24 results on '"Josef Pichler"'
Search Results
2. Federated learning enables big data for rare cancer boundary detection
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Sarthak Pati, Ujjwal Baid, Brandon Edwards, Micah Sheller, Shih-Han Wang, G. Anthony Reina, Patrick Foley, Alexey Gruzdev, Deepthi Karkada, Christos Davatzikos, Chiharu Sako, Satyam Ghodasara, Michel Bilello, Suyash Mohan, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J. Preetha, Felix Sahm, Klaus Maier-Hein, Maximilian Zenk, Martin Bendszus, Wolfgang Wick, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, John Garrett, Matthew Larson, Robert Jeraj, Stuart Currie, Russell Frood, Kavi Fatania, Raymond Y. Huang, Ken Chang, Carmen Balaña Quintero, Jaume Capellades, Josep Puig, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Gaurav Shukla, Spencer Liem, Gregory S. Alexander, Joseph Lombardo, Joshua D. Palmer, Adam E. Flanders, Adam P. Dicker, Haris I. Sair, Craig K. Jones, Archana Venkataraman, Meirui Jiang, Tiffany Y. So, Cheng Chen, Pheng Ann Heng, Qi Dou, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Keřkovský, Tereza Kopřivová, Marek Dostál, Václav Vybíhal, Michael A. Vogelbaum, J. Ross Mitchell, Joaquim Farinhas, Joseph A. Maldjian, Chandan Ganesh Bangalore Yogananda, Marco C. Pinho, Divya Reddy, James Holcomb, Benjamin C. Wagner, Benjamin M. Ellingson, Timothy F. Cloughesy, Catalina Raymond, Talia Oughourlian, Akifumi Hagiwara, Chencai Wang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Alexandre Xavier Falcão, Samuel B. Martins, Bernardo C. A. Teixeira, Flávia Sprenger, David Menotti, Diego R. Lucio, Pamela LaMontagne, Daniel Marcus, Benedikt Wiestler, Florian Kofler, Ivan Ezhov, Marie Metz, Rajan Jain, Matthew Lee, Yvonne W. Lui, Richard McKinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Derrick Murcia, Eric Fu, Rourke Haas, John Thompson, David Ryan Ormond, Chaitra Badve, Andrew E. Sloan, Vachan Vadmal, Kristin Waite, Rivka R. Colen, Linmin Pei, Murat Ak, Ashok Srinivasan, J. Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, Fanny Morón, Jacob Mandel, Konstantinos Kamnitsas, Ben Glocker, Luke V. M. Dixon, Matthew Williams, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I. Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M. Kardamakis, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Bing Luo, Laila Poisson, Ning Wen, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Marion Smits, Sebastian R. van der Voort, Ahmed Alafandi, Fatih Incekara, Maarten M. J. Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W. Schouten, Hendrikus J. Dubbink, Arnaud J. P. E. Vincent, Martin J. van den Bent, Pim J. French, Stefan Klein, Yading Yuan, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Simone P. Niclou, Olivier Keunen, Ann-Christin Hau, Martin Vallières, David Fortin, Martin Lepage, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B. Chambless, Akshitkumar Mistry, Reid C. Thompson, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Thomas C. Booth, Alysha Chelliah, Marc Modat, Haris Shuaib, Carmen Dragos, Aly Abayazeed, Kenneth Kolodziej, Michael Hill, Ahmed Abbassy, Shady Gamal, Mahmoud Mekhaimar, Mohamed Qayati, Mauricio Reyes, Ji Eun Park, Jihye Yun, Ho Sung Kim, Abhishek Mahajan, Mark Muzi, Sean Benson, Regina G. H. Beets-Tan, Jonas Teuwen, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M. Buatti, Aikaterini Kotrotsou, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Hassan F. Shaykh, Joel Saltz, Prateek Prasanna, Sampurna Shrestha, Kartik M. Mani, David Payne, Tahsin Kurc, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A. Velastin, Godwin Ogbole, Mayowa Soneye, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu’aibu, Adeleye Dorcas, Farouk Dako, Amber L. Simpson, Mohammad Hamghalam, Jacob J. Peoples, Ricky Hu, Anh Tran, Danielle Cutler, Fabio Y. Moraes, Michael A. Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Brian Bialecki, Sailaja Marella, Cynthia Price, Lisa Cimino, Charles Apgar, Prashant Shah, Bjoern Menze, Jill S. Barnholtz-Sloan, Jason Martin, and Spyridon Bakas
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Science - Abstract
Federated ML (FL) provides an alternative to train accurate and generalizable ML models, by only sharing numerical model updates. Here, the authors present the largest FL study to-date to generate an automatic tumor boundary detector for glioblastoma.
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- 2022
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3. Frequency and characteristics of bacterial and viral low-grade infections of the intervertebral discs: a prospective, observational study
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Wolfgang Senker, Stefan Aspalter, Christian Radl, Josef Pichler, Stefan Doppler, Serge Weis, Christine Webersinke, Helga Wagner, Philipp Hermann, Martin Aichholzer, Kathrin Aufschnaiter-Hießböck, Wolfgang Thomae, Nico Stroh, Thomas Hauser, and Andreas Gruber
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Low back pain ,Bacterial colonization ,Intervertebral discs ,Low-grade infection ,Modic changes ,Cutibacterium acnes ,Orthopedic surgery ,RD701-811 - Abstract
Abstract Study design Monocentric, prospective, observational study. Objective The clinical relevance of bacterial colonization of intervertebral discs is controversial. This study aimed to determine a possible relationship between bacterial and viral colonization and low-grade infection of the discs. Methods We investigated 447 disc samples from 392 patients. Microbiological culture was used to examine the samples for bacterial growth, polymerase chain reaction (PCR) was used for detection of herpes simplex virus types 1 and 2 (HSV-1, HSV-2) and Cytomegalovirus (CMV), and histopathological analysis was used to detect signs of inflammation. The results were compared between subgroups organized according to gender, age, location of the samples, surgical approach, preoperative C-reactive protein (CRP), preoperative and 6 months postoperative Oswestry Disability Index (ODI) and Neck Disability Index (NDI), and Modic changes (MC) of the corresponding endplates. Also, we assessed the occurrence of postoperative infections within 6 months. Results Microbiological culture was positive in 38.78% of the analyzed intervertebral discs. Altogether, 180 bacteria were isolated. Coagulase-negative staphylococci (CONS) (23.41%) and Cutibacterium acnes (18.05%) were the most frequently detected microorganisms. None of HSV-1, HSV-2, or CMV were detected. Male patients (p = 0.00036) and cervical segments (p = 0.00001) showed higher rates of positive culture results. Ventral surgical approaches ( p
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- 2022
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4. Effect of different dietary fibre sources on the zootechnical performance, feeding behaviour and intestinal physiology of growing and finishing pigs
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Josef Pichler, Florian Hemetsberger, Melanie Buchberger, Christiane Schwarz, and Karl Schedle
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fattening pig ,dietary fibre sources ,behaviour ,gut physiology ,Animal culture ,SF1-1100 - Abstract
The aim of this study was to determine the effect of different sources of fibre in the diets of fattening pigs on performance, feeding behaviour and intestinal physiology. A total of 60 barrows and gilts (initial body weight 28.4 ± 0.4 kg) were allotted to four dietary treatments: control (CON), lignocellulose (LC), mycelium (MYC) and corn gluten feed (CGF). Diets were calculated to provide balanced available nutrient contents. Including MYC in the diet resulted in an increased average daily gain (P < 0.05) compared to CON and CGF, and improved gain to feed ratio (P < 0.05) compared to LC. Pigs in CON (P < 0.05) ate the fewest but largest meals, whereas treatment CGF (P < 0.05) showed the opposite effect, resulting in the same daily feeder occupation time. Regarding intestinal physiology, in ileum, no differences were observed between the contents of short chain fatty acids (SCFA), lactic acid and biogenic amines. In the colon, MYC showed an increased concentration of acetic acid (P < 0.05) as well as the total content of SCFA (P < 0.05), compared to LC and CGF. Distinct fermentation profiles of ammonia were recorded in ileal and colonic digesta, although contents remained below harmful concentrations. Morphometrical measurements showed differences between the fibre sources LC and MYC, as well as LC and the CON in all investigated gut sections. These results provide evidence that the inclusion of specific dietary fibre sources/contents can positively influence the gut morphology and performance of pigs. However, further studies are needed regarding the mode of action and physico-chemical characteristics of the different fibre sources as a precondition for their successful application in pig diets.
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- 2022
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5. Author Correction: Federated learning enables big data for rare cancer boundary detection
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Sarthak Pati, Ujjwal Baid, Brandon Edwards, Micah Sheller, Shih-Han Wang, G. Anthony Reina, Patrick Foley, Alexey Gruzdev, Deepthi Karkada, Christos Davatzikos, Chiharu Sako, Satyam Ghodasara, Michel Bilello, Suyash Mohan, Philipp Vollmuth, Gianluca Brugnara, Chandrakanth J. Preetha, Felix Sahm, Klaus Maier-Hein, Maximilian Zenk, Martin Bendszus, Wolfgang Wick, Evan Calabrese, Jeffrey Rudie, Javier Villanueva-Meyer, Soonmee Cha, Madhura Ingalhalikar, Manali Jadhav, Umang Pandey, Jitender Saini, John Garrett, Matthew Larson, Robert Jeraj, Stuart Currie, Russell Frood, Kavi Fatania, Raymond Y. Huang, Ken Chang, Carmen Balaña, Jaume Capellades, Josep Puig, Johannes Trenkler, Josef Pichler, Georg Necker, Andreas Haunschmidt, Stephan Meckel, Gaurav Shukla, Spencer Liem, Gregory S. Alexander, Joseph Lombardo, Joshua D. Palmer, Adam E. Flanders, Adam P. Dicker, Haris I. Sair, Craig K. Jones, Archana Venkataraman, Meirui Jiang, Tiffany Y. So, Cheng Chen, Pheng Ann Heng, Qi Dou, Michal Kozubek, Filip Lux, Jan Michálek, Petr Matula, Miloš Keřkovský, Tereza Kopřivová, Marek Dostál, Václav Vybíhal, Michael A. Vogelbaum, J. Ross Mitchell, Joaquim Farinhas, Joseph A. Maldjian, Chandan Ganesh Bangalore Yogananda, Marco C. Pinho, Divya Reddy, James Holcomb, Benjamin C. Wagner, Benjamin M. Ellingson, Timothy F. Cloughesy, Catalina Raymond, Talia Oughourlian, Akifumi Hagiwara, Chencai Wang, Minh-Son To, Sargam Bhardwaj, Chee Chong, Marc Agzarian, Alexandre Xavier Falcão, Samuel B. Martins, Bernardo C. A. Teixeira, Flávia Sprenger, David Menotti, Diego R. Lucio, Pamela LaMontagne, Daniel Marcus, Benedikt Wiestler, Florian Kofler, Ivan Ezhov, Marie Metz, Rajan Jain, Matthew Lee, Yvonne W. Lui, Richard McKinley, Johannes Slotboom, Piotr Radojewski, Raphael Meier, Roland Wiest, Derrick Murcia, Eric Fu, Rourke Haas, John Thompson, David Ryan Ormond, Chaitra Badve, Andrew E. Sloan, Vachan Vadmal, Kristin Waite, Rivka R. Colen, Linmin Pei, Murat Ak, Ashok Srinivasan, J. Rajiv Bapuraj, Arvind Rao, Nicholas Wang, Ota Yoshiaki, Toshio Moritani, Sevcan Turk, Joonsang Lee, Snehal Prabhudesai, Fanny Morón, Jacob Mandel, Konstantinos Kamnitsas, Ben Glocker, Luke V. M. Dixon, Matthew Williams, Peter Zampakis, Vasileios Panagiotopoulos, Panagiotis Tsiganos, Sotiris Alexiou, Ilias Haliassos, Evangelia I. Zacharaki, Konstantinos Moustakas, Christina Kalogeropoulou, Dimitrios M. Kardamakis, Yoon Seong Choi, Seung-Koo Lee, Jong Hee Chang, Sung Soo Ahn, Bing Luo, Laila Poisson, Ning Wen, Pallavi Tiwari, Ruchika Verma, Rohan Bareja, Ipsa Yadav, Jonathan Chen, Neeraj Kumar, Marion Smits, Sebastian R. van der Voort, Ahmed Alafandi, Fatih Incekara, Maarten M. J. Wijnenga, Georgios Kapsas, Renske Gahrmann, Joost W. Schouten, Hendrikus J. Dubbink, Arnaud J. P. E. Vincent, Martin J. van den Bent, Pim J. French, Stefan Klein, Yading Yuan, Sonam Sharma, Tzu-Chi Tseng, Saba Adabi, Simone P. Niclou, Olivier Keunen, Ann-Christin Hau, Martin Vallières, David Fortin, Martin Lepage, Bennett Landman, Karthik Ramadass, Kaiwen Xu, Silky Chotai, Lola B. Chambless, Akshitkumar Mistry, Reid C. Thompson, Yuriy Gusev, Krithika Bhuvaneshwar, Anousheh Sayah, Camelia Bencheqroun, Anas Belouali, Subha Madhavan, Thomas C. Booth, Alysha Chelliah, Marc Modat, Haris Shuaib, Carmen Dragos, Aly Abayazeed, Kenneth Kolodziej, Michael Hill, Ahmed Abbassy, Shady Gamal, Mahmoud Mekhaimar, Mohamed Qayati, Mauricio Reyes, Ji Eun Park, Jihye Yun, Ho Sung Kim, Abhishek Mahajan, Mark Muzi, Sean Benson, Regina G. H. Beets-Tan, Jonas Teuwen, Alejandro Herrera-Trujillo, Maria Trujillo, William Escobar, Ana Abello, Jose Bernal, Jhon Gómez, Joseph Choi, Stephen Baek, Yusung Kim, Heba Ismael, Bryan Allen, John M. Buatti, Aikaterini Kotrotsou, Hongwei Li, Tobias Weiss, Michael Weller, Andrea Bink, Bertrand Pouymayou, Hassan F. Shaykh, Joel Saltz, Prateek Prasanna, Sampurna Shrestha, Kartik M. Mani, David Payne, Tahsin Kurc, Enrique Pelaez, Heydy Franco-Maldonado, Francis Loayza, Sebastian Quevedo, Pamela Guevara, Esteban Torche, Cristobal Mendoza, Franco Vera, Elvis Ríos, Eduardo López, Sergio A. Velastin, Godwin Ogbole, Mayowa Soneye, Dotun Oyekunle, Olubunmi Odafe-Oyibotha, Babatunde Osobu, Mustapha Shu’aibu, Adeleye Dorcas, Farouk Dako, Amber L. Simpson, Mohammad Hamghalam, Jacob J. Peoples, Ricky Hu, Anh Tran, Danielle Cutler, Fabio Y. Moraes, Michael A. Boss, James Gimpel, Deepak Kattil Veettil, Kendall Schmidt, Brian Bialecki, Sailaja Marella, Cynthia Price, Lisa Cimino, Charles Apgar, Prashant Shah, Bjoern Menze, Jill S. Barnholtz-Sloan, Jason Martin, and Spyridon Bakas
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Science - Published
- 2023
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6. MRI Response Assessment in Glioblastoma Patients Treated with Dendritic-Cell-Based Immunotherapy
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Johanna Heugenhauser, Malik Galijasevic, Stephanie Mangesius, Georg Goebel, Johanna Buchroithner, Friedrich Erhart, Josef Pichler, Georg Widhalm, Günther Stockhammer, Sarah Iglseder, Christian F. Freyschlag, Stefan Oberndorfer, Karin Bordihn, Gord von Campe, Thomas Czech, Birgit Surböck, Tadeja Urbanic Purkart, Christine Marosi, Thomas Felzmann, and Martha Nowosielski
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radiologic response criteria ,immunotherapy ,glioblastoma ,iRANO ,mRANO ,volumetric measurements ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: In this post hoc analysis we compared various response-assessment criteria in newly diagnosed glioblastoma (GB) patients treated with tumor lysate-charged autologous dendritic cells (Audencel) and determined the differences in prediction of progression-free survival (PFS) and overall survival (OS). Methods: 76 patients enrolled in a multicenter phase II trial receiving standard of care (SOC, n = 40) or SOC + Audencel vaccine (n = 36) were included. MRI scans were evaluated using MacDonald, RANO, Vol-RANO, mRANO, Vol-mRANO and iRANO criteria. Tumor volumes (T1 contrast-enhancing as well as T2/FLAIR volumes) were calculated by semiautomatic segmentation. The Kruskal-Wallis-test was used to detect differences in PFS among the assessment criteria; for correlation analysis the Spearman test was used. Results: There was a significant difference in median PFS between mRANO (8.6 months) and Vol-mRANO (8.6 months) compared to MacDonald (4.0 months), RANO (4.2 months) and Vol-RANO (5.4 months). For the vaccination arm, median PFS by iRANO was 6.2 months. There was no difference in PFS between SOC and SOC + Audencel. The best correlation between PFS/OS was detected for mRANO (r = 0.65) and Vol-mRANO (r = 0.69, each p < 0.001). A total of 16/76 patients developed a pure T2/FLAIR progressing disease, and 4/36 patients treated with Audencel developed pseudoprogression. Conclusion: When comparing different response-assessment criteria in GB patients treated with dendritic cell-based immunotherapy, the best correlation between PFS and OS was observed for mRANO and Vol-mRANO. Interestingly, iRANO was not superior for predicting OS in patients treated with Audencel.
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- 2022
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7. Innovating Industry With Research: eknows and Sysparency.
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Verena Geist, Michael Moser, Josef Pichler, and Florian Schnitzhofer
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- 2024
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8. Iterative Design and Evaluation of a Low-Code Development Platform for Welding Robot Control.
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Bernhard Schenkenfelder, Michael Moser, Michael Pfeiffer 0005, Josef Pichler, Christian Salomon, and Mario Winterer
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- 2023
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9. Using AI-Based Code Completion for Domain-Specific Languages.
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Christina Piereder, Günter Fleck, Verena Geist, Michael Moser, and Josef Pichler
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- 2023
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10. PASDA: A partition-based semantic differencing approach with best effort classification of undecided cases.
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Johann Glock, Josef Pichler, and Martin Pinzger 0001
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- 2024
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11. Towards Attribute Grammar Mining by Symbolic Execution.
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Michael Moser, Josef Pichler, and Andreas Pointner
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- 2022
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12. On the Creation and Maintenance of a Documentation Generator in an Applied Research Context.
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Bernhard Dorninger, Michael Moser, Josef Pichler, Michael Rappl, and Jakob Sautter
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- 2022
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13. PASDA: A Partition-based Semantic Differencing Approach with Best Effort Classification of Undecided Cases.
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Johann Glock, Josef Pichler, and Martin Pinzger 0001
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- 2023
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14. Early Postoperative Treatment versus Initial Observation in CNS WHO Grade 2 and 3 Oligodendroglioma: Clinical Outcomes and DNA Methylation Patterns
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Maximilian J. Mair, Annette Leibetseder, Gerwin Heller, Rainer Puhr, Erwin Tomasich, Sebastian Goldberger, Teresa Hatziioannou, Adelheid Wöhrer, Georg Widhalm, Karin Dieckmann, Martin Aichholzer, Serge Weis, Tim von Oertzen, Julia Furtner, Josef Pichler, Matthias Preusser, and Anna S. Berghoff
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Adult ,Cancer Research ,Brain Neoplasms ,Oligodendroglioma ,Methyltransferases ,DNA Methylation ,World Health Organization ,Isocitrate Dehydrogenase ,Oncology ,Lomustine ,Vincristine ,Procarbazine ,Temozolomide ,Humans ,Prospective Studies ,Retrospective Studies - Abstract
Purpose: The treatment of oligodendroglioma consists of tumor resection and radiochemotherapy. The timing of radiochemotherapy remains unclear, and predictive biomarkers are limited. Experimental Design: Adult patients diagnosed with isocitrate dehydrogenase (IDH)-mutated, 1p/19q-codeleted CNS WHO grade 2 and 3 oligodendroglioma at the Medical University of Vienna and the Kepler University Hospital Linz (Austria) in 1992 to 2019 were included. Progression-free (PFS) and overall survival (OS) between early postoperative treatment and initial observation were compared using propensity score–weighted Cox regression models. DNA methylation analysis of tumor tissue was performed using Illumina MethylationEPIC 850k microarrays. Results: One hundred thirty-one out of 201 (65.2%) patients with CNS WHO grade 2 and 70 of 201 (34.8%) with grade 3 oligodendroglioma were identified. Eighty-three of 201 (41.3%) patients underwent early postoperative treatment, of whom 56 of 83 (67.5%) received radiochemotherapy, 15 of 84 (18.1%) radiotherapy (RT) only and 12 of 83 (14.5%) chemotherapy only. Temozolomide-based treatment was administered to 64 of 68 (94.1%) patients, whereas RT + procarbazine, lomustine (CCNU), and vincristine (PCV) were applied in 2 of 69 (3.5%) patients. Early treatment was not associated with PFS [adjusted hazard ratio (HR) 0.74; 95% CI, 0.33–1.65, P = 0.459] or OS (adjusted HR: 2.07; 95% CI, 0.52–8.21, P = 0.302) improvement. Unsupervised clustering analysis of DNA methylation profiles from patients receiving early treatment revealed two methylation clusters correlating with PFS, whereas no association of clustering with O6-methylguanine methyltransferase (MGMT) promoter methylation, CNS WHO grade, extent of resection, and treating center could be observed. Conclusions: In this retrospective study, early postoperative treatment was not associated with improved PFS/OS in oligodendroglioma. The potentially predictive value of whole-genome methylation profiling should be validated in prospective trials.
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- 2022
15. Data from Early Postoperative Treatment versus Initial Observation in CNS WHO Grade 2 and 3 Oligodendroglioma: Clinical Outcomes and DNA Methylation Patterns
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Anna S. Berghoff, Matthias Preusser, Josef Pichler, Julia Furtner, Tim von Oertzen, Serge Weis, Martin Aichholzer, Karin Dieckmann, Georg Widhalm, Adelheid Wöhrer, Teresa Hatziioannou, Sebastian Goldberger, Erwin Tomasich, Rainer Puhr, Gerwin Heller, Annette Leibetseder, and Maximilian J. Mair
- Abstract
Purpose:The treatment of oligodendroglioma consists of tumor resection and radiochemotherapy. The timing of radiochemotherapy remains unclear, and predictive biomarkers are limited.Experimental Design:Adult patients diagnosed with isocitrate dehydrogenase (IDH)-mutated, 1p/19q-codeleted CNS WHO grade 2 and 3 oligodendroglioma at the Medical University of Vienna and the Kepler University Hospital Linz (Austria) in 1992 to 2019 were included. Progression-free (PFS) and overall survival (OS) between early postoperative treatment and initial observation were compared using propensity score–weighted Cox regression models. DNA methylation analysis of tumor tissue was performed using Illumina MethylationEPIC 850k microarrays.Results:One hundred thirty-one out of 201 (65.2%) patients with CNS WHO grade 2 and 70 of 201 (34.8%) with grade 3 oligodendroglioma were identified. Eighty-three of 201 (41.3%) patients underwent early postoperative treatment, of whom 56 of 83 (67.5%) received radiochemotherapy, 15 of 84 (18.1%) radiotherapy (RT) only and 12 of 83 (14.5%) chemotherapy only. Temozolomide-based treatment was administered to 64 of 68 (94.1%) patients, whereas RT + procarbazine, lomustine (CCNU), and vincristine (PCV) were applied in 2 of 69 (3.5%) patients. Early treatment was not associated with PFS [adjusted hazard ratio (HR) 0.74; 95% CI, 0.33–1.65, P = 0.459] or OS (adjusted HR: 2.07; 95% CI, 0.52–8.21, P = 0.302) improvement. Unsupervised clustering analysis of DNA methylation profiles from patients receiving early treatment revealed two methylation clusters correlating with PFS, whereas no association of clustering with O6-methylguanine methyltransferase (MGMT) promoter methylation, CNS WHO grade, extent of resection, and treating center could be observed.Conclusions:In this retrospective study, early postoperative treatment was not associated with improved PFS/OS in oligodendroglioma. The potentially predictive value of whole-genome methylation profiling should be validated in prospective trials.
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- 2023
16. Data from MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial
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Wolfgang Wick, Guido Reifenberger, Johannes Hüsing, Spyros Kollias, Peter Vajkoczy, Jürgen Meixensberger, Guido Nikkhah, Josef Pichler, Krisztian Homicsko, Roger Stupp, Roland Goldbrunner, Christine Marosi, Uwe Schlegel, Jörg C. Tonn, Michael Platten, Oliver Bähr, Ralf Ketter, Hans-Georg Wirsching, Michael C. Sabel, Ulrich Herrlinger, Peter Hau, Oliver Schnell, Antje Wick, Joachim P. Steinbach, Jörg Felsberg, Bärbel Kästner, Ghazaleh Tabatabai, and Michael Weller
- Abstract
Purpose: Rechallenge with temozolomide (TMZ) at first progression of glioblastoma after temozolomide chemoradiotherapy (TMZ/RT→TMZ) has been studied in retrospective and single-arm prospective studies, applying temozolomide continuously or using 7/14 or 21/28 days schedules. The DIRECTOR trial sought to show superiority of the 7/14 regimen.Experimental Design: Patients with glioblastoma at first progression after TMZ/RT→TMZ and at least two maintenance temozolomide cycles were randomized to Arm A [one week on (120 mg/m2 per day)/one week off] or Arm B [3 weeks on (80 mg/m2 per day)/one week off]. The primary endpoint was median time-to-treatment failure (TTF) defined as progression, premature temozolomide discontinuation for toxicity, or death from any cause. O6-methylguanine DNA methyltransferase (MGMT) promoter methylation was prospectively assessed by methylation-specific PCR.Results: Because of withdrawal of support, the trial was prematurely closed to accrual after 105 patients. There was a similar outcome in both arms for median TTF [A: 1.8 months; 95% confidence intervals (CI), 1.8–3.2 vs. B: 2.0 months; 95% CI, 1.8–3.5] and overall survival [A: 9.8 months (95% CI, 6.7–13.0) vs. B: 10.6 months (95% CI, 8.1–11.6)]. Median TTF in patients with MGMT-methylated tumors was 3.2 months (95% CI, 1.8–7.4) versus 1.8 months (95% CI, 1.8–2) in MGMT-unmethylated glioblastoma. Progression-free survival rates at 6 months (PFS-6) were 39.7% with versus 6.9% without MGMT promoter methylation.Conclusions: Temozolomide rechallenge is a treatment option for MGMT promoter-methylated recurrent glioblastoma. Alternative strategies need to be considered for patients with progressive glioblastoma without MGMT promoter methylation. Clin Cancer Res; 21(9); 2057–64. ©2015 AACR.
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- 2023
17. Data from A Phase II, Randomized, Study of Weekly APG101+Reirradiation versus Reirradiation in Progressive Glioblastoma
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Stephanie E. Combs, Martin Bendszus, Michael Platten, Claudia Kunz, Christian Hartmann, Jürgen Debus, Inga Harting, Elena Vetlova, Josef Pichler, Andreas von Deimling, Maximilian G. Schliesser, Benedikt Wiestler, Oliver Heese, Tobias Martens, Grigory Kobyakov, Klaus Junge, Harald Fricke, and Wolfgang Wick
- Abstract
Purpose: Preclinical data indicate anti-invasive activity of APG101, a CD95 ligand (CD95L)–binding fusion protein, in glioblastoma.Experimental Design: Patients (N = 91) with glioblastoma at first or second progression were randomized 1:2 between second radiotherapy (rRT; 36 Gy; five times 2 Gy per week) or rRT+APG101 (400 mg weekly i.v.). Patient characteristics [N = 84 (26 patients rRT, 58 patients rRT+APG101)] were balanced.Results: Progression-free survival at 6 months (PFS-6) rates were 3.8% [95% confidence interval (CI), 0.1–19.6] for rRT and 20.7% (95% CI, 11.2–33.4) for rRT+APG101 (P = 0.048). Median PFS was 2.5 (95% CI, 2.3–3.8) months and 4.5 (95% CI, 3.7–5.4) months with a hazard ratio (HR) of 0.49 (95% CI, 0.27–0.88; P = 0.0162) adjusted for tumor size. Cox regression analysis adjusted for tumor size revealed a HR of 0.60 (95% CI, 0.36–1.01; P = 0.0559) for rRT+APG101 for death of any cause. Lower methylation levels at CpG2 in the CD95L promoter in the tumor conferred a stronger risk reduction (HR, 0.19; 95% CI, 0.06–0.58) for treatment with APG101, suggesting a potential biomarker.Conclusions: CD95 pathway inhibition in combination with rRT is an innovative concept with clinical efficacy. It warrants further clinical development. CD95L promoter methylation in the tumor may be developed as a biomarker. Clin Cancer Res; 20(24); 6304–13. ©2014 AACR.
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- 2023
18. Supplementary Figure 1 from MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial
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Wolfgang Wick, Guido Reifenberger, Johannes Hüsing, Spyros Kollias, Peter Vajkoczy, Jürgen Meixensberger, Guido Nikkhah, Josef Pichler, Krisztian Homicsko, Roger Stupp, Roland Goldbrunner, Christine Marosi, Uwe Schlegel, Jörg C. Tonn, Michael Platten, Oliver Bähr, Ralf Ketter, Hans-Georg Wirsching, Michael C. Sabel, Ulrich Herrlinger, Peter Hau, Oliver Schnell, Antje Wick, Joachim P. Steinbach, Jörg Felsberg, Bärbel Kästner, Ghazaleh Tabatabai, and Michael Weller
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Supplementary Figure 1. MMSE assessment at study entry, during treatment, and at follow-up
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- 2023
19. Acknowledgement from A Phase II, Randomized, Study of Weekly APG101+Reirradiation versus Reirradiation in Progressive Glioblastoma
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Stephanie E. Combs, Martin Bendszus, Michael Platten, Claudia Kunz, Christian Hartmann, Jürgen Debus, Inga Harting, Elena Vetlova, Josef Pichler, Andreas von Deimling, Maximilian G. Schliesser, Benedikt Wiestler, Oliver Heese, Tobias Martens, Grigory Kobyakov, Klaus Junge, Harald Fricke, and Wolfgang Wick
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Acknowledgement. List of investigators and other study stuff at the individual sites.
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- 2023
20. CONSORT from A Phase II, Randomized, Study of Weekly APG101+Reirradiation versus Reirradiation in Progressive Glioblastoma
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Stephanie E. Combs, Martin Bendszus, Michael Platten, Claudia Kunz, Christian Hartmann, Jürgen Debus, Inga Harting, Elena Vetlova, Josef Pichler, Andreas von Deimling, Maximilian G. Schliesser, Benedikt Wiestler, Oliver Heese, Tobias Martens, Grigory Kobyakov, Klaus Junge, Harald Fricke, and Wolfgang Wick
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CONSORT Statement
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- 2023
21. Suppl Figures from A Phase II, Randomized, Study of Weekly APG101+Reirradiation versus Reirradiation in Progressive Glioblastoma
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Stephanie E. Combs, Martin Bendszus, Michael Platten, Claudia Kunz, Christian Hartmann, Jürgen Debus, Inga Harting, Elena Vetlova, Josef Pichler, Andreas von Deimling, Maximilian G. Schliesser, Benedikt Wiestler, Oliver Heese, Tobias Martens, Grigory Kobyakov, Klaus Junge, Harald Fricke, and Wolfgang Wick
- Abstract
Suppl Figures S1-S4. S1: Genomic Localization of the CpG2 in the CD95 L promoter. S2: Survival probability according to CpG2 methylation status. S3: Survival probability according to CD95L expression as detected by IHC. S4 a and b: Cox regression data for CpG1 and 2 in the CD95L promoter.
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- 2023
22. Supplementary Tables 1-7 from MGMT Promoter Methylation Is a Strong Prognostic Biomarker for Benefit from Dose-Intensified Temozolomide Rechallenge in Progressive Glioblastoma: The DIRECTOR Trial
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Wolfgang Wick, Guido Reifenberger, Johannes Hüsing, Spyros Kollias, Peter Vajkoczy, Jürgen Meixensberger, Guido Nikkhah, Josef Pichler, Krisztian Homicsko, Roger Stupp, Roland Goldbrunner, Christine Marosi, Uwe Schlegel, Jörg C. Tonn, Michael Platten, Oliver Bähr, Ralf Ketter, Hans-Georg Wirsching, Michael C. Sabel, Ulrich Herrlinger, Peter Hau, Oliver Schnell, Antje Wick, Joachim P. Steinbach, Jörg Felsberg, Bärbel Kästner, Ghazaleh Tabatabai, and Michael Weller
- Abstract
Supplementary Tables 1-7. Supplementary Table 1. Safety and tolerability. Supplementary Table 2. Outcome by MGMT promoter methylation status and treatment arm. Supplementary Table 3. Outcome by interval from last TMZ administration and MGMT promoter methylation status. Supplementary Table 4. Adherence to Mini Mental Status data collection over the course of the study. Supplementary Table 5. Treatment effect (Arm B versus Arm A) on EORTC-QLQ-C30 and -BN20 scales evaluated at timepoint 90 days Supplementary Table 6. Absolute changes of (0-100) score points of quality of life (as assessed by the EORTC-QLQ-C30 and -BN20 scales) within one treatment cycle of 28 days in Arms A and B, along with local p-values for difference in slopes. Supplementary Table 7. Adherence to EORTC-QLQ-BN20 and -C30 data collection over the course of the study.
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- 2023
23. Trabectedin for recurrent WHO grade 2 or 3 meningioma: A randomized phase II study of the EORTC Brain Tumor Group (EORTC-1320-BTG)
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Charlotte Bronnimann, Antonio Silvani, Vassilis Golfinopoulos, François Ducray, Martin Bendszus, Michael Weller, Marc Sanson, Paul Clement, Felix Sahm, Riccardo Soffietti, Niklas Thon, Corneel Coens, Florence Lefranc, Josef Pichler, Christian Mawrin, Veronique Lorgis, Lucy Brazil, Matthias Preusser, Emilie Le Rhun, Elodie Vauleon, Jacoline E C Bromberg, Alison Cameron, Juan Manuel Sepúlveda, Jordi Bruna, Joanne Lewis, Alice Bonneville-Levard, Christine Marosi, Sarah Dumont, Maximilian J. Mair, Sara Erridge, Julia Furtner, Jaap C. Reijneveld, Philipp Sievers, Wolfgang Wick, Giuseppe Lombardi, Petter Brandal, Carmen Balana, Thierry Gorlia, Neurology, and CCA - Cancer Treatment and quality of life
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Oncology ,Cancer Research ,medicine.medical_specialty ,Bevacizumab ,Clinical Investigations ,Phases of clinical research ,World Health Organization ,meningioma ,DNA methylation class ,SDG 3 - Good Health and Well-being ,Internal medicine ,Clinical endpoint ,medicine ,Meningeal Neoplasms ,Humans ,Progression-free survival ,Trabectedin ,Performance status ,business.industry ,Brain Neoplasms ,Hazard ratio ,clinical trial ,Chemotherapy regimen ,quality of life ,trabectedin ,Neurology (clinical) ,Neoplasm Recurrence, Local ,business ,Meningioma ,medicine.drug - Abstract
Background No systemic treatment has been established for meningioma progressing after local therapies. Methods This randomized, multicenter, open-label, phase II study included adult patients with recurrent WHO grade 2 or 3 meningioma. Patients were 2:1 randomly assigned to intravenous trabectedin (1.5 mg/m2 every 3 weeks) or local standard of care (LOC). The primary endpoint was progression-free survival (PFS). Secondary endpoints comprised overall survival (OS), objective radiological response, safety, quality of life (QoL) assessment using the QLQ-C30 and QLQ-BN20 questionnaires, and we performed tissue-based exploratory molecular analyses. Results Ninety patients were randomized (n = 29 in LOC, n = 61 in trabectedin arm). With 71 events, median PFS was 4.17 months in the LOC and 2.43 months in the trabectedin arm (hazard ratio [HR] = 1.42; 80% CI, 1.00-2.03; P = .294) with a PFS-6 rate of 29.1% (95% CI, 11.9%-48.8%) and 21.1% (95% CI, 11.3%-32.9%), respectively. Median OS was 10.61 months in the LOC and 11.37 months in the trabectedin arm (HR = 0.98; 95% CI, 0.54-1.76; P = .94). Grade ≥3 adverse events occurred in 44.4% of patients in the LOC and 59% of patients in the trabectedin arm. Enrolled patients had impeded global QoL and overall functionality and high fatigue before initiation of systemic therapy. DNA methylation class, performance status, presence of a relevant co-morbidity, steroid use, and right hemisphere involvement at baseline were independently associated with OS. Conclusions Trabectedin did not improve PFS and OS and was associated with higher toxicity than LOC treatment in patients with non-benign meningioma. Tumor DNA methylation class is an independent prognostic factor for OS.
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- 2022
24. CTNI-07. LOMUSTINE/TEMOZOLOMIDE CHEMOTHERAPY FOR NEWLY DIAGNOSED MGMT-METHYLATED IDHWT GLIOBLASTOMA ACCORDING TO CETEG/NOA-09: REAL-WORLD EXPERIENCE IN A MULTICENTER COHORT
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Johannes Weller, Thomas Zeyen, Uwe Schlegel, Lazaros Lazaridis, Jan-Michael Werner, Julia Onken, Pia Zeiner, Richard Drexler, Peter Hau, Clemens Seidel, Lucia Grosse, Hans Clusmann, Michael Sabel, Florian Ringel, Josef Pichler, Oliver Grauer, Thomas Hundsberger, Oliver Schnell, Maximilian J Mair, Martin Uhl, Friederike Schmidt-Graf, Martin Glas, Norbert Galldiks, Meike Unteroberdörster, Joachim Steinbach, Franz Ricklefs, Mirjam Renovanz, Daniel Ivanov Delev, Merih O Turgut, Oliver R Flesch, Debora Cipriani, Matthias Preusser, Sied Kebir, Martin Misch, Roland Goldbrunner, Manfred Westphal, Ghazaleh Tabatabai, Niklas Schäfer, Matthias Schneider, Hartmut Vatter, Frank Giordano, Christina Schaub, and Ulrich Herrlinger
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Cancer Research ,Oncology ,Neurology (clinical) - Abstract
INTRODUCTION The CeTeG/NOA-09 trial demonstrated superior median overall survival (mOS, 48.1 months) in MGMT-methylated glioblastoma treated with lomustine/temozolomide compared to temozolomide. We retrospectively analyzed an off-study cohort of patients treated with lomustine/temozolomide to gather real-world data on this new regimen. METHODS Adult patients from 20 centers in Germany, Austria and Switzerland were included. Inclusion criteria were MGMT-methylated IDHwt glioblastoma newly diagnosed prior to end of 2020, and lomustine/temozolomide treatment as part of first-line therapy. RESULTS 321 patients with a median age of 57 years (range, 21-78) and a median follow-up of 19.9 months were included. In the whole cohort, mOS was 41.0 months (95%CI, 33.0 – not reached). In patients starting lomustine/temozolomide immediately upon initiation of radiotherapy strictly following the CeTeG protocol (88%), mOS was 52.8 months (35.8 – not reached) as compared to 24.6 months (17.6 – not reached) in patients starting lomustine/temozolomide after completion of radiotherapy/concomitant temozolomide (12%, logrank test: p = 0.06). Patients with a KPS < 80 had a shorter mOS of 19.7 months (95%CI, 16.6 – not reached) compared to 41.0 months (33.0 – not reached, p = 0.009) in KPS 80-100. Gross total resection (GTR, 53.9%) was associated with longer mOS (52.8 months, 95%CI 24.1 – not reached) compared to partial resection/biopsy (30.5 months, 95%CI 36.8 – not reached, p=0.004). Multivariable Cox regression analysis confirmed GTR (HR 0.66, p = 0.033) and younger age ( ≤ 50 years: HR 0.42, p = 0.001), but not KPS (80-100 vs. lower: HR 0.66, p = 0.12) as independent prognostic factors. DISCUSSION In this real-world multicenter cohort, survival was similar to the promising results of CeTeG/NOA-09. Further analyses should investigate a potentially reduced benefit from lomustine/temozolomide in patients with low KPS/no GTR and a possible detrimental effect from deferred lomustine/temozolomide initiation. The median follow-up is admittedly short, updated data will be presented.
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- 2022
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