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Adler, Clemens ; Ahammed, Zubayer ; Allgower, Chris ; Anderson, Mike ; Averichev, Georgy S. ; Balewski, Jan ; Barannikova, Olga ; Barnby, Lee Stuart ; Baudot, Jérome ; Bekele, Selemon ; Belaga, Victoria Vladimirovna ; Bellwied, Rene ; Berger, Jens ; Bichsel, Hans ; Bland, Leslie C. ; Blyth, Charles O. ; Bonner, Billy E. ; Bossingham, R. ; Boucham, Abdelkrim ; Brandin, Andrei V. ; Caines, Helen Louise ; Calderón de la Barca Sánchez, Manuel ; Cardenas, Andrés ; Carroll, J. ; Castillo Castellanos, Javier Ernesto ; Castro, M. ; Cebra, Daniel A. ; Chattopadhyay, S. ; Chen, M. L. ; Chen, Y. ; Chernenko, Sergey P. ; Cherney, Michael Gerard ; Chikanian, Alexei ; Choi, B. ; Christie, William ; Coffin, Jean Pierre ; Conin, Laurent ; Cormier, Thomas Michael ; Cramer, John G. ; Crawford, Henry J. ; DeMello, M. ; Deng, W. S. ; Derevschikov, Anatoly A. ; Didenko, Lidia ; Draper, James E. ; Dunin, V. B. ; Dunlop, James C. ; Eckardt, Volker ; Efimov, Leonid G. ; Emelianov, V. ; Engelage, Jon M. ; Eppley, Geary Wareham ; Erazmus, Barbara Ewa ; Fachini, Patricia ; Ferguson, M. I. ; Finch, Evan ; Fisyak, Yuri V. ; Flierl, Dominik Bernhard ; Foley, K. J. ; Gagunashvili, N. ; Gans, J. ; Germain, Marie ; Geurts, Frank ; Ghazikhanian, Vahe ; Grabski, J. ; Grachov, Oleg A. ; Greiner, D. ; Grigoriev, Vladislav A. ; Gushin, E. ; Hallman, Timothy J. ; Hardtke, David H. ; Harris, John W. ; Heffner, Michael D. ; Heppelmann, Steven Francis ; Herston, T. ; Hippolyte, Boris ; Hirsch, Andrew S. ; Hjort, Eric ; Hoffmann, Gerald W. ; Horsley, M. ; Huang, Huan Zhong ; Humanic, Thomas J. ; Hümmler, Holm Gero ; Igo, George J. ; Ishihara, A. ; Ivanshin, Yu. I. ; Jacobs, Peter Martin ; Jacobs, William W. ; Janik, Michał ; Johnson, I. ; Jones, Peter Graham ; Judd, Eleanor G. ; Kaneta, Kaneta ; Kaplan, Morton ; Keane, Declan ; Khodinov, A. ; Kisiel, Adam Ryszard ; Klay, Jennifer Lynn ; Klein, Spencer Robert ; Klyachko, A. ; Konstantinov, A. S. ; Kotchenda, L. ; Kovalenko, A. D. ; Kramer, M. ; Kravtsov, Peter ; Krueger, Keith William ; Kuhn, Christian Claude ; Kulikov, Anatoly I. ; Kunde, Gerd J. ; Kunz, Christopher Lee ; Kutuev, R. Kh. ; Kuznetsov, A. A. ; Lamas-Valverde, Jose ; Lamont, Matthew A. C. ; Landgraf, Jeffery M. ; Lange, S. ; Lansdell, Curtis Patrick Leon ; Lasiuk, Brian ; Laue, Frank ; Lebedev, Alexei ; LeCompte, T. ; Leontiev, V. M. ; Leszczynski, P. ; LeVine, Micheal J. ; Li, Q. ; Li, Q. ; Lindenbaum, Sam J. ; Lisa, Michael A. ; Ljubicic, Tonko A. ; Llope, William Joseph ; LoCurto, G. ; Long, H. ; Longacre, Ronald S. ; Lopez-Noriega, M. ; Love, William A. ; Lynn, David ; Madansky, L. ; Majka, Richard Daniel ; Maliszewski, A. ; Margetis, Spyridon ; Martin, L. ; Marx, Jay N. ; Matis, Howard S. ; Matulenko, Yuri A. ; McShane, Tom S. ; Melnick, Yu. ; Meščanin, Aleksei P. ; Milosevich, Z. ; Minaev, Nikolai G. ; Mitchell, J. ; Moiseenko, V. A. ; Moltz, D. ; Moore, C. F. ; Morozov, V. ; de Moura, M. M. ; Munhoz, Marcelo Gameiro ; Mutchler, G. S. ; Nelson, John M. ; Nevski, P. ; Nikitin, Vladimir A. ; Nogach, Larisa V. ; Norman, B. ; Nurušev, Sandibek B. ; Nystrand, Joakim Ingemar ; Odyniec, Grazyna Janina ; Ogawa, Akio ; Ogilvie, C. A. ; Oldenburg, Markus D. ; Olson, Douglas L. ; Paic, Guy ; Pandey, S. U. ; Panebratsev, Yuri ; Panitkin, Sergei Yurievich ; Pavlinov, A. I. ; Pawlak, Tomasz Jan ; Perevoztchikov, V. ; Peryt, Wiktor Stanislaw ; Petrov, V. A. ; Pinganaud, W. ; Platner, E. ; Pluta, Jan Marian ; Porile, Norbert T. ; Porter, Jeffrey Brent ; Poskanzer, Arthur M. ; Potrebenikova, E. ; Prindle, Duncan J. ; Pruneau, Claude A. ; Radomski, S. ; Rai, Gulshan ; Ravel, Olivier ; Ray, Robert L. ; Razin, Sergej V. ; Reichhold, Dennis Michael ; Reid, Jeffrey G. ; Retiere, Fabrice ; Ridiger, Alexey ; Ritter, Hans Georg ; Roberts, Jabus B. ; Rogachevski, O. V. ; Roy, Christelle Sophie ; Russ, D. ; Rykov, Vladimir L. ; Sakrejda, Iwona ; Sandweiss, Jack H. ; Saulys, A. C. ; Savin, Igor A. ; Schambach, Joachim ; Scharenberg, Rolf Paul ; Schmitz, Norbert ; Schroeder, Lee S. ; Schüttauf, Andreas ; Seger, Janet Elizabeth ; Seliverstov, D. ; Seyboth, Peter ; Shestermanov, Konstantin E. ; Shimanskii, S. S. ; Shvetcov, V. S. ; Skoro, Goran P. ; Smirnov, Nikolai ; Snellings, Raimond ; Sowinski, James ; Spinka, Harold. M. ; Srivastava, Brijesh Kumar ; Stephenson, Edward J. ; Stock, Reinhard ; Stolpovsky, Alexander ; Strichanov, Michail Nikolaevič ; Stringfellow, Blair ; Ströbele, Herbert ; Struck, Christof ; Suaide, Alexandre Alarcon do Passo ; Sugarbaker, Evan R. ; Suire, Christophe Pierre ; Symons, Timothy James MacNeil ; Toledo, Alejandro Szanto de ; Szarwas, Piotr ; Takahashi, Jun ; Tang, Aihong ; Thomas, James H. ; Tikhomirov, V. ; Trainor, Thomas A. ; Trentalange, Stephen ; Tokarev, Mikhail V. ; Tonjes, Marguerite Belt ; Trofimov, V. ; Tsai, Oleg D. ; Turner, K. ; Ullrich, Thomas ; Underwood, David G. ; Van Buren, Gene ; VanderMolen, A. M. ; Vanyashin, A. ; Vasilevski, I. M. ; Vasiliev, Alexander Nikolaevich ; Vigdor, Steven E. ; Voloshin, Sergei ; Wang, F. ; Ward, H. ; Wells, R. ; Wenaus, T. ; Westfall, Gary D. ; Whitten, Charles A. ; Wieman, Howard ; Willson, Robert ; Wissink, Scott W. ; Witt, Richard ; Xu, N. ; Xu, Z. ; Yakutin, A. E. ; Yamamoto, E. ; Yang, J. ; Yepes, Pablo P. ; Yokosawa, A. ; Yurevich, Vladimir Yurevich ; Zanevski, Y. V. ; Zhang, J. ; Zhang, W. M. ; Zoulkarneev, R. ; Zubarev, A. N.
We report results on the ratio of midrapidity antiproton-to-proton yields in Au+Au collisions at sqrt[sNN] = 130 GeV per nucleon pair as measured by the STAR experiment at RHIC. Within the rapidity and transverse momentum range of | y|<0.5 and 0.4<pt<1.0 GeV/c, the ratio is essentially independent of either transverse momentum or rapidity, with an average of 0.65±0.01(stat)±0.07(syst) for minimum bias collisions. Within errors, no strong centrality dependence is observed. The results indicate that at this RHIC energy, although the p-p-bar pair production becomes important at midrapidity, a significant excess of baryons over antibaryons is still present.
Groneberg, Jan David Alexander ; Scutaru, Cristian ; Lauks, Mathias ; Takemura, Masaya ; Fischer, Tanja Christina ; Kölzow, Silvana ; Mark, Anke van ; Uibel, Stefanie ; Wagner, Ulrich ; Vitzthum, Karin ; Beck, Fabian ; Mache, Stefanie ; Kreiter, Carolin ; Kusma, Bianca ; Friedebold, Annika ; Zell, Hanna ; Gerber, Alexander ; Bock, Johanna ; Al-Mutawakl, Khaled ; Donat, Johannnes ; Geier, Maria Victoria ; Pilzner, Carolin ; Welker, Pia ; Joachim, Ricarda ; Bias, Harald ; Götting, Michael ; Sakr, Mohannad ; Addicks, Johann P. ; Börger, Julia-Annik ; Jensen, Anna-Maria ; Grajewski, Sonja ; Shami, Awfa ; Neye, Niko ; Kröger, Stefan ; Hoffmann, Sarah ; Kloss, Lisa ; Mayer, Sebastian ; Puk, Clemens ; Henkel, Ulrich ; Rospino, Robert ; Schilling, Ute ; Krieger, Evelyn ; Westphal, Gesa ; Meyer-Falcke, Andreas ; Hupperts, Hagen ; Roux, Andrés de ; Tropp, Salome ; Weiland, Marco ; Mühlbach, Janette ; Steinberg, Johannes ; Szerwinski, Anne ; Falahkohan, Sepiede ; Sudik, Claudia ; Bircks, Anna ; Noga, Oliver ; Dickgreber, Nicolas ; Dinh, Quoc-Thai ; Golpon, Heiko ; Kloft, Beatrix ; Groneberg, Rafael Neill B. ; Witt, Christian ; Wicker, Sabine ; Zhang, Li ; Springer, Jochen ; Kütting, Birgitta ; Mingomataj, Ervin C. ; Fischer, Axel ; Schöffel, Norman ; Unger, Volker ; Quarcoo, David
Due to an increasing awareness of the potential hazardousness of air pollutants, new laws, rules and guidelines have recently been implemented globally. In this respect, numerous studies have addressed traffic-related exposure to particulate matter using stationary technology so far. By contrast, only few studies used the advanced technology of mobile exposure analysis. The Mobile Air Quality Study (MAQS) addresses the issue of air pollutant exposure by combining advanced high-granularity spatial-temporal analysis with vehicle-mounted, person-mounted and roadside sensors. The MAQS-platform will be used by international collaborators in order 1) to assess air pollutant exposure in relation to road structure, 2) to assess air pollutant exposure in relation to traffic density, 3) to assess air pollutant exposure in relation to weather conditions, 4) to compare exposure within vehicles between front and back seat (children) positions, and 5) to evaluate "traffic zone"- exposure in relation to non-"traffic zone"-exposure. Primarily, the MAQS-platform will focus on particulate matter. With the establishment of advanced mobile analysis tools, it is planed to extend the analysis to other pollutants including including NO2, SO2, nanoparticles, and ozone.
Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2, Germany, March 2020
(2020)
Münchhoff, Maximilian ; Mairhofer, Helga ; Nitschko, Hans ; Grzimek-Koschewa, Natascha ; Hoffmann, Dieter ; Berger, Annemarie ; Rabenau, Holger ; Widera, Marek ; Ackermann, Nikolaus ; Konrad, Regina ; Zange, Sabine ; Graf, Alexander ; Krebs, Stefan ; Blum, Helmut ; Sing, Andreas ; Liebl, Bernhard ; Wölfel, Roman ; Ciesek, Sandra ; Drosten, Christian ; Protzer, Ulrike ; Böhm, Stephan ; Keppler, Oliver Till
Containment strategies and clinical management of coronavirus disease (COVID-19) patients during the current pandemic depend on reliable diagnostic PCR assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we compare 11 different RT-PCR test systems used in seven diagnostic laboratories in Germany in March 2020. While most assays performed well, we identified detection problems in a commonly used assay that may have resulted in false-negative test results during the first weeks of the pandemic.
Bauer, Jochen ; Hechtel, Michael ; Konrad, Christoph ; Holzwarth, Martin ; Mayr, Andreas ; Schneider, Sven ; Franke, Jörg ; Hoffmann, Hilko ; Zinnikus, Ingo ; Feld, Thomas ; Runge, Mathias ; Hinz, Oliver
In the upcoming years, the internet of things (IoT)will enrich daily life. The combination of artificial intelligence(AI) and highly interoperable systems will bring context-sensitive multi-domain services to reality. This paper describesa concept for an AI-based smart living platform with open-HAB, a smart home middleware, and Web of Things (WoT) askey components of our approach. The platform concept con-siders different stakeholders, i.e. the housing industry, serviceproviders, and tenants. These activities are part of the Fore-Sight project, an AI-driven, context-sensitive smart living plat-form.
Alber, Thomas ; Bartke, Jerzy ; Białkowska, Helena ; Bloomer, Matthew A. ; Bock, Rudolf ; Braithwaite, Wilfred J. ; Brinkmann, Dittmar ; Brockmann, Robert ; Bunčić, Predrag ; Chan, Phaikying ; Chase, S. I. ; Cramer, Pauline B. ; Cramer, John G. ; Derado, Ivan ; Eberlein, Björn ; Eckardt, Volker ; Eschke, Jürgen ; Ferenc, Daniel ; Fleischmann, B. ; Foka, Panagiota ; Freund, Peter ; Fuchs, Michael ; Gładysz-Dziaduś, Ewa ; Harris, John W. ; Hoffmann, Matthias ; Jacobs, Peter Martin ; Kabana, Sonia ; Kadija, Krešo ; Kosiec, Jacek ; Kowalski, Marek ; Lahanas, Michael ; Lee, Jae-Yun ; Ljubicic, Ante Jr. ; Margetis, Spyridon ; Mitchell, Jeffery Thomas ; Morse, Richard J. ; Nappi, Eugenio ; Odyniec, Grazyna Janina ; Paic, Guy ; Panagiotou, Apostolos D. ; Petridis, Athanasios ; Piper, Andreas ; Posa, Francesco ; Poskanzer, Arthur M. ; Pugh, Howel G. ; Rai, Gulshan ; Rauch, Wolfgang Hans ; Renfordt, Rainer Arno Ernst ; Retyk, Waldemar ; Roland, Gunther ; Rothard, Hermann ; Runge, Kay ; Sandoval, Andres ; Schambach, Joachim ; Schmitz, Norbert ; Schmoetten, Emile ; Schneider, Ingo ; Sendelbach, Ralf ; Seyboth, Peter ; Seyerlein, Jürgen ; Skrzypczak, Ewa ; Stefansky, Piotr ; Teitelbaum, Lawrence Paul ; Tonse, Shaheen ; Trainor, Thomas A. ; Vasileiadis, Georgios ; Vassiliou, Maria ; Wenig, Siegfried ; Wensveen, Martinus ; Wosiek, Barbara
We present the measured correlation functions for pi+ pi-, pi- pi- and pi+ pi+ pairs in central S+Ag collisions at 200 GeV per nucleon. The Gamov function, which has been traditionally used to correct the correlation functions of charged pions for the Coulomb interaction, is found to be inconsistent with all measured correlation functions. Certain problems which have been dominating the systematic uncertainty of the correlation analysis are related to this inconsistency. It is demonstrated that a new Coulomb correction method, based exclusively on the measured correlation function for pi+ pi- pairs, may solve the problem.
Koyanagi, Masamichi ; Haendeler, Judith ; Badorff, Cornel ; Brandes, Ralf ; Hoffmann, Jörg ; Pandur, Petra D. ; Zeiher, Andreas M. ; Kühl, Michael ; Dimmeler, Stefanie
Human endothelial circulating progenitor cells (CPCs) can differentiate to cardiomyogenic cells during co-culture with neonatal rat cardiomyocytes. Wnt proteins induce myogenic specification and cardiac myogenesis. Here, we elucidated the effect of Wnts on differentiation of CPCs to cardiomyogenic cells. CPCs from peripheral blood mononuclear cells were isolated from healthy volunteers and co-cultured with neonatal rat cardiomyocytes. 6–10 days after co-culture, cardiac differentiation was determined by α-sarcomeric actinin staining of human lymphocyte antigen-positive cells (fluorescence-activated cell-sorting analysis) and mRNA expression of human myosin heavy chain and atrial natriuretic peptide. Supplementation of co-cultures with Wnt11-conditioned medium significantly enhanced the differentiation of CPCs to cardiomyocytes (1.7 ± 0.3-fold), whereas Wnt3A-conditioned medium showed no effect. Cell fusion was not affected by Wnt11-conditioned medium. Because Wnts inhibit glycogen synthase kinase-3β, we further determined whether the glycogen synthase kinase-3β inhibitor LiCl also enhanced cardiac differentiation of CPCs. However, LiCl (10 mm) did not affect CPC differentiation. In contrast, Wnt11-conditioned medium time-dependently activated protein kinase C (PKC). Moreover, the PKC inhibitors bisindolylmaleimide I and III significantly blocked differentiation of CPCs to cardiomyocytes. PKC activation by phorbol 12-myristate 13-acetate significantly increased CPC differentiation to a similar extent as compared with Wnt11-conditioned medium. Our data demonstrate that Wnt11, but not Wnt3A, augments cardiomyogenic differentiation of human CPCs. Wnt11 promotes cardiac differentiation via the non-canonical PKC-dependent signaling pathway.
Nitric oxide (NO) plays an important role in the regulation of the functional integrity of the endothelium. The intracellular reaction of NO with reactive cysteine groups leads to the formation of S-nitrosothiols. To investigate the regulation of S-nitrosothiols in endothelial cells, we first analyzed the composition of the S-nitrosylated molecules in endothelial cells. Gel filtration revealed that more than 95% of the detected S-nitrosothiols had a molecular mass of more than 5000 Da. Moreover, inhibition of de novosynthesis of glutathione using N-butyl-sulfoximine did not diminish the overall cellular S-NO content suggesting that S-nitrosylated glutathione quantitatively plays only a minor role in endothelial cells. Having demonstrated that most of the S-nitrosothiols are proteins, we determined the regulation of the S-nitrosylation by pro-inflammatory and pro-atherogenic factors, such as TNFα and mildly oxidized low density lipoprotein (oxLDL). TNFα and oxLDL induced denitrosylation of various proteins as assessed by Saville-Griess assay, by immunostaining with an anti-S-nitrosocysteine antibody, and by a Western blot approach. Furthermore, the caspase-3 p17 subunit, which has previously been shown to be S-nitrosylated and thereby inhibited, was denitrosylated by TNFα treatment suggesting thatS-nitrosylation and denitrosylation are important regulatory mechanisms in endothelial cells contributing to the integrity of the endothelial cell monolayer.
Clinical outcomes of cancer-associated isolated superficial vein thrombosis in daily practice
(2022)
Langer, Florian ; Gerlach, Horst E. ; Schimke, Alexandra ; Heinken, Andreas ; Hoffmann, Ulrich ; Noppeney, Thomas ; Pittrow, David ; Klotsche, Jens ; Rabe, Eberhard ; Bauersachs, Rupert
Highlights
• In acute isolated SVT, the prevalence of cancer is almost 7 %.
• Cancer increases the SVT-associated VTE risk at 3 and 12 months.
• Cancer patients with isolated SVT may benefit from prolonged anticoagulation.
Abstract
Background: Despite significant progress in the understanding of paraneoplastic deep vein thrombosis (DVT) and pulmonary embolism (PE), little is known about the outcomes of cancer-associated superficial vein thrombosis (SVT) in daily practice.
Methods: INSIGHTS-SVT was a prospective observational study on patients with acute isolated SVT. Primary outcome measure was symptomatic venous thromboembolism (VTE), a composite of DVT, PE, and SVT extension/recurrence, at 3 months. Clinically relevant bleeding was also assessed.
Results: Of 1151 patients included, 6.7 % either had active cancer at baseline or were diagnosed with cancer during 12 months of follow-up. At 3 months, symptomatic VTE had occurred in 13.0 % and 5.4 % of cancer and non-cancer patients, respectively (HR 2.6, 95 % CI 1.3–5.0). Regarding secondary outcomes, cancer patients had increased risks of DVT and PE (HR 3.9, 95 % CI 1.3–11.8) and hospitalization due to VTE (HR 11.0, 95 % CI 2.5–49.0). The rate of clinically relevant bleeding was numerically higher in the cancer cohort (3.9 % vs 1.3 %, HR 3.1, 95 % CI 0.9–10.7). At 12 months, the primary composite outcome had occurred in 15.6 % and 11.9 % of cancer and non-cancer patients, respectively (HR 1.9, 95 % CI 1.0–3.5). After adjusting for additional risk factors, including age, history of DVT/PE and cardiovascular risk factors/diseases, the association of cancer with the primary outcome remained statistically significant.
Conclusion: Cancer patients with isolated SVT are at significant risk of symptomatic VTE. While most events occur within 3 months, the VTE risk remains elevated up to one year of follow-up.
ClinicalTrials.gov identifier: NCT02699151.
Théry, Clotilde ; Witwer, Kenneth W. ; Aikawa, Elena ; Alcaraz, Maria Jose ; Anderson, Johnathon D. ; Andriantsitohaina, Ramaroson ; Antoniou, Anna ; Arab, Tanina ; Archer, Fabienne ; Atkin-Smith, Georgia K. ; Ayre, D. Craig ; Bach, Jean-Marie ; Bachurski, Daniel ; Baharvand, Hossein ; Balaj, Leonora ; Baldacchino, Shawn ; Bauer, Natalie N. ; Baxter, Amy A. ; Bebawy, Mary ; Beckham, Carla ; Zavec, Apolonija Bedina ; Benmoussa, Abderrahim ; Berardi, Anna C. ; Bergese, Paolo ; Bielska, Ewa ; Blenkiron, Cherie ; Bobis-Wozowicz, Sylwia ; Boilard, Eric ; Boireau, Wilfrid ; Bongiovanni, Antonella ; Borràs, Francesc E. ; Bosch, Steffi ; Boulanger, Chantal M. ; Breakefield, Xandra ; Breglio, Andrew M. ; Brennan, Meadhbh Aín ; Brigstock, David R. ; Brisson, Alain ; Broekman, Marike L. D. ; Bromberg, Jacqueline F. ; Bryl-Gorecka, Paulina ; Buch, Shilpa ; Buck, Amy H. ; Burger, Dylan ; Busatto, Sara ; Buschmann, Dominik ; Bussolati, Benedetta ; Buzás, Edit I. ; Byrd, James Bryan ; Camussi, Giovanni ; Carter, David R. F. ; Caruso, Sarah ; Chamley, Lawrence W. ; Chang, Yu-Ting ; Chen, Chihchen ; Chen, Shuai ; Cheng, Lesley ; Chin, Andrew R. ; Clayton, Aled ; Clerici, Stefano P. ; Cocks, Alex ; Cocucci, Emanuele ; Coffey, Robert J. ; Cordeiro-da-Silva, Anabela ; Couch, Yvonne ; Coumans, Frank A. W. ; Coyle, Beth ; Crescitelli, Rossella ; Criado, Miria Ferreira ; D’Souza-Schorey, Crislyn ; Das, Saumya ; Chaudhuri, Amrita Datta ; de-Candia, Paola ; De Santana, Eliezer F. ; De Wever, Olivier ; del Portillo, Hernando A. ; Demaret, Tanguy ; Deville, Sarah ; Devitt, Andrew ; Dhondt, Bert ; Di Vizio, Dolores ; Dieterich, Lothar C. ; Dolo, Vincenza ; Dominguez Rubio, Ana Paula ; Dominici, Massimo ; Dourado, Mauricio R. ; Driedonks, Tom A. P. ; Duarte, Filipe V. ; Duncan, Heather M. ; Eichenberger, Ramon Marc ; Ekström, Karin ; El Andaloussi, Samir ; Elie-Caille, Celine ; Erdbrügger, Uta ; Falcón-Pérez, Juan M. ; Fatima, Farah ; Fish, Jason E. ; Flores-Bellver, Miguel ; Försönits, András ; Frelet-Barrand, Annie ; Fricke, Fabia ; Fuhrmann, Gregor ; Gabrielsson, Susanne ; Gámez-Valero, Ana ; Gardiner, Chris ; Gärtner, Kathrin ; Gaudin, Raphael ; Gho, Yong Song ; Giebel, Bernd ; Gilbert, Caroline ; Gimona, Mario ; Giusti, Ilaria ; Goberdhan, Deborah C. I. ; Görgens, André ; Gorski, Sharon M. ; Greening, David W. ; Groß, Julia Christina ; Gualerzi, Alice ; Gupta, Gopal N. ; Gustafson, Dakota ; Handberg, Aase ; Haraszti, Réka Ágnes ; Harrison, Paul ; Hegyesi, Hargita ; Hendrix, An ; Hill, Andrew F. ; Hochberg, Fred H. ; Hoffmann, Karl F. ; Holder, Beth ; Holthofer, Harry ; Hosseinkhani, Baharak ; Hu, Guoku ; Huang, Yiyao ; Huber, Veronica ; Hunt, Stuart ; Ibrahim, Ahmed Gamal-Eldin ; Ikezu, Tsuneya ; Inal, Jameel M. ; Isin, Mustafa ; Ivanova, Alena ; Jackson, Hannah K. ; Jacobsen, Soren ; Jay, Steven M. ; Jayachandran, Muthuvel ; Jenster, Guido ; Jiang, Lanzhou ; Johnson, Suzanne M. ; Jones, Jennifer C. ; Jong, Ambrose ; Jovanovic-Talisman, Tijana ; Jung, Stephanie ; Kalluri, Raghu ; Kano, Shin-ichi ; Kaur, Sukhbir ; Kawamura, Yumi ; Keller, Evan T. ; Khamari, Delaram ; Khomyakova, Elena ; Khvorova, Anastasia ; Kierulf, Peter ; Kim, Kwang Pyo ; Kislinger, Thomas ; Klingeborn, Mikael ; Klinke, David J. ; Kornek, Miroslaw ; Kosanović, Maja M. ; Kovács, Árpád Ferenc ; Krämer-Albers, Eva-Maria ; Krasemann, Susanne ; Krause, Mirja ; Kurochkin, Igor V. ; Kusuma, Gina D. ; Kuypers, Sören ; Laitinen, Saara ; Langevin, Scott M. ; Languino, Lucia R. ; Lannigan, Joanne ; Lässer, Cecilia ; Laurent, Louise C. ; Lavieu, Gregory ; Lázaro-Ibáñez, Elisa ; Le Lay, Soazig ; Lee, Myung-Shin ; Lee, Yi Xin Fiona ; Lemos, Debora S. ; Lenassi, Metka ; Leszczynska, Aleksandra ; Li, Isaac T. S. ; Liao, Ke ; Libregts, Sten F. ; Ligeti, Erzsebet ; Lim, Rebecca ; Lim, Sai Kiang ; Linē, Aija ; Linnemannstöns, Karen ; Llorente, Alicia ; Lombard, Catherine Ann ; Lorenowicz, Magdalena J. ; Lörincz, Ákos M. ; Lötvall, Jan ; Lovett, Jason ; Lowry, Michelle C. ; Loyer, Xavier ; Lu, Quan ; Lukomska, Barbara ; Lunavat, Taral Rameshchand ; Maas, Sybren L. N. ; Malhi, Harmeet ; Marcilla, Antonio ; Mariani, Jacopo ; Mariscal, Javier ; Martens-Uzunova, Elena S. ; Martin-Jaular, Lorena ; Martinez, M. Carmen ; Martins, Vilma Regina ; Mathieu, Mathilde ; Mathivanan, Suresh ; Maugeri, Marco ; McGinnis, Lynda K. ; McVey, Mark J. ; Meckes, David G. ; Meehan, Katie ; Mertens, Inge ; Minciacchi, Valentina R. ; Möller, Andreas ; Møller Jørgensen, Malene ; Morales-Kastresana, Aizea ; Morhayim, Jess ; Mullier, François ; Muraca, Maurizio ; Musante, Luca ; Mussack, Veronika ; Muth, Dillon C. ; Myburgh, Kathryn H. ; Najrana, Tanbir ; Nawaz, Muhammad ; Nazarenko, Irina ; Nejsum, Peter ; Neri, Christian ; Neri, Tommaso ; Nieuwland, Rienk ; Nimrichter, Leonardo ; Nolan, John P. ; Nolte-’t Hoen, Esther N. M. ; Hooten, Nicole Noren ; O’Driscoll, Lorraine ; O’Grady, Tina ; O’Loghlen, Ana ; Ochiya, Takahiro ; Olivier, Martin ; Ortiz, Alberto ; Ortiz, Luis A. ; Osteikoetxea, Xabier ; Østergaard, Ole ; Ostrowski, Matias ; Park, Jaesung ; Pegtel, Dirk Michiel ; Peinado, Hector ; Perut, Francesca ; Pfaffl, Michael ; Phinney, Donald G. ; Pieters, Bartijn C. H. ; Pink, Ryan Charles ; Pisetsky, David S. ; Pogge von Strandmann, Elke ; Polakovicova, Iva ; Poon, Ivan K. H. ; Powell, Bonita H. ; Prada, Ilaria ; Pulliam, Lynn ; Quesenberry, Peter ; Radeghieri, Annalisa ; Raffai, Robert L. ; Raimondo, Stefania ; Rak, Janusz ; Ramirez, Marcel I. ; Raposo, Graça ; Rayyan, Morsi S. ; Regev-Rudzki, Neta ; Ricklefs, Franz Lennard ; Robbins, Paul D. ; Roberts, David D. ; Rodrigues, Silvia C. ; Rohde, Eva ; Rome, Sophie ; Rouschop, Kasper M. ; Rughetti, Aurelia ; Russell, Ashley E. ; Saá, Paula ; Sahoo, Susmita ; Salas-Huenuleo, Edison ; Sánchez, Catherine ; Saugstad, Julie A. ; Saul, Meike J. ; Schiffelers, Raymond M. ; Schneider, Raphael ; Schøyen, Tine Hiorth ; Scott, Aaron ; Shahaj, Eriomina ; Sharma, Shivani ; Shatnyeva, Olga ; Shekari, Faezeh ; Shelke, Ganesh Vilas ; Shetty, Ashok K. ; Shiba, Kiyotaka ; Siljander, Pia R.-M. ; Silva, Andreia M. ; Skowronek, Agata ; Snyder, Orman L. ; Soares, Rodrigo Pedro ; Sódar, Barbara W. ; Soekmadji, Carolina ; Sotillo, Javier ; Stahl, Philip D. ; Stoorvogel, Willem ; Stott, Shannon L. ; Strasser, Erwin F. ; Swift, Simon ; Tahara, Hidetoshi ; Tewari, Muneesh ; Timms, Kate ; Tiwari, Swasti ; Tixeira, Rochelle ; Tkach, Mercedes ; Toh, Wei Seong ; Tomasini, Richard ; Torrecilhas, Ana Claudia ; Tosar, Juan Pablo ; Toxavidis, Vasilis ; Urbanelli, Lorena ; Vader, Pieter ; Balkom, Bastiaan Wilhelmus Maria van ; Grein, Susanne G. van der ; Van Deun, Jan ; Herwijnen, Martijn J. C. van ; Van Keuren-Jensen, Kendall R. ; Niel, Guillaume van ; Royen, Martin E. van ; Wijnen, Andre J. van ; Vasconcelos, M. Helena ; Vechetti, Ivan J. ; Veit, Tiago D. ; Vella, Laura J. ; Velot, Émilie ; Verweij, Frederik ; Vestad, Beate ; Viñas, Jose Luis ; Visnovitz, Tamás ; Vukman, Krisztina V. ; Wahlgren, Jessica ; Watson, Dionysios C. ; Wauben, Marca H. M. ; Weaver, Alissa ; Webber, Jason P. ; Weber, Viktoria ; Wehman, Ann M. ; Weiss, Daniel J. ; Welsh, Joshua A. ; Wendt, Sebastian ; Wheelock, Åsa M. ; Wiener, Zoltán ; Witte, Leonie ; Wolfram, Joy ; Xagorari, Angeliki ; Xander, Patricia ; Xu, Jing ; Yan, Xiaomei ; Yáñez-Mó, María ; Yin, Hang ; Yuana, Yuana ; Zappulli, Valentina ; Zarubova, Jana ; Žėkas, Vytautas ; Zhang, Jian-ye ; Zhao, Zezhou ; Zheng, Lei ; Zheutlin, Alexander R. ; Zickler, Antje Maria ; Zimmermann, Pascale ; Zivkovic, Angela M. ; Zocco, Davide ; Zuba-Surma, Ewa K.
The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
Pinter, Andreas ; Hoffmann, Matthias ; Reich, Kristian ; Augustin, Matthias ; Kaplan, Kadriye ; Gudjónsdóttir, Sigrún Dögg ; Delvin, Thomas ; Mrowietz, Ulrich
Background: Brodalumab is a fully human monoclonal immunoglobulin IgG2 antibody that binds to the human IL-17 receptor subunit A and by that inhibits the biologic action of IL-17A, IL-17F, IL-17C and IL-17E. Therapy with fumaric acid esters (FAE) is a well established and widely used first-line systemic treatment for subjects with moderate-to-severe plaque psoriasis. Objectives: To compare brodalumab to FAE in terms of clinical efficacy, patient-reported outcomes and safety in subjects with moderate-to-severe plaque psoriasis who were naïve to systemic treatment. Methods: Eligible subjects were randomized 1 : 1 to 210 mg brodalumab injections or oral FAE according to product label in this 24-week, open-label, assessor-blinded, multi-centre, head-to-head phase 4 trial. The primary endpoints were having PASI75 and having sPGA score of 0 or 1 (sPGA 0/1). Subjects with missing values for the primary endpoints were considered non-responders. Results: A total of 210 subjects were randomized. 91/105 subjects completed brodalumab treatment and 58/105 subjects completed FAE treatment. At Week 24, significantly more subjects in the brodalumab group compared to the FAE group had PASI75 (81.0% vs. 38.1%, P < 0.001) and sPGA 0/1 (64.8% vs. 20.0%, P < 0.001). In the brodalumab group, the median time to both PASI75 and to PASI90 was significantly shorter than in the FAE group (4.1 weeks vs. 16.4 weeks, and 7.4 weeks vs. 24.4 weeks, respectively, P < 0.0001 for both). The rate of adverse events was lower in subjects treated with brodalumab compared to subjects treated with FAE (616.4 vs. 1195.8 events per 100 exposure years). No new safety signals were detected for brodalumab. Conclusions: Brodalumab was associated with rapid and significant improvements in signs and symptoms of moderate-to-severe plaque psoriasis, with a superior efficacy profile to what was observed with FAE in systemic-naïve subjects over 24 weeks.