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2. Characterization of VSV-GP morphology by cryo-EM imaging and SEC-MALS

Author

Dongyue Xin, Leela Kurien, Katherine Briggs, Adrian Schimek, Richard Dambra, Daniel Hochdorfer, Tanja A. Arnouk, Marija Brgles, Saurabh Gautam, Dominik Hotter, Johannes Solzin, Thomas Kriehuber, Joseph Ashour, Adam Vigil, Michael Hawley, and Xiaorong He

Subjects
vesicular stomatitis virus, VSV-GP, virus particle morphology, cryo-EM, SEC-MALS, analytical HPLC, Genetics, QH426-470, Cytology, QH573-671
Abstract

Vesicular stomatitis virus expressing the glycoprotein of the lymphocytic choriomeningitis virus (VSV-GP) is a promising platform for oncolytic viruses and cancer vaccines. In this work, cryoelectron microscopy (cryo-EM) imaging was employed to directly visualize VSV-GP particles. Several different subpopulations of virus particle morphology were observed. Definition and fraction counting of subpopulations enabled quantitative comparison of subpopulation profiles between several VSV-GP samples. In developing an orthogonal method with higher throughput, we showed that the morphological profile of the VSV-GP particles can be characterized by size exclusion chromatography coupled with a multi-angle light scattering detector (SEC-MALS) based on a novel shape-based separation mechanism. Together, the two complementary techniques enable the analysis of morphological profile for VSV-GP and potentially other non-spherical viruses or nanoparticles.

Published
2025
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3. Efficacy and safety of gene therapy with onasemnogene abeparvovec in children with spinal muscular atrophy in the D-A-CH-region: a population-based observational studyResearch in context

Author

Claudia Weiß, Lena-Luise Becker, Johannes Friese, Astrid Blaschek, Andreas Hahn, Sabine Illsinger, Oliver Schwartz, Günther Bernert, Maja von der Hagen, Ralf A. Husain, Klaus Goldhahn, Janbernd Kirschner, Astrid Pechmann, Marina Flotats-Bastardas, Gudrun Schreiber, Ulrike Schara, Barbara Plecko, Regina Trollmann, Veronka Horber, Ekkehard Wilichowski, Matthias Baumann, Andrea Klein, Astrid Eisenkölbl, Cornelia Köhler, Georg M. Stettner, Sebahattin Cirak, Oswald Hasselmann, Angela M. Kaindl, Sven F. Garbade, Jessika Johannsen, Andreas Ziegler, Petra Baum, Manuela Baumgartner, Astrid Bertsche, Markus Blankenburg, Jonas Denecke, Marcus Deschauer, Matthias Eckenweiler, Tobias Geis, Martin Groß, René Günther, Tim Hagenacker, Eckard Hamelmann, Christoph Kamm, Birgit Kauffmann, Jan Christoph Koch, Wolfgang Löscher, Albert Ludolph, Pascal Martin, Alexander Mensch, Gerd Meyer zu Hörste, Christoph Neuwirth, Susanne Petri, Manuel Pühringer, Imke Rathmann, Dorothee Schäfer, Mareike Schimmel, Bertold Schrank, Olivia Schreiber-Katz, Anette Schwerin-Nagel, Martin Smitka, Meike Steinbach, Elisabeth Steiner, Johannes Stoffels, Manuela Theophil, Raffi Topakian, Matthias Türk, Matthias Vorgerd, Maggie C. Walter, Markus Weiler, Gert Wiegand, Gilbert Wunderlich, Claudia Diana Wurster, Daniel Zeller, Moritz Metelmann, Fiona Zeiner, Veronika Pilshofer, Mika Rappold, Josefine Pauschek, Christof Reihle, Annette Karolin Homma, Paul Lingor, Bettina Henzi, Tabea Reinhardt, Dorothea Holzwarth, Wolfgang Wittmann, Stefan Kappel, Maren Freigang, Benjamin Stolte, Kyriakos Martakis, Georg Classen, Doris Roland-Schäfer, Daniela Steuernagel, Hans Hartmann, Sophie Fischer, Marieke Wermuth, Mohamad Tareq Muhandes, Anna Hotter, Zeljko Uzelac, Steffen Naegel, Sarah Wiethoff, Nathalie Braun, Bogdan Bjelica, Heike Kölbel, Daniela Angelova-Toshkina, Bernd Wilken, Alma Osmanovic, Barbara Fiedler, Maike Tomforde, Thomas Voelkl, Arpad von Moers, Petra Müller, Bettina Behring, Anne Güttsches, Peter Reilich, Wolfgang Wick, Corinna Stoltenburg, Simon Witzel, Julia Bellut, Georg Friedrich Hoffmann, Kathrin Mörtlbauer, Alexandra Ille, Michael Schroth, Joenna Driemeyer, Luisa Semmler, Cornelia Müller, Katharina Dörnbrack, Michael Zemlin, Stephanie Geitmann, Hanna Sophie Lapp, Svenja Brakemeier, Tascha Gehrke, Klearchos Ntemiris, Nadja Kaiser, Sabine Borowski, Barbara Ramadan, Ulf Hustedt, Tobias Baum, Ilka Schneider, Esra Akova-Oztürk, Katharina Vill, Zylfie Dibrani, Camilla Wohnrade, Adela Della-Marina, Lisa Jung, Timo Deba, Joachim Zobel, Jens Schallner, Christina Kraut, Peter Vollmann, Stephanie Schüssler, Melanie Roeder, Miriam Hiebeler, Nicole Berberich, Joanna Schneider, Brigitte Brauner, Stefan Kölker, Elke Pernegger, Magdalena Gosk-Tomek, Sarah Braun, Deike Weiss, Gerrit Machetanz, Thorsten Langer, Christina Saier, Sandra Baumann, Sabine Hettrich, Gabriel Dworschak, Katharina Müller-Kaempffer, Isabelle Dittes, Andreas Thimm, Lisa Quinten, Kristina Albers, Andrea Bevot, Christa Bretschneider, Johannes Dorst, Thomas Kendzierski, Iris Hannibal, Jasmin Bischofberger, Tilman Riesmeier, Andrea Gangfuß, Eva Johann to Settel, Michael Grässl, Susan Fiebig, Carmen Hollerauer, Lea Seeber, Ina Krahwinkler, Irene Lange, Federica Montagnese, Marcel Mann-Richter, Alexandra Wagner, Christine Leypold, Afshin Saffari, Elmecker Anna, Anna Wiesenhofer, Eva-Maria Wendel, Paula-Sophie Steffens, Sabine Wider, Adrian Tassoni, Andrea Dall, Franziska Busch, Daniela Zeisler, Maria Wessel, Jaqueline Lipka, Andrea Hackemer, Loreen Plugge, Eva Jansen, Erdmute Roth, Joachim Schuster, Anna Koelsch, Birgit Warken-Madelung, Michaela Schwippert, Britta Holtkamp, Katja Köbbing, Sander Claeys, Sandy Foerster, Simone Thiele, Heidi Rochau-Trumpp, Annette George, Moritz Niesert, Tanja Neimair, Katia Vettori, Julia Haverkamp, Jila Taherpour, Juliane Hug, Franziska Wenzel, Christina Bant, Ute Baur, Kathrin Bühner, Melina Schlag, Lena Ruß, Hanna Küpper, Anja Müller, Kurt Wollinsky, Therese Well, Antonia Leinert, Barbara Andres, Heymut Omran, Nicole Claus, Anna Hagenmeyer, Marion Schnurr, Vladimir Dukic, Albert Christian Ludolph, Sabine Specht, Verena Angermair, Anna Hüpper, Daniela Banholzer, Sabine Stein, Tim Kampowski, Marion Richmann, Sylke Nicolai, Omar Atta, Birgit Meßmer, Heike de Vries, Elisabeth Rotenfusser, Alma Oscmanovic, Isabelle Renger, Hélène Guillemot, Ilka Lehnert, Mike Grünwedel, Laura Grimm, Guido Stocker, Annegret Hoevel, Theresa Stadler, Michal Fischer, Sibylle Vogt, Axel Gebert, Susanne Goldbach, Hanns Lochmüller, Wolfgang Müller-Felber, Ulrike Schara-Schmidt, Kristina Probst-Schendzielorz, Annina Lang, Maren Nitzsche, Julie Hammer, Katharina Müller-Kaempfer, Corinna Wirner-Piotrowski, Lieske van der Stam, Anke Bongartz, Cornelia Enzmann, Joël Fluss, Elea Galiart, David Jacquier, Dominique Baumann Metzler, and Anne Tscherter

Subjects
Spinal muscular atrophy, Gene addition therapy, SMA, Onasemnogene abeparvovec, Gene therapy, Zolgensma, Public aspects of medicine, RA1-1270
Abstract

