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97 citation(s) found for "Ma, Hsin-I".

COVID-19 Impact on Interventional Pulmonology Training
Kalchiem‐Dekel, Or , Schwalk, Audra, Patel, Niral M. , Lin, I‐Hsin , Beattie, Jason , Husta, Bryan , Chawla, Mohit , Sachdeva, Ashutosh , Akulian, Jason , Musani, Ali I., Argento, A. Christine , Lee, Hans J. , Mullon, John J., Desai, Neeraj, Lee, Robert P. , Hsia, David W.

ATS Scholar | April 13, 2021 | Volume: 2 | Issue: 2 | Pages: 236-248

10.34197/ats-scholar.2020-0126oc | PMID 34409418 Get It

Abstract Background The impact of the coronavirus disease (COVID-19) pandemic extends beyond the realms of patient care and healthcare resource use to include medical education; however, the repercussions of COVID-19 on the quality of training and trainee perceptions have yet to be explored. Objective The purpose of this study was to determine the degree of interventional pulmonology (IP) fellows’ involvement in the care of COVID-19 and its impact on fellows’ clinical education, procedure skills, and postgraduation employment search. Methods An internet-based survey was validated and distributed among IP fellows in North American fellowship training programs. Results Of 40 eligible fellows, 38 (95%) completed the survey. A majority of fellows (76%) reported involvement in the care of patients with COVID-19. Fellows training in the Northeast United States reported involvement in the care of a higher number of patients with COVID-19 than in other regions (median, 30 [interquartile range, 20–50] vs. 10 [5–13], respectively; P < 0.01). Fifty-two percent of fellows reported redeployment outside IP during COVID-19, mostly into intensive care units. IP procedure volume decreased by 21% during COVID-19 compared with pre–COVID-19 volume. This decrease was mainly accounted for by a reduction in bronchoscopies. A majority of fellows (82%) reported retainment of outpatient clinics during COVID-19 with the transition from face-to-face to telehealth-predominant format. Continuation of academic and research activities during COVID-19 was reported by 86% and 82% of fellows, respectively. After graduation, all fellows reported having secured employment positions. Conclusion Although IP fellows were extensively involved in the care of patients with COVID-19, most IP programs retained educational activities through the COVID-19 outbreak. The impact of the decrease in procedure volume on trainee competency would be best addressed individually within each training program. These data may assist in focusing efforts regarding the education of medical trainees during the current and future healthcare crises.
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. 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A. , Hussain, Salik , Hutabarat, Martina , Hwang, Hui-Yun, Ieni, Antonio , Ikeda, Fumiyo , Imagawa, Yusuke , Imbriano, Carol , Imoto, Masaya , Inman, Denise M. , Inoki, Ken , Iozzo, Renato V. , Iribarren, Pablo , Ishaq, Mohd , Ishimwe, Nestor , Ismail, Nahed , Issazadeh‐Navikas, Shohreh , Itakura, Eisuke , Ito, Daisuke , Ivankovic, Davor , Ivanova, Saška , Iyer, Anand Krishnan V. , Izquierdo, José M. , Jacobo‐Herrera, Nadia , Jacquin, Élise , Jadiya, Pooja , Jaeschke, Hartmut , Jagannath, Chinnaswamy, Jakobsson, Johan , Janji, Bassam , Jansen‐Dürr, Pidder , Jansson, Patric J. , Januszewski, Sławomir, Jeltsch‐David, Hélène , Jenny, Andreas , Jensen, Thomas E. , Jessen, Niels , Jia, Lijun , Jia, Rui , Jiang, Qing , Jiang, Richeng , Jiang, Teng , Jiang, Xuejun , Jiang, Yu , Jiménez-Sánchez, María , Jin, Fengyan , Jin, Li , Jin, Luqi, Jin, Si , Joffre, Carine , Johnston, Simon A. , Jokitalo, Eija , Juárez, Esmeralda , Juhász, Gábor , Jun, Youngsoo , Jung, Chang Hwa , Jung, Sung‐Chul , Jungbluth, Heinz , Jungverdorben, Johannes , Just, Steffen , Kaasik, Allen , Kaganovich, Daniel , Kain, Renate , Kajimura, Shingo , Kalamvoki, Maria , Kalia, Manjula , Kalinowski, Danuta S. , Kaludercic, Nina , Kalvari, Ioanna , Kamińska, Joanna , Kanamori, Hiromitsu , Kang, Chanhee , Kang, Rui , Kang, Sang Sun , Kaniyappan, Senthilvelrajan , Kanki, Tomotake , Kanneganti, Thirumala‐Devi , Kanthasamy, Arthi , Kantorow, Marc , Kapuy, Orsolya , Karim, Md. 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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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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. 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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. La , Lai, Zhibing, Lamark, Trond , Lane, Jon D. , Lang, Charles H. , Lange, Carsten, Langel, Ülo , Lapaquette, Pierre , LaRusso, Nicholas F. , Lastres‐Becker, Isabel , Lavandero, Sergio , Law, Hkw , Layfield, Robert , Leduc‐Gaudet, Jean‐Philippe , Lee, He-Jin, Lee, Jae Man , Lee, Jun Hee , Lee, Seung‐Jae , Lee, Ying‐Ray , Lefebvre, Christophe , Legouis, Renaud , Leitinger, Gerd , Lenz, Heinz Josef, León, Yolanda, Leopoldino, Andréia Machado , Leung, Chi-Ting, Levine, Beth , Li, Jing , Li, Ke, Li, Min , Li, Min , Li, Pin‐Lan , Li, Tiangang , Li, Zhiqiang, Lian, Jiqin , Liang, Chengyu, Liang, Qiangrong , Liao, Mingzhi , Lilly, Mary A. , Lin, Liang , Lin, Pei‐Hui , Lin, Xueying , Linden, Rafael , Ling, Shuo‐Chien , Lingor, Paul , Linnemann, Amelia K , Liou, Yih‐Cherng , Lira, Vitor Agnew , Liu, Chunfeng , Liu, Cui Hua , Liu, Hao , Liu, Hsiao‐Sheng , Liu, Julia C. , Liu, Longhua , Liu, Meilian , Liu, Qin , Liu, Xiao-Hong, Liu, Xiaodong , Liu, Xingguo , Liu, Xuedong , Liu, Yang, Liu, Yang, Lizard, Gérard , Llorente, Alicia , Long, Qi , Long, Yun Chau, López, Manuela G. , Lőrincz, Péter , Lovat, Penny E. , Lu, Jin‐Jian , Lum, Julian J., Lünemann, Jan D. , Luo, Shouqing , Ma, Changle , Ma, Mengxiao , Ma, Ning‐Fang , Macián, Fernando , MacKeigan, Jeffrey P. , Majello, Barbara , Malorni, Walter , Mandell, Michael A. , Manjili, Masoud H. , Manjithaya, Ravi R. , Manque, Patrício , Manzoni, Claudia , Mao, Kai, Marconi, Anna Maria , Margeta, Marta , Marinelli, Oliviero , Marshall, Richard Scott , Marten, Mark R. , Martens, Sascha , Martin, Sara, Martín-Acebes, Miguel A. , Martín‐Burriel, Inmaculada , Martina, José A. , Martinet, Wim , Martinez, Jennifer , Martínez‐Velázquez, Moisés , Martinez-Lopez, Nuria, Martins‐Marques, Tânia , Masclaux‐Daubresse, Céline , Masson, Glenn Robert , Masuelli, Laura , Masyuk, Tetyana V., Matarrese, Paola , Mattoscio, Domenico , Mauriz, Jose Luis , Mauvezin, Caroline , Maverakis, Emanual Michael , Mazzoccoli, Gianluigi , McDonald, Christine , McLaughlin, BethAnn , Mechta‐Grigoriou, Fatima , Meijer, Annemarie H. , Meng, Tian, Menna‐Barreto, Rubem F. S. , Menon, Manoj B., Mercer, Carol A. , Mercier, Anne E., Merighi, Adalberto , Merla, Giuseppe , Miller, Dana L. , Miller, Silke , Milošević, Ira , Minina, Elena A. , Mirzaei, Mehdi, Mishra, Paras Kumar , Miyamoto, Shigeki, Miyazawa, Keisuke, Mograbi, Baharia , Mohanty, Abhishek , Mohapatra, Sipra , Mohmmed, Asif , Moles, Anna , Molinari, Maurizio , Mollace, Vincenzo , Møller, Andreas Buch , Mora, Ana Lucia , Mora, Marina, Morelli, Elena, Moreno, Sandra , Moresi, Viviana , Morga, Benjamín , Moritz, Orson L. , Moriyama, Mariko, Mostowy, Serge , Moustaïd‐Moussa, Naïma , Muller, Sylviane , Munjal, Ashok Kumar , Muñoz‐Cánoves, Pura , Münz, Christian , Muratori, Claudia, Murphy, John Patrick , Nabissi, Massimo , Nah, Jihoon , Nakagawa, Ichiro, Nakatogawa, Hitoshi , Nardacci, Roberta , Narita, Masashi , Neri, Luca Maria , Neufeld, Thomas P. , Nezis, Ioannis P. , Ni, Hong‐Min , Nicolao, María Celeste , Nilsson, Per Gunnar , Ning, Shunbin , Nóbrega, Clévio , Nolan, Trevor M. , Novak, Ivana, Nozawa, Takashi , Nussbaum-Krammer, Carmen I. , O’Sullivan, Timothy E., Oehme, Ina , Ohmuraya, Masaki , Okamoto, Koji , Oku, Masahide, Omary, M. Bishr , Önal, Gizem , Ong, Sang‐Ging , Ortona, Elena , Osta, Rosario , Otegui, Marisa S. , Ottobrini, Luisa , Outeiro, Tiago F. , Øynebråten, Inger , Pajvani, Utpal B. , Pallet, Nicolas , Palumbo, Camilla , Pampaloni, Francesco , Pan, Lifeng , Pan, Wenliang, Pandey, Udai Bhan , Panzarini, Elisa , Papaleo, Elena , Park, Eun Chan , Park, Joon Tae , Park, Sang Chul , Parola, Abraham H. , Parys, Jan B. , Patel, Hemal H. , Patschan, Daniel , Pei, Jianming, Peled‐Zehavi, Hadas , Penna, Fabio , Pérez-Lara, Ángel , Pérez‐Pérez, María Esther , Periyasamy, Palsamy , Perrotta, Cristiana , Perrotta, Ida Daniela , Petersen, Morten , Petrache, Irina , Philips, Jennifer A. , Picca, Anna , Pierdominici, Marina , Pietrocola, Federico , Pignata, Claudio , Pinton, Paolo , Plantinga, Theo S. , Plaza‐Zabala, Ainhoa , Plotnikov, Egor Y. , Plun‐Favreau, Hélène , Pluta, Ryszard , Popova, Blagovesta, Porta, Helena , Post, Martin , Poulton, Joanna , Promponas, Vasilis J. , Proud, Christopher G. , Puri, Rajat , Qi, Xiaopeng , Qian, Wenbin , Qiang, Lei , Qiu, Yu, Quarleri, Jorge Fabián , Ragusa, Michael J. , Rahimi, Nader , Rangarajan, Pundi Narasimhan , Rao, Lang , Rao, Rekha, Razani, Babak , Régnier, Jean-Claude , Reichert, Andreas S , Reue, Karen , Ricci, Jean‐Ehrland , Ricci, Roméo , Rikihisa, Yasuko , Roberts, Helen C., Roberts, Luke D., Roccheri, Maria Carmela , Rodney, George Gerald , Rodrigues, Tiago, Rodrı́guez, Amaia , Barrueco, Ruth Rodriguez , Rodríguez‐Rocha, Humberto , Roelofs, Jeroen , Rolka, Krzysztof , Romeo-Guitart, David , Roperto, Sante , Roth, Kevin A. , Roth, Lynn , Rovere‐Querini, Patrizia , Rubinsztein, David Chaim , Rudolf, Emil, Rudolf, Rüdiger, Ryan, Kevin M. , Ryu, Kwon‐Yul , Sachdev, Ulka , Sacher, Michael, Sadoshima, Junichi , Safren, Nathaniel , Sagona, Antonia P. , Sahay, Gaurav , Sahebkar, Amirhossein , Sahin, Ozgur, Sahni, Sumit , Saito, Shigeru , Sakai, Ryohei , Sanderson, J. 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. G. , Takáts, Szabolcs , Talwar, Priti , Tan, Chong Teik , Tanaka, Motomasa , Tanida, Isei , Tatenhorst, Lars , Tavernarakis, Nektarios, Taylor, Allen, Taylor, Gregory A., Taylor, Joan M. , Tchetina, Elena V. , Tee, Andrew R. , Tegeder, Irmgard , Teis, David , Teixeira-Clerc, Fatima , Tekirdağ, Kumsal Ayşe, Tepikin, Alexei V. , Testillano, Pilar S. , Tettamanti, Gianluca , Thellung, Stefano , Thomas, Sufi Mary , Thukral, Lipi , Till, Andreas , Todi, Sokol V. , Todorova, Krassimira O. , Tong, Benjamin Chun‐Kit , Tooze, Sharon A. , Torgersen, Maria Lyngaas , Toyokuni, Shinya , Trajković, Vladimir , Tramontano, Donatella , Trelford, Charles B. , Triola, Gemma , Tschan, Mario P. , Tse, Hung‐Fat , Tsugawa, Hitoshi , Tümtaş, Yasin , Tuñón, María Jesús , Turcotte, Sandra , Turk, Boris , Türk, