Citations
Mayo Clinic
48 citation(s) found for "Ma, Shuo".
Gene-mapping study of extremes of cerebral small vessel disease reveals TRIM47 as a strong candidate
Mishra, Aniket , Duplàa, Cécile , Suzuki, Hideaki , Li, Shuo , Bartz, Traci M. , Jian, Xueqiu , Zhao, Wei , Hofer, Edith , Wittfeld, Katharina , Bis, Joshua C, Adams, Hieab H.H. , Satizábal, Claudia L. , Gottesman, Rebecca F., Gampawar, Piyush , Weiß, Stefan , Yu, Miao , Lopez, Oscar L., Vernooij, Meike W. , Soumaré, Aïcha , Smith, Jennifer A. , Zhu, Yi‐Cheng , Rotter, Jerome I. , Dufouil, Carole , Maniega, Susana Muñoz , Lathrop, Mark, Boerwinkle, Erik, Schmidt, Reinhold, Ihara, Masafumi , Joutel, Anne , Tournier‐Lasserve, Elisabeth , Mosley, Thomas H. , DeCarli, Charles , Tzourio, Christophe , Kardia, Sharon L. R., Teumer, Alexander , Schmidt, Helena , Wardlaw, Joanna M. , Fornage, Myriam , Guðnason, Vilmundur , Longstreth, W.T. , Couffinhal, Thierry , Debette, Stéphanie , Zhao, Wei , Sargurupremraj, Muralidharan , DeCarli, Charles , Suzuki, Hideaki , Sargurupremraj, Muralidharan , Bülow, Robin , Weiss, Stefan , Völker, Uwe , Smith, Jennifer A , Yang, Qiong , Amouyel, Philippe , Tzourio, Christophe , Teumer, Alexander , van Duijn, Cornelia M , Matthews, Paul M , Debette, Stephanie , Wardlaw, Joanna Marguerite , Adams, Hieab H H , Satizabal, Claudia L , Rotter, Jerome I , Vojinović, Dina , Zilhäo, Nuno R. , Harris, Sarah , Auwera, Sandra Van der , Luciano, Michelle , Bis, Joshua C, Bastin, Mark E. , Beiser, Alexa , Völker, Uwe , Kacprowski, Tim , Knopman, David S. , Morris, Zoë , Hernández, Maria del Carmen Valdés , Mazoyer, Bernard , Launer, Lenore J. , Deary, Ian J. , Amouyel, Philippe , Psaty, Bruce M. , Grabe, Hans Jörgen , Duijn, Cornelia M. van , Ikram, M. Arfan , Seshadri, Sudha , Matthews, Paul M.
Brain | December 8, 2021 | Volume: 145 | Issue: 6 | Pages: 1992-2007
10.1093/brain/awab432
| PMID 35511193
Abstract Cerebral small vessel disease is a leading cause of stroke and a major contributor to cognitive decline and dementia, but our understanding of specific genes underlying the cause of sporadic cerebral small vessel disease is limited. We report a genome-wide association study and a whole-exome association study on a composite extreme phenotype of cerebral small vessel disease derived from its most common MRI features: white matter hyperintensities and lacunes. Seventeen population-based cohorts of older persons with MRI measurements and genome-wide genotyping (n = 41 326), whole-exome sequencing (n = 15 965), or exome chip (n = 5249) data contributed 13 776 and 7079 extreme small vessel disease samples for the genome-wide association study and whole-exome association study, respectively. The genome-wide association study identified significant association of common variants in 11 loci with extreme small vessel disease, of which the chr12q24.11 locus was not previously reported to be associated with any MRI marker of cerebral small vessel disease. The whole-exome association study identified significant associations of extreme small vessel disease with common variants in the 5′ UTR region of EFEMP1 (chr2p16.1) and one probably damaging common missense variant in TRIM47 (chr17q25.1). Mendelian randomization supports the causal association of extensive small vessel disease severity with increased risk of stroke and Alzheimer’s disease. Combined evidence from summary-based Mendelian randomization studies and profiling of human loss-of-function allele carriers showed an inverse relation between TRIM47 expression in the brain and blood vessels and extensive small vessel disease severity. We observed significant enrichment of Trim47 in isolated brain vessel preparations compared to total brain fraction in mice, in line with the literature showing Trim47 enrichment in brain endothelial cells at single cell level. Functional evaluation of TRIM47 by small interfering RNAs-mediated knockdown in human brain endothelial cells showed increased endothelial permeability, an important hallmark of cerebral small vessel disease pathology. Overall, our comprehensive gene-mapping study and preliminary functional evaluation suggests a putative role of TRIM47 in the pathophysiology of cerebral small vessel disease, making it an important candidate for extensive in vivo explorations and future translational work.
Influence of Preoperative and Postoperative Factors on Prolonged Length of Stay and Readmission After Minimally Invasive Radical Prostatectomy
Wilson, Robert R. , Hemal, Ashok K. , Liu, Shuo , Craven, Tim, Pathak, Ram A. , Pathak, Ram A , Wilson, Robert R A , Petrou, Steven
Journal of Endourology | September 22, 2021 | Volume: 36 | Issue: 3 | Pages: 327-334
10.1089/end.2021.0571
| PMID 34549603
Background: The mean length of stay (LOS) after minimally invasive radical prostatectomy (MI-RP) is <2 days. Our main objective was to utilize the National Surgical Quality Improvement Program (NSQIP) database to evaluate preoperative factors that may contribute to prolonged hospital stay and readmission. Materials and Methods: Utilizing the NSQIP database, records for surgery with the Current Procedural Terminology code 55866 (prostatectomy) between 2007 and 2017 were evaluated. Chi-square and t -tests were used to assess the effects of preoperative factors on prolonged LOS and rates of hospital readmission within 30 days. Odds ratios (ORs), p -values, and confidence intervals were determined using multivariable logistic regression. Results: A total of 40,764 patients underwent MI-RP between 2007 and 2017. Of these, 11.7% reported an LOS of >2 days, whereas 3.9% of patients were readmitted to the hospital within 30 days. Preoperative congestive heart failure within 30 days of surgery was shown to be strongly associated with both prolonged LOS (OR = 6.16) and readmission (OR = 3.28). Bleeding requiring transfusion was demonstrated to be the most significant postoperative factor for prolonged LOS (OR = 23.9), whereas unplanned intubation was shown to be the most significant postoperative factor for readmission (OR = 57.1). Body mass index (BMI) >30 was associated with both prolonged LOS and increase in readmission. Conclusions: Upon NSQIP database analysis, cardiopulmonary factors and BMI were demonstrated to have negative impacts on postoperative quality indicators. Patients with comorbidities should be counseled preoperatively concerning their individual risk factors. Mitigation of these factors is important in ensuring optimal outcomes.
Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2 : A genome‐wide association study in over 12,000 non‐demented participants
Grenier‐Boley, Benjamin , Simino, Jeannette , Adams, Hieab H.H. , White, Charles C. , Terzikhan, Natalie, Cruchaga, Carlos , Knol, Maria J. , Li, Shuo , Schraen, Susanna, Grove, Megan L. , Satizábal, Claudia L. , Amin, Najaf , Younkin, Steven G., Initiative, Alzheimer's Disease Neuroimaging, Gottesman, Rebecca F., Buée, Luc , Uitterlinden, André G. , DeCarli, Charles , Bressler, Jan , DeStefano, Anita L. , Dartigues, Jean‐François, Boerwinkle, Eric , Tzourio, Christophe , Fornage, Myriam , Jager, Phil De, Reitz, Christiane, Mosley, Thomas H. , Lambert, Jean‐Charles , Duijn, Cornelia M. van , DeCarli, Charles , Younkin, Steven, Cruchaga, Carlos , Adams, Hieab H H , Satizabal, Claudia L , Tzourio, Christophe , van Duijn, Cornelia M , Damotte, Vincent , Lee, Sven J. van der , Chouraki, Vincent Antoine , Tosto, Giuseppe , Berr, Claudine , Initiative, Alzheimer's Disease Neuroimaging, Beiser, Alexa , Knopman, David S. , Yang, Qiong , Ikram, M. Arfan , Amouyel, Philippe , Jager, Philip L. De , Seshadri, Sudha
Alzheimer's & Dementia | May 18, 2021 | Volume: 17 | Issue: 10 | Pages: 1663-1674
10.1002/alz.12333
| PMID 34002480
Abstract Introduction There is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures. Methods We included 12,369 non‐demented participants from eight population‐based studies. Imputed genetic data and measured plasma Aβ1‐40, Aβ1‐42 levels and Aβ1‐42/Aβ1‐40 ratio were used to perform genome‐wide association studies, and gene‐based and pathway analyses. Significant variants and genes were followed up for their association with brain positron emission tomography Aβ deposition and AD risk. Results Single‐variant analysis identified associations with apolipoprotein E ( APOE ) for Aβ1‐42 and Aβ1‐42/Aβ1‐40 ratio, and BACE1 for Aβ1‐40. Gene‐based analysis of Aβ1‐40 additionally identified associations for APP , PSEN2 , CCK , and ZNF397 . There was suggestive evidence for interaction between a BACE1 variant and APOE ε4 on brain Aβ deposition. Discussion Identification of variants near/in known major Aβ‐processing genes strengthens the relevance of plasma‐Aβ levels as an endophenotype of AD.
Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition) 1
Klionsky, Daniel J., Abdel‐Aziz, Amal Kamal , Abdellatif, Mahmoud , Abdoli, Asghar , Abel, Steffen , Abeliovich, Hagai , Abildgaard, Marie H. , Abudu, Yakubu Princely , Acevedo‐Arozena, Abraham , Adamopoulos, Iannis E. , Adeli, Khosrow , Adolph, Timon E. , Adornetto, Annagrazia , Aflaki, Elma, Agam, Galila , Aggarwal, Bharat B. , Agnello, Maria, Agostinis, Patrizia , Agrewala, Javed N. , Agrotis, Alexander , Aguilar, Patricia V., Ahmad, S. Tariq, Ahumada-Castro, Ulises , Aits, Sonja , Aizawa, Shu, Akkoç, Yunus , Akoumianaki, Tonia, Akpinar, Hafize Aysin , Al‐Abd, Ahmed M. , Al-Akra, Lina, Gharaibeh, Abeer , Alaoui‐Jamali, Moulay A. , Alberti, Simon , Alessandri, Cristiano , Alonso, Alicia , Altan‐Bonnet, Nihal , Álvarez, Élida, Alves, Sara , Costa, Cristine Alvès da , Alzaharna, Mazen M. , Amadio, Marialaura , Amantini, Consuelo , Amaral, Cristina , Ambrosio, Susanna , Amer, Amal O. , Ammanathan, Veena , An, Zhenyi, Andrabi, Shaida A. , Andres, Allen M. , Ann, David K. , Anozie, Uche C. , Ansari, Mohammad Y. , Antas, Pedro , Antebi, Adam , Antón, Zuriñe , Anwar, Tahira , Apétoh, Lionel , Araki, Toshiyuki , Araki, Yasuhiro , Araya, Jun , Arévalo, María‐Ángeles , Argüelles, Sandro , Arias, Esperanza , Arikkath, Jyothi , Ariosa, Aileen, Aroca, Ángeles , Arroyo, Daniela S., Arsov, Ivica, Artero, Rubén , Asaro, Dalia Maria Lucia, Ashur‐Fabian, Osnat , Atanasov, Atanas G. , Au, Alicia K. , Auberger, Patrick , Auner, Holger W. , Aurelian, Laure , Avagliano, Laura , Ávalos, Yenniffer , Aveleira, Célia A. , Aydın, Yücel , Ayyadevara, Srinivas , Azzopardi, Maria , Baba, Misuzu, Backer, Jonathan , Bae, Soo Han , Baehrecke, Eric H. , Bagetta, Giacinto , Bagniewska‐Zadworna, Agnieszka , Bai, Hua , Bai, Xiyuan , Bairagi, Nandadulal , Baksi, Shounak , Balbi, Teresa , Ballester, María , Balazadeh, Salma , Balzan, Rena , Bandopadhyay, Rina , Banerjee, Sulagna , Bánréti, Ágnes , Baracca, Alessandra , Barbati, Cristiana , Bargiela, Ariadna , Barilà, Daniela , Barlow, Peter G. , Barmada, Sami J. , Barreiro, Esther , Bártek, Jiří , Bartel, Bonnie , Bartolomé, Alberto , Barve, Gaurav , Bassham, Diane C. , Baulieu, E.E. , Baumgarner, Bradley L. , Bayry, Jagadeesh , Beale, Rupert , Beau, Isabelle , Beaumatin, Florian , Bechara, Luiz Roberto Grassmann , Beck, George R. , Beers, Michael F. , Begun, Jakob , Behrends, Christian , Bejarano, Eloy , Bel, Shai , Belaïd, Amine , Belgareh‐Touzé, Naïma, Bellarosa, Cristina , Belleudi, Francesca , Belló-Pérez, Melissa , Beltran, Jackeline Soares de Oliveira , Beltran, Sebastián, Benbrook, Doris M. , Bendorius, Mykolas , Benítez, Bruno A. , Benito‐Cuesta, Irene , Bensalem, Julien , Berchtold, Martin W. , Berezowska, Sabina , Bergamaschi, Daniele , Berliocchi, Laura , Berlioz‐Torrent, Clarisse , Bernard, Amélie , Besirli, Cagri G. , Besteiro, Sébastien , Betin, Virginie M.S., Beyaert, Rudi , Bezbradica, Jelena S. , Bhaskar, Kiran , Bhatia‐Kiššová, Ingrid, Bhattacharya, Sujoy , Bhuiyan, Md. Shenuarin , Bi, Xiaolin , Biden, Trevor J. , Bijian, Krikor , Billes, Viktor , Binart, Nadine , Bincoletto, Cláudia , Blanco, Gonzalo , Blas‐García, Ana , Błasiak, Janusz , Blomgran, Robert , Blum, Janice S. , Boada-Romero, Emilio, Boban, Mirta , Boeuf, Philippe , Boland, Barry , Bomont, Pascale , Bonaldo, Paolo , Bonam, Srinivasa Reddy , Bonfili, Laura , Bootman, Martin D. , Bordi, Matteo , Borner, Christoph , Bornhäuser, Beat , Bose, Santanu , Botas, Juan , Boulanger, Chantal M. , Bourgeois, Benjamin , Bourke, Nollaig M. , Bousquet, Guilhem , Boya, Patricia , Bozhkov, Peter V. , Bozi, Luiz H. M. , Bozkurt, Tolga O. , Pedro, José Manuel Bravo‐San , Brest, Patrick , Bringer, Marie-Agnès , Briones‐Herrera, Alfredo , Broaddus, V. Courtney, Brodersen, Peter , Brodsky, Jeffrey L. , Bronson, Paola G. , Bronstein, Jeff M. , Brown, Rhoderick E. , Brum, Patrı́cia C. , Bruno, Daniele , Bryson‐Richardson, Robert J. , Bucci, Cecilia , Buchrieser, Carmen , Bueno, Marta , Buchan, J. Ross , Buckingham, Erin M., Budak, Hikmet , Budini, Mauricio , Bultynck, Geert , Burada, Florin , Burgoyne, Joseph R. , Burón, María I. , Bustos, Victor , Büttner, Sabrina , Byrd, Aaron , Cabas, Isabel , Cabrera, Sandra , Cadwell, Ken , Cai, Jingjing , Cai, Lu , Cai, Qian , Calbet, José A. L. , Caldwell, Guy A. , Call, Jarrod A. , Calvani, Riccardo , Calvo, Ana Cristina , Calvo‐Rubio, Miguel , Câmara, Niels Olsen Saraiva , Camonis, Jacques , Camougrand, Nadine , Campanella, Michelangelo , Campbell, Edward M. , Campos, Juliane C. , Camuzard, Olivier , Cancino, Jorge , Caniggia, Isabella , Canonico, Barbara , Cantı́, Carles , Cao, Bin , Caramés, B. , Cardenal‐Muñoz, Elena , Cárdenas, César , Cárdenas, Luis , Cardoso, Sandra M. , Carew, Jennifer S. , Carle, Georges F. , Carleton, Gillian , Carloni, Silvia , Carneiro, Letícia A. M. , Carosi, Julian M. , Carra, Serena , Carrier, Alice , Carter, A. Brent, Carvalho, Andreia Neves , Casanova, Magali , Casas, Josefina , Cassioli, Chiara , Castillo, Karen , Castillo‐Lluva, Sonia , Castoldi, Francesca , Castori, Marco , Castro, Ariel F. , Castro‐Hernández, Javier , Cavadas, Cláudia , Cavaliere, Federica, Cavallini, Gabriella , Cavinato, Maria , Rica, Paula Cebollada , Cechowska‐Pasko, Marzanna , Cerqueira, João , Cerutti, Janete M. , Çetintaş, Vildan Bozok , Cetrullo, Silvia , Chagin, Andrei S. , Chai, Chee‐Yin , Chakrabarti, Gopal , Chakraborty, Tapas , Chakraborty, Trinad , Chami, Mounia , Chamilos, Georgios , Chan, David W. , Chan, Edmond Y. W., Chan, Ho Yin Edwin , Chan, Helen H., Chan, Hung , Chan, Matthew T.V. , Chan, Yau Sang , Chang, Hao‐Chun , Chang, Kai , Chao, Jie , Charlet‐Berguerand, Nicolas , Chatterjee, Samrat , Chaube, Shail K. , Chaudhary, Anu , Chauhan, Santosh , Chaum, Edward , Checler, Frédéric , Cheetham, Michael E. , Chen, Chang‐Shi , Chen, Jian‐Fu , Chen, Liam L., Chen, Mingliang , Chen, Mu‐Kuan , Chen, Ning , Chen, Wei , Chen, Xinming , Chen, Xiongwen , Chen, Yan , Chen, Ye‐Guang , Chen, Yingyu , Chen, Yongqiang , Chen, Zhefan Stephen , Chen, Zhihua , Cheng, Xiu‐Tang , Cheng, Yiyun , Cheng, Zhiyong , Cheong, Jit Kong , Cherry, Sara , Cheung, Chi F., Cheung, Chun Hei Antonio , Cheung, King‐Ho , Chevet, Éric , Chi, Richard J., Chiaradonna, Ferdinando , Chiariello, M , Chica, Nathalia , Chiocca, Susanna , Chiong, Mario , Chiou, Shih‐Hwa , Chiramel, Abhilash I., Chiurchiù, Valerio , Cho, Dong-Hyung, Choe, Seong‐Kyu , Choi, Augustine M.K. , Choi, Mary E. , Choudhury, Kamalika Roy , Chow, Norman , Chua, Jason P. , Chua, John Jia En , Chung, Hyewon , Chung, Kin Pan , Chung, So‐Hyang , Chung, Yuen-Li, Ciechomska, Iwona A. , Cinque, Laura , Çırak, Sebahattin , Clarke, Robert , Clementi, Emilio , Coccia, Eliana M. , Codogno, Patrice , Colasanti, Tania , Colasuonno, Fiorella , Colbert, Robert A. , Colell, Anna , Coll, Núria S. , Collins, Mark O. , Colombo, Marı́a I. , Colón‐Ramos, Daniel A. , Cominetti, Márcia R. , Consiglio, Antonella , Conte, A. , Contu, Viorica Raluca , Cookson, Mark , Coombs, Kevin M. , Costa, Maria do Carmo , Costantino, Sarah , Costelli, Paola , Criollo, Alfredo , Crippa, V. , Cristofani, Riccardo , Csizmadia, Tamás , Cui, Bing , Cui, Yixian , Culetto, Emmanuel , Cumino, Andrea C. , Cybulsky, Andrey V. , Czaja, Mark J. , Czuczwar, Stanisław J. , D’Adamo, Stefania , D’Amelio, Marcello , D’Orazi, Gabriella , Silva, James Almada da , Dafsari, Hormos Salimi , Daglia, Maria , Dai, Xiaoxia , Dai, Yun , Dai, Yuyuan , Col, Jessica Dal , Dalhaimer, Paul , Valle, Luisa Dalla , Dallenga, Tobias , Dalmasso, Guillaume , Dando, Ilaria , Das, Hiranmoy , Dasari, Santosh K. , Dash, Srikanta, Dauphinee, Adrian N. , Davies, Jeffrey S. , Dávila, Valeria A. , Davis, Roger J. , Naidu, Sharadha Dayalan , Bosscher, Karolien De , Leonibus, Chiara De , Barbosa, Mayara Garcia de Mattos , Meyer, Guido R.Y. De , Palma, Clara De , Virgilio, Claudio De , Zio, Daniela De , Decuypere, Jean-Paul , Deehan, Mark , Deflorian, Gianluca , Dehay, Benjamin , Delaney, Joe R. , Delorme‐Axford, Elizabeth , Demers, Nicholas D. , Deng, Hongbin , Dengjel, Jörn , Dent, Paul, DePamphilis, Melvin L., Descoteaux, Albert , Devis, Laura , Devkota, Sushil , Devuyst, Olivier , Dewson, Grant , Dharmasivam, Mahendiran , Domenico, Fabio Di , Fazio, Pietro Di , Fonzo, Alessio Di , Guardo, Giovanni Di , Guglielmo, Gianni M. Di , Leo, Luca Di , Malta, Chiara Di , Nardo, Alessia Di, Rienzo, Martina Di , Diao, Jiajie , Diaz-Araya, Guillermo, Díaz‐Laviada, Inés , Dickinson, Jared M. , Diederich, Marc , Dieudé, Mélanie , Ding, Shiping , Ding, Wen-Xing, Dinić, Jelena , Dinić, Miroslav , Dinkova‐Kostova, Albena T. , Distler, Jörg H. W. , Đokić, Jelena , Emre, Serap , Dong, Xiaonan , Dong, Zhiwu , Dorn, Gerald W. , Dou, Juan, Dowaidar, Moataz , Drucker, Liat , Du, Ailian , Du, Guangwei , Du, Hai‐Ning , Toit, André du , Duan, Shao-Bin , Duan, Xiaoqiong , Duarte, Sónia , Dupont, Nicolas , Durán, Raúl V. , Dyshlovoy, Sergey A. , Ebrahimi‐Fakhari, Darius , Eckhart, Leopold , Edelstein, Charles L. , Efferth, Thomas , Eid, Nabil , Eisenberg, Tobias , Eissa, N. Tony, Ejarque, Miriam , Andaloussi, Abdeljabar El, El‐Hage, Nazira , Eleuteri, Anna Maria , El‐Shafey, Eman S. , Elgendy, Mohamed , Elizalde, María Mercedes , Elsässer, Hans‐Peter , Elsherbiny, Eslam S. , Emre, N. C. Tolga , Eng, Christina H. , Engedal, Nikolai , Engelsen, Agnete S. T. , Enserink, Jorrit M. , Escalante, Ricardo , Esclatine, Audrey , Eskelinen, Eeva‐Liisa , Espert, Lucile , Eusebio, Makandjou-Ola , Facchiano, Antonio , Facchiano, Francesco , Fadeel, Bengt , Fader, Claudio M., Faesen, Alex C. , Fairlie, W. Douglas , Falcó, Alberto , Fan, Daping , Fan, Jie , Fang, Evandro Fei , Fang, Yanshan , Fang, Yognqi, Farfel‐Becker, Tamar, Faure, Mathias , Fazeli, Gholamreza , Fedele, Anthony O., Feldman, Arthur M. , Feng, Jiachun , Feng, Lifeng , Feng, Wei , Araujo, Thaís Fenz , Ferguson, Thomas A., Fernández, Álvaro F. , Fernández‐Veledo, Sonia , Fernie, Alisdair R. , Ferrante, Anthony W. , Ferraresi, Alessandra , Ferrari, M , Ferreira, Julio Cesar Batista , Ferro‐Novick, Susan , Figueras, António , Filadi, Riccardo , Filigheddu, Nicoletta , Fimia, Gian María , Finetti, Francesca , Finkbeiner, Steven , Fisher, Edward A. , Fisher, Paul B. , Fliesler, Steven J. , Flo, Trude Helen , Florance, Ida , Florey, Oliver , Florio, Tullio , Fodor, Erika , Forlino, Antonella , Fortini, Paola , Fracassi, Anna , Franconi, Flavia , Frankel, Lisa B. , Fröhlich, Leopold F. , Fuentes, José M. , Fujiki, Yukio , Fulda, Simone , Furuya, Norihiko , Gack, Michaela U. , Gaffke, Lidia , Galadari, Sehamuddin , Galasso, Alessia , Galindo, Marı́a F. , Kankanamalage, Sachith Gallolu , Galluzzi, Lorenzo, Galy, Vincent , Gammoh, Noor , Ganley, Ian G. , Gao, Feng , Gao, Minghui , Gao, Ping , Gao, Wentao , Gao, Xiaobo , Garcerá, Ana , Garcia, María Noé , García, Verónica , Portillo, Francisco Garcı́a-del , García‐Escudero, Vega , García‐García, Aracely , García‐Macía, Marina , García‐Moreno, Diana , García‐Ruiz, Carmen , García‐Sanz, Patricia , Garg, Abhishek D. , Garofalo, Tina , Gassen, Nils C. , Gatica, Damián , Geiss‐Friedlander, Ruth , Genschik, Pascal , Gerbino, Valeria , Gerhardt, Christoph , Germain, Kyla , Germain, Marc , Afshar, Elham Ghasemipour, Ghavami, Saeid , Ghosh, Manosij , Giamas, Georgios , Giatromanolaki, Alexandra , Gibson, Gary E. , Ginet, Vanessa, Girardin, Stephen E. , Giridharan, Mridhula, Giuliano, Sandy , Giulivi, Cecilia , Giuriato, Sylvie , Giustiniani, Julien , Gluschko, Alexander , Goder, Veit , Goginashvili, Alexander , Gołąb, Jakub , Golebiewska, Anna , Gomes, Luciana Rodrigues, Gomez, Rodrigo Enrique, Gómez‐Sánchez, Rubén , Gómez‐Sintes, Raquel , Gong, Qingqiu , González‐Gallego, Javier , González‐Polo, Rosa A. , González‐Reyes, José A. , González-Rodríguez, Patricia , Goping, Ing Swie , Gorbunov, Nikolai V., Görgülü, Kıvanç , Gorojod, Roxana Mayra , Gorski, Sharon M. , Gotor, Cecilia , Gözüaçık, Devrim , Graef, Martin , Gräler, Markus H. , Granatiero, Veronica, Grasso, Daniel , Gray, Joshua P. , Greenhough, Alexander , Gregory, Stephen L. , Griffin, Edward F., Gros, Frédéric , Grose, Charles , Gross, Angelina S. , Грубер, Флориан , Grumati, Paolo , Gu, Xueyan , Guan, Jun‐Lin , Guardia, Carlos M. , Guda, Kishore , Guerra, Flora , Guerri, Consuelo , Guha, Prasun , Guillén, Carlos , Gujar, Shashi , Gukovskaya, Anna S. , Gukovsky, Ilya , Gunst, Jan , Günther, Andreas , Guo, Chuanyong , Guo, Chun , Guo, Hongqing , Guo, Ming , Gupta, Pawan , Gupta, Swapnil , Gupta, Veer Bala , Gupta, Vivek , Gutterman, David D. , H.B., Ranjitha, Haber, James E. , Hać, Aleksandra , Haidar, Mansour , Halldén, Gunnel , Hamacher‐Brady, Anne , Hamasaki, Maho , Hansen, Malene , Hao, Zijian, Harada, Masaru , Harhaji‐Trajkovic, Ljubica , Hariharan, Nirmala , Haspel, Jeffrey A. , Haucke, Volker , Hawkins, Wayne D. , Haynes, Cole M. , Hays, Thomas S. , He, Congcong , He, Qin , He, Rong‐Rong , He, You‐Wen , Heakal, Yasser, Heberle, Alexander Martin , Hejtmancik, J. Fielding , Henkel, Vanessa, Herb, Marc , Herman-Antosiewicz, Anna , Hernández, Agustín , Hernández, Carlos , Hernández-Díaz, Sergio , Hernández–Gea, Virginia , Herpin, Amaury , Herreros, Judit , Hervás, Javier H. , Hesselson, Daniel , Hetz, Claudio , Higuchi, Yujiro , Hilfiker, Sabine , Hill, Joseph A., Ho, Emmanuel A. , Ho, Idy H. T. , Ho, Philip Wing‐Lok , Ho, Shu‐Leong , Ho, Wan Yun, Hoet, Peter , Hofius, Daniel , Höhn, Annika , Hong, Yi-Ren Hong Chang-Won, Hooper, Lora V. , Hsin, I‐Lun , Hu, Bing , Hu, Dong , Hu, Wei , Hu, Zhuowei , Hua, Jinlian, Huan, Chongmin , Huang, Chuanshu , Huang, Chunling , Huang, Haishan , Huang, Michael , Huang, Shan , Huang, Tianzhi , Huang, Xing , Huang, Yuxiang , Hubert, Virginie , Hübner, Christian A. , Hughes, Stephanie M. , Hughes, William E. , Hummer, Gerhard , Hurley, James H. , Hussain, Sabah N. 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H. , Ma, Ning-Fang, Ma, Quanhong , Ma, Xinliang , Ma, Yueyun , Ma, Zhenyi , MacDougald, Ormond A. , MacIntosh, Gustavo C. , Macleod, Kay F. , Maday, Sandra , Madeo, Frank , Madesh, Muniswamy , Madl, Tobias , Madrigal‐Matute, Julio , Maeda, Akiko, Maejima, Yasuhiro , Magariños, Marta , Mahavadi, Poornima , Maiani, Emiliano , Maiese, Kenneth , Maiti, Panchanan , Maiuri, Maria Chiara , Major, Michael Ben, Makareeva, Elena , Malik, Fayaz , Mallilankaraman, Karthik , Maloyan, Alina , Mammadova, Najiba, Man, Gene Chi Wai , Manai, Federico , Mancias, Joseph D. , Mandelkow, Eva‐Maria , Manfredi, Angelo A. , Manshian, Bella B. , Manzano, Raquel , Marchese, Chiara , Marchetti, Sandrine , Marcucci, F, Mardente, Stefania , Mareninova, Olga A. , Mari, Muriel , Marinelli, Sara , Mariño, Guillermo , Mariotto, Sofia , Martin, Alexandre , Martin, Katie R. , Martin, Sara L. , Martín‐Segura, Adrián , Martin-Burriel, Inmaculada, Martín-Rincón, Marcos , Martín‐Sanz, Paloma , Martinez, Aitor , Martı́nez, Ana , Martinez-Lopez, Nuria, Martínez‐Vicente, Marta , Martins, Daniel Oliveira , Martins, Joilson O. , Martins, Waleska K. , Martins-Marques, Tania, Marzetti, Emanuele , Masaldan, Shashank , Masclaux-Daubresse, Celine, Mashek, Douglas G. , Massa, Valentina , Massieu, Lourdes , Masyuk, Anatoliy I. , Masyuk, Tetyana V., Matheu, Ander , Matoba, Satoaki , Matsuzaki, Sachiko , Mattar, Pamela , Mattè, Alessandro , Mauriz, José L., Mauthe, Mario , Maycotte, Paola , Mayer, Johanna , Mazzoni, Cristina , Mazzulli, Joseph R. , McCarty, Nami , McGill, Mitchell R. , McKenna, Sharon L. , McLoughlin, Fionn , McNiven, Mark A., McWilliams, Thomas G. , Medeiros, Tania , Medina, Diego L., Megeney, Lynn A. , Megyeri, Klára , Mehrpour, Maryam , Mehta, Jawahar L. , Meijer, Alfred J., Mejlvang, Jakob , Meléndez, Alicia , Melk, Annette, Memişoğlu, Gönen , Mendes, A.F. , Meng, Delong , Meng, Fei, Mercier, A., Mergny, Jean‐Louis , Merkley, Seth D. , Meske, Volker, Mestre, Ana Cecilia, Metur, Shree Padma, Meyer, C., Meyer, Hemmo , Mi, Wenyi , Mialet‐Perez, Jeanne , Miao, Jun‐Ying, Micale, Lucia , Miki, Yasuo, Milan, Enrico , Milczarek, Małgorzata , Miller, Samuel I. , Millward, Steven W. , Mirzaei, Hamed, Mirzaei, Hamid Reza , Mirzaei, Mehdi , Mishra, Amit , Mishra, Nandita , Mishra, Paras Kumar, Misirkić, Maja , Misasi, Roberta, Misra, Amit , Misso, Gabriella , Mitchell, Claire H. , Mitou, Géraldine, Miura, Tetsuji , Miyazaki, Makoto, Miyazaki, Mitsunori , Miyazaki, Taiga , Miyazawa, Keisuke, Mizushima, Noboru , Mogensen, Trine H. , Mohammadinejad, Reza , Mohamud, Yasir , Mohanty, Abhishek , Möhlmann, Torsten , Moley, Kelle H. , Möller, Andreas, Mollereau, Bertrand , Mollinedo, Faustino, Montagna, Costanza , Monteiro, Mervyn J. , Montella, Andrea , Montes, L. 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Amer, Ribeiro‐Rodrigues, Teresa , Riccio, Victoria , Richardson, Des R. , Risbud, Makarand V. , Risueño, Ruth M. , Ritis, Konstantinos, Rizza, Salvatore , Rizzuto, Rosario , Roberts, Scott J. , Roberts, Luke D., Robinson, Katherine J. , Rocchi, Stéphane , Rodrigues, Tiago , Silva, Vagner Ramon Rodrigues , Rodriguez-Barrueco, Ruth, Rodríguez‐Henche, Nieves , Rogers, Robert S. , Rogov, Vladimir V., Rojo, Ana I. , Romanello, Vanina, Romani, Luigina , Romano, Alessandra , Romano, Patricia Silvia , Romeo-Guitart, David, Romero, Luís C. , Romero, Montserrat , Roney, Joseph C. , Rongo, Christopher , Rosenfeldt, Mathias T. , Rosenstiel, Philip , Rosenwald, Anne , Roth, Steven, Rouschop, Kasper M.A. , Roussel, Benoit D. , Roux, Sophie , Rovere–Querini, Patrizia, Roy, Ajit , Rozières, Aurore , Ruano, Diego , Rubtsova, Maria P. , Ruckdeschel, Klaus, Ruckenstuhl, Christoph , Rudolf, Emil, Rudolf, Rüdiger, Ruggieri, Alessandra , Ruparelia, Avnika A. , Rusmini, P. , Russell, Ryan R., Russo, Gian Luigi , Russo, Maria , Russo, Rossella , Ryabaya, O. O. , Sabater-Arcis, María , Sacher, M, Sachse, Carsten , Sadhu, Abhishek , Säftig, Paul , Sahebkar, Amirhossein, Şahin, Mustafa , Şahin, Özgür , Saito, Nayuta , Saito, Tsunenori , Sakai, Yasuyoshi , Sakamaki, Jun-Ichi , Saksela, Kalle , Salazar, Gloria , Salazar-Degracia, Anna, Salekdeh, Ghasem Hosseini , Saluja, Ashok K. , Sampaio‐Marques, Belém , Sánchez, Marı́a C. , Sánchez-Alcázar, José A., Sanchez‐Vera, Victoria , Sancho‐Shimizu, Vanessa , Santambrogio, Laura , Santana, Magda M., Santoni, G, Sanz, Alberto , Saran, Shweta , Sardiello, Marco, Sargeant, Timothy J. , Sarin, Apurva , Sarkar, Chinmoy, Sarkar, Sovan , Sarrias, Maria-Rosa, Sarkar, Surajit , Sarmah, Dipanka Tanu, Sarparanta, J. , Sathyanarayan, Aishwarya , Ranganayaki, S. , Scaglione, K. Matthew , Scatozza, Francesca , Schafer, Zachary T. , Schaible, Ulrich E., Schapira, Anthony H.V. , Scharl, Michael , Schein, Catherine H. , Schiaffino, Maria Vittoria , Schiappacassi, Mónica , Schindl, Rainer , Schlattner, Uwe , Schmidt, Oliver, Schmitt, Roland , Schmidt, Stephen D., Schmitz, Ingo , Schmukler, Eran, Schneider, Anja , Schneider, Bianca E. , Schober, Romana , Schoijet, Alejandra C. , Schramm, M., Schröder, Bernd , Schuh, Kai , Schüller, Christoph , Schulze, Ryan J. , Schürmanns, Lea , Schwamborn, Jens C. , Schwarten, Melanie , Scott, Melanie J. , Scotto, Kathleen W., Scrima, Andrea , Scrivo, Aurora , Sebastián, David , Sebti, Salwa , Sedej, Simon , Segev, Nava , Seglen, Per O., Selleck, Scott B. , Selsby, Joshua, Sendtner, Michael , Şentürk, Şerif , Seranova, Elena, Sergi, Consolato M., Serra-Moreno, Ruth , Sesaki, Hiromi , Settembre, Carmine, Setty, Subba Rao Gangi , Sgarbi, Gianluca , Sha, Ou , Shacka, John J., Shah, Javeed A. , Shang, Dantong, Shao, Feng, Sharbati, Soroush , Sharkey, Lisa M. , Sharma, Dipali , Sharma, Gaurav, Sharma, Kulbhushan , Sharma, Pawan , Sharma, Surendra, Shen, Han‐Ming , Shen, Hongtao , Shen, Jiangang , Shen, Ming , Shen, Weili , Shen, Zheni, Sheng, Rui , Sheng, Zu-Hang, Shi, Jianjian , Shi, Ying–Hong , Shiba‐Fukushima, Kahori, Shieh, Jeng‐Jer , Shimada, Yohta , Shimizu, Shigeomi, Shimozawa, Makoto , Shintani, Takahiro , Shoemaker, Christopher J. , Shojaei, Shahla, Shoji, Ikuo , Shravage, Bhupendra V. , Shridhar, Viji, Shu, Chih‐Wen , Shu, Hong-Bing, Shui, Ke, Shukla, Arvind Kumar , Shutt, Timothy E. , Sica, Valentina , Siddiqui, Aleem , Sierra-Torre, Virginia, Signorelli, Santiago , Silva, Bruno Jorge de Andrade , Silva, Johnatas D. , Silva-Pavez, Eduardo , Silvente‐Poirot, Sandrine , Simmonds, Rachel E. , Singh, Anurag K. , Singh, Rajat Kumar , Singh, Shivendra V. , Singh, Shrawan Kumar , Singh, Sudha , Singh, Sunaina , Singh, Surinder Pal , Sinha, Debasish, Sinha, Rohit A. , Sinha, Sangita, Sirko, Agnieszka , Sivridis, Efthimios L., Skendros, Panagiotis , Sohn, Eun Jung , Sok, Sophia P. M. , Soldati, Thierry , Soler, Rosa M. , Somarelli, Jason A. , Sonawane, Avinash , Song, Fuyong, Song, Hyun Kyu , Song, Kunhua , Sorice, Maurizio , Soukas, Alexander A. , Soukup, Sandra‐Fausia , Sousa, Diana , Sousa, Nadia, Bharath, M. M. Srinivas , Clair, Daret St., Stagni, Venturina, Staiano, Leopoldo , Stankov, Metodi V. , Stathopulos, Peter B. , Stefan, Katja, Stefan, Sven Marcel , Stefanis, Leonidas, Steffan, Joan S. , Steinkasserer, Alexander , Stenmark, Harald, Sterneckert, Jared , Stevens, Craig , Storch, Stephan , Strappazzon, Flavie , Strohecker, Anne M. , Stupack, Dwayne G., Su, Huanxing , Su, Ling‐Yan , Suarez-Fontes, Ana Márcia , Subirada, Paula V., Sudhandiran, Ganapasam, Sue, Carolyn M. , Sui, Xinbing , Summers, Corey M., Sun, Guangchao , Sun, Zhongjie , Sunahara, Karen K. S. , Susztak, Katalin, Šutovský, Peter , Suzuki, Hidekazu , Sweeney, Gary , Symons, J. David , Sze, Stephen Cho Wing , Szewczyk, Nathaniel J. , Tabęcka-Łonczynska, Anna, Tabolacci, Claudio , Taegtmeyer, Heinrich, Tagaya, Mitsuo , Tai, Haoran , Tait, Stephen W. G., Takahashi, Yoshinori , Tam, Chit , Tam, Shing Yau , Tampellini, Davide , Tamura, Atsushi , Tan, Eng-King, Tan, Ya‐Qin , Tanaka, Masaki , Tang, Daolin , Tang, Jingfeng , Tang, Tie-Shan , Tao, Zhipeng , Taouis, Mohammed , Tavernarakis, Nektarios, Taylor, Allen, Teixeira, Natércia , Tekirdağ, Kumsal Ayşe, Tencomnao, Tewin , Tenreiro, Sandra , Tharaux, Pierre‐Louis , Thedieck, Kathrin , Thekkinghat, Arvind A. , Thinwa, Josephine , Thirumalaikumar, Venkatesh P. , Thomes, Paul G. , Thorburn, Andrew , Thum, Thomas, Thumm, Michael , Tian, Ling, Tichý, Aleš , Timmerman, Vincent , Titorenko, Vladimir I. , Toivonen, Janne M. , Tomaipitinca, Luana , Tomar, Dhanendra , Tomás‐Zapico, Cristina , Tomić, Sergej , Tong, Chao, Tong, Xin , Torgersen, Maria L., Torii, Satoru , Torres-López, Liliana , Torriglia, Alicia , Towers, Christina G. , Towns, Roberto, Tran, Quynh‐Giao , Travassos, Leonardo H. , Tremel, Shirley , Trougakos, Ioannis P., Tsao, Betty P. , Tse, Tak Fu, Tsvetkov, Andrey S. , Tumbarello, David A. , Tyler, Jessica K., Tyutereva, Elena V. , Uchiyama, Yasuo , Ugun‐Klusek, Aslihan , Uhlig, Holm H. , Ułamek-Kozioł, Marzena, Ulasov, Ilya V. , Umekawa, Midori, Ungermann, Christian , Urbe, Sylvie, Uribe-Carretero, Elisabet , Uversky, Vladimir N. , Vaccaro, María I. , Vahsen, Björn F. , Vakifahmetoglu-Norberg, Helin, Valdor, Rut , Valente, Maria João , Valko, Ayelén , Vallée, Richard, Valverde, Ángela M. , Berghe, Greet Van den, Veen, Stijn van der , Kaer, Luc Van , Loosdregt, Jorg van , Wijk, Sjoerd J. L. van , Vandenberghe, Wim , Vanhorebeek, Ilse , Vannier-Santos, Marcos A., Vannini, Nicola , Vanrell, M. Cristina, Vantaggiato, Chiara , Varela‐Nieto, Isabel , Varga, Máté , Vasconcelos, M. Helena , Vats, Somya , Vega-Rubín-de-Celis, Silvia , Velasco, Guillermo , Velázquez, Ariadna P., Vellai, Tibor , Vellenga, Edo , Verdier, Mireille , Verginis, Panayotis , Vergne, Isabelle , Verkade, Paul , Verma, Manish , Verstreken, Patrik , Vervliet, Tim , Vervoorts, Jörg , Víctor, Víctor M., Vidoni, Chiara , Vieira, Otília V. , Vierstra, Richard D., Viganò, Sonia , Vihinen, Helena , Vijayan, Vinoy, Vila, Miquel , Villalba, José M., Villalobo, Antonio , Villarejo‐Zori, Beatriz , Vincent, Olivier , Vindis, Cécile , Viret, Christophe , Vocadlo, David J. , Voitsekhovskaja, Olga V. , Volonté, Cinzia , Volta, Mattia , Vomero, Marta , Haefen, Clarissa von, Vooijs, Marc , Voos, Wolfgang , Vučićević, Ljubica , Waguri, Satoshi , Waite, Kenrick A., Wakatsuki, Shuji , Walker, David W., Walker, Mark J. , Walter, Jochen, Wandosell, Francisco , Wang, Bo , Wang, Chao-Yung, Wang, Chen , Wang, Chenran, Wang, Chenwei , Wang, Cun-Yu, Wang, Fengming, Wang, Han, Wang, Hexiang , Wang, Hong‐Gang , Wang, Jianrong, Wang, Jigang , Wang, Jun-Dong , Wang, Kui , Wang, Lianrong, Wang, Liming , Wang, Maggie Haitian, Wang, Meiqing , Wang, Nanbu , Wang, Pengwei , Wang, Ping , Wang, Ping, Wang, Q., Wang, Qiong , Wang, Wentao , Wang, Xinnan, Wang, Xuejun , Wang, Yan, Wang, Yanchang , Wang, Yanzhuang , Wang, Yihua , Wang, Yu , Wang, Yuqi , Wang, Zhe, Wang, Zhenyu , Wang, Zhouguang , Watanabe, Eizo, Watchon, Maxinne , Wawrzyńska, Anna , Weaver, Timothy E., Węgrzyn, Grzegorz, Wehman, Ann M. , Wei, Huafeng , Wei, Taotao , Wei, Yongjie, Weiergräber, Oliver H. , Weihl, Conrad C., Weindl, Günther , Weiskirchen, Ralf , Wen, Runxia H. , Werner, Antonia, Weykopf, Beatrice , Whitton, J. Lindsay , Wiktorska, Katarzyna , Wildenberg, Manon E. , Wileman, Tom, Wilkinson, Simon , Williams, Brett, Williams, Robin S. B. , Williamson, Peter R. , Wilson, Richard A. , Winsor, Nathaniel J. , Wodrich, Harald , Woehlbier, Ute , Wollert, Thomas , Wong, Richard W., Wong, Vincent Kam Wai , Wong, W. Wei-Lynn, Wu, Anguo , Wu, Kenneth K., Wu, Shan‐Ying , Wu, William Ka Kei , Wu, Shufang, Wu, Xiaoqing , Wu, Yao‐Wen , Wu, Yihua , Xavier, Ramnik J. , Xia, Hongguang , Xia, Lixin , Xia, Zhengyuan , Ge, Xiang , Xiang, Jin , Xiang, Mingliang , Xiang, Wei , Xiao, Guozhi , Xiao, Hengyi , Xiao, Hongtao , Xiao, Jian, Xiao, Lan , Xiao, Shi , Xiao, Yin , Xie, Baoming, Xie, Zhiping , Xie, Min , Xie, Yuxiang , Xie, Zhonglin, Xilouri, Maria , Xu, En , Xu, Jin‐Rong , Xu, Liang , Xu, Xiulong , Xue, Yu , Yakhine-Diop, Sokhna M. S. , Yamaguchi, Masamitsu , Yamamoto, Ai , Yamashina, Shunhei, Yan, Shengmin , Yan, Shian-Jang, Yan, Zhen , Yang, Chuanbin , Yang, Dun-Sheng, Yang, Huan , Yang, Huang-Tian, Yang, Hui , Yang, Jing , Yang, Jingyu , Yang, Ling , Liu, Yang , Yang, Ming , Yang, Seungwon, Yang, Shu , Yang, Shun-Fa , Yang, Wannian, Yang, Wei , Yang, Xiaoyong , Yang, Yi , Yao, Xiaoqiang , Yao, Yong-Gang , Yao, Yong-ming, Yasui, Takahiro , Yazdankhah, Meysam, Yi, Cong , Yin, Xiao-Ming , Yin, Yanhai , Yin, Zhangyuan , Yin, Ziyi , Ying, Meidan , Ying, Zheng, Yip, Calvin K. , Yiu, Stephanie Pei Tung , Yoo, Young Hyun , Yoshimori, Tamotsu, Yousefi, Bahman, Yu, Boxuan , Yu, Haiyang , Yu, Jun, Li, Yu , Yu, Ming‐Lung , Yu, Seong-Woon, Yu, Victor C. , Yu, Zhengping, Yuan, Junying , Yuan, Ling‐Qing , Yuan, Shilin , Yuan, Yanggang , Yuan, Zengqiang , Yue, Jianbo , Yue, Zhenyu , Yung, Raymond , Zacks, David, Zaffagnini, Gabriele , Zambelli, Vanessa O. , Zanella, Isabella , Zang, Qun S. , Zanivan, Sara , Zappavigna, Silvia , Zaragoza, P. , Zarbalis, Konstantinos S., Zarebkohan, Amir , Zarrouk, Amira , Zeitlin, Scott, Zeng, Jialiu , Zeng, Judeng , Žerovnik, Eva , Zhan, Lixuan , Zhang, Donna D., Zhang, Hong , Zhang, Honghe , Zhang, Huafeng , Zhang, Huaye, Zhang, Huiling , Zhang, Jianbin , Zhang, Jingpu , Zhang, Kalin Yanbo , Zhang, Leshuai W. , Zhang, Lu , Zhang, Luoying , Zhang, Menghuan, Zhang, Peng , Zhang, Sheng , Zhang, Xiangnan, Zhang, Xiao-Wei, Zhang, Xiaolei , Zhang, Xiaoyan , Zhang, Xin , Zhang, Xinxin , Zhang, Yang, Zhang, Yi , Zhang, Yingdong , Zhang, Yuanyuan , Zhang, Yuchen , Zhang, Zhe , Zhang, Zhibing , Zhang, Zili , Zhao, Haobin, Zhao, Lei , Zhao, Shuang , Zhao, Tongbiao , Zhao, Ying, Zhao, Yongchao , Zhao, Yongliang , Zhao, Yuting , Zheng, Guoping , Zheng, Kai, Zheng, Ling , Zheng, Shizhong , Zheng, Xi‐Long , Zheng, Zu‐Guo , Zhivotovsky, Boris, Zhong, Qing , Zhou, Ao, Zhou, Ben , Zhou, Cefan , Zhou, Gang , Zhou, Hongbo , Zhou, Kailiang, Zhou, Rongjia , Zhou, Yanshuang, Zhou, Yinghong , Zhou, Yubin , Zhou, Zhengyu, Zhou, Zhou , Zhu, Binglin , Zhu, Changlian , Zhu, Guo‐Qing , Zhu, Haining , Zhu, Hongxin, Zhu, Yanping , Zhu, Yushan , Zhuang, Haixia , Zhuang, Xiaohong , Zimmermann, Christine , Żołądek, Teresa , Zong, Wei‐Xing, Zorov, Dmitry B. , Zorzano, Antonio, Zou, Weiping, Zou, Zhen , Zou, Zhengzhi, Zuryn, Steven , Kenchappa, Chandra Shekar, Li, Zuguo , Lin, Yong , Sluimer, Judith C. , Stallings, Christina L. , Tong, Chun-Kit, Wang, Ping , Hu, Bo , Lee, Edward B. , Tse, Hung‐Fat , Suszták, Katalin , Lei, Yu Leo , Yu, M-L , Dai, Yun , Bartolome, Alberto , Brown, Rhoderick E , Passos, João F , Paneni, Francesco , Sahin, Özgür , Pereira de Almeida, Luis , Ren, Jun , Bornhauser, Beat , Kumar, Sharad , Sampaio-Marques, Belém , Ludovico, Paula , Luftig, Micah , Begun, Jakob , Krasnodembskaya, Anna D , Dafsari, Hormos Salimi , Chevet, Eric , Tse, Hung-Fat , Barmada, Sami , Ebrahimi-Fakhari, Darius , Cavadas, Claudia , Sue, Carolyn M , Cardenal-Muñoz, Elena , Lee, Edward B , Golebiewska, Anna , Calbet, Jose A L , Boya, Patricia , Maday, Sandra , Klionsky, Daniel J. , Abdelfatah, Sara , Abdoli, Asghar , Agarwal, Anupam , Ahmed, Zubair M. , Alcocer‐Gómez, Elísabet , Ali, Muhammad , Al‐Bari, Md. Abdul Alim , Aliwaini, Saeb H. , Alizadeh, Javad , Almacellas, Eugènia , Almasan, Alexandru , Alonso, G. , Altieri, Dario C. , Andersen, Stig Uggerhøj , Andrade-Silva, Magaiver , Angelini, Sabrina , Apostolova, Nadezda , Arasaki, Kohei , Araújo, Wagner L. , Arden, Catherine , Arimoto, Hirokazu , Armstrong-James, Darius P. H. , Pelloquin, Laetitia , Aschner, Michael , Ashrafizadeh, Milad , Autelli, Riccardo , Aveic, Sanja , Avin‐Wittenberg, Tamar , Ayton, Scott , Backues, Steven K. , Bae, Dong-Hun , Bae, Ok‐Nam , Baek, Ahruem , Baek, Seung‐Hoon , Baek, Sung Hee , Bai, Jie , Bai, Yidong , Baldari, Cosima T. , Balduini, Walter , Ballabio, Andrea , Banerjee, Sreeparna , Bao, Yan , Baptista, Maurı́cio S. , Barreto, George Emilio , Basagoudanavar, Suresh H. , Bast, Robert C. , Basu, Alakananda , Batoko, Henri , Batten, Isabella , Behrens, Georg M. N. , Bei, Roberto , Behl, Christian , Bello‐Morales, Raquel , Beltrán, Sebastián , Bergami, Matteo , Bergmann, Andreas , Berthoux, Lionel , Bhattacharya, Resham , Bhattacharyya, Shalmoli , Bhutia, Sujit Kumar , Bi, Lanrong , Birgisdottir, Åsa Birna , Bjørkøy, Geir , Blomgren, Klas , Boada-Romero, Emilio , Boesze‐Battaglia, Kathleen , Bonifacino, Juan S. , Boone, Brian A. , Borthakur, Gautam , Bosch, Jürgen , Bose, Santanu , Botana, Luis Miguel , Boulton, Michael E. , Bourdenx, Mathieu , Brackney, Doug E. , Brandts, Christian , Braun, Ralf J. , Braus, Gerhard H. , Bravo, Roberto , Brody, Steven L. , Brown, Carolyn Nicole , Brumell, John Hunter , Brunetti‐Pierri, Nicola , Buitrago‐Molina, Laura Elisa , Buraschi, Simone , Buch, Shilpa J. , Butturini, Elena , Cairó, Montserrat , Caldwell, Kim A. , Campbell‐Valois, François‐Xavier , Campello, Silvia , Campesi, Ilaria , Almeida, Danilo Cândido de , Canesi, Laura , Caraglia, Michele , Carchman, Evie H. , Carmona‐Gutiérrez, Didac , Carnevali, Oliana , Carrier, Lucie , Carroll, Bernadette , Carter, A. Brent , Casas, Caty , Castillo, Eliseo F. , Castro‐Caldas, Margarida , Castro‐Obregón, Susana , Catz, Sergio , Cayuela, María Luisa , Cecarini, Valentina , Cecconi, Francesco , Cenci, Simone , Ceperuelo‐Mallafré, Victòria , Cervia, Davide , Chae, Han–Jung , Chakrabarti, Oishee , Chan, Edmond Y. W., Chan, Edward D. , Chandra, Partha Kumar , Chang, Chih‐Peng , Chang, Chunmei , Chapman, Tracey , Chen, Guang‐Chao , Chen, Leilei , Chen, Lin , Chen, Quan , Chen, Ruey‐Hwa , Chen, Shi , Chen, Wei‐Qiang , Chen, Xu , Chen, Yu-Jen , Chen, Yujie , Chen, Zhi , Chen, Zhijian J. , Chen, Zhixiang , Cheng, Hanhua , Cheng, Jun , Cheng, Shi‐Yuan , Cheng, Wei Nee , Cheng, Xiaodong , Chen, Zhong , Cheong, Heesun , Chernyak, Boris V. , Chi, Richard J., Chiang, Aks , Chiarelli, Roberto , Chu, Charleen T. , Chung, Seockhoon , Cianfanelli, Valentina , Cifuentes, Mariana , Cirone, Mara , Clague, Michael J. , Cohen, Ehud , Cohen, Mickaël M. , Čolić, Miodrag J , Combaret, Lydie , Comincini, Sergio , Conte, Andrea, Conti, Fabrizio , Coppens, Isabelle , Corasaniti, Maria Tiziana , Corkery, Dale , Cordes, Nils , Cortese, Katia , Coto‐Montes, Ana M. , Crack, Peter John , Crespo, José L. , Cuadrado, Antonio , Cui, Jun , Cui, Yong , D’Arcangelo, Daniela , D’Lugos, Andrew C. , Dagda, Ruben Karim , Dagdas, Yasin , Daμμe, Markus , Dantuma, Nico P. , Darling, April L. , Dasarathy, Srinivasan , Daumke, Oliver , Davis, Tanja , Amicis, Francesca De , Felice, Francesca De , Franceschi, Lucia De , Milito, Angelo De , Nunzio, Cosimo De , Santi, Mauro De , Debnath, Jayanta , DeBosch, Brian J. , DeGregori, James V. , Rio, Gabriel del , Delbridge, Lea M.D. , Delpino, M. Victoria , Demarchi, Francesca , Dembitz, Vilma , Deng, Zhiqiang , Denton, Donna , Der, Channing J , Deretić, Vojo , Dhiman, Rohan , Bernardo, Diego di , Cristina, Manlio Di , Nardo, Alessia Di, Sano, Federica Di , Diallinas, George , Diaz-Araya, Guillermo, Đikić, Ivan , Ding, Wen‐Xing , Dini, Luciana , Dionne, Marc , Diwan, Abhinav , Dixon, Ian , Djavaheri‐Mergny, Mojgan , Dobrinski, Ina , Dobrovinskaya, Oxana R. , Dobrowolski, Radek , Dobson, Renwick C. J. , Donadelli, Massimo , Dong, Bo, Dötsch, Volker , Dou, Huan , Dridi, Sami , Du, Caigan , Du, Li‐Lin , Dubrovska, Anna , Dunlop, Elaine A. , Dwarakanath, Bilikere Srinivasa Rao , Eftekharpour, Eftekhar , Eichinger, Ludwig , Eissa, N. Tony , Eissa, Sanaa , El‐Naggar, Shahenda , Eliopoulos, Aristides G. , Elks, Philip M. , Emerling, Brooke M. , Engelbrecht, Anna‐Mart , Escobar‐Henriques, Mafalda , Fabriàs, Gemma , Fabrizi, Cinzia , Falkenburger, Björn H. , Fan, Yanbo , Fanto, Manolis , Feng, Du , Feng, Yibin , Feng, Yuchen , Fernández-Checa, José Carlos , Filippi‐Chiela, Eduardo Cremonese , Filomeni, Giuseppe , Fineschi, Vittorio , Flamigni, Flavio , Follo, Carlo , Fon, Edward A , Fornai, Francesco , Fraldi, Alessandro , Franco, Brunella , Franco, Rodrigo , Friedman, Scott L. , Frühbeck, Gema , Fujita, Naonobu , Fujiwara, Yuuki , Fukuda, Mitsunori , Furic, Luc , Fusco, Carmela , Galluzzi, Lorenzo, Gan, Boyi , Gao, Hui , Gao, Shou‐Jiang , Gargini, Ricardo , Garry, Robert F. , Ge, Liang , Ge, Wanzhong , Gelfi, Cecilia , Gentle, Ian Edward , Gewirtz, David A , Ghigo, Alessandra , Giampietri, Claudia , Gibson, Spencer B. , Giniger, Edward , Giorgi, Carlotta , Girão, Henrique , Goldstone, David C. , Gomez‐Puerto, Maria Catalina , Goñi, Félix M. , González‐Hernández, Tomás , Gorbatyuk, Marina S. , Goruppi, Sandro , Gottlieb, Roberta A. , Gozes, Illana , Green, Douglas R. , Grinstaff, Mark W. , Grune, Tilman , Guntur, Anyonya R. , Guo, Lian‐Wang , Gupta, Shashi Kumar , Gustafsson, Åsa B. , Haapasalo, Annakaisa , Hadano, Shinji , Hafrén, Anders , Hall, Belinda S. , Hamann, Andréa , Han, Weidong , Hanson, Phyllis I. , Haroon, Nigil , Harris, James , Hasegawa, Takafumi , Nagoor, Noor Hasima , Hay, Bruce A. , Hayrabedyan, Soren , He, Yu‐Ying , Helgason, G. Vignir , Hergovich, Alexander , Hernández–Gea, Virginia , Heussler, Volker Theo , Hlavacek, William S. , Hobbs, G. Aaron , Hochstrasser, Mark , Hofman, Paul , Holmberg, Carina I. , Hombrebueno, José R. , Hoppe, Thorsten , Horos, Rastislav , Hoshida, Yujin , Hsu, Hsin‐Yun , Hu, Li‐Fang , Hu, Ming Chang , Hu, Ronggui , Hu, Yu‐Chen , Hua, Fang , Hua, Jinlian, Hua, Yingqi , Huang, Canhua , Huang, Chuanxin , Huang, Kun , Huang, Rui , Huber, Tobias Bruno , Humbert, Magali , Hussey, Patrick J. , Hwang, Hui‐Yun , Hwang, Seungmin , Imai, Yuzuru , Iovanna, Juan , Ippolito, Giuseppe , Irazoqui, Javier E. , Ishaq, Mohd, Ishikawa, Makoto , Isidoro, Ciro , Izumi, Masanori , Jäättelä, Marja , Jabir, Majid Sakhi , Jackson, William T. , Jacomin, Anne‐Claire , Jakobi, Arjen J. , Jantsch, Jonathan , Jassey, Alagie , Jean, Steve , Jendelová, Pavla , Jewell, Jenna L. , Ji, Jing , Jiang, Liwen , Jin, Eun‐Jung , Jin, Hongchuan , Jin, Meiyan , Jo, Eun‐Kyeong , Johansen, Terje , Johnson, Gail V.W. , Jolly, Mohit Kumar , Joosten, Leo A. B. , Jordán, Joaquı́n , Joseph, Bertrand , Ju, Dianwen , Ju, Jeong-Sun , Ju, Jingfang , Judith, Delphine , Jung, Yong‐Keun , Kaarniranta, Kai , Kabuta, Tomohiro , Kahana, Alon , Kaminskyy, Vitaliy O. , Kanasaki, Keizo , Kanthasamy, Anumantha G. , Karamouzis, Michalis V. , Karmakar, Parimal , Katare, Rajesh , Kaufmann, Stefan H. E. , Kaushik, Susmita , Kawasaki, Kiyoshi, Ke, Po‐Yuan , Keating, Damien J. , Kehrl, John H. , Keller, Christian W. , Kemper, Jongsook Kim , Kermorgant, Stéphanie , Ketteler, Robin , Khambu, Bilon , Kim, Deok Ryong, Kim, Eun Young , Kim, Jin Kyung , Kim, Jin‐Hoi , Kim, Ju Hwan , Kim, Keun Il , Kim, Peter Kijun , Kinghorn, Kerri J. , Kirkin, Vladimir , Киселев, С. Л. , Kittler, Josef T. , Knorr, Roland L. , Ko, Ben C.B. , Ko, Jiunn‐Liang , Kobayashi, Hotaka , Koenig, Ulrich , Koike, Masato , Kohlwein, Sepp Dieter , Komatsu, Masaaki , Kopp, Benjamin T. , Korcsmaros, Tamas Douglas , Korolchuk, Viktor I. , Kotler, Mónica L. , Koukourakis, Michael Ioannis , Kovács, Tibor, Koya, Daisuke , Kozako, Tomohiro , Krämer, Helmut , Kroemer, Guido , Ktistakis, Nicholas T. , Kuchitsu, Kazuyuki , Kumar, Ashok , Kumar, Deepak, Kundu, Mondira , Kurgan, Lukasz , Kutateladze, Tatiana G. , Kwon, Ho Jeong , Kwon, Taeg Kyu , Kyrmizi, Irene , Spada, Albert R. 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Thomas , Sandri, Marco F. , Santaguida, Stefano , Sanz, Alberto, Sanz, Pascual , Sathyanarayanan, Ranganayaki, Schaefer, Liliana , Scharl, Michael M. , Schätzl, Hermann M. , Scheper, Wiep , Scheuring, David , Schott, Micah B. , Schramm, Michael, Schröder, Bernd, Schüller, Christoph, Scialò, Filippo , Sciarretta, Sebastiano , Scovassi, Anna Ivana , Segatori, Laura , Seiliez, Iban , Seki, Ekihiro , Sellke, Frank W. , Sergi, Consolato Maria , Settembre, Carmine , Shao, Changshun , Sheng, Zhi , Shi, Xiaobing , Shimozawa, Makoto, Shoji, Ikuo, Shridhar, Viji , Shu, Hong‐Bing , Sierra, Amanda , Sierra‐Torre, Virginia , Sil, Payel , Simon, Anna Katharina , Simon, Hans‐Uwe , Simons, Matias , Singh, Lalit Pukhrambam , Sirohi, Kapil , Sivridis, Efthimios , Skirycz, Aleksandra , Slaninová, Iva , Smaili, Soraya Soubhi , Smertenko, Andrii , Smith, Matthew D., Soenen, Stefaan J. , Solaini, Giancarlo , Soleimanpour, Scott A. , Solovchenko, Alexei E. , Song, Fuyong, Song, Ju‐Xian , Song, Zhiyin , Soria, Leandro R. , Spagnuolo, Paul A. , Spector, Stephen A. , Stalnecker, Clint A. , Stefan, Katja, Stefanis, Leonidas , Stenmark, Harald , Stevens, Craig, Stoka, Veronika , Stork, Björn , Su, Longxiang , Subauste, Carlos S. , Subbian, Selvakumar , Sun, Jun , Sun, Kang, Sun, Meng‐Xiang , Sun, Qiming , Sun, Yi Ning , Sundberg, Eva , Tabęcka-Łonczyńska, Anna , Tacke, Frank , Tafani, Marco , Tait, Stephen W. 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G.
Autophagy | March 24, 2021 | Volume: 17 | Issue: 1 | Pages: 1-382
Complete Responses in Relapsed/Refractory Acute Myeloid Leukemia (AML) Patients on a Weekly Dosing Schedule of Vibecotamab (XmAb14045), a CD123 x CD3 T Cell-Engaging Bispecific Antibody; Initial Results of a Phase 1 Study
Bashey, Asad, Foran, James M. , Mawad, Raya, Egan, Daniel , Blum, William , Yang, Allen S., Johnson, Chelsea, Zheng, Shuo , Ravandi, Farhad , Stock, Wendy , Pastore, Alessandro, Zheng, Shuo, Yılmaz, Musa , Mims, Alice S
Blood | November 4, 2020 | Volume: 136 | Issue: Supplement 1 | Pages: 4-5
Background: Blasts and leukemic stem cells of acute myeloid leukemia (AML) as well as several other hematologic malignancies express CD123, potentially providing a target for novel therapies. Vibecotamab (XmAb14045, SQZ622) is a potent bispecific antibody targeting both CD123 and CD3 that stimulates targeted T cell-mediated killing of CD123-expressing cells, regardless of T cell antigen specificity. It is a full-length immunoglobulin molecule designed to be dosed intermittently. Methods: Patients with relapsed or refractory AML, B-cell acute lymphoblastic leukemia (B-ALL), blast phase chronic myelogenous leukemia, or blastic plasmacytoid dendritic cell neoplasm were eligible to enroll on this first-in-human, multicenter, open-label phase 1 dose-escalation study (XmAb14045-01) with standard 3+3 design. The primary objective was to estimate the maximum tolerated dose (MTD) or recommended dose and schedule of vibecotamab. Secondary objectives included safety, preliminary antileukemic activity, and pharmacokinetics/pharmacodynamics of vibecotamab. Treatment was administered weekly in 28-day cycles, using a weight-based dose with 3 escalating doses in the first week followed by escalating weekly doses. Therapy was continued for as long as tolerated and there was continuing evidence of therapeutic benefit in the opinion of the investigator. Treatment response was assessed by the 2017 European LeukemiaNet (ELN) criteria after Cycle 1 and after each odd-numbered cycle. CRS was graded using the CRS revised grading system (Lee et al., Blood, 2014). Results: At data cut-off, 104 patients with AML, 1 with B-cell ALL, and 1 with CML as their primary diagnosis have been treated at dosages from 0.003 to 12.0 µg/kg vibecotamab. Patients had a median age of 63 years and were heavily pretreated (median of 3 prior therapies [range 1-8], including 32 (30%) who had undergone prior allogeneic stem cell transplantation). The recommended initial priming dose is 0.75 µg/kg; no MTD has been identified. CRS or its component symptoms was the most common treatment-emergent adverse event (TEAE). CRS occurred in 62 of 106 patients (85% grade 1-2, 15% grade ≥3), the majority on the first dose. Additional events consistent with CRS or infusion related reaction were seen in 24% of subjects (chills, fever, tachycardia, hypotension, etc.), and they were mostly mild or moderate severity. No myelosuppression requiring dose modification or evidence of tumor lysis syndrome was seen. Response of CR (2), CRi (3) or MLFS (2) was observed in 7/51 patients (ORR=14%) treated at higher dose levels (0.75 µg/kg). Stable Disease was observed in an additional 36 patients (71%). No CR, CRi, or morphologic leukemia-free state (MLFS) responses were observed at lower doses. Antileukemic activity occurred quickly; 6 out of 7 responders achieved at least a MLFS response after first cycle. A characterization of responders versus non-responders revealed responding patients harbor a lower burden of disease and specific T-cell subtypes. No association was found between response status and CD123 target expression on AML blasts. Conclusions: Vibecotamab demonstrated evidence of antileukemic activity in heavily pretreated patients with relapsed/refractory AML treated at the ≥0.75 µg/kg doses cohorts, with a 14% response rate. CRS was the most common toxicity but was generally manageable with premedications. The study is ongoing with further optimization of dose and schedule. Biomarker data suggest a population of AML patients that are more likely to respond. Additional information will be provided at the time of the meeting. Disclosures Ravandi: Celgene: Consultancy, Honoraria; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Orsenix: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Astellas: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Macrogenics: Research Funding. Stock:Adaptive Biotechnologies: Consultancy, Membership on an entity's Board of Directors or advisory committees; Research to Practice: Honoraria; American Society of Hematology: Honoraria; Leukemia and Lymphoma Society: Research Funding; Novartis: Research Funding; Abbvie: Honoraria, Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; UpToDate: Honoraria. Foran:Xencor: Research Funding; H3Biosciences: Research Funding; Agios: Honoraria, Research Funding; Trillium: Research Funding; Takeda: Research Funding; Kura Oncology: Research Funding; Aptose: Research Funding; Aprea: Research Funding; Actinium: Research Funding; Boehringer Ingelheim: Research Funding; Abbvie: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Revolution Medicine: Consultancy. Mawad:Adaptive Biotechnologies: Speakers Bureau; Abbvie: Speakers Bureau. Blum:Celyad: Research Funding; Amerisource Bergen: Honoraria; Syndax: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Research Funding; Xencor: Research Funding. Yang:Xencor: Current Employment, Current equity holder in publicly-traded company; Jazz Pharmaceuticals: Current equity holder in publicly-traded company, Ended employment in the past 24 months. Pastore:Novartis NIBR East Hanover New Jersey: Current Employment, Current equity holder in publicly-traded company; Memorial Sloan Kettering Cancer Center: Ended employment in the past 24 months. Johnson:Xencor: Current Employment, Current equity holder in publicly-traded company. Zheng:Xencor: Current Employment, Current equity holder in publicly-traded company; Tocagen: Ended employment in the past 24 months. Yilmaz:Pint Pharma: Honoraria; Pfizer: Research Funding; Daicho Sankyo: Research Funding. Mims:Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Agios: Consultancy; Novartis: Speakers Bureau.
Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities
Armstrong, Nicola J. , Mather, Karen A. , Sargurupremraj, Muralidharan , Knol, Maria J. , Malik, Rainer, Satizábal, Claudia L. , Yanek, Lisa R., Wen, Wei , Guðnason, Vilmundur , Dueker, Nicole , Elliott, Lloyd T. , Hofer, Edith, Bis, Joshua C. , Jahanshad, Neda , Li, Shuo , Logue, Mark, Scholz, Markus , Smith, Albert V. , Trompet, Stella , Alfaro‐Almagro, Fidel , Ames, David, Amin, Najaf , Beiser, Alexa S., Brodaty, Henry , Fennema‐Notestine, Christine , Gampawar, Piyush , Gottesman, Rebecca, Griffanti, Ludovica , Kral, Brian G. , Lampe, Leonie, Liewald, David C. , Maillard, Pauline , Marchini, Jonathan, Bastin, Mark E., Pirpamer, Lukas , Roshchupkin, Gennady V. , Stott, David J., Thalamuthu, Anbupalam , Tzourio, Christophe , Grond, Jeroen van der , Vernooij, Meike W. , Witte, A. Veronica , Wright, Margaret J. , Yang, Qiong, Siggurdsson, Siggi, Psaty, Bruce M., Villringer, Arno , Schmidt, Helena, Duijn, Cornelia M. van , Jukema, J. Wouter , Dichgans, Martin , Sacco, Ralph L., Kremen, William S., Becker, Lewis C. , Thompson, Paul M., Mosley, Thomas H. , Wardlaw, Joanna M. , Ikram, M. Arfan , Adams, Hieab H.H. , Seshadri, Sudha , Sachdev, Perminder S. , Smith, Stephen M. , Launer, L. J., Longstreth, W.T. , DeCarli, Charles , Schmidt, Reinhold, Fornage, Myriam , Debette, Stéphanie , DeCarli, Charles , Dichgans, Martin , Wardlaw, Joanna Marguerite , Thalamuthu, Anbupalam , Wen, Wei , Adams, Hieab H H , Satizabal, Claudia L , Seshadri, Sudha , Brodaty, Henry , Sachdev, Perminder S , Wright, Margaret J , Tzourio, Christophe , van Duijn, Cornelia M , Debette, Stephanie , Smith, Albert V , Maillard, Pauline , Hofer, Edith , Luciano, Michelle , Vojinović, Dina , Xia, Rui , Amouyel, Philippe , Deary, Ian J. , Jack, Clifford R. , Jenkinson, Mark , Jiang, Jiyang , Kwok, John B. , Marchini, Jonathan , Mazoyer, Bernard , Romero, José R. , Schofield, Peter R. , Schroeter, Matthias L , Trollor, Julian N , Morris, Zoë , Psaty, Bruce M. , Håberg, Asta K , Wright, Clinton B. , Thompson, Paul M. , Nyquist, Paul
Stroke | June 10, 2020 | Volume: 51 | Issue: 7 | Pages: 2111-2121
10.1161/strokeaha.119.027544
| PMID 32517579
Background and Purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Methods: Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC. Results: In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 ( NBEAL ), 10q23.1 ( TSPAN14/FAM231A ), and 10q24.33 ( SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 ( NOS3 ) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype. Conclusions: Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.
Glucocorticoid Receptor Expression Correlates with Clinical Outcome in Myeloma Patients Treated with Glucocorticoid-Containing Regimens.
Ma, Chunguang , Tessel, Michael A., Zhang, Lijun , Barlogie, Bart , Shaughnessy, John D. , Krett, Nancy , Ma, Shuo , Zhan, Fenghuang , Ma, Chunguang, Rajkumar, S. Vincent , Singhal, Seema , Rosen, Steven T.
Blood | April 18, 2020 | Volume: 112 | Issue: 11 | Pages: 1700-1700
10.1182/blood.v112.11.1700.1700
Abstract Glucocorticoid (GC) is an effective anti-myeloma agent by directly inducing apoptosis and growth inhibition in myeloma cells. The anti-myeloma action of GC is mediated by its intracellular receptor, the glucocorticoid receptor (GR). The response to GC is variable among myeloma patients and resistance to glucocorticoid treatment develops almost invariably. The mechanism regulating glucocorticoid-sensitivity in not well understood, although it has been hypothesized that the regulation might occur at both the receptor (GR) and post-receptor level. In MM.1 myeloma cell lines, we observed significant down-regulation of GR expression as the cells develop GC-resistance, suggesting that GR expression level is an important determinant of GC-response. Here we present evidence that GR expression level directly correlates with the clinical outcome in myeloma patients who were treated with GC-containing regimens. First, using a quantitative real-time PCR analysis, we performed a retrospective analysis of GR gene expression on bone marrow plasma cell samples from 35 patients with newly diagnosed myeloma who were then treated on the ECOG study E1A00. This is a phase 3 trial which randomized patients to dexamethasone (dex) alone vs. dex in combination with thalidomide. Pre-treatment expression levels of GR-alpha, GR-beta and GR-P splicing isoforms were measured for 35 patients, of whom, 10 had post-treatment samples available. Interestingly, a large variation of the GR expression levels was observed across the patient samples, with the GR-alpha being the predominant isoform. However, a clear correlation between GR expression and treatment response was not seen, likely due to the small sample size. To access a larger patient pool, we retrospectively analyzed the GR expression levels using the cDNA microarray data from the Arkansas group on 351 newly diagnosed myeloma patients treated with Total Therapy 2, of which dexamethasone was an essential component throughout the treatment course. Of the 351 patients, both event-free (EFS) and overall survivals (OS) were compared between 49 patients (14%) with low levels of GR expression and the rest (86%) with high levels of GR expression. Strikingly, the cases with low levels of GR expression were associated with statistically significantly worse EFS and OS compared to those with high levels of GR expression, with the 5-year EFS of 20% vs. 52% and OS of 34% vs. 68%, P < 0.01. In summary, we have shown for the first time that the baseline level of glucocorticoid receptor expression in newly diagnosed myeloma patients predicts their clinical response to GC-containing regimen and the overall clinical outcome.
Intranasal delivery of 9-cis retinoic acid reduces beta-amyloid deposition via inhibiting astrocyte-mediated inflammation
Zhao, Hong , Li, Zhuo , Yang, Shuo , Zheng, Jiaolin , Gao, Hongmei , Gu, Yingli , Fu, Yuan , Li, Zhuo , Li, Shuo , Yang, Shuo, Li, Dandan, Ling, Yun , Li, Longxuan , Zhao, Jing
Aging | March 25, 2020 | Volume: 12 | Issue: 6 | Pages: 5469-5478
Phase Ib trial of AVL-292, a covalent inhibitor of Bruton's tyrosine kinase (Btk), in chronic lymphocytic leukemia (CLL) and B-non-Hodgkin lymphoma (B-NHL).
Brown, Jennifer R. , Sharman, Jeff P. , Harb, Wael A., Kelly, Kevin R. , Schreeder, Marshall T., Sweetenham, John , Foran, James M. , Gabrilove, Janice , Evans, Erica , Lounsbury, Heather, Silver, Bruce A., Singh, Juswinder , Stiede, Kathryn, Westlin, William , Witowski, Steven R., Mahadevan, Daruka , Barr, Paul M. , Kipps, Thomas J. , Ma, Shuo , O’Brien, Susan
Journal of Clinical Oncology | March 11, 2020 | Volume: 30 | Issue: 15_suppl | Pages: 8032-8032
10.1200/jco.2012.30.15_suppl.8032
8032 Background: Btk supports activation, survival, and proliferation of malignant B cells in CLL and B-NHL. AVL-292 is an oral, potent (IC50 < 0.5nM), selective small molecule covalent inhibitor of Btk. Methods: Patients (pts) with previously treated CLL or B-NHL were administered AVL-292 in escalating cohorts of 125, 250, or 400 mg po QD using a 3+3 design in continuous 28 day cycles until progressive disease (PD) or toxicity. Key objectives were safety, DLT, MTD, PK, and Btk occupancy. Plasma AVL-292 levels were assessed by LC-MS-MS. Btk occupancy by AVL-292 was assessed by covalent probe assay in peripheral blood mononuclear cells. Results: 12 pts have enrolled (3 each at 125 and 250 mg and 6 at 400 mg: 5M/7F; median age 68 years, range 45-79; median 2.5 prior therapies, range 1-10) including 8 CLL (2 with 17p-, 2 with 11q22-, 2 with both 17p-/11q22-; 2 mutated IGHV, 5 unmutated IGHV, 1 missing) and 4 B-NHL (1 diffuse large B cell lymphoma (DLBCL); 1 follicular (FL); 2 marginal zone (MZL)). Median time on treatment is 65 days, range 28-158. Ten of 12 pts continue on treatment: 1 pt (DLBCL) discontinued for PD after 1 cycle and 1 pt (FL) for DLT (Gr 4 plts; 400 mg QD). No other DLTs or grade 4 adverse events (AEs) have occurred and MTD has not been reached. Most frequent AEs reported include transient diarrhea, rash/skin infection, URI, nausea, and fatigue. Gr 3 AEs include 1 atrial fibrillation (not drug related) and 1 ANC low (probably drug related). To date, 8 of 8 CLL patients have stable disease (SD) with median 28% decrease from baseline lymph node measurement (range 3-40% decrease). Six of 8 pts with CLL experienced increased ALC in cycle 1: median increase 89.5% (range 50-212%). Two of 4 NHL pts have SD (both MZL), 1 PD (DLBCL), and 1 not evaluable due to DLT (FL). Full Btk occupancy was achieved with dose levels ≥ 250 mg. Multiple dose PK exposure (AUClast) was linear with no accumulation from Day 1 to 15. Conclusions: AVL-292 was well tolerated from 125-400 mg po QD and early efficacy analysis in CLL and B-NHL shows 10/11 efficacy evaluable pts with SD. Full Btk occupancy was achieved with ≥ 250 mg QD and PK was predictable with no accumulation. Dose escalation is ongoing and MTD cohort expansion is planned.
Phase 1 Study Of Single Agent CC-292, a Highly Selective Bruton's Tyrosine Kinase (BTK) Inhibitor, In Relapsed/Refractory Chronic Lymphocytic Leukemia (CLL)
Brown, Jennifer R. , Harb, Wael A., Hill, Brian T. , Gabrilove, Janice , Sharman, Jeff P. , Schreeder, Marshall T., Foran, James M. , Miller, Thomas P. , Kelly, Kevin R. , Mahadevan, Daruka , Barnett, Evelyn, Marine, Jeffrey, Nava-Parada, Pilar , Azaryan, Ada, Mei, Jay , Barr, Paul M. , Burger, Jan A. , Ma, Shuo , Kipps, Thomas J.
Blood | October 12, 2019 | Volume: 122 | Issue: 21 | Pages: 1630-1630
10.1182/blood.v122.21.1630.1630
Abstract Introduction CC-292, an oral, highly selective, small-molecule irreversible-inhibitor of Btk is under investigation for the treatment of CLL and other B-cell malignancies. This phase 1 trial investigated the safety, dose limiting toxicities (DLT), and clinical activity of CC-292 monotherapy in subjects with relapsed or refractory (R/R) CLL or non-Hodgkin's lymphoma. This interim analysis focused on the safety and clinical activity in subjects with CLL and small cell lymphocytic leukemia (SLL). Methods Eligible subjects with R/R (≥ 1 prior therapy) CLL/SLL were treated with monotherapy CC-292 in a dose-escalation study with doses ranging from 125 mg to 1000 mg QD and BID dose levels of 375 mg and 500 mg. As a maximum tolerated dose was not established, CLL patients have been enrolled in an early dose expansion cohort of 750 mg QD and preliminary recommended phase 2 dose expansion cohort at 500 mg BID. All subjects received continuous dosing in 28-day cycles until progressive disease or intolerable toxicity. Clinical activity was investigator assessed per the 2008 iwCLL criteria. Results 83 subjects with R/R CLL/SLL have been enrolled as of June 30, 2013. Baseline characteristics include median age of 67 years (34-89), 52% Rai stage 3/4 disease, median 3 prior therapies (1-12), and 34% refractory to last treatment. Poor-risk factors were present in 67% of subjects, including del11q (22%), del17p (24%), and unmutated IgVH (54%). 67% of subjects remain on study. Subjects have received a median of 6 treatment cycles (0.2-21.6). The most frequent grade 3/4 adverse events (AEs) included neutropenia (21%), thrombocytopenia (15%), pneumonia (10%), and anemia (8%). Rates of febrile neutropenia were low (4%). The most common treatment-emergent AEs (≥ 10% of subjects) were diarrhea (59.7%), fatigue (37.5%), neutropenia (26.4%), thrombocytopenia (26.4%), nausea (26.4%), pyrexia (22.2%), headache (19.4%), cough (19.4%), upper respiratory infection (16.7%), peripheral edema (15.3%), abdominal pain (15.3%), dizziness (13.9%), muscle spasms (13.9%), contusion (13.9%), anemia (12.5%), pneumonia (12.5%), sinusitis (12.5%), and urinary tract infection (11.1%). One CLL patient at the 500 mg BID dose level has experienced a drug-related adverse event of grade 4 thrombocytopenia during Cycle 1 that was assessed as a DLT. The number of patients discontinuing study treatment due to AEs was low (2.4%). Results are summarized for efficacy-evaluable patients treated at the 4 dose levels where at least a partial response (PR) was achieved (750 mg, 1000 mg, 375 mg bid and 500 mg bid) (n = 55). During cycle 1, 89% experienced a ≥ 25% increase in absolute lymphocyte count (ALC), which usually resolved with continued treatment. The table below details the best responses achieved to date. In subjects with del11q, del17p, unmutated IgVH, and no high-risk genomic factors, the PR rate was 42% (5/12), 25% (3/12), 44% (7/16), and 47% (7/15), respectively. Importantly, nodal responses were induced in the majority of subjects receiving BID dosing (375 mg: 67%; 500 mg: 62%) with an overall PR rate of 40%. When achieved, nodal responses were typically observed by cycle 2 and were sustained with continued treatment. Although the sample size is small, subjects treated at 375 mg or 500 mg BID showed continued lymph node size reduction over time from cycle 2 (mean reduction of 42% and 45%, respectively) to cycle 7 (mean reduction of 60% and 71%, respectively). Conclusion CC-292 is well tolerated as an oral daily therapy. Single-agent therapy with CC-292 is sufficient to achieve high nodal and partial response rates in relapsed/refractory CLL subjects, including those with high-risk genomic features. These results support continued development of CC-292 for the treatment of patients with CLL/SLL. Disclosures: Brown: Pharmacyclics: Consultancy; Genentech: Consultancy; Celgene: Consultancy, Research Funding; Emergent: Consultancy; Onyx: Consultancy; Sanofi Aventis: Consultancy; Vertex: Consultancy; Novartis: Consultancy; Genzyme: Research Funding. Off Label Use: The abstract shows scientific information on CC292 which is an investigational product developed by Celgene. This investigational product is not approved by any health authority for any indication. Harb:Celgene: Research Funding. Hill:Celgene: Honoraria, Research Funding. Sharman:Celgene: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Gilead: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Cylene Pharmaceuticals: Consultancy, Research Funding; Avila Pharmaceuticals: Consultancy, Research Funding. Barr:Celgene: Consultancy. Foran:Celgene: Research Funding. Burger:Pharmalytics: Research Funding; Gilead: Research Funding. Mahadevan:Novartis: Speakers Bureau; Millennium: Speakers Bureau. Ma:Genentech: Consultancy; Abbvie: Consultancy. Barnett:Celgene: Employment, Equity Ownership. Marine:Celgene: Employment, Equity Ownership. Nava-Parada:Celgene: Employment, Equity Ownership. Azaryan:Celgene: Employment, Equity Ownership. Mei:Celgene: Employment, Equity Ownership. Kipps:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding.