Search

Your search keyword '"Grunwald, Stephan"' showing total 32 results
Start Over Author "Grunwald, Stephan"
32 results on '"Grunwald, Stephan"'

1. Transcriptional reprogramming by mutated IRF4 in lymphoma

Author

Schleussner, Nikolai, Cauchy, Pierre, Franke, Vedran, Giefing, Maciej, Fornes, Oriol, Vankadari, Naveen, Assi, Salam A., Costanza, Mariantonia, Weniger, Marc A., Akalin, Altuna, Anagnostopoulos, Ioannis, Bukur, Thomas, Casarotto, Marco G., Damm, Frederik, Daumke, Oliver, Edginton-White, Benjamin, Gebhardt, J. Christof M., Grau, Michael, Grunwald, Stephan, Hansmann, Martin-Leo, Hartmann, Sylvia, Huber, Lionel, Kärgel, Eva, Lusatis, Simone, Noerenberg, Daniel, Obier, Nadine, Pannicke, Ulrich, Fischer, Anja, Reisser, Anja, Rosenwald, Andreas, Schwarz, Klaus, Sundararaj, Srinivasan, Weilemann, Andre, Winkler, Wiebke, Xu, Wendan, Lenz, Georg, Rajewsky, Klaus, Wasserman, Wyeth W., Cockerill, Peter N., Scheidereit, Claus, Siebert, Reiner, Küppers, Ralf, Grosschedl, Rudolf, Janz, Martin, Bonifer, Constanze, and Mathas, Stephan

Published
2023
Full Text
View/download PDF

2. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial

Author

Abe, Wakana, Adan De Varona, Tania, Adiatullina, Daria, Aguilar Zapata, Daniel, Ahlers, Kevin, Aimo, Carolina, Akere, Ayoade, Akimova, Elena, Alatorre Alexander, Jorge, Aldrich, Logan, Ali Garcia, Ismael, Ali García, Karim, Allison, Lee, Alonso Zuñiga, Rosa, Aloysius, Ivan, Altclas, Javier, Alvarisqueta, Andres, Antila, Martti, Anton, Camila, Árboix Alamo, Elisabet, Arora, Samir, Avilés Felix, Ramón Alejandro, Bakhtina, Natalya, Barbero-Becerra, Varenka, Barragan-Reyes, Armando, Barreira, Alejandro, Barrett, Mitchell, Beran, Jiri, Berki, Nikolett, Berki, Viktoria, Betten, Richard, Binelli, Claudia, Brunzová, Lenka, Bussolari, Cecilia, Byargeon, Karianna, Bytnar, Justyna, Camberos, Carlos, Campos Corzo, Pedro, Cannon, Grazia, Canovi, Valentina, Carla da Rosa, Simone, Moser, Ana Caroline, Carrera Rivas, Luis, Casas, Marcelo Martin, Castañeda-Méndez, Paulo, Cavalcante, Ana, Cherepova, Eugenia, Chermenskii, Alexei, Clark, Lauren, Codeluppi, Mauro, Coelho, Flavia, Contreras, Belinda, Cran, Alex, Dao, Taylor, Dharma, Chrisette, Di Castri, Cosimo, Diaz Balocchi, Victoria, Durán, Omar, Earl, Kara, Ellery, Adam, Endo, Tomoko, Everding, Andrea, Fischer, Rainald, Fonseca, Benedito, Franklin, Chelsea C., Franz, Susan-Beatrice, Fumagalli, Anna, Galindo-Amaya, Mauricio, Galli, Mariagiulia, Gerna, Laura, Gil Ureña, Karolly, Gomes Antila, Henrikki, Gomes Maricato, Laura Ines, Goncalvez, Gabriela, Gonzalez, Martin, González-Lama, Jesús, Granier, Stephen, Granier, Jacob, Grunwald, Stephan, Guardeño-Ropero, David, Guberti, Monica, Guduri, Sridhar, Guerrero García, Carolina, Haggiagi, Jehad, Hale, Kacie, Hayashi, Toshimasa, Hermes, Maiara, Hernandez Colin, Dante, Hirai, Yuji, Hojo, Masayuki, Homma, Tetsuya, Hour, Billy, Huber, Andreas, Iacovelli, Diego, Ishibashi, Noriomi, Iwabe, Yutaro, Izumi, Shinyu, Jessen, Arne, Jessen, Heiko, Jeudy, Wilner, Jiménez Marcos, Marta, Johnson, Rebecca, Juárez-Hernández, Eva, Kabasawa, Kiyomi, Kamińska, Katarzyna, Kawabe, Megumi, Kemp, Angela, Khmelnitskiy, Oleg, Klassen, Carina, Kobrynska, Olena, Koleckar, Pavel, Korn, Stephanie, Kornmann, Marc, Kostenko, Viktor, Kovalchuk, Evgenii, Kovalchuk, Yana, Kümmerle, Tim, Lachmund, Ulrike, Lammersmann, Kerstin, Lastebasse, Flávio, Lattuada, Ivana, Lauer, Felicitas, Lebed, Kyrylo, Lebed, Olga, Lecona-Garcia, Diego, Leoni, Maria Christina, Lima, Marina, Little, Raymond, Little, Holly, Lizardi-Díaz, Andrea, Lobo-Becker, Michele, Luppi, Francesco, Macias, Veronica, Maesaki, Shigefumi, Magnaghi, Cristiano, Mancini, Annalisa, Mazur, Stanisław, Melnikova, Tatiana, Menchaca, Sergio, Menendez-Perez, Ibrahim, Międlar, Ewa, Mizunuma, Shuuichi, Mochalova, Anastasiya, Mohamed, Mihad, Moll, Theresa, Montalvo, Camila, Mottola, Amber, Mück, Birgit, Mussi Brugnolli, Rebeca, Nanda, Akanksha, Neuner, Dörthe, Ngwueke, Agatha, Noe, Sebastian, Novacek, Martin, Nuzzolo-Shihadeh, Laura, Obiekwe, Emeka, Ocampo Gaytán, Isaias G., Ohmagari, Norio, Ohta, Shin, Onyewuchi, Ptuonye, Pankov, Iurii, Pedrosa, Maurício, Peré, Yael, Pereyra, Alejandro, Perez, Eliana, Perez-Alba, Eduardo, Perpiña Lozano, Paloma, Perrei, Tanya, Peterson, Dena, Pierroti, Ligia, Pineda-Cárdenas, Felipe, Plascencia Sanchez, Teresa, Poletti, Camila, Pomaranzi, Chiara, Portes, Lisette, Postel, Nils, Ramirez, Monica, Ramírez, Isabel, Ramirez-Baena, Miguel, Ramjee, Mahadev, Ratti, Giovanna, Reeve, Jackie, Reichert, Petr, Reichertová, Petra, Reyes Garcia, Edgar Alejandro, Ricardo, Celso, Rodríguez Rodríguez, Nicomedes, Roldán Sánchez, Jaun, Romero-Lopez, Matilde, Rosales, Tyrone, Rosales, Harvey, Roshan, Mohamed, Roshan, Simran, Rovere Querini, Patrizia, Rutter, Heather, Sachwani, Sadaf, Sagara, Hironori, Sakai, Jun, Samson, Nina, Sánchez Mijangos, José Héctor, Sánchez, Liliana, Sánchez-González, Ana, Sandford, Micko, Santana, Laura, Santos de Carvalho, Felipe, Sasao, Reiko, Sato, Lubna, Scheuermann, Elizabeth, Schmidt, Olaf, Seki, Masafumi, Shaikh, Safia, Shimada, Daishi, Shinkai, Masaharu, Shinoda, Masahiro, Smith, Jackie, Solorzano, Fernando, Soncini, Silvia, Soregine, Katalin, Sosa, Erica, Sowade, Olalekan, Špinková, Veronika, Staniford, Ruth, Steigemann, Iska, Steiner, Vivien, Strelkov, Vladimir, Suárez Pineda, Cintya R., Suenaga, Hiroki, Suzaki, Shintaro, Swayze, Hannah, Tada, Yuji, Takeshita, Yuichiro, Takiguchi, Yasuo, Tanaka, Akihiko, Tarumoto, Norihito, Tatarintseva, Albina, Taubert, Michelle, Terenya, Elizaveta, Tinoco, César, Tomiyasu, Tomohiro, Torres-Vidal, Gladys, Trejo-Aguiar, Gabriela, Tsushima, Kenji, Tunstall, Emma, Turrà, Caterina, Valdes, Yoandy, Valencia Castro, Nelly, Visconti, Guilherme, Vitali, Giordano, Vutikullird, Apinya, Watti, Jezdancher, Werth, Doreen, Wilson, Cheyanne, Wilson, Philippe, Workman, Amy, Wörle, Pamela, Wyen, Christoph, Yamaguchi, Yoshiko, Yamamoto, Kei, Montgomery, Hugh, Hobbs, F D Richard, Padilla, Francisco, Arbetter, Douglas, Templeton, Alison, Seegobin, Seth, Kim, Kenneth, Campos, Jesus Abraham Simón, Arends, Rosalinda H, Brodek, Bryan H, Brooks, Dennis, Garbes, Pedro, Jimenez, Julieta, Koh, Gavin C K W, Padilla, Kelly W, Streicher, Katie, Viani, Rolando M, Alagappan, Vijay, Pangalos, Menelas N, and Esser, Mark T

Published
2022
Full Text
View/download PDF

3. SARS-CoV-2 seroprevalence among people living with HIV in the German HIV-1 Seroconverter Cohort, 2020–2022.

Author

Hohn, Oliver, Meixenberger, Karolin, Volkwein, Alexander, Körner, Kyra, Icli, Suheda, Koppe, Uwe, Hower, Martin, Bremer, Viviane, Gunsenheimer-Bartmeyer, Barbara, Bannert, Norbert, Knechten, Heribert, Panstruga, Petra, Schühlen, Helmut, Isner, Caroline, Wesselmann, Hans, Schürmann, Dirk, Bohr, Ulrich, Jessen, Heiko, Jessen, Arne B., and Grunwald, Stephan

Subjects
COVID-19 pandemic, HIV-positive persons, SEROPREVALENCE, MIXED infections, SARS-CoV-2
Abstract

Objectives: People living with HIV (PLWH) are a risk group for severe symptoms and higher mortality during COVID-19. We analyzed the dynamic rise of SARS-CoV-2 seroprevalence induced by coinfections and vaccinations in PLWH in the first three years of the pandemic in Germany and compared it with corresponding data available for the general population. Methods: Each month on average 93 blood samples from the German HIV-1 Seroconverter Cohort, a prospective longitudinal multicenter study that includes PLWH whose date of seroconversion is well defined, were received. The samples from 1569 PLWH were tested for the presence of anti-S1 and if positive, also for anti-N antibodies. Results: In 2020 the number of anti-S1 positive cases/month was between 0.0 and 6.9% (average 1.6%). Since then the anti-S1 prevalence increased reaching already 35% (33/94) in May 2021. At that time 3.2% of the cases were also anti-N positive. In 2022 the average anti-S1 seroprevalence reached 97.5%. In the vaccination era a positive anti-N response was associated with a younger age and females were overrepresented among anti-S1/anti-N negative samples (assuming no vaccination or infection). Conclusions: The average 1.6% anti-S1 seroprevalence in the cohort in 2020 was comparable to that in the general population (1.3%). The increase in anti-S1 seroprevalence in the first half of 2021 occurred slightly earlier. This increase was likely caused by the prioritization of PLWH at the early stage of the vaccination campaign and by infections during the third wave of the pandemic. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

5. Monogenic variants in dystonia: an exome-wide sequencing study

Author

Zech, Michael, Jech, Robert, Boesch, Sylvia, Škorvánek, Matej, Weber, Sandrina, Wagner, Matias, Zhao, Chen, Jochim, Angela, Necpál, Ján, Dincer, Yasemin, Vill, Katharina, Distelmaier, Felix, Stoklosa, Malgorzata, Krenn, Martin, Grunwald, Stephan, Bock-Bierbaum, Tobias, Fečíková, Anna, Havránková, Petra, Roth, Jan, Příhodová, Iva, Adamovičová, Miriam, Ulmanová, Olga, Bechyně, Karel, Danhofer, Pavlína, Veselý, Branislav, Haň, Vladimír, Pavelekova, Petra, Gdovinová, Zuzana, Mantel, Tobias, Meindl, Tobias, Sitzberger, Alexandra, Schröder, Sebastian, Blaschek, Astrid, Roser, Timo, Bonfert, Michaela V, Haberlandt, Edda, Plecko, Barbara, Leineweber, Birgit, Berweck, Steffen, Herberhold, Thomas, Langguth, Berthold, Švantnerová, Jana, Minár, Michal, Ramos-Rivera, Gonzalo Alonso, Wojcik, Monica H, Pajusalu, Sander, Õunap, Katrin, Schatz, Ulrich A, Pölsler, Laura, Milenkovic, Ivan, Laccone, Franco, Pilshofer, Veronika, Colombo, Roberto, Patzer, Steffi, Iuso, Arcangela, Vera, Julia, Troncoso, Monica, Fang, Fang, Prokisch, Holger, Wilbert, Friederike, Eckenweiler, Matthias, Graf, Elisabeth, Westphal, Dominik S, Riedhammer, Korbinian M, Brunet, Theresa, Alhaddad, Bader, Berutti, Riccardo, Strom, Tim M, Hecht, Martin, Baumann, Matthias, Wolf, Marc, Telegrafi, Aida, Person, Richard E, Zamora, Francisca Millan, Henderson, Lindsay B, Weise, David, Musacchio, Thomas, Volkmann, Jens, Szuto, Anna, Becker, Jessica, Cremer, Kirsten, Sycha, Thomas, Zimprich, Fritz, Kraus, Verena, Makowski, Christine, Gonzalez-Alegre, Pedro, Bardakjian, Tanya M, Ozelius, Laurie J, Vetro, Annalisa, Guerrini, Renzo, Maier, Esther, Borggraefe, Ingo, Kuster, Alice, Wortmann, Saskia B, Hackenberg, Annette, Steinfeld, Robert, Assmann, Birgit, Staufner, Christian, Opladen, Thomas, Růžička, Evžen, Cohn, Ronald D, Dyment, David, Chung, Wendy K, Engels, Hartmut, Ceballos-Baumann, Andres, Ploski, Rafal, Daumke, Oliver, Haslinger, Bernhard, Mall, Volker, Oexle, Konrad, and Winkelmann, Juliane

Published
2020
Full Text
View/download PDF

8. A new type of transcriptional reprogramming by an IRF4 mutation in lymphoma

Author

Schleussner, Nikolai, primary, Cauchy, Pierre, additional, Franke, Vedran, additional, Giefing, Maciej, additional, Fornes, Oriol, additional, Vankadari, Naveen, additional, Assi, Salam, additional, Costanza, Mariantonia, additional, Weniger, Marc A., additional, Akalin, Altuna, additional, Anagnostopoulos, Ioannis, additional, Bukur, Thomas, additional, Casarotto, Marco G., additional, Damm, Frederik, additional, Daumke, Oliver, additional, Edginton-White, Benjamin, additional, Gebhardt, J. Christof M., additional, Grau, Michael, additional, Grunwald, Stephan, additional, Hansmann, Martin-Leo, additional, Hartmann, Sylvia, additional, Huber, Lionel, additional, Kärgel, Eva, additional, Lusatis, Simone, additional, Noerenberg, Daniel, additional, Obier, Nadine, additional, Pannicke, Ulrich, additional, Pfaus, Anja, additional, Reisser, Anja, additional, Rosenwald, Andreas, additional, Schwarz, Klaus, additional, Sundararaj, Srinivasan, additional, Weilemann, Andre, additional, Winkler, Wiebke, additional, Xu, Wendan, additional, Lenz, Georg, additional, Rajewsky, Klaus, additional, Wasserman, Wyeth W., additional, Cockerill, Peter N., additional, Scheidereit, Claus, additional, Siebert, Reiner, additional, Küppers, Ralf, additional, Grosschedl, Rudolf, additional, Janz, Martin, additional, Bonifer, Constanze, additional, and Mathas, Stephan, additional

Published
2022
Full Text
View/download PDF

9. Covid-19 triage in the emergency department 2.0: how analytics and AI transform a human-made algorithm for the prediction of clinical pathways

Author

Bartenschlager, Christina C., Grieger, Milena, Erber, Johanna, Neidel, Tobias, Borgmann, Stefan, Vehreschild, Jörg J., Steinbrecher, Markus, Rieg, Siegbert, Stecher, Melanie, Dhillon, Christine, Ruethrich, Maria M., Jakob, Carolin E. M., Hower, Martin, Heller, Axel R., Vehreschild, Maria, Wyen, Christoph, Messmann, Helmut, Piepel, Christiane, Brunner, Jens O., Hanses, Frank, Römmele, Christoph, Spinner, Christoph, Ruethrich, Maria Madeleine, Lanznaster, Julia, Wille, Kai, Tometten, Lukas, Dolff, Sebastian, von Bergwelt-Baildon, Michael, Merle, Uta, Rothfuss, Katja, Isberner, Nora, Jung, Norma, Göpel, Siri, vom Dahl, Juergen, Degenhardt, Christian, Strauss, Richard, Gruener, Beate, Eberwein, Lukas, Hellwig, Kerstin, Rauschning, Dominic, Neufang, Mark, Westhoff, Timm, Raichle, Claudia, Akova, Murat, Jensen, Bjoern-Erik, Schubert, Joerg, Grunwald, Stephan, Friedrichs, Anette, Trauth, Janina, de With, Katja, Guggemos, Wolfgang, Kielstein, Jan, Heigener, David, Markart, Philipp, Bals, Robert, Stieglitz, Sven, Voigt, Ingo, Taubel, Jorg, and Milovanovic, Milena

Subjects
ddc:610
Abstract

The Covid-19 pandemic has pushed many hospitals to their capacity limits. Therefore, a triage of patients has been discussed controversially primarily through an ethical perspective. The term triage contains many aspects such as urgency of treatment, severity of the disease and pre-existing conditions, access to critical care, or the classification of patients regarding subsequent clinical pathways starting from the emergency department. The determination of the pathways is important not only for patient care, but also for capacity planning in hospitals. We examine the performance of a human-made triage algorithm for clinical pathways which is considered a guideline for emergency departments in Germany based on a large multicenter dataset with over 4,000 European Covid-19 patients from the LEOSS registry. We find an accuracy of 28 percent and approximately 15 percent sensitivity for the ward class. The results serve as a benchmark for our extensions including an additional category of palliative care as a new label, analytics, AI, XAI, and interactive techniques. We find significant potential of analytics and AI in Covid-19 triage regarding accuracy, sensitivity, and other performance metrics whilst our interactive human-AI algorithm shows superior performance with approximately 73 percent accuracy and up to 76 percent sensitivity. The results are independent of the data preparation process regarding the imputation of missing values or grouping of comorbidities. In addition, we find that the consideration of an additional label palliative care does not improve the results.

Published
2023

10. Efficacy and safety of intramuscular administration of tixagevimab–cilgavimab for early outpatient treatment of COVID-19 (TACKLE): a phase 3, randomised, double-blind, placebo-controlled trial

Author

Montgomery, Hugh, primary, Hobbs, F D Richard, additional, Padilla, Francisco, additional, Arbetter, Douglas, additional, Templeton, Alison, additional, Seegobin, Seth, additional, Kim, Kenneth, additional, Campos, Jesus Abraham Simón, additional, Arends, Rosalinda H, additional, Brodek, Bryan H, additional, Brooks, Dennis, additional, Garbes, Pedro, additional, Jimenez, Julieta, additional, Koh, Gavin C K W, additional, Padilla, Kelly W, additional, Streicher, Katie, additional, Viani, Rolando M, additional, Alagappan, Vijay, additional, Pangalos, Menelas N, additional, Esser, Mark T, additional, Abe, Wakana, additional, Adan De Varona, Tania, additional, Adiatullina, Daria, additional, Aguilar Zapata, Daniel, additional, Ahlers, Kevin, additional, Aimo, Carolina, additional, Akere, Ayoade, additional, Akimova, Elena, additional, Alatorre Alexander, Jorge, additional, Aldrich, Logan, additional, Ali Garcia, Ismael, additional, Ali García, Karim, additional, Allison, Lee, additional, Alonso Zuñiga, Rosa, additional, Aloysius, Ivan, additional, Altclas, Javier, additional, Alvarisqueta, Andres, additional, Antila, Martti, additional, Anton, Camila, additional, Árboix Alamo, Elisabet, additional, Arora, Samir, additional, Avilés Felix, Ramón Alejandro, additional, Bakhtina, Natalya, additional, Barbero-Becerra, Varenka, additional, Barragan-Reyes, Armando, additional, Barreira, Alejandro, additional, Barrett, Mitchell, additional, Beran, Jiri, additional, Berki, Nikolett, additional, Berki, Viktoria, additional, Betten, Richard, additional, Binelli, Claudia, additional, Brunzová, Lenka, additional, Bussolari, Cecilia, additional, Byargeon, Karianna, additional, Bytnar, Justyna, additional, Camberos, Carlos, additional, Campos Corzo, Pedro, additional, Cannon, Grazia, additional, Canovi, Valentina, additional, Carla da Rosa, Simone, additional, Moser, Ana Caroline, additional, Carrera Rivas, Luis, additional, Casas, Marcelo Martin, additional, Castañeda-Méndez, Paulo, additional, Cavalcante, Ana, additional, Cherepova, Eugenia, additional, Chermenskii, Alexei, additional, Clark, Lauren, additional, Codeluppi, Mauro, additional, Coelho, Flavia, additional, Contreras, Belinda, additional, Cran, Alex, additional, Dao, Taylor, additional, Dharma, Chrisette, additional, Di Castri, Cosimo, additional, Diaz Balocchi, Victoria, additional, Durán, Omar, additional, Earl, Kara, additional, Ellery, Adam, additional, Endo, Tomoko, additional, Everding, Andrea, additional, Fischer, Rainald, additional, Fonseca, Benedito, additional, Franklin, Chelsea C., additional, Franz, Susan-Beatrice, additional, Fumagalli, Anna, additional, Galindo-Amaya, Mauricio, additional, Galli, Mariagiulia, additional, Gerna, Laura, additional, Gil Ureña, Karolly, additional, Gomes Antila, Henrikki, additional, Gomes Maricato, Laura Ines, additional, Goncalvez, Gabriela, additional, Gonzalez, Martin, additional, González-Lama, Jesús, additional, Granier, Stephen, additional, Granier, Jacob, additional, Grunwald, Stephan, additional, Guardeño-Ropero, David, additional, Guberti, Monica, additional, Guduri, Sridhar, additional, Guerrero García, Carolina, additional, Haggiagi, Jehad, additional, Hale, Kacie, additional, Hayashi, Toshimasa, additional, Hermes, Maiara, additional, Hernandez Colin, Dante, additional, Hirai, Yuji, additional, Hojo, Masayuki, additional, Homma, Tetsuya, additional, Hour, Billy, additional, Huber, Andreas, additional, Iacovelli, Diego, additional, Ishibashi, Noriomi, additional, Iwabe, Yutaro, additional, Izumi, Shinyu, additional, Jessen, Arne, additional, Jessen, Heiko, additional, Jeudy, Wilner, additional, Jiménez Marcos, Marta, additional, Johnson, Rebecca, additional, Juárez-Hernández, Eva, additional, Kabasawa, Kiyomi, additional, Kamińska, Katarzyna, additional, Kawabe, Megumi, additional, Kemp, Angela, additional, Khmelnitskiy, Oleg, additional, Klassen, Carina, additional, Kobrynska, Olena, additional, Koleckar, Pavel, additional, Korn, Stephanie, additional, Kornmann, Marc, additional, Kostenko, Viktor, additional, Kovalchuk, Evgenii, additional, Kovalchuk, Yana, additional, Kümmerle, Tim, additional, Lachmund, Ulrike, additional, Lammersmann, Kerstin, additional, Lastebasse, Flávio, additional, Lattuada, Ivana, additional, Lauer, Felicitas, additional, Lebed, Kyrylo, additional, Lebed, Olga, additional, Lecona-Garcia, Diego, additional, Leoni, Maria Christina, additional, Lima, Marina, additional, Little, Raymond, additional, Little, Holly, additional, Lizardi-Díaz, Andrea, additional, Lobo-Becker, Michele, additional, Luppi, Francesco, additional, Macias, Veronica, additional, Maesaki, Shigefumi, additional, Magnaghi, Cristiano, additional, Mancini, Annalisa, additional, Mazur, Stanisław, additional, Melnikova, Tatiana, additional, Menchaca, Sergio, additional, Menendez-Perez, Ibrahim, additional, Międlar, Ewa, additional, Mizunuma, Shuuichi, additional, Mochalova, Anastasiya, additional, Mohamed, Mihad, additional, Moll, Theresa, additional, Montalvo, Camila, additional, Mottola, Amber, additional, Mück, Birgit, additional, Mussi Brugnolli, Rebeca, additional, Nanda, Akanksha, additional, Neuner, Dörthe, additional, Ngwueke, Agatha, additional, Noe, Sebastian, additional, Novacek, Martin, additional, Nuzzolo-Shihadeh, Laura, additional, Obiekwe, Emeka, additional, Ocampo Gaytán, Isaias G., additional, Ohmagari, Norio, additional, Ohta, Shin, additional, Onyewuchi, Ptuonye, additional, Pankov, Iurii, additional, Pedrosa, Maurício, additional, Peré, Yael, additional, Pereyra, Alejandro, additional, Perez, Eliana, additional, Perez-Alba, Eduardo, additional, Perpiña Lozano, Paloma, additional, Perrei, Tanya, additional, Peterson, Dena, additional, Pierroti, Ligia, additional, Pineda-Cárdenas, Felipe, additional, Plascencia Sanchez, Teresa, additional, Poletti, Camila, additional, Pomaranzi, Chiara, additional, Portes, Lisette, additional, Postel, Nils, additional, Ramirez, Monica, additional, Ramírez, Isabel, additional, Ramirez-Baena, Miguel, additional, Ramjee, Mahadev, additional, Ratti, Giovanna, additional, Reeve, Jackie, additional, Reichert, Petr, additional, Reichertová, Petra, additional, Reyes Garcia, Edgar Alejandro, additional, Ricardo, Celso, additional, Rodríguez Rodríguez, Nicomedes, additional, Roldán Sánchez, Jaun, additional, Romero-Lopez, Matilde, additional, Rosales, Tyrone, additional, Rosales, Harvey, additional, Roshan, Mohamed, additional, Roshan, Simran, additional, Rovere Querini, Patrizia, additional, Rutter, Heather, additional, Sachwani, Sadaf, additional, Sagara, Hironori, additional, Sakai, Jun, additional, Samson, Nina, additional, Sánchez Mijangos, José Héctor, additional, Sánchez, Liliana, additional, Sánchez-González, Ana, additional, Sandford, Micko, additional, Santana, Laura, additional, Santos de Carvalho, Felipe, additional, Sasao, Reiko, additional, Sato, Lubna, additional, Scheuermann, Elizabeth, additional, Schmidt, Olaf, additional, Seki, Masafumi, additional, Shaikh, Safia, additional, Shimada, Daishi, additional, Shinkai, Masaharu, additional, Shinoda, Masahiro, additional, Smith, Jackie, additional, Solorzano, Fernando, additional, Soncini, Silvia, additional, Soregine, Katalin, additional, Sosa, Erica, additional, Sowade, Olalekan, additional, Špinková, Veronika, additional, Staniford, Ruth, additional, Steigemann, Iska, additional, Steiner, Vivien, additional, Strelkov, Vladimir, additional, Suárez Pineda, Cintya R., additional, Suenaga, Hiroki, additional, Suzaki, Shintaro, additional, Swayze, Hannah, additional, Tada, Yuji, additional, Takeshita, Yuichiro, additional, Takiguchi, Yasuo, additional, Tanaka, Akihiko, additional, Tarumoto, Norihito, additional, Tatarintseva, Albina, additional, Taubert, Michelle, additional, Terenya, Elizaveta, additional, Tinoco, César, additional, Tomiyasu, Tomohiro, additional, Torres-Vidal, Gladys, additional, Trejo-Aguiar, Gabriela, additional, Tsushima, Kenji, additional, Tunstall, Emma, additional, Turrà, Caterina, additional, Valdes, Yoandy, additional, Valencia Castro, Nelly, additional, Visconti, Guilherme, additional, Vitali, Giordano, additional, Vutikullird, Apinya, additional, Watti, Jezdancher, additional, Werth, Doreen, additional, Wilson, Cheyanne, additional, Wilson, Philippe, additional, Workman, Amy, additional, Wörle, Pamela, additional, Wyen, Christoph, additional, Yamaguchi, Yoshiko, additional, and Yamamoto, Kei, additional

Published
2022
Full Text
View/download PDF

11. Clinical characteristics of monkeypox virus infections among men with and without HIV : A large outbreak cohort in Germany

Author

Hoffmann, Christian, primary, Jessen, Heiko, additional, Wyen, Christoph, additional, Grunwald, Stephan, additional, Noe, Sebastian, additional, Teichmann, Jörn, additional, Krauss, Anja‐Sophie, additional, Kolarikal, Henning, additional, Scholten, Stefan, additional, Schuler, Christoph, additional, Bickel, Markus, additional, Roll, Clemens, additional, Kreckel, Peter, additional, Köppe, Siegfried, additional, Straub, Matthias, additional, Klausen, Gerd, additional, Lenz, Johannes, additional, Esser, Stefan, additional, Jensen, Björn, additional, Rausch, Michael, additional, Unger, Stefan, additional, Pauli, Ramona, additional, Härter, Georg, additional, Müller, Matthias, additional, Masuhr, Anja, additional, Schäfer, Guido, additional, Seybold, Ulrich, additional, Schellberg, Sven, additional, Schneider, Jochen, additional, Monin, Malte Benedikt, additional, Wolf, Eva, additional, Spinner, Christoph D., additional, and Boesecke, Christoph, additional

Published
2022
Full Text
View/download PDF

12. Clinical characteristics of monkeypox virus infections among men with and without HIV: A large outbreak cohort in Germany.

Author

Hoffmann, Christian, Jessen, Heiko, Wyen, Christoph, Grunwald, Stephan, Noe, Sebastian, Teichmann, Jörn, Krauss, Anja‐Sophie, Kolarikal, Henning, Scholten, Stefan, Schuler, Christoph, Bickel, Markus, Roll, Clemens, Kreckel, Peter, Köppe, Siegfried, Straub, Matthias, Klausen, Gerd, Lenz, Johannes, Esser, Stefan, Jensen, Björn, and Rausch, Michael

Subjects
DIAGNOSIS of HIV infections, MEN, MONKEYPOX, RETROSPECTIVE studies, ACQUISITION of data, SEVERITY of illness index, EPIDEMICS, MEDICAL records, DESCRIPTIVE statistics, MEN who have sex with men, COMORBIDITY, SYMPTOMS
Abstract

Background: Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV. Methods: This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). Results: By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre‐exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20–67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV. Conclusions: In this preliminary cohort analysis from a current large outbreak among MSM in Germany, the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed. [ABSTRACT FROM AUTHOR]

Published
2023
Full Text
View/download PDF

14. Neurological symptoms and complications in predominantly hospitalized COVID-19 patients: Results of the European multinational Lean European Open Survey on SARS-Infected Patients (LEOSS)

Author

Kleineberg, Nina N., Knauss, Samuel, Gülke, Eileen, Pinnschmidt, Hans O., Jakob, Carolin E. M., Lingor, Paul, Hellwig, Kerstin, Berthele, Achim, Höglinger, Günter, Fink, Gereon R., Endres, Matthias, Gerloff, Christian, Klein, Christine, Stecher, Melanie, Classen, Annika Y., Rieg, Siegbert, Borgmann, Stefan, Hanses, Frank, Haselberger, Martina, Merle, Uta, Dolff, Sebastian, Degenhardt, Christian, Jensen, Björn-Erik O., Vehreschild, Maria J. G. T., Erber, Johanna, Franke, Christiana, Warnke, Clemens, Spinner, Christoph, Lanzster, Julia, Jensen, Björn, Vehreschild, Maria, Hower, Martin, Rüthrich, Maria Madeleine, Rothfuss, Katja, Piepel, Christiane, Wyen, Christopf, Römmele, Christoph, Eberwein, Lukas, Käding, Kadja, Wille, Kai, Haake, Hendrik, Voigt, Ingo, Tometten, Lukas, Neufang, Mark, Jung, Norma, Schultheis, Beate, Raichle, Claudia, von Bergwelt-Baildon, Michael, Göpel, Siri, Strauß, Richard, Rauschning, Dominic, Isberner, Nora, Walter, Lorenz, Milovanovic, Mile, D'Hooghe, Marie, Grunwald, Stephan, Akova, Murat, Markart, Philipp, Grüner, Beate, Kielstein, Jan, Guggemos, Wolfgang, Trauth, Janina, Heigener, David, Beutel, Gernot, Gramatniece, Alise, de With, Katja, Bals, Robert, Friedrichs, Anette, Röseler, Stefani, Müller-Jörger, Gabriele, Ritter, Annika, Vehreschild, Jörg Janne, Pilgram, Lisa, Schons, Max, de Miranda, Susana Nunes, Schulze, Nick, Fuhrmann, Sandra, Claßen, Annika, Franke, Bernd, Praßer, Fabian, Lablans, Martin, and LEOSS Study Group

Subjects
medicine.medical_specialty, Nausea, medicine.medical_treatment, Medizin, Disease, SARS‐CoV‐2, COVID‐19, Internal medicine, medicine, Extracorporeal membrane oxygenation, Humans, Clinical significance, ddc:610, Stroke, business.industry, SARS-CoV-2, Headache, COVID-19, Neurodegenerative Diseases, Odds ratio, Original Articles, medicine.disease, Neurology, neurological manifestations, Delirium, Original Article, Neurology (clinical), medicine.symptom, Complication, business
Abstract

Background and purpose During acute coronavirus disease 2019 (COVID‐19) infection, neurological signs, symptoms and complications occur. We aimed to assess their clinical relevance by evaluating real‐world data from a multinational registry. Methods We analyzed COVID‐19 patients from 127 centers, diagnosed between January 2020 and February 2021, and registered in the European multinational LEOSS (Lean European Open Survey on SARS‐Infected Patients) registry. The effects of prior neurological diseases and the effect of neurological symptoms on outcome were studied using multivariate logistic regression. Results A total of 6537 COVID‐19 patients (97.7% PCR‐confirmed) were analyzed, of whom 92.1% were hospitalized and 14.7% died. Commonly, excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%) were reported. In patients with a complicated or critical disease course (53%) the most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (ICB; 2.2%). ICB peaked in the critical disease phase (5%) and was associated with the administration of anticoagulation and extracorporeal membrane oxygenation (ECMO). Excessive tiredness (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.20–1.68) and prior neurodegenerative diseases (OR 1.32, 95% CI 1.07–1.63) were associated with an increased risk of an unfavorable outcome. Prior cerebrovascular and neuroimmunological diseases were not associated with an unfavorable short‐term outcome of COVID‐19. Conclusion Our data on mostly hospitalized COVID‐19 patients show that excessive tiredness or prior neurodegenerative disease at first presentation increase the risk of an unfavorable short‐term outcome. ICB in critical COVID‐19 was associated with therapeutic interventions, such as anticoagulation and ECMO, and thus may be an indirect complication of a life‐threatening systemic viral infection., We retrospectively analyzed data from 6537 predominantly hospitalized COVID‐19 patients registered in the European multinational Lean European Open Survey on SARS‐Infected Patients (LEOSS) registry between January 2020 and February 2021. Common neurological symptoms were excessive tiredness (28.0%), headache (18.5%), nausea/emesis (16.6%), muscular weakness (17.0%), impaired sense of smell (9.0%) and taste (12.8%), and delirium (6.7%). Most frequent neurological complications were ischemic stroke (1.0%) and intracerebral bleeding (2.2%) in patients with a complicated or critical disease course. Excessive tiredness (odds ratio [OR] 1.42) and prior neurodegenerative disease (OR 1.32) were associated with an increased risk of an unfavorable outcome.

Published
2021

15. Failure on voxilaprevir, velpatasvir, sofosbuvir and efficacy of rescue therapy

Author

Dietz, Julia, primary, Di Maio, Velia Chiara, additional, de Salazar, Adolfo, additional, Merino, Dolores, additional, Vermehren, Johannes, additional, Paolucci, Stefania, additional, Kremer, Andreas E., additional, Lara, Magdalena, additional, Pardo, Maria Rodriguez, additional, Zoller, Heinz, additional, Degasperi, Elisabetta, additional, Peiffer, Kai-Henrik, additional, Sighinolfi, Laura, additional, Téllez, Francisco, additional, Graf, Christiana, additional, Ghisetti, Valeria, additional, Schreiber, Jonas, additional, Fernández-Fuertes, Elisa, additional, Boglione, Lucio, additional, Muñoz-Medina, Leopoldo, additional, Stauber, Rudolf, additional, Gennari, William, additional, Figueruela, Blanca, additional, Santos, Jesús, additional, Lampertico, Pietro, additional, Zeuzem, Stefan, additional, Ceccherini-Silberstein, Francesca, additional, García, Federico, additional, Sarrazin, Christoph, additional, Aghemo, Alessio, additional, Allice, Tiziano, additional, Andreoni, Massimo, additional, Angelico, Mario, additional, Baldanti, Fausto, additional, Barbaliscia, Silvia, additional, Bertoli, Ada, additional, Borghi, Vanni, additional, Calvaruso, Vincenza, additional, Cariti, Giuseppe, additional, Craxì, Antonio, additional, Francioso, Simona, additional, Perno, Carlo Federico, additional, Pozzoni, Pietro, additional, Toniutto, Pier Luigi, additional, Zazzi, Maurizio, additional, Pérez, Ana Belén, additional, Quilez, Cristina, additional, Alados, Juan Carlos, additional, Cabezas, Joaquin, additional, Ruiz-Tapiador, Juan Ignacio Arenas, additional, Jimenez, Miguel, additional, Pascasio-Acevedo, Juan Manuel, additional, Rodriguez, Manuel Alberto Macias, additional, Zabal, Jose Miguel Rosales, additional, Deltoro, Miguel García, additional, Sapiña, Ana María Martinez, additional, Fuentes, Ana, additional, Chueca, Natalia, additional, Berg, Christoph P., additional, Herrmann, Andreas, additional, Stallmach, Andreas, additional, Port, Kerstin, additional, Katja Deterding, M., additional, Wedermeyer, Heiner, additional, Cornberg, Markus, additional, Manns, Michael P., additional, Moreno, Christophe, additional, Wiesch, Julian Schulze zur, additional, Piecha, Felix, additional, Lohse, Ansgar, additional, Siebler, Jürgen, additional, Kordecki, Nikolaus, additional, Magenta, Lorenzo, additional, Jäger, Burkhard, additional, Möller, Hjördis, additional, Heyne, Renate, additional, Beyer, Tomas, additional, Grunwald, Stephan, additional, Baumgarten, Axels, additional, Jägel-Guedes, Eva, additional, and Schmidt, Wolfgang, additional

Published
2021
Full Text
View/download PDF

16. Structural and functional characterization of the N-terminal acetyltransferase NatC

Author

Grunwald, Stephan

Subjects
post-translational modification, Naa30 Naa35 Naa38 complex, ribosome-binding, enzyme kinetics, structural biology, 500 Naturwissenschaften und Mathematik::570 Biowissenschaften, Biologie::572 Biochemie, x-ray crystallography, Michaelis-Menten kinetics, Nα-acetyltransferase
Abstract

N-terminal acetylation is one of the most abundant protein modifications in eukaryotes, affecting an estimated 80% of all human proteins and has diverse implications for the stability, folding, half-life, interaction ability and subcellular targeting of the acetylated protein. This irreversible modification is catalysed by a highly conserved family of N-terminal acetyltransferases (NATs). Eight different NATs have been described in eukaryotes so far, which differ in their substrate specificity, their subunit composition and their subcellular localization. The only major eukaryotic NAT that has thus far eluded structural determination, is the heterotrimeric NatC complex, consisting of the catalytic subunit Naa30 and the two auxiliary subunits Naa35 and Naa38. In this work, five structures of the Saccharomyces cerevisiae NatC complex in the absence and presence of CoA and two peptide substrates are presented. The structural analyses show that the large auxiliary subunit Naa35 is the central assembly hub of NatC that forms extensive interactions with the catalytic subunit Naa30 and the small auxiliary subunit Naa38. Thus, Naa35 wraps around Naa30 in an open ring-like tertiary structure and its N-terminus embraces Naa38 around almost its entire circumference. Most strikingly, the architecture of the NatC complex completely differs from that of the heterodimeric NAT complexes NatA and NatB. Most importantly, the position of the NatC auxiliary subunit relative to the catalytic subunit shows the exact opposite arrangement seen in the NatA and NatB auxiliary subunits. NatC structures in complex with two cognate peptides corresponding to the N-terminus of yeast Arl3 and the viral Gag protein provided structural insight into NatC substrate specificity and show that the peptides are bound in an elongated hydrophobic substrate binding pocket that is formed in between subunits Naa30 and Naa35. Binding of the high-affinity Gag peptide, but not of the Arl3 peptide, resulted in large ligand-induced structural rearrangements of the substrate binding loop. Accordingly, in acetyltransferase assays, the Gag peptide displayed a 10-fold increased catalytic efficiency compared to Arl3. Based on a comprehensive structure-function study, a catalytic mechanism for the NatC complex was proposed. Finally, by comparing the NatC structure to the ribosome-bound NatA structure and supported by structure-based mutagenesis, a model for the ribosome-bound NatC complex is presented., Die N-terminale Acetylierung ist eine der am häufigsten vorkommenden Proteinmodifizierungen in Eukaryoten, welche geschätzte 80% aller humanen Proteine betrifft und weitreichende Auswirkungen auf die Stabilität, Faltung, Lebensdauer, das Interaktionsvermögen und die subzelluläre Verteilung des acetylierten Proteins hat. Diese irreversible Modifikation wird von einer stark konservierten Familie N-terminaler Acetyltransferasen (NATs) katalysiert. Acht verschiedene NATs wurden bisher in Eukaryonten beschrieben, welche sich durch ihre Substratspezifität, Untereinheiten-Zusammensetzung und ihre subzelluläre Lokalisation unterscheiden. Die einzige eukaryotische N-terminale Acetyltransferase die bisher nicht strukturell charakterisiert werden konnte, ist der heterotrimere NatC-Komplex, welcher aus der katalytischen Untereinheit Naa30 und den beiden unterstützenden Untereinheiten Naa35 und Naa38 besteht. In dieser Arbeit werden fünf verschiedene Strukturen des Saccharomyces cerevisiae NatC-Komplexes in Gegenwart und Abwesenheit von Coenzyme A und zwei Substratpeptiden vorgestellt. Die strukturelle Analyse zeigt, dass die große Neben-Untereinheit Naa35 die zentrale strukturgebende Funktion einnimmt und umfangreiche Interaktionen mit der katalytischen Untereinheit Naa30 und der kleinen Untereinheit Naa38 eingeht. Naa35 umhüllt auf diese Weise Naa30 in einer offen-ringförmigen Tertiärstruktur. In ähnlicher Weise wickelt sich der N-terminus von Naa35 fast vollständig um den gesamten Kreisumfang von Naa38. Zwei NatC Strukturen im Komplex mit Peptiden der natürlichen Substrate Arl3 (aus Hefe) und dem viralen Gag-Protein ermöglichen einen strukturellen Einblick in die Substratspezifität von NatC und zeigen weiterhin die Bindung der beiden Peptide in einer langgestreckten, hydrophoben Substrat-Bindetasche, welche zwischen den beiden Untereinheiten Naa35 und Naa38 gebildet wird. Die Bindung des Gag-Peptides, aber nicht die von Arl3, resultiert in einer großen Ligand-induzierten strukturellen Neuordnung der Substrat-Bindeschlaufe. Demgemäß zeigt das Gag-Peptid eine zehnfach erhöhte katalytische Effizienz im Vergleich zu Arl3. Auf Basis der umfangreichen Struktur-Funktions-Studien wurde ein katalytischer Mechanismus für den NatC Komplex vorgeschlagen. Aufgrund des Vergleichs der NatC-Struktur mit der Ribosom-gebundenen NatA-Struktur, unterstützt durch strukturbasierte Mutagenese, wird ein Modell für den Ribosomen-gebundenen NatC Komplex präsentiert.

Published
2020
Full Text
View/download PDF

18. COVID-19 in people living with human immunodeficiency virus: A case series of 33 patients

Author

Härter, Georg, primary, Spinner, Christoph D., additional, Roider, Julia, additional, Bickel, Markus, additional, Krznaric, Ivanka, additional, Grunwald, Stephan, additional, Schabaz, Farhad, additional, Gillor, Daniel, additional, Postel, Nils, additional, Mueller, Matthias C., additional, Müller, Markus, additional, Römer, Katja, additional, Schewe, Knud, additional, and Hoffmann, Christian, additional

Published
2020
Full Text
View/download PDF

19. Engineering Ralstonia eutropha for Production of Isobutanol (IBT) Motor Fuel from Carbon Dioxide, Hydrogen, and Oxygen Project Final Report

Author

Sinskey, Anthony J., primary, Worden, Robert Mark, additional, Brigham, Christopher, additional, Lu, Jingnan, additional, Quimby, John Westlake, additional, Gai, Claudia, additional, Speth, Daan, additional, Elliott, Sean, additional, Fei, John Qiang, additional, Bernardi, Amanda, additional, Li, Sophia, additional, Grunwald, Stephan, additional, Grousseau, Estelle, additional, Maiti, Soumen, additional, and Liu, Chole, additional

Published
2013
Full Text
View/download PDF

20. Immune deficiency is a risk factor for severe COVID‐19 in people living with HIV.

Author

Hoffmann, Christian, Casado, José L., Härter, Georg, Vizcarra, Pilar, Moreno, Ana, Cattaneo, Dario, Meraviglia, Paola, Spinner, Christoph D., Schabaz, Farhad, Grunwald, Stephan, and Gervasoni, Cristina

Subjects
IMMUNOLOGICAL deficiency syndrome complications, HIV infections, RESEARCH, STATISTICS, COVID-19, CONFIDENCE intervals, AGE distribution, MULTIVARIATE analysis, MEDICAL cooperation, DISEASES, ANTIRETROVIRAL agents, RNA, SEVERITY of illness index, DESCRIPTIVE statistics, ODDS ratio, LONGITUDINAL method
Abstract

Objectives: A prior T cell depletion induced by HIV infection may carry deleterious consequences in the current COVID‐19 pandemic. Clinical data on patients co‐infected with HIV and SARS‐CoV‐2 are still scarce. Methods: This multicentre cohort study evaluated risk factors for morbidity and mortality of COVID‐19 in people living with HIV (PLWH), infected with SARS‐CoV‐2 in three countries in different clinical settings. COVID‐19 was clinically classified as to be mild‐to‐moderate or severe. Results: Of 175 patients, 49 (28%) had severe COVID‐19 and 7 (4%) patients died. Almost all patients were on antiretroviral therapy (ART) and in 94%, HIV RNA was below 50 copies/mL prior to COVID‐19 diagnosis. In the univariate analysis, an age 50 years or older, a CD4+ T cell nadir of < 200/µl, current CD4+ T cells < 350/µl and the presence of at least one comorbidity were significantly associated with severity of COVID‐19. No significant association was found for gender, ethnicity, obesity, a detectable HIV RNA, a prior AIDS‐defining illness, or tenofovir (which was mainly given as alafenamide) or protease inhibitor use in the current ART. In a multivariate analysis, the only factor associated with risk for severe COVID‐19 was a current CD4+ T cell count of < 350/µl (adjusted odds ratio 2.85, 95% confidence interval 1.26‐6.44, p=0.01). The only factor associated with mortality was a low CD4 T cell nadir. Conclusions: In PLWH, immune deficiency is a possible risk factor for severe COVID‐19, even in the setting of virological suppression. There is no evidence for a protective effect of PIs or tenofovir alafenamide. [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

21. An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells

Author

Garcia-Mata, Rafael, Schrade, Katharina, Tröger, Jessica, Eldahshan, Adeeb, Zühlke, Kerstin, Abdul Azeez, Kamal R., Elkins, Jonathan M., Neuenschwander, Martin, Oder, Andreas, Elkewedi, Mohamed, Jaksch, Sarah, Andrae, Karsten, Li, Jinliang, Fernandes, Joao, Müller, Paul Markus, Grunwald, Stephan, Marino, Stephen A., Vukićević, Tanja, Eichhorst, Jenny, Wiesner, Burkhard, Weber, Marcus, Kapiloff, Michael, Rocks, Oliver, Daumke, Oliver, Wieland, Thomas, Knapp, Stefan, Kries, Jens Peter von, Klussmann, Enno, Garcia-Mata, Rafael, Schrade, Katharina, Tröger, Jessica, Eldahshan, Adeeb, Zühlke, Kerstin, Abdul Azeez, Kamal R., Elkins, Jonathan M., Neuenschwander, Martin, Oder, Andreas, Elkewedi, Mohamed, Jaksch, Sarah, Andrae, Karsten, Li, Jinliang, Fernandes, Joao, Müller, Paul Markus, Grunwald, Stephan, Marino, Stephen A., Vukićević, Tanja, Eichhorst, Jenny, Wiesner, Burkhard, Weber, Marcus, Kapiloff, Michael, Rocks, Oliver, Daumke, Oliver, Wieland, Thomas, Knapp, Stefan, Kries, Jens Peter von, and Klussmann, Enno

Abstract

Stimulation of renal collecting duct principal cells with antidiuretic hormone (arginine-vasopressin, AVP) results in inhibition of the small GTPase RhoA and the enrichment of the water channel aquaporin-2 (AQP2) in the plasma membrane. The membrane insertion facilitates water reabsorption from primary urine and fine-tuning of body water homeostasis. Rho guanine nucleotide exchange factors (GEFs) interact with RhoA, catalyze the exchange of GDP for GTP and thereby activate the GTPase. However, GEFs involved in the control of AQP2 in renal principal cells are unknown. The A-kinase anchoring protein, AKAP-Lbc, possesses GEF activity, specifically activates RhoA, and is expressed in primary renal inner medullary collecting duct principal (IMCD) cells. Through screening of 18,431 small molecules and synthesis of a focused library around one of the hits, we identified an inhibitor of the interaction of AKAP-Lbc and RhoA. This molecule, Scaff10-8, bound to RhoA, inhibited the AKAP-Lbc-mediated RhoA activation but did not interfere with RhoA activation through other GEFs or activities of other members of the Rho family of small GTPases, Rac1 and Cdc42. Scaff10-8 promoted the redistribution of AQP2 from intracellular vesicles to the periphery of IMCD cells. Thus, our data demonstrate an involvement of AKAP-Lbc-mediated RhoA activation in the control of AQP2 trafficking.

Published
2018

22. An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells

Author

Schrade, Katharina, primary, Tröger, Jessica, additional, Eldahshan, Adeeb, additional, Zühlke, Kerstin, additional, Abdul Azeez, Kamal R., additional, Elkins, Jonathan M., additional, Neuenschwander, Martin, additional, Oder, Andreas, additional, Elkewedi, Mohamed, additional, Jaksch, Sarah, additional, Andrae, Karsten, additional, Li, Jinliang, additional, Fernandes, Joao, additional, Müller, Paul Markus, additional, Grunwald, Stephan, additional, Marino, Stephen F., additional, Vukićević, Tanja, additional, Eichhorst, Jenny, additional, Wiesner, Burkhard, additional, Weber, Marcus, additional, Kapiloff, Michael, additional, Rocks, Oliver, additional, Daumke, Oliver, additional, Wieland, Thomas, additional, Knapp, Stefan, additional, von Kries, Jens Peter, additional, and Klussmann, Enno, additional

Published
2018
Full Text
View/download PDF

23. [clc] Kinetic and stoichiometric characterization of organoautotrophic growth of Ralstonia eutropha on formic acid in fed-batch and continuous cultures

Author

Grunwald, Stephan, Mottet, Alexis, Grousseau, Estelle, Plassmeier, Jens K., Uribelarrea, Jean-Louis, Gorret, Nathalie, Sinskey, Anthony J., Popovic, Milan K., Guillouet, Stephane E., Harvard University--MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology. Department of Biology, Massachusetts Institute of Technology. Engineering Systems Division, Grunwald, Stephan, Grousseau, Estelle, Plassmeier, Jens K., and Sinskey, Anthony J.

Subjects
mental disorders
Abstract

Formic acid, acting as both carbon and energy source, is a safe alternative to a carbon dioxide, hydrogen and dioxygen mix for studying the conversion of carbon through the Calvin–Benson–Bassham (CBB) cycle into value-added chemical compounds by non-photosynthetic microorganisms. In this work, organoautotrophic growth of Ralstonia eutropha on formic acid was studied using an approach combining stoichiometric modeling and controlled cultures in bioreactors. A strain deleted of its polyhydroxyalkanoate production pathway was used in order to carry out a physiological characterization. The maximal growth yield was determined at 0.16 Cmole Cmole[superscript −1] in a formate-limited continuous culture. The measured yield corresponded to 76% to 85% of the theoretical yield (later confirmed in pH-controlled fed-batch cultures). The stoichiometric study highlighted the imbalance between carbon and energy provided by formic acid and explained the low growth yields measured. Fed-batch cultures were also used to determine the maximum specific growth rate (μ[subscript max] = 0.18 h[superscript −1]) and to study the impact of increasing formic acid concentrations on growth yields. High formic acid sensitivity was found in R eutropha since a linear decrease in the biomass yield with increasing residual formic acid concentrations was observed between 0 and 1.5 g l[superscript −1]., United States. Advanced Research Projects Agency-Energy, MIT-France Seed Fund (Grant), Centre National de la Recherche Scientifique (France) (French Ministry of Higher Education and Research. Post-doctoral Grant)

Published
2014

24. Kinetic and stoichiometric characterization of organoautotrophic growth of Ralstonia eutropha on formic acid in fed-batch and continuous cultures

Author

Grunwald, Stephan, Mottet, Alexis, Grousseau, Estelle, Plassmeier, Jens K, Popovic, Milan K, Uribelarrea, Jean-Louis, Gorret, Nathalie, Guillouet, Stéphane, Sinskey, Anthony, Department of Biology, Massachusetts Institute of Technology (MIT)-Howard Hugues Medical Institute, Department of Biotechnology, Beuth Hochschule für Technik, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Division of Health Sciences and Technology, Massachusetts Institute of Technology (MIT), Engineering Systems Division [Cambridge , USA], US Department of Energy, Advanced Research Project Agency - Energy (ARPA-E), Deutsche Gesellschaft fur Internationale Zusammenarbeit (GIZ) GmbH, French National Center for Scientific Research (CNRS), French Ministry of Higher Education and Research following the France-MIT Energy Forum, MIT-France Seed Fund, Howard Hughes Medical Institute (HHMI)-Massachusetts Institute of Technology (MIT), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, mental disorders
Abstract

Formic acid, acting as both carbon and energy source, is a safe alternative to a carbon dioxide, hydrogen and dioxygen mix for studying the conversion of carbon through the Calvin-Benson-Bassham (CBB) cycle into value-added chemical compounds by non-photosynthetic microorganisms. In this work, organoautotrophic growth of Ralstoniaeutropha on formic acid was studied using an approach combining stoichiometric modeling and controlled cultures in bioreactors. A strain deleted of its polyhydroxyalkanoate production pathway was used in order to carry out a physiological characterization. The maximal growth yield was determined at 0.16 Cmole Cmole(-1) in a formate-limited continuous culture. The measured yield corresponded to 76% to 85% of the theoretical yield (later confirmed in pH-controlled fed-batch cultures). The stoichiometric study highlighted the imbalance between carbon and energy provided by formic acid and explained the low growth yields measured. Fed-batch cultures were also used to determine the maximum specific growth rate ((max)=0.18h(-1)) and to study the impact of increasing formic acid concentrations on growth yields. High formic acid sensitivity was found in Reutropha since a linear decrease in the biomass yield with increasing residual formic acid concentrations was observed between 0 and 1.5gl(-1).

Published
2015

25. Bimodal antagonism of PKA signalling by ARHGAP36

Author

Eccles, Rebecca L., primary, Czajkowski, Maciej T., additional, Barth, Carolin, additional, Müller, Paul Markus, additional, McShane, Erik, additional, Grunwald, Stephan, additional, Beaudette, Patrick, additional, Mecklenburg, Nora, additional, Volkmer, Rudolf, additional, Zühlke, Kerstin, additional, Dittmar, Gunnar, additional, Selbach, Matthias, additional, Hammes, Annette, additional, Daumke, Oliver, additional, Klussmann, Enno, additional, Urbé, Sylvie, additional, and Rocks, Oliver, additional

Published
2016
Full Text
View/download PDF

28. Kinetic and stoichiometric characterization of organoautotrophic growth of R alstonia eutropha on formic acid in fed-batch and continuous cultures.

Author

Plassmeier, Jens K., Grunwald, Stephan, Grousseau, Estelle, Sinskey, Anthony, Popović, Milan K., Mottet, Alexis, Uribelarrea, Jean-Louis, Gorret, Nathalie, and Guillouet, Stéphane E.

Subjects
*RALSTONIA eutropha, *AUTOTROPHIC bacteria, *FORMIC acid, *STOICHIOMETRY, *POLYHYDROXYALKANOATES synthesis, *CALVIN cycle, *CONTINUOUS culture (Microbiology)
Abstract

Formic acid, acting as both carbon and energy source, is a safe alternative to a carbon dioxide, hydrogen and dioxygen mix for studying the conversion of carbon through the Calvin- Benson- Bassham ( CBB) cycle into value-added chemical compounds by non-photosynthetic microorganisms. In this work, organoautotrophic growth of R alstonia eutropha on formic acid was studied using an approach combining stoichiometric modeling and controlled cultures in bioreactors. A strain deleted of its polyhydroxyalkanoate production pathway was used in order to carry out a physiological characterization. The maximal growth yield was determined at 0.16 Cmole Cmole−1 in a formate-limited continuous culture. The measured yield corresponded to 76% to 85% of the theoretical yield (later confirmed in pH-controlled fed-batch cultures). The stoichiometric study highlighted the imbalance between carbon and energy provided by formic acid and explained the low growth yields measured. Fed-batch cultures were also used to determine the maximum specific growth rate (μmax = 0.18 h−1) and to study the impact of increasing formic acid concentrations on growth yields. High formic acid sensitivity was found in R eutropha since a linear decrease in the biomass yield with increasing residual formic acid concentrations was observed between 0 and 1.5 g l−1. [ABSTRACT FROM AUTHOR]

Published
2015
Full Text
View/download PDF

30. Clinical characteristics of monkeypox virus infections among men with and without HIV: A large outbreak cohort in Germany

Author

Hoffmann, Christian, Jessen, Heiko, Wyen, Christoph, Grunwald, Stephan, Noe, Sebastian, Teichmann, Joern, Krauss, Anja-Sophie, Kolarikal, Henning, Scholten, Stefan, Schuler, Christoph, Bickel, Markus, Roll, Clemens, Kreckel, Peter, Koeppe, Siegfried, Straub, Matthias, Klausen, Gerd, Lenz, Johannes, Esser, Stefan, Jensen, Bjoern, Rausch, Michael, Unger, Stefan, Pauli, Ramona, Haerter, Georg, Muller, Matthias, Masuhr, Anja, Schaefer, Guido, Seybold, Ulrich, Schellberg, Sven, Schneider, Jochen, Monin, Malte Benedikt, Wolf, Eva, Spinner, Christoph D., Boesecke, Christoph, Hoffmann, Christian, Jessen, Heiko, Wyen, Christoph, Grunwald, Stephan, Noe, Sebastian, Teichmann, Joern, Krauss, Anja-Sophie, Kolarikal, Henning, Scholten, Stefan, Schuler, Christoph, Bickel, Markus, Roll, Clemens, Kreckel, Peter, Koeppe, Siegfried, Straub, Matthias, Klausen, Gerd, Lenz, Johannes, Esser, Stefan, Jensen, Bjoern, Rausch, Michael, Unger, Stefan, Pauli, Ramona, Haerter, Georg, Muller, Matthias, Masuhr, Anja, Schaefer, Guido, Seybold, Ulrich, Schellberg, Sven, Schneider, Jochen, Monin, Malte Benedikt, Wolf, Eva, Spinner, Christoph D., and Boesecke, Christoph

Abstract

Background Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV. Methods This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). Results By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20-67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV. Conclusions In this preliminary cohort analysis from a current large outbreak among MSM in Germany, the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed.

31. A multimorphic mutation in IRF4 causes human autosomal dominant combined immunodeficiency.

Author

Fornes O, Jia A, Kuehn HS, Min Q, Pannicke U, Schleussner N, Thouenon R, Yu Z, de Los Angeles Astbury M, Biggs CM, Galicchio M, Garcia-Campos JA, Gismondi S, Gonzalez Villarreal G, Hildebrand KJ, Hönig M, Hou J, Moshous D, Pittaluga S, Qian X, Rozmus J, Schulz AS, Staines-Boone AT, Sun B, Sun J, Uwe S, Venegas-Montoya E, Wang W, Wang X, Ying W, Zhai X, Zhou Q, Akalin A, André I, Barth TFE, Baumann B, Brüstle A, Burgio G, Bustamante JC, Casanova JL, Casarotto MG, Cavazzana M, Chentout L, Cockburn IA, Costanza M, Cui C, Daumke O, Del Bel KL, Eibel H, Feng X, Franke V, Gebhardt JCM, Götz A, Grunwald S, Hoareau B, Hughes TR, Jacobsen EM, Janz M, Jolma A, Lagresle-Peyrou C, Lai N, Li Y, Lin S, Lu HY, Lugo-Reyes SO, Meng X, Möller P, Moreno-Corona N, Niemela JE, Novakovsky G, Perez-Caraballo JJ, Picard C, Poggi L, Puig-Lombardi ME, Randall KL, Reisser A, Schmitt Y, Seneviratne S, Sharma M, Stoddard J, Sundararaj S, Sutton H, Tran LQ, Wang Y, Wasserman WW, Wen Z, Winkler W, Xiong E, Yang AWH, Yu M, Zhang L, Zhang H, Zhao Q, Zhen X, Enders A, Kracker S, Martinez-Barricarte R, Mathas S, Rosenzweig SD, Schwarz K, Turvey SE, and Wang JY

Subjects
Mice, Animals, Humans, B-Lymphocytes, DNA metabolism, Mutation, Interferon Regulatory Factors, Gene Expression Regulation
Abstract

Interferon regulatory factor 4 (IRF4) is a transcription factor (TF) and key regulator of immune cell development and function. We report a recurrent heterozygous mutation in IRF4, p.T95R, causing an autosomal dominant combined immunodeficiency (CID) in seven patients from six unrelated families. The patients exhibited profound susceptibility to opportunistic infections, notably Pneumocystis jirovecii , and presented with agammaglobulinemia. Patients' B cells showed impaired maturation, decreased immunoglobulin isotype switching, and defective plasma cell differentiation, whereas their T cells contained reduced T H 17 and T FH populations and exhibited decreased cytokine production. A knock-in mouse model of heterozygous T95R showed a severe defect in antibody production both at the steady state and after immunization with different types of antigens, consistent with the CID observed in these patients. The IRF4 T95R variant maps to the TF's DNA binding domain, alters its canonical DNA binding specificities, and results in a simultaneous multimorphic combination of loss, gain, and new functions for IRF4. IRF4 T95R behaved as a gain-of-function hypermorph by binding to DNA with higher affinity than IRF4 WT . Despite this increased affinity for DNA, the transcriptional activity on IRF4 canonical genes was reduced, showcasing a hypomorphic activity of IRF4 T95R . Simultaneously, IRF4 T95R functions as a neomorph by binding to noncanonical DNA sites to alter the gene expression profile, including the transcription of genes exclusively induced by IRF4 T95R but not by IRF4 WT . This previously undescribed multimorphic IRF4 pathophysiology disrupts normal lymphocyte biology, causing human disease.

Published
2023
Full Text
View/download PDF

32. Kinetic and stoichiometric characterization of organoautotrophic growth of Ralstonia eutropha on formic acid in fed-batch and continuous cultures.

Author

Grunwald S, Mottet A, Grousseau E, Plassmeier JK, Popović MK, Uribelarrea JL, Gorret N, Guillouet SE, and Sinskey A

Subjects
Autotrophic Processes, Cupriavidus necator chemistry, Kinetics, Models, Biological, Polyhydroxyalkanoates metabolism, Bioreactors microbiology, Cupriavidus necator growth & development, Cupriavidus necator metabolism, Formates metabolism
Abstract

Formic acid, acting as both carbon and energy source, is a safe alternative to a carbon dioxide, hydrogen and dioxygen mix for studying the conversion of carbon through the Calvin-Benson-Bassham (CBB) cycle into value-added chemical compounds by non-photosynthetic microorganisms. In this work, organoautotrophic growth of Ralstonia eutropha on formic acid was studied using an approach combining stoichiometric modeling and controlled cultures in bioreactors. A strain deleted of its polyhydroxyalkanoate production pathway was used in order to carry out a physiological characterization. The maximal growth yield was determined at 0.16 Cmole Cmole(-1) in a formate-limited continuous culture. The measured yield corresponded to 76% to 85% of the theoretical yield (later confirmed in pH-controlled fed-batch cultures). The stoichiometric study highlighted the imbalance between carbon and energy provided by formic acid and explained the low growth yields measured. Fed-batch cultures were also used to determine the maximum specific growth rate (μmax  = 0.18 h(-1) ) and to study the impact of increasing formic acid concentrations on growth yields. High formic acid sensitivity was found in R eutropha since a linear decrease in the biomass yield with increasing residual formic acid concentrations was observed between 0 and 1.5 g l(-1) ., (© 2014 The Authors. Microbial Biotechnology published by John Wiley & Sons Ltd and Society for Applied Microbiology.)

Published
2015
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results