonance imaging (MRI) and the biomarkers neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), chitinase3-like protein 1 (CHI3L1), Tau and Aβ1-42 in CSF and NfL and GFAP in serum. GFAP and CHI3L1 expression was studied in post-mortem brain tissue in additional cases. CSVD cases with higher serum NfL and GFAP levels had a higher modified Rankin Scale (mRS) and NIHSS score and lower CSF Aβ1-42 levels, whereas the CSF NfL and CHI3L1 levels were positively correlated with the WMH load. Moreover, the serum GFAP levels significantly correlated with the neurocognitive functions. Pathological analyses in CSVD revealed a high density of GFAP-immunoreactive fibrillary astrocytic processes in the periventricular white matter and clusters of CHI3L1-immunoreactive astrocytes in the basal ganglia and thalamus. Thus, besides NfL, serum GFAP is a highly promising fluid biomarker of sporadic CSVD, because it does not only correlate with the clinical severity but also correlates with the cognitive function in patients.}, language = {en} } @article{KotlyarKrebsSolimandoetal.2023, author = {Kotlyar, Mischa J. and Krebs, Markus and Solimando, Antonio Giovanni and Marquardt, Andr{\´e} and Burger, Maximilian and K{\"u}bler, Hubert and Bargou, Ralf and Kneitz, Susanne and Otto, Wolfgang and Breyer, Johannes and Vergho, Daniel C. and Kneitz, Burkhard and Kalogirou, Charis}, title = {Critical evaluation of a microRNA-based risk classifier predicting cancer-specific survival in renal cell carcinoma with tumor thrombus of the inferior vena cava}, series = {Cancers}, volume = {15}, journal = {Cancers}, number = {7}, issn = {2072-6694}, doi = {10.3390/cancers15071981}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-311040}, year = {2023}, abstract = {(1) Background: Clear cell renal cell carcinoma extending into the inferior vena cava (ccRCC\(^{IVC}\)) represents a clinical high-risk setting. However, there is substantial heterogeneity within this patient subgroup regarding survival outcomes. Previously, members of our group developed a microRNA(miR)-based risk classifier — containing miR-21-5p, miR-126-3p and miR-221-3p expression — which significantly predicted the cancer-specific survival (CSS) of ccRCC\(^{IVC}\) patients. (2) Methods: Examining a single-center cohort of tumor tissue from n = 56 patients with ccRCC\(^{IVC}\), we measured the expression levels of miR-21, miR-126, and miR-221 using qRT-PCR. The prognostic impact of clinicopathological parameters and miR expression were investigated via single-variable and multivariable Cox regression. Referring to the previously established risk classifier, we performed Kaplan-Meier analyses for single miR expression levels and the combined risk classifier. Cut-off values and weights within the risk classifier were taken from the previous study. (3) Results: miR-21 and miR-126 expression were significantly associated with lymphonodal status at the time of surgery, the development of metastasis during follow-up, and cancer-related death. In Kaplan-Meier analyses, miR-21 and miR-126 significantly impacted CSS in our cohort. Moreover, applying the miR-based risk classifier significantly stratified ccRCC\(^{IVC}\) according to CSS. (4) Conclusions: In our retrospective analysis, we successfully validated the miR-based risk classifier within an independent ccRCC\(^{IVC}\) cohort.}, language = {en} } @article{SemlerAnderlStraubUttneretal.2018, author = {Semler, Elisa and Anderl-Straub, Sarah and Uttner, Ingo and Diehl-Schmid, Janine and Danek, Adrian and Einsiedler, Beate and Fassbender, Klaus and Fliessbach, Klaus and Huppertz, Hans-J{\"u}rgen and Jahn, Holger and Kornhuber, Johannes and Landwehrmeyer, Bernhard and Lauer, Martin and Muche, Rainer and Prudlo, Johannes and Schneider, Anja and Schroeter, Matthias L. and Ludolph, Albert C. and Otto, Markus}, title = {A language-based sum score for the course and therapeutic intervention in primary progressive aphasia}, series = {Alzheimer's Research \& Therapy}, volume = {10}, journal = {Alzheimer's Research \& Therapy}, organization = {FLTD consortium}, doi = {10.1186/s13195-018-0345-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236277}, year = {2018}, abstract = {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.}, language = {en} }