Summary: Background: Real-world data on gene addition therapy (GAT) with onasemnogene abeparvovec (OA), including all age groups and with or without symptoms of the disease before treatment are needed to provide families with evidence-based advice and realistic therapeutic goals. Aim of this study is therefore a population-based analysis of all patients with SMA treated with OA across Germany, Austria and Switzerland (D-A-CH). Methods: This observational study included individuals with Spinal Muscular Atrophy (SMA) treated with OA in 29 specialized neuromuscular centers in the D-A-CH-region. A standardized data set including WHO gross motor milestones, SMA validated motor assessments, need for nutritional and respiratory support, and adverse events was collected using the SMArtCARE registry and the Swiss-Reg-NMD. Outcome data were analyzed using a prespecified statistical analysis plan including potential predictors such as age at GAT, SMN2 copy number, past treatment, and symptom status. Findings: 343 individuals with SMA (46% male, 54% female) with a mean age at OA of 14.0 months (range 0–90, IQR 20.0 months) were included in the analysis. 79 (23%) patients were clinically presymptomatic at the time of treatment. 172 (50%) patients received SMN2 splice-modifying drugs prior to GAT (risdiplam: n = 16, nusinersen: n = 154, both: n = 2). Functional motor improvement correlated with lower age at GAT, with the best motor outcome in those younger than 6 weeks, carrying 3 SMN2 copies, and being clinically presymptomatic at time of treatment. The likelihood of requiring ventilation or nutritional support showed a significantly increase with older age at the time of GAT and remained stable thereafter. Pre-treatment had no effect on disease trajectories. Liver-related adverse events occurred significantly less frequently up to 8 months of age. All other adverse events showed an even distribution across all age and weight groups. Interpretation: Overall, motor, respiratory, and nutritional outcome were dependent on timing of GAT and initial symptom status. It was best in presymptomatic children treated within the first six weeks of life, but functional motor scores also increased significantly after treatment in all age groups up to 24 months. Additionally, OA was best tolerated when administered at a young age. Our study therefore highlights the need for SMA newborn screening and immediate treatment to achieve the best possible benefit-risk ratio. Funding: The SMArtCARE and Swiss-Reg-NMD registries are funded by different sources (see acknowledgements).

Published
2024
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5. Safety, tolerability, and efficacy of subcutaneous efgartigimod in patients with chronic inflammatory demyelinating polyradiculoneuropathy (ADHERE): a multicentre, randomised-withdrawal, double-blind, placebo-controlled, phase 2 trial

Author

Grinzinger, Susanne, Wanschitz, Julia, Seifert-Held, Thomas, Claeys, Kristl G., Baets, Jonathan, Remiche, Gauthier, Bissay, Véronique, Dubuisson, Nicolas, Delstanche, Stephanie, Tarnev, Ivaylo, Genov, Krasimir, Tsvetanov, Plamen, Milanov, Ivan, Zhao, Chongbo, Bu, Bitao, Yu, Xuefan, Li, Wei, Jiang, Haishan, Da, Yuwei, Lu, Zuneng, Liang, Hui, Guo, Fuqiang, Li, Zunbo, Zou, Zhangyu, Hong, Daojun, Yang, Huan, Guo, Junhong, Shi, Jianquan, Tu, Jianglong, He, Dian, Wang, Yiqi, Ding, Jing, Zhang, Yali, Zhao, Yuanqi, Xu, Renxi, Yue, Yunhua, Guo, Aihong, Wang, Yuzhong, Talab, Radomir, Harbo, Thomas, Sindrup, Soeren, De Seze, Jérôme, Sacconi, Sabrina, Péréon, Yann, Echaniz-Laguna, Andoni, Magy, Laurent, Nicolas, Guillaume, Taithe, Frédéric, Cassereau, Julien, Debs, Rabab, Shakarishvili, Roman, Tsiskaridze, Alexander, Mania, Maka, Janelidze, Marina, Janelidze, Tamar, Schroeter, Michael, Skripuletz, Thomas, Lee, De-Hyung, Klehmet, Juliane, Hotter, Benjamin, Hoffmann, Olaf, Baum, Petra, Zschuentzsch, Jana, Pitarokoili, Kalliopi, Stettner, Mark, Bereczki, Dániel, Pánczél, Gyula, Abraham, Alon, Dori, Amir, Lampl, Yair, Manganelli, Fiore, Morino, Stefania, Padovani, Alessandro, Siciliano, Gabriele, Schenone, Angelo, Magri, Francesca, Mazzeo, Anna, Giannini, Fabio, Sorbi, Sandro, Chiò, Adriano, Kuwahara, Motoi, Okuno, Tatsusada, Okamoto, Tomoko, Kokubun, Norito, Nishiyama, Kazutoshi, Kaida, Kenichi, Bokuda, Kota, Katsuno, Masahisa, Yabe, Ichiro, Saji, Etsuji, Yokota, Takanori, Hatanaka, Yuki, Nakahara, Jin, Sugimoto, Takamichi, Tanaka, Fumiaki, Tomita, Satoshi, Yamano, Yoshihisa, Hayashi, Tomohiro, Yamazaki, Hiroki, Tokashiki, Takashi, Horiuchi, Kazuhiro, Karelis, Guntis, Eftimov, Filip, Banach, Marta, Chyrchel-Paszkiewicz, Urszula, Kochanowicz, Jan, Selmaj, Krzysztof, Zielinski, Tomasz, Banaszkiewicz, Krzysztof, Mitrea, Dan, Scutaru-Kadar, Ana-Maria, Axelerad, Any, Stuchevskaya, Fatima, Boyko, Alexey, Khabirov, Farit, Trushnikova, Tatiana, Goncharova, Zoya, Suponeva, Natalia, Dorogov, Nikolay, Yakupov, Eduard, Raicevic, Ranko, Miletic Drakulic, Svetlana, Cabrera Serrano, Macarena, Muñoz Blanco, Jose Luis, Guerrero Sola, Antonio, Aguera Morales, Eduardo, Diaz Marin, Carmen, Juntas Morales, Raúl, Yeh, Jiann-Horng, Sung, Jia-Ying, Huang, Han-Wei, Tsai, Nai-Wen, Guo, Yuh-Cherng, Chao, Chi-Chao, Ro, Long-Sun, Sengun, Ihsan, Terzi, Murat, Alpaydin Baslo, Sezin, Koç, Filiz, Necdet Karli, Hamdi, Shulga, Olga, Smolko, Dmytro, Doroshenko, Oleksandr, Tomakh, Nataliya, Kyrychenko, Alla, Seliuk, Olga, Kalbus, Oleksandr, Skrypchenko, Iryna, Novakovska, Olha, Carod-Artal, Francisco Javier, Rinaldi, Simon, Brennan, Kathryn, Ellis, Simon, Carr, Aisling, Matthews, Emma, Traub, Rebecca, Mozaffar, Tahseen, Elliott, Matthew, Bhavaraju-Sanka, Ratna, Nance, Christopher, Levine, Todd, Lisak, Robert, Pasnoor, Mamatha, Pulley, Michael, Roy, Bhaskar, Govindarajan, Raghav, Sahagian, Gregory, Khella, Sami, Jacob, Daniel, Kushlaf, Hani, Sivakumar, Kumaraswamy, Melamed, Isaac, Sharma, Khema, Quick, Adam, Ubogu, Eroboghene, Lacomis, David, Isa, Arnaldo, Brannagan, Thomas, Chen, Shan, Katz, Jonathan, Feinberg, Marc, Pavlakis, Pantelis, Lange, Dale, Gudesblatt, Mark, Tandan, Rup, Gable, Karissa, Rivner, Michael, Barnes, Benjamin, Luke, Donna, Mahuwala, Zabeen, Macwan, Samir, Kwon, Patrick, Scott, James, Altamimi, Sadiq, Sabharwal, Priyanka, Allen, Jeffrey A, Lin, Jie, Basta, Ivana, Dysgaard, Tina, Eggers, Christian, Guptill, Jeffrey T, Gwathmey, Kelly G, Hewamadduma, Channa, Hofman, Erik, Hussain, Yessar M, Kuwabara, Satoshi, Le Masson, Gwendal, Leypoldt, Frank, Chang, Ting, Lipowska, Marta, Lowe, Murray, Lauria, Giuseppe, Querol, Luis, Simu, Mihaela-Adriana, Suresh, Niraja, Tse, Anissa, Ulrichts, Peter, Van Hoorick, Benjamin, Yamasaki, Ryo, Lewis, Richard A, and van Doorn, Pieter A

Published
2024
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7. Association of Fluid Balance and Hemoglobin Decline With Neurological Outcome After Aneurysmal Subarachnoid Hemorrhage

Author

Truckenmueller, Peter, Wolf, Stefan, Wasilewski, David, Vajkoczy, Peter, Früh, Anton, Baro, Norbert, Bauer, Miriam, Barner, Christoph, Dengler, Nora F., von Dincklage, Falk, Finger, Tobias, Francis, Roland, Hotter, Benjamin, Hunsicker, Oliver, Jussen, Daniel, Jüttler, Eric, Pohrt, Anne, Salih, Farid, Schaumann, Andreas, Witsch, Jens, Nagel, Christoph, Lemcke, Johannes, Meier, Ullrich, Podlesik, Dino, Schackert, Gabriele, Juratli, Tareq A., Huttner, Hagen, Schwab, Stefan, Staykov, Dimitre, Hagedorn, Sabine, Müller, Daniela, Müller, Oliver, Sarge, Robert, Sure, Ulrich, Bardutzky, Jürgen, Niesen, Wolf-Dirk, Lange, Katharina, Malinova, Vesna, Mielke, Dorothee, Rohde, Veit, Päsler, Dennis, Reinhardt, Stephanie, Schroeder, Henry W.S., Czorlich, Patrick, Regelsberger, Jan, Sauvigny, Thomas, Westphal, Manfred, Ehlert, Angelika, Gremmer, Rudolf, Beyer, Christian, Beyer, Desiree, Huthmann, Alexandra, Kerz, Thomas, Landscheidt, Julia, Schürer, Ludwig, Schul, David B., Meyer, Bernhard, Ryang, Yu-Mi, Toeroek, Elisabeth, Wostrack, Maria, Arouk, Wasim, Al-Jehani, Hosam, Fritsch, Michael, Al-Jehani, Hosam, Alturk, Abdulrahman Y., Sinclair, David B., Beck, Jürgen, Fung, Christian, Soell, Nicole, Engel, Doortje C., Hildebrandt, Gerhard, Huscher, Karen, Lange, Heidrun, Hutchinson, Peter, and Tseng, Ming-Yuan

Published
2024
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15. Serum neurofilament light chain in myasthenia gravis subgroups: An exploratory cohort and case–Control study

Author

Frauke Stascheit, Annette Aigner, Philipp Mergenthaler, Benjamin Hotter, Sarah Hoffmann, Sophie Lehnerer, Christian Meisel, and Andreas Meisel

Subjects
serum neurofilament light chain, myasthenia gravis, antibody status, biomarker, disease severity, Neurology. Diseases of the nervous system, RC346-429
Abstract

BackgroundThis study aimed to evaluate the association of neurofilament light chain (Nfl) with neuromuscular destruction and disease severity in the serum of patients with myasthenia gravis (MG).Materials and methodsSera from 134 patients with MG with varying degrees of disease severity and autoantibody (Abs) status were analyzed and compared to controls in a cross-sectional design. Prospectively, we additionally measured serum NfL (sNfl) levels in patients with MG longitudinally for up to 3 years. Based on linear regression, differences between patients and controls were assessed. With correlation coefficients and mixed linear regression, the association among sNfl levels, socio-demographics, disease activity (Quantitative Myasthenia Gravis (QMG) score and Myasthenia Gravis Activities of Daily Living (MG-ADL) scale), Abs-status (acetylcholine receptor antibody (AChR-Abs), muscle-specific receptor tyrosine kinase antibody (MuSK-Abs), lipoprotein-related protein 4 (LRP4), and seronegative), Abs titer, treatment regime (pyridostigmine, steroids, and immunosuppressive therapies), and thymectomy were investigated.ResultssNfl levels were higher in patients with MG compared to controls (median: 11.2 vs. 7.88), where sNfl levels were highest in anti-AChR-Abs positive patients (median 12.6), followed by anti-MuSK-Abs positive, anti-LRP4-Abs positive, and seronegative patients. Adjusting for age and sex, sNfl levels of patients with MG were on average 35% higher compared to controls (35.1, 95% CI: 8.4;68.3) and highest for patients with seronegative MG (44.35; 95% CI 16.47; 78.90). We found no relevant relationship between individual changes in sNfl and changes in QMG and MG-ADL scores.ConclusionsNfl levels are higher in patients with MG than in controls but were not consistently associated with clinical severity. Thus, sNfl is not a suitable biomarker to monitor individual disease progression in patients with MG.

Published
2023
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19. Biomarkers to improve functional outcome prediction after ischemic stroke: Results from the SICFAIL, STRAWINSKI, and PREDICT studies.

Author

Montellano, Felipe A, Rücker, Viktoria, Ungethüm, Kathrin, Penalba, Anna, Hotter, Benjamin, Giralt, Marina, Wiedmann, Silke, Mackenrodt, Daniel, Morbach, Caroline, Frantz, Stefan, Störk, Stefan, Whiteley, William N, Kleinschnitz, Christoph, Meisel, Andreas, Montaner, Joan, Haeusler, Karl Georg, and Heuschmann, Peter U

Published
2024
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22. Unmet Need for Social and Emotional Support and Lack of Recalled Screening Is Associated with Depression in the Long-Term Course After Stroke

Author

Padberg I, Hotter B, Liebenau A, Knispel P, Lehnerer S, Heel S, Wellwood I, and Meisel A

Subjects
health care quality, social-care, risk management, stroke, depression, Public aspects of medicine, RA1-1270
Abstract

Inken Padberg,1 Benjamin Hotter,1,2 Andrea Liebenau,1 Petra Knispel,1,3 Sophie Lehnerer,1,2 Sabine Heel,4 Ian Wellwood,5 Andreas Meisel1–3 1Center for Stroke Research Berlin (CSB), Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany; 2Neurocure Clinical Research Center, Department of Neurology, Charité Universitätsmedizin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Berlin, Germany; 3Berliner Schlaganfall-Allianz e.V., Berlin, Germany; 4Zentrum für Ambulante Neuropsychologie und Verhaltenstherapie (ZANV), Berlin, Germany; 5Department of Public-Health and Primary Care, University of Cambridge, Cambridge, UKCorrespondence: Inken Padberg Tel +49 30 450 560142Fax +49 30 450 560952Email inken.padberg@charite.dePurpose: Details on adequate care and prevalence of depression in long-term stroke aftercare are limited. We aimed to determine long-term depression rates after stroke and to test for an association between depression and inadequate screening, socio-economic complications and lack of sub-optimal care.Patients and Methods: In this cross-sectional study, 57 patients were re-invited into the clinic 2– 3 years after stroke. Patients were interviewed about recalled screening concerning depression and unmet needs. Depression, the patient’s social situation, and confounders were assessed by standardized scores.Results: In our study, 20% (n = 11) of patients were classified as depressed by the HDRS-17 score result. However, only 36% of all patients recalled to have been previously screened for depression and only 43% of those patients also recalled out-patient screening. Patients classified as depressed reported significantly lower recalled screening rates (9% vs 43%; p = 0.036) and higher rates of self-reported unmet need with emotional problems (72% vs 18%; p

Published
2020

24. Recovery of Chronic Inflammatory Demyelinating Polyneuropathy on Treatment With Ocrelizumab in a Patient With Co-Existing Multiple Sclerosis

Author

Michael Auer MD PhD, Harald Hegen MD PhD PD, Anna Hotter MD, Wolfgang Löscher MD MSc, Klaus Berek MD, Anne Zinganell MD, Elena Fava MD, Paul Rhomberg MD, Florian Deisenhammer MD MSc, and Franziska Di Pauli MD PhD

Subjects
Neurology. Diseases of the nervous system, RC346-429
Abstract

The chimeric anti-CD20 antibody rituximab has demonstrated good efficacy as an off-label treatment in chronic inflammatory demyelinating polyneuropathy (CIDP), while the humanized anti-CD20 antibody ocrelizumab has been approved for treatment of multiple sclerosis (MS), whereas there is no evidence for its use in CIDP so far. We present a patient suffering from CIDP and MS, both refractory to standard treatment and both showing marked improvement on ocrelizumab. To the best of our knowledge, this is a unique report of CIDP with an almost full electrophysiological recovery on ocrelizumab which could be considered as a potential treatment option for refractory CIDP.

Published
2022
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25. Cavity sub- and superradiance for transversely driven atomic ensembles

Author

Christoph Hotter, Laurin Ostermann, and Helmut Ritsch

Subjects
Physics, QC1-999
Abstract

Large atomic ensembles coupled to a single optical resonator mode can be steered to strongly enhanced or suppressed collective emission via phase controlled excitation. Employing the Tavis-Cummings model we find so far unreported phenomena. Using a second order cumulant expansion we predict that a homogeneously excited ensemble equally distributed between odd and even sites along the cavity mode is extremely subradiant as long as the average excitation remains below 50%, but shows pulsed emission for inversion. The combination of these two properties enables the implementation of an efficient cavity-enhanced Ramsey probing featuring a fast readout and minimal heating with particular advantages for atomic clock transitions. For continuous illumination the nonlinear atom-field interaction induces regular superradiant self-pulsing. Additionally, we observe an increased pulse delay time in comparison to an excitation through the cavity.

Published
2023
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28. Guanylate-Binding Proteins 2 and 5 Exert Broad Antiviral Activity by Inhibiting Furin-Mediated Processing of Viral Envelope Proteins

Author

Braun, Elisabeth, Hotter, Dominik, Koepke, Lennart, Zech, Fabian, Groß, Rüdiger, Sparrer, Konstantin M.J., Müller, Janis A., Pfaller, Christian K., Heusinger, Elena, Wombacher, Rebecka, Sutter, Kathrin, Dittmer, Ulf, Winkler, Michael, Simmons, Graham, Jakobsen, Martin R., Conzelmann, Karl-Klaus, Pöhlmann, Stefan, Münch, Jan, Fackler, Oliver T., Kirchhoff, Frank, and Sauter, Daniel

Published
2019
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29. Legal and ethical framework for global health information and biospecimen exchange - an international perspective

Author

Lara Bernasconi, Selçuk Şen, Luca Angerame, Apolo P. Balyegisawa, Damien Hong Yew Hui, Maximilian Hotter, Chung Y. Hsu, Tatsuya Ito, Francisca Jörger, Wolfgang Krassnitzer, Adam T. Phillips, Rui Li, Louise Stockley, Fabian Tay, Charlotte von Heijne Widlund, Ming Wan, Creany Wong, Henry Yau, Thomas F. Hiemstra, Yagiz Uresin, and Gabriela Senti

Subjects
Data sharing, Biobanking, Big data, Research policies, International exchange, Medical philosophy. Medical ethics, R723-726
Abstract

Abstract Background The progress of electronic health technologies and biobanks holds enormous promise for efficient research. Evidence shows that studies based on sharing and secondary use of data/samples have the potential to significantly advance medical knowledge. However, sharing of such resources for international collaboration is hampered by the lack of clarity about ethical and legal requirements for transfer of data and samples across international borders. Main text Here, the International Clinical Trial Center Network (ICN) reports the legal and ethical requirements governing data and sample exchange (DSE) across four continents. The most recurring requirement is ethical approval, whereas only in specific conditions approval of national health authorities is required. Informed consent is not required in all sharing situations. However, waiver of informed consent is only allowed in certain countries/regions and under certain circumstances. The current legal and ethical landscape appears to be very complex and under constant evolution. Regulations differ between countries/regions and are often incomplete, leading to uncertainty. Conclusion With this work, ICN illuminates the unmet need for a single international collaborative framework to facilitate DSE. Harmonising requirements for global DSE will reduce inefficiency and waste in research. There are many challenges to realising this ambitious vision, including inconsistent terminology and definitions, and heterogeneous and dynamic legal constraints. Here, we identify areas of agreement and significant difference as a necessary first step towards facilitating international collaboration. We propose the establishment of a working group to continue the comparison across jurisdictions, create a standardised glossary and define a set of basic principles and fundamental requirements for DSE.

Published
2020
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30. High-Throughput Determination of Infectious Virus Titers by Kinetic Measurement of Infection-Induced Changes in Cell Morphology.

Author

Hotter, Dominik, Kunzelmann, Marco, Kiefer, Franziska, Leukhardt, Chiara, Fackler, Carolin, Jäger, Stefan, and Solzin, Johannes

Subjects
*NEWCASTLE disease virus, *CELL morphology, *TITERS, *DATA analysis, *ANALYTICAL solutions
Abstract

Infectivity assays are the key analytical technology for the development and manufacturing of virus-based therapeutics. Here, we introduce a novel assay format that utilizes label-free bright-field images to determine the kinetics of infection-dependent changes in cell morphology. In particular, cell rounding is directly proportional to the amount of infectious virus applied, enabling rapid determination of viral titers in relation to a standard curve. Our kinetic infectious virus titer (KIT) assay is stability-indicating and, due to its sensitive readout method, provides results within 24 h post-infection. Compared to traditional infectivity assays, which depend on a single readout of an infection endpoint, cumulated analysis of kinetic data by a fit model results in precise results (CV < 20%) based on only three wells per sample. This approach allows for a high throughput with ~400 samples processed by a single operator per week. We demonstrate the applicability of the KIT assay for the genetically engineered oncolytic VSV-GP, Newcastle disease virus (NDV), and parapoxvirus ovis (ORFV), but it can potentially be extended to a wide range of viruses that induce morphological changes upon infection. The versatility of this assay, combined with its independence from specific instruments or software, makes it a promising solution to overcome the analytical bottleneck in infectivity assays within the pharmaceutical industry and as a routine method in academic research. [ABSTRACT FROM AUTHOR]

Published
2024
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31. CPT1a gene expression reverses the inflammatory and anti-phagocytic effect of 7-ketocholesterol in RAW264.7 macrophages

Author

Priscila Calle, Angeles Muñoz, Anna Sola, and Georgina Hotter

Subjects
Macrophage, 7-ketocholesterol, CPT1a, Phagocytosis, Inflammation, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Abstract Background Macrophage are specialized cells that contributes to the removal of detrimental contents via phagocytosis. Lipid accumulation in macrophages, whether from phagocytosis of dying cells or from circulating oxidized low-density lipoproteins, alters macrophage biology and functionality. It is known that carnitine palmitoyl transferase 1-a (CPT1a) gene encodes an enzyme involved in fatty acid oxidation and, therefore, lipid content. However, the potential of CPT1a to activate macrophage phagocytic function have not been elucidated. Methods Using a murine macrophage cell line, RAW264.7, we determine if intracellular accumulation of 7-ketocholesterol (7-KC) modulates macrophage phagocytic function through CPT1a gene expression. In addition, the effects of CPT1a genetic modification on macrophage phenotype and phagocytosis has been studied. Results Our results revealed that CPT1a gene expression decreased by the accumulation of 7-KC at the higher dose of 7-KC. This was concomitant with an impair ability to phagocytize bioparticles and an inflammatory phenotype. GW3965 treatment, which have shown to facilitate the efflux of cholesterol, eliminated the intracellular lipid droplets of 7-KC-laden macrophages, increased the gene expression of CPT1a, diminished the gene expression of the inflammatory marker iNOS and restored macrophage phagocytosis. Furthermore, CPT1a Knockdown per se was detrimental for macrophage phagocytosis whereas transcriptional activation of CPT1a heightened the uptake of bioparticles. Conclusions Altogether, our findings indicate that downregulation of CPT1a by lipid content modulates macrophage phagocytosis and inflammatory phenotype.

Published
2019
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32. Social work support and unmet social needs in life after stroke: a cross-sectional exploratory study

Author

Sophie Lehnerer, Benjamin Hotter, Inken Padberg, Petra Knispel, Dike Remstedt, Andrea Liebenau, Ulrike Grittner, Ian Wellwood, Andreas Meisel, and on behalf of the BSA Long Term Care Study Group

Subjects
Stroke, Long-term care, Social situation, Unmet social needs, Assessment tools, Screening social work, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Stroke patients are often affected by long-term disabilities with needs concerning social issues. There is relatively little consideration of social recovery of patients and the support required to return to work, receive social benefits, participate in daily life activities, maintain contact with family and friends and to organize financial affairs. In our study we aimed to investigate if existing tools record social needs adequately. We analyzed the current provision of social support provided in long-term care after stroke and whether unmet social needs were associated with quality of life, caregiver burden, overall function and degree of disability. Methods Our analysis is part of the Managing Aftercare of Stroke study (MAS-I), a cross-sectional exploratory study of patient needs 2–3 years after initial stroke. Assessment tools included the Nikolaus-score (social situation), the EuroQoL (quality of life), the German Burden Scale for Family Caregivers (caregiver burden), the modified Rankin Scale (disability / dependence), Stroke Impact Scale (function and degree of disability) and the Stroke Survivor Needs Questionnaire (unmet needs). Results Overall 57 patients were included in MAS-I, with ten patients classified in urgent need of socio-economic support according to the Nikolaus-score. Patients with lower than normal Nikolaus-score had a higher degree of disability. Thirty percent of all patients had never received professional social support. Social worker contact happened mostly during the stay in acute hospital or rehabilitation institution. Only four patients (11%) reported long-term support after discharge. Apart from social worker contact during acute care, 43% of patients had unmet needs in the long-term aftercare. Forty percent of all patients included in MAS-I were recommended for social work intervention after an in-depth analysis of their situation. Finally, we saw that unmet social needs were associated with lower quality of life and higher caregiver burden. Conclusions Our data suggest significant unmet needs in social care in long-term stroke patients. Screening tools for unmet social needs such as the Nikolaus-score do not holistically report patients’ needs. Trial registration Clinicaltrials.Gov NCT02320994. Registered 19 December 2014 (retrospectively registered).

Published
2019
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33. Biomarkers of immune capacity, infection and inflammation are associated with poor outcome and mortality after stroke - the PREDICT study

Author

A. Mengel, L. Ulm, B. Hotter, H. Harms, S. K. Piper, U. Grittner, J. Montaner, C. Meisel, A. Meisel, and S. Hoffmann

Subjects
Ischemic stroke, Biomarkers, Mortality, Outcome, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Almost 40% of stroke patients have a poor outcome at 3 months after the index event. Predictors for stroke outcome in the early acute phase may help to tailor stroke treatment. Infection and inflammation are considered to influence stroke outcome. Methods In a prospective multicenter study in Germany and Spain, including 486 patients with acute ischemic stroke, we used multivariable regression analysis to investigate the association of poor outcome with monocytic HLA-DR (mHLA-DR) expression, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-alpha) and lipopolysaccharide-binding protein (LBP) as markers for immunodepression, inflammation and infection. Outcome was assessed at 3 months after stroke via a structured telephone interview using the modified Rankin Scale (mRS). Poor outcome was defined as a mRS score of 3 or higher which included death. Furthermore, a time-to-event analysis for death within 3 months was performed. Results Three-month outcome data was available for 391 patients. Female sex, older age, diabetes mellitus, atrial fibrillation, stroke-associated pneumonia (SAP) and higher National Institute of Health Stroke Scale (NIHSS) score as well as lower mHLA-DR levels, higher IL-6 and LBP-levels at day 1 were associated with poor outcome at 3 months in bivariate analysis. Furthermore, multivariable analysis revealed that lower mHLA-DR expression was associated with poor outcome. Female sex, older age, atrial fibrillation, SAP, higher NIHSS score, lower mHLA-DR expression and higher IL-6 levels were associated with shorter survival time in bivariate analysis. In multivariable analysis, SAP and higher IL-6 levels on day 1 were associated with shorter survival time. Conclusions SAP, lower mHLA-DR-expression and higher IL-6 levels on day one are associated with poor outcome and shorter survival time at 3 months after stroke onset. Trial registration www.clinicaltrials.gov, NCT01079728, March 3, 2010.

Published
2019
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34. Calprotectin in Chronic Inflammatory Demyelinating Polyneuropathy and Variants—A Potential Novel Biomarker of Disease Activity

Author

Frauke Stascheit, Benjamin Hotter, Sarah Klose, Christian Meisel, Andreas Meisel, and Juliane Klehmet

Subjects
calprotectin (S100A8/S100A9), serum neurofilament light chain, chronic inflammatory demyelinating polyneuropathy, CIDP variants, biomarker, Neurology. Diseases of the nervous system, RC346-429
Abstract

Background: In chronic inflammatory demyelinating polyneuropathy (CIDP), there is an urgent need for biomarkers to monitor ongoing disease activity. Serum calprotectin (CLP) induces signaling pathways involved in inflammatory processes and has been shown to correlate with markers of disease activity in other autoimmune disorders. Thus, we wanted to study the potential value of CLP in comparison to serum neurofilament light chain (sNfl) to monitor disease activity.Materials and Methods: Sera from 63 typical and atypical CIDP and 6 MMN patients with varying degrees of disease activity were analyzed in comparison with 40 healthy controls (HC) in a cross-sectional design. Association of CLP and sNfl levels with socio-demographics, disease duration, CIDP disease activity scale (CDAS), and impairment status [medical research council-sum score (MRC-SS), the inflammatory neuropathy cause and treatment disability score (INCAT-DS), grip strength, and maximum walking distance], patient-reported outcome (PRO) parameters [SF-36 questionnaire, Beck's depression index (BDI), and fatigue severity scale (FSS)], as well as treatment regime were investigated using uni- and multivariate analysis.Results: CLP and sNfl levels were significantly higher in all CIDP patients compared to HC (p = 0.0009). Multivariate analysis adjusted for age and gender revealed that CLP acts as an independent predictor for CIDP and MMN. CLP was significantly associated with active disease course according to CDAS and correlated with MRC-SS, whereas sNfl correlated with parameters of disease impairment. There was no correlation with PRO, except for sNfl and the mental health composite score. Subgroup analysis revealed no differences between typical CIDP and atypical variants.Conclusions: CLP was elevated in CIDP and variants and was associated with active disease course, whereas sNfl shows further potential as biomarker of axonal degeneration. Thus, CLP might be a suitable additive biomarker for measurement of ongoing inflammation, which is greatly needed to guide better patient care in CIDP.

Published
2021
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38. Nuclear PYHIN proteins target the host transcription factor Sp1 thereby restricting HIV-1 in human macrophages and CD4+ T cells.

Author

Matteo Bosso, Caterina Prelli Bozzo, Dominik Hotter, Meta Volcic, Christina M Stürzel, Annika Rammelt, Yi Ni, Stephan Urban, Miriam Becker, Mario Schelhaas, Sabine Wittmann, Maria H Christensen, Florian I Schmidt, Thomas Gramberg, Konstantin M J Sparrer, Daniel Sauter, and Frank Kirchhoff

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Members of the family of pyrin and HIN domain containing (PYHIN) proteins play an emerging role in innate immunity. While absent in melanoma 2 (AIM2) acts a cytosolic sensor of non-self DNA and plays a key role in inflammasome assembly, the γ-interferon-inducible protein 16 (IFI16) restricts retroviral gene expression by sequestering the transcription factor Sp1. Here, we show that the remaining two human PYHIN proteins, i.e. myeloid cell nuclear differentiation antigen (MNDA) and pyrin and HIN domain family member 1 (PYHIN1 or IFIX) share this antiretroviral function of IFI16. On average, knock-down of each of these three nuclear PYHIN proteins increased infectious HIV-1 yield from human macrophages by more than an order of magnitude. Similarly, knock-down of IFI16 strongly increased virus transcription and production in primary CD4+ T cells. The N-terminal pyrin domain (PYD) plus linker region containing a nuclear localization signal (NLS) were generally required and sufficient for Sp1 sequestration and anti-HIV-1 activity of IFI16, MNDA and PYHIN1. Replacement of the linker region of AIM2 by the NLS-containing linker of IFI16 resulted in a predominantly nuclear localization and conferred direct antiviral activity to AIM2 while attenuating its ability to form inflammasomes. The reverse change caused nuclear-to-cytoplasmic relocalization of IFI16 and impaired its antiretroviral activity but did not result in inflammasome assembly. We further show that the Zn-finger domain of Sp1 is critical for the interaction with IFI16 supporting that pyrin domains compete with DNA for Sp1 binding. Finally, we found that human PYHIN proteins also inhibit Hepatitis B virus and simian vacuolating virus 40 as well as the LINE-1 retrotransposon. Altogether, our data show that IFI16, PYHIN1 and MNDA restrict HIV-1 and other viral pathogens by interfering with Sp1-dependent gene expression and support an important role of nuclear PYHIN proteins in innate antiviral immunity.

Published
2020
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39. Species-specific host factors rather than virus-intrinsic virulence determine primate lentiviral pathogenicity

Author

Simone Joas, Erica H. Parrish, Clement W. Gnanadurai, Edina Lump, Christina M. Stürzel, Nicholas F. Parrish, Gerald H. Learn, Ulrike Sauermann, Berit Neumann, Kerstin Mätz Rensing, Dietmar Fuchs, James M. Billingsley, Steven E. Bosinger, Guido Silvestri, Cristian Apetrei, Nicolas Huot, Thalia Garcia-Tellez, Michaela Müller-Trutwin, Dominik Hotter, Daniel Sauter, Christiane Stahl-Hennig, Beatrice H. Hahn, and Frank Kirchhoff

Subjects
Science
Abstract

In contrast to HIV, simian immunodeficiency viruses (SIV) do not cause disease in their hosts, and the reasons for this are unclear. Here, Joas et al. incorporate two putative HIV virulence factors into SIV and study effects in infected monkeys, suggesting that species-specific host factors are responsible for HIV pathogenesis.

Published
2018
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40. Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Author

Coleman, A, Santos, R Dar, Decolongon, J, Sturrock, A, Bardinet, E, Ret, C Jauff, Justo, D, Lehericy, S, Marelli, C, Nigaud, K, Valabrègue, R, van den Bogaard, SJA, Dumas, E M, van der Grond, J, t'Hart, EP, Jurgens, C, Witjes-Ane, M-N, Arran, N, Callaghan, J, Stopford, C, Frost, C, Jones, R, Hobbs, N, Lahiri, N, Ordidge, R, Owen, G, Pepple, T, Read, J, Say, M, Wild, E, Patel, A, Fox, N C, Gibbard, C, Malone, I, Crawford, H, Whitehead, D, Keenan, S, Cash, D M, Berna, C, Bechtel, N, Bohlen, S, Man, A Hoff, Kraus, P, Axelson, E, Wang, C, Acharya, T, Lee, S, Monaco, W, Campbell, C, Queller, S, Whitlock, K, Campbell, M, Frajman, E, Milchman, C, O'Regan, A, Labuschagne, I, Stout, J, Landwehrmeyer, B, Craufurd, D, Scahill, R, Hicks, S, Kennard, C, Johnson, H, Tobin, A, Rosas, HD, Reilmann, R, Borowsky, B, Pourchot, C, Andrews, S C, Bachoud-Lévi, Anne-Catherine, Bentivoglio, Anna Rita, Biunno, Ida, Bonelli, Raphael, Burgunder, Jean-Marc, Dunnett, Stephen, Ferreira, Joaquim, Handley, Olivia, Heiberg, Arvid, Illmann, Torsten, Landwehrmeyer, G. Bernhard, Levey, Jamie, Ramos-Arroyo, Maria A., Nielsen, Jørgen, Koivisto, Susana Pro, Päivärinta, Markku, Roos, Raymund A.C., Sebastián, A Rojo, Tabrizi, Sarah, Vandenberghe, Wim, Verellen-Dumoulin, Christine, Uhrova, Tereza, Wahlström, Jan, Zaremba, Jacek, Baake, Verena, Barth, Katrin, Garde, Monica Bascuñana, Betz, Sabrina, Bos, Reineke, Callaghan, Jenny, Come, Adrien, Guedes, Leonor Correia, Ecker, Daniel, Finisterra, Ana Maria, Fullam, Ruth, Gilling, Mette, Gustafsson, Lena, Handley, Olivia J, Hvalstedt, Carina, Held, Christine, Koppers, Kerstin, Lamanna, Claudia, Laurà, Matilde, Descals, Asunción Martínez, Martinez-Horta, Saül, Mestre, Tiago, Minster, Sara, Monza, Daniela, Mütze, Lisanne, Oehmen, Martin, Orth, Michael, Padieu, Hélène, Paterski, Laurent, Peppa, Nadia, Di Renzo, Martina, Rialland, Amandine, Røren, Niini, Šašinková, Pavla, Timewell, Erika, Townhill, Jenny, Cubillo, Patricia Trigo, da Silva, Wildson Vieira, van Walsem, Marleen R, Whalstedt, Carina, Witjes-Ané, Marie-Noelle, Witkowski, Grzegorz, Wright, Abigail, Zielonka, Daniel, Zielonka, Eugeniusz, Zinzi, Paola, Bonelli, Raphael M., Lilek, Sabine, Hecht, Karen, Herranhof, Brigitte, Holl, Anna, Kapfhammer, Hans-Peter, Koppitz, Michael, Magnet, Markus, Müller, Nicole, Otti, Daniela, Painold, Annamaria, Reisinger, Karin, Scheibl, Monika, Schöggl, Helmut, Ullah, Jasmin, Braunwarth, Eva-Maria, Brugger, Florian, Buratti, Lisa, Hametner, Eva-Maria, Hepperger, Caroline, Holas, Christiane, Hotter, Anna, Hussl, Anna, Müller, Christoph, Poewe, Werner, Seppi, Klaus, Sprenger, Fabienne, Wenning, Gregor, Boogaerts, Andrea, Calmeyn, Godelinde, Delvaux, Isabelle, Liessens, Dirk, Somers, Nele, Dupuit, Michel, Minet, Cécile, van Paemel, Dominique, Ribaï, Pascale, van Reijen, Dimphna, Klempír, Jirí, Majerová, Veronika, Roth, Jan, Stárková, Irena, Hjermind, Lena E., Jacobsen, Oda, Nielsen, Jørgen E., Larsen, Ida Unmack, Vinther-Jensen, Tua, Hiivola, Heli, Hyppönen, Hannele, Martikainen, Kirsti, Tuuha, Katri, Allain, Philippe, Bonneau, Dominique, Bost, Marie, Gohier, Bénédicte, Guérid, Marie-Anne, Olivier, Audrey, Prundean, Adriana, Scherer-Gagou, Clarisse, Verny, Christophe, Babiloni, Blandine, Debruxelles, Sabrina, Duché, Charlotte, Goizet, Cyril, Jameau, Laetitia, Lafoucrière, Danielle, Spampinato, Umberto, Barthélémy, Rekha, De Bruycker, Christelle, Carette, Maryline Cabaret Anne-Sophie, Defebvre, Eric Decorte Luc, Delliaux, Marie, Delval, Arnaud, Destee, Alain, Dujardin, Kathy, Lemaire, Marie-Hélène, Manouvrier, Sylvie, Peter, Mireille, Plomhouse, Lucie, Sablonnière, Bernard, Simonin, Clémence, Thibault-Tanchou, Stéphanie, Vuillaume, Isabelle, Bellonet, Marcellin, Berrissoul, Hassan, Blin, Stéphanie, Courtin, Françoise, Duru, Cécile, Fasquel, Véronique, Godefroy, Olivier, Krystkowiak, Pierre, Mantaux, Béatrice, Roussel, Martine, Wannepain, Sandrine, Azulay, Jean-Philippe, Delfini, Marie, Eusebio, Alexandre, Fluchere, Frédérique, Mundler, Laura, Anheim, Mathieu, Julié, Celine, Boukbiza, Ouhaid Lagha, Longato, Nadine, Rudolf, Gabrielle, Tranchant, Christine, Zimmermann, Marie-Agathe, Kosinski, Christoph Michael, Milkereit, Eva, Probst, Daniela, Reetz, Kathrin, Sass, Christian, Schiefer, Johannes, Schlangen, Christiane, Werner, Cornelius J., Gelderblom, Harald, Priller, Josef, Prüß, Harald, Spruth, Eike Jakob, Ellrichmann, Gisa, Herrmann, Lennard, Hoffmann, Rainer, Kaminski, Barbara, Kotz, Peter, Prehn, Christian, Saft, Carsten, Lange, Herwig, Maiwald, Robert, Löhle, Matthias, Maass, Antonia, Schmidt, Simone, Bosredon, Cecile, Storch, Alexander, Wolz, Annett, Wolz, Martin, Capetian, Philipp, Lambeck, Johann, Zucker, Birgit, Boelmans, Kai, Ganos, Christos, Heinicke, Walburgis, Hidding, Ute, Lewerenz, Jan, Münchau, Alexander, Schmalfeld, Jenny, Stubbe, Lars, Zittel, Simone, Diercks, Gabriele, Dressler, Dirk, Gorzolla, Heike, Schrader, Christoph, Tacik, Pawel, Ribbat, Michael, Longinus, Bernhard, Bürk, Katrin, Möller, Jens Carsten, Rissling, Ida, Mühlau, Mark, Peinemann, Alexander, Städtler, Michael, Weindl, Adolf, Winkelmann, Juliane, Ziegler, Cornelia, Bechtel, Natalie, Beckmann, Heike, Bohlen, Stefan, Hölzner, Eva, Reilmann, Ralf, Rohm, Stefanie, Rumpf, Silke, Schepers, Sigrun, Weber, Natalia, Dose, Matthias, Leythäuser, Gabriele, Marquard, Ralf, Raab, Tina, Wiedemann, Alexandra, Buck, Andrea, Connemann, Julia, Geitner, Carolin, Kesse, Andrea, Landwehrmeyer, Bernhard, Lang, Christina, Lezius, Franziska, Nepper, Solveig, Niess, Anke, Schneider, Ariane, Schwenk, Daniela, Süßmuth, Sigurd, Trautmann, Sonja, Weydt, Patrick, Cormio, Claudia, Sciruicchio, Vittorio, Serpino, Claudia, de Tommaso, Marina, Capellari, Sabina, Cortelli, Pietro, Galassi, Roberto, Rizzo, Giovanni, Poda, Roberto, Scaglione, Cesa, Bertini, Elisabetta, Ghelli, Elena, Ginestroni, Andrea, Massaro, Francesca, Mechi, Claudia, Paganini, Marco, Piacentini, Silvia, Pradella, Silvia, Romoli, Anna Maria, Sorbi, Sandro, Abbruzzese, Giovanni, di Poggio, Monica Bandettini, Ferrandes, Giovanna, Mandich, Paola, Marchese, Roberta, Albanese, Alberto, Di Bella, Daniela, Castaldo, Anna, Di Donato, Stefano, Gellera, Cinzia, Genitrini, Silvia, Mariotti, Caterina, Nanetti, Lorenzo, Paridi, Dominga, Soliveri, Paola, Tomasello, Chiara, De Michele, Giuseppe, Di Maio, Luigi, Massarelli, Marco, Peluso, Silvio, Roca, Alessandro, Russo, Cinzia Valeria, Salvatore, Elena, Sorrentino, Pierpaolo, Amico, Enrico, Favellato, Mariagrazia, Griguoli, Annamaria, Mazzante, Irene, Petrollini, Martina, Squitieri, Ferdinando, D'Alessio, Barbara, Esposito, Chiara, Bentivoglio, Rita, Frontali, Marina, Guidubaldi, Arianna, Ialongo, Tamara, Jacopini, Gioia, Piano, Carla, Romano, Silvia, Soleti, Francesco, Spadaro, Maria, van Hout, Monique S.E., Verhoeven, Marloes E., van Vugt, Jeroen P.P., de Weert, A. Marit, Bolwijn, J.J.W., Dekker, M., Kremer, B., Leenders, K.L., van Oostrom, J.C.H., van den Bogaard, Simon J.A., Dumas, Eve M., 't Hart, Ellen P., Kremer, Berry, Verstappen, C.C.P., Aaserud, Olaf, C, Jan Frich, Wehus, Ragnhild, Bjørgo, Kathrine, Fannemel, Madeleine, Gørvell, Per F., Lorentzen, Eirin, Retterstøl, Lars, Stokke, Bodil, Bjørnevoll, Inga, Sando, Sigrid Botne, Dziadkiewicz, Artur, Nowak, Malgorzata, Robowski, Piotr, Sitek, Emilia, Slawek, Jaroslaw, Soltan, Witold, Szinwelski, Michal, Blaszcyk, Magdalena, Boczarska-Jedynak, Magdalena, Ciach-Wysocka, Ewelina, Gorzkowska, Agnieszka, Jasinska-Myga, Barbara, Klodowska-Duda, Gabriela, Opala, Gregorz, Stompel, Daniel, Banaszkiewicz, Krzysztof, Bocwinska, Dorota, Bojakowska-Jaremek, Kamila, Dec, Malgorzata, Krawczyk, Malgorzata, Rudzinska, Monika, Szczygiel, Elzbieta, Szczudlik, Andrzej, Wasielewska, Anna, Wójcik, Magdalena, Bryl, Anna, Ciesielska, Anna, Klimberg, Aneta, Marcinkowski, Jerzy, Samara, Husam, Sempolowicz, Justyna, Gogol, Anna, Janik, Piotr, Kwiecinski, Hubert, Jamrozik, Zygmunt, Antczak, Jakub, Jachinska, Katarzyna, Krysa, Wioletta, Rakowicz, Maryla, Richter, Przemyslaw, Rola, Rafal, Ryglewicz, Danuta, Sienkiewicz-Jarosz, Halina, Stepniak, Iwona, Sulek, Anna, Zdzienicka, Elzbieta, Zieora-Jakutowicz, Karolina, Ferreira, Joaquim J, Coelho, Miguel, Mendes, Tiago, Valadas, Anabela, Andrade, Carlos, Gago, Miguel, Garrett, Carolina, Guerra, Maria Rosália, Herrera, Carmen Durán, Garcia, Patrocinio Moreno, Barbera, Miquel Aguilar, Guia, Dolors Badenes, Hernanz, Laura Casas, Catena, Judit López, Ferrer, Pilar Quiléz, Sebastián, Ana Rojo, Carruesco, Gemma Tome, Bas, Jordi, Busquets, Núria, Calopa, Matilde, Robert, Misericordia Floriach, Viladrich, Celia Mareca, Idiago, Jesús Miguel Ruiz, Riballo, Antonio Villa, Cubo, Esther, Polo, Cecilia Gil, Mariscal, Natividad, Rivadeneyra, Perez Jessica, Barrero, Francisco, Morales, Blas, Fenollar, María, García, Rocío García-Ramos, Ortega, Paloma, Villanueva, Clara, Alegre, Javier, Bascuñana, Mónica, Caldentey, Juan Garcia, Ventura, Marta Fatás, Ribas, Guillermo García, de Yébenes, Justo García, Moreno, José Luis López-Sendón, Frech, Fernando Alonso, Ruíz, Pedro J García, Martínez-Descals, Asunción, Guerrero, Rosa, Artiga, María José Saiz, Sánchez, Vicenta, Perea, María Fuensanta Noguera, Fortuna, Lorenza, Manzanares, Salvadora, Reinante, Gema, Torres, María Martirio Antequera, Moreau, Laura Vivancos, González González, Sonia, Guisasola, Luis Menéndez, Salvador, Carlos, Martín, Esther Suaréz San, Ramirez, Inés Legarda, Gorospe, Aranzazú, Lopera, Mónica Rodriguez, Arques, Penelope Navas, Rodríguez, María José Torres, Pastor, Barbara Vives, Gaston, Itziar, Martinez-Jaurrieta, Maria Dolores, Moreno, Jose Manuel Garcia, Lucena, Carolina Mendez, Damas, Fatima, Cortegana, Hermoso Eva Pacheco, Peña, José Chacón, Redondo, Luis, Carrillo, Fátima, Teresa Cáceres, María, Mir, Pablo, Suarez, María José Lama, Vargas-González, Laura, Bosca, Maria E., Brugada, Francisco Castera, Burguera, Juan Andres, Campos, Anabel, Vilaplana, Garcia Carmen Peiró, Berglund, Peter, Constantinescu, Radu, Fredlund, Gunnel, Høsterey-Ugander, Ulrika, Linnsand, Petra, Neleborn-Lingefjärd, Liselotte, Wentzel, Magnus, Loutfi, Ghada, Olofsson, Carina, Stattin, Eva-Lena, Westman, Laila, Wikström, Birgitta, Stebler, Yanik, Kaelin, Alain, Romero, Irene, Schüpbach, Michael, Weber Zaugg, Sabine, Hauer, Maria, Gonzenbach, Roman, Jung, Hans H., Mihaylova, Violeta, Petersen, Jens, Jack, Roisin, Matheson, Kirsty, Miedzybrodzka, Zosia, Rae, Daniela, Simpson, Sheila A, Summers, Fiona, Ure, Alexandra, Vaughan, Vivien, Akhtar, Shahbana, Crooks, Jenny, Curtis, Adrienne, de Souza, Jenny, Piedad, John, Rickards, Hugh, Wright, Jan, Coulthard, Elizabeth, Gethin, Louise, Hayward, Beverley, Sieradzan, Kasia, Armstrong, Matthew, Barker, Roger A., O'Keefe, Deidre, Di Pietro, Anna, Fisher, Kate, Goodman, Anna, Hill, Susan, Kershaw, Ann, Mason, Sarah, Paterson, Nicole, Raymond, Lucy, Swain, Rachel, Guzman, Natalie Valle, Busse, Monica, Butcher, Cynthia, Clenaghan, Catherine, Hunt, Sarah, Jones, Lesley, Jones, Una, Khalil, Hanan, Owen, Michael, Price, Kathleen, Rosser, Anne, Edwards, Maureen, Ho, Carrie, Hughes, Teresa, McGill, Marie, Pearson, Pauline, Porteous, Mary, Smith, Paul, Brockie, Peter, Foster, Jillian, Johns, Nicola, McKenzie, Sue, Rothery, Jean, Thomas, Gareth, Yates, Shona, Burrows, Liz, Chu, Carol, Fletcher, Amy, Gallantrae, Deena, Hamer, Stephanie, Harding, Alison, Klöppel, Stefan, Kraus, Alison, Laver, Fiona, Lewis, Monica, Longthorpe, Mandy, Markova, Ivana, Raman, Ashok, Robertson, Nicola, Silva, Mark, Thomson, Aileen, Wild, Sue, Yardumian, Pam, Evans, Carole, Gallentrae, Deena, Hobson, Emma, Jamieson, Stuart, Musgrave, Hannah, Rowett, Liz, Toscano, Jean, Bourne, Colin, Clapton, Jackie, Clayton, Carole, Dipple, Heather, Freire-Patino, Dawn, Grant, Janet, Gross, Diana, Hallam, Caroline, Middleton, Julia, Murch, Ann, Thompson, Catherine, Alusi, Sundus, Davies, Rhys, Foy, Kevin, Gerrans, Emily, Pate, Louise, Andrews, Thomasin, Dougherty, Andrew, Golding, Charlotte, Kavalier, Fred, Laing, Hana, Lashwood, Alison, Robertson, Dene, Ruddy, Deborah, Santhouse, Alastair, Whaite, Anna, Bruno, Stefania, Doherty, Karen, Haider, Salman, Hensman, Davina, Lahiri, Nayana, Novak, Marianne, Patel, Aakta, Rosser, Elisabeth, Taylor, Rachel, Warner, Thomas, Wild, Edward, Arran, Natalie, Bek, Judith, Craufurd, David, Hare, Marianne, Howard, Liz, Huson, Susan, Johnson, Liz, Jones, Mary, Murphy, Helen, Oughton, Emma, Partington-Jones, Lucy, Rogers, Dawn, Sollom, Andrea, Snowden, Julie, Stopford, Cheryl, Thompson, Jennifer, Trender-Gerhard, Iris, Verstraelen, Nichola, Westmoreland, Leann, Armstrong, Richard, Dixon, Kathryn, Nemeth, Andrea H, Siuda, Gill, Valentine, Ruth, Harrison, David, Hughes, Max, Parkinson, Andrew, Soltysiak, Beverley, Bandmann, Oliver, Bradbury, Alyson, Gill, Paul, Fairtlough, Helen, Fillingham, Kay, Foustanos, Isabella, Kazoka, Mbombe, O'Donovan, Kirsty, Taylor, Cat, Tidswell, Katherine, Quarrell, Oliver, Lau, Puay Ngoh, Pica, Emmanul, Tan, Louis, Moss, Davina J Hensman, Pardiñas, Antonio F, Langbehn, Douglas, Lo, Kitty, Leavitt, Blair R, Roos, Raymund, Durr, Alexandra, Mead, Simon, Holmans, Peter, and Tabrizi, Sarah J

Published
2017
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41. QuantumCumulants.jl: A Julia framework for generalized mean-field equations in open quantum systems

Author

David Plankensteiner, Christoph Hotter, and Helmut Ritsch

Subjects
Physics, QC1-999
Abstract

A full quantum mechanical treatment of open quantum systems via a Master equation is often limited by the size of the underlying Hilbert space. As an alternative, the dynamics can also be formulated in terms of systems of coupled differential equations for operators in the Heisenberg picture. This typically leads to an infinite hierarchy of equations for products of operators. A well-established approach to truncate this infinite set at the level of expectation values is to neglect quantum correlations of high order. This is systematically realized with a so-called cumulant expansion, which decomposes expectation values of operator products into products of a given lower order, leading to a closed set of equations. Here we present an open-source framework that fully automizes this approach: first, the equations of motion of operators up to a desired order are derived symbolically using predefined canonical commutation relations. Next, the resulting equations for the expectation values are expanded employing the cumulant expansion approach, where moments up to a chosen order specified by the user are included. Finally, a numerical solution can be directly obtained from the symbolic equations. After reviewing the theory we present the framework and showcase its usefulness in a few example problems.

Published
2022
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42. Mitochondrial Transplantation Enhances Phagocytic Function and Decreases Lipid Accumulation in Foam Cell Macrophages

Author

Soraya Játiva, Priscila Calle, Selene Torrico, Ángeles Muñoz, Miriam García, Ivet Martinez, Anna Sola, and Georgina Hotter

Subjects
macrophage, foam cell, 7-ketocholesterol, CPT1a, phagocytosis, inflammation, Biology (General), QH301-705.5
Abstract

Macrophages have mechanisms for eliminating cholesterol from cells. If excess cholesterol is not eliminated from the macrophages, then transformation into a foam cell may occur. Foam cells are a hallmark of the atherosclerotic lesions that contribute to the development and rupture of atherosclerotic plaques. Several in vitro and in vivo studies have shown changes in the macrophage phenotype and improved phagocytosis after the acquisition of functional mitochondria. However, the effect of mitochondrial transplantation on promoting phagocytosis and phenotypic changes in lipid-loaded macrophages leading to foam cells has not been studied. We aimed to prove that the transplantation of healthy mitochondria to highly cholesterol-loaded macrophages induces macrophage phagocytosis and reduces the macrophage shift towards foam cells. For this purpose, using a murine macrophage cell line, RAW264.7, we determined if mitochondria transplantation to 7-ketocholesterol (7-KC)-loaded macrophages reduced lipid accumulation and modified their phagocytic function. We evidenced that mitochondrial transplantation to 7-KC-loaded macrophages reestablished phagocytosis and reduced lipid content. In addition, CPT1a expression and anti-inflammatory cytokines were restored after mitochondrial transplantation. We have developed a potential therapeutic approach to restore foam cell functionality.

Published
2022
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45. A mutualistic bacterium rescues a green alga from an antagonist.

Author

Carrasco Flores, David, Hotter, Vivien, Trang Vuong, Yu Hou, Yuko Bando, Scherlach, Kirstin, Burgunter-Delamare, Bertille, Hermenau, Ron, Komor, Anna J., Aiyar, Prasad, Rose, Magdalena, Sasso, Severin, Arndt, Hans-Dieter, Hertweck, Christian, and Mittag, Maria

Subjects
*GREEN algae, *CHLAMYDOMONAS reinhardtii, *ALGAL growth, *ALGAE culture, *MODE shapes
Abstract

Photosynthetic protists, known as microalgae, are key contributors to primary production on Earth. Since early in evolution, they coexist with bacteria in nature, and their mode of interaction shapes ecosystems. We have recently shown that the bacterium Pseudomonas protegens acts algicidal on the microalga Chlamydomonas reinhardtii. It secretes a cyclic lipopeptide and a polyyne that deflagellate, blind, and lyse the algae [P. Aiyar et al., Nat. Commun. 8, 1756 (2017) and V. Hotter et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2107695118 (2021)]. Here, we report about the bacterium Mycetocola lacteus, which establishes a mutualistic relationship with C. reinhardtii and acts as a helper. While M. lacteus enhances algal growth, it receives methionine as needed organic sulfur and the vitamins B1, B3, and B5 from the algae. In tripartite cultures with the alga and the antagonistic bacterium P. protegens, M. lacteus aids the algae in surviving the bacterial attack. By combining synthetic natural product chemistry with high-resolution mass spectrometry and an algal Ca2+ reporter line, we found that M. lacteus rescues the alga from the antagonistic bacterium by cleaving the ester bond of the cyclic lipopeptide involved. The resulting linearized seco acid does not trigger a cytosolic Ca2+ homeostasis imbalance that leads to algal deflagellation. Thus, the algae remain motile, can swim away from the antagonistic bacteria and survive the attack. All three involved genera cooccur in nature. Remarkably, related species of Pseudomonas and Mycetocola also act antagonistically against C. reinhardtii or as helper bacteria in tripartite cultures. [ABSTRACT FROM AUTHOR]

Published
2024
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46. Multifocal motor neuropathy as a mimic of amyotrophic lateral sclerosis: Serum neurofilament light chain as a reliable diagnostic biomarker.

Author

Kleinveld, Vera E. A., Keritam, Omar, Horlings, Corinne G. C., Cetin, Hakan, Wanschitz, Julia, Hotter, Anna, Zirch, Laura S., Zimprich, Fritz, Topakian, Raffi, Müller, Petra, Oel, Dierk, Quasthoff, Stefan, Erdler, Marcus, Rauschka, Helmut, Grinzinger, Susanne, Jecel, Julia, Gaulhofer, Petra, Castek, Barbara, Stadler, Klaus, and Löscher, Wolfgang N.

Abstract

Introduction/Aims: The clinical presentation of multifocal motor neuropathy (MMN) may mimic early amyotrophic lateral sclerosis (ALS) with predominant lower motor neuron (LMN) involvement, posing a diagnostic challenge. Both diseases have specific treatments and prognoses, highlighting the importance of early diagnosis. The aim of this study was to assess the diagnostic value of serum neurofilament light chain (NfL) in differentiating MMN from LMN dominant ALS. Methods: NfL was measured in serum in n = 37 patients with MMN and n = 37 age‐ and sex‐matched patients with LMN dominant ALS, to determine the diagnostic accuracy. Clinical and demographic data were obtained at the time of NfL sampling. Results: Serum NfL concentration was significantly lower in MMN patients compared to ALS patients (mean 20.7 pg/mL vs. 59.4 pg/mL, p <.01). NfL demonstrated good diagnostic value in discriminating the two groups (AUC 0.985 [95% CI 0.963–1.000], sensitivity 94.6%, specificity 100%, cut‐off 44.00 pg/mL). Discussion: NfL could be a helpful tool in differentiating MMN from LMN dominant ALS in those patients in whom electrophysiological and clinical examinations remain inconclusive early in the diagnostic process. [ABSTRACT FROM AUTHOR]

Published
2024
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48. Microencapsulated macrophages releases conditioned medium able to prevent epithelial to mesenchymal transition

Author

Anna Sola, Laura Saenz del Burgo, Jesús Ciriza, Rosa Maria Hernandez, Gorka Orive, Jorge Martin Cordero, Priscila Calle, Jose Luis Pedraz, and Georgina Hotter

Subjects
cell microencapsulation, biomaterials, alginate, drug delivery, renal failure, mesenchymal stem cells, Therapeutics. Pharmacology, RM1-950
Abstract

Epithelial to mesenchymal transition (EMT) has emerged as a key process in the development of renal fibrosis. In fact, EMT-derived fibroblasts contribute to the progression of chronic renal disease. In addition, anti-inflammatory M2 macrophages have exhibited a great influence on renal fibrosis. However, because of the high impact that the inputs of different environmental cytokines have on their phenotype, macrophages can easily lose this property. We aim to known if microencapsulated macrophages on M2-inducing alginate matrices could preserve macrophage phenotype and thus release factors able to act on epithelial cells to prevent the epithelial differentiation towards mesenchymal cells. We reproduced an in vitro model of EMT by treating adipose-derived stem cells with all-trans retinoic acid (ATRA) and induced their transformation toward epithelia. Dedifferentiation of epithelial cells into a mesenchymal phenotype occurred when ATRA was retired, thus simulating EMT. Results indicate that induction of M2 phenotype by IL-10 addition in the alginate matrix produces anti-inflammatory cytokines and increases the metabolic activity and the viability of the encapsulated macrophages. The released conditioned medium modulates EMT and maintains healthy epithelial phenotype. This could be used for in vivo cell transplantation, or alternatively as an external releaser able to prevent epithelial to mesenchymal transformation for future anti-fibrotic therapies.

Published
2018
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50. Selection bias in clinical stroke trials depending on ability to consent

Author

Benjamin Hotter, Lena Ulm, Sarah Hoffmann, Mira Katan, Joan Montaner, Alejandro Bustamante, and Andreas Meisel

Subjects
Stroke, Clinical trial, Informed consent, Ethics, Methods, Selection bias, Neurology. Diseases of the nervous system, RC346-429
Abstract

Abstract Background Clinical trials are the hallmark of evidence-based medicine, but recruitment is often challenging, especially in stroke trials investigating patients not being able to give informed consent. In some nations, ethics committees will not approve of inclusion in a clinical study via consent of a legal representative. The ethical dilemma of including or excluding those patients has not been properly addressed, as there is little data on the effect of stroke characteristics on the ability to give informed consent. Methods To examine differences between patients able and unable to consent at inclusion to an acute stroke trial, we conducted a post-hoc analysis of monitoring records from a multicentric interventional trial. These records listed patients who gave informed consent by themselves and those who needed a legal representative to do so. This exemplary STRAWINSKI trial aimed at improving stroke outcome by biomarker-guided antibiotic treatment of stroke associated pneumonia and included patients within 40 h after stroke onset, suffering from MCA infarctions with an NIHSS score > 9 at admission. Standard descriptive and associative statistics were calculated to compare baseline characteristics and outcome measures between patients who were able to consent and those who were not. Results We identified the person giving consent in 228 out of 229 subjects. Patients with inability to consent were older (p

Published
2017
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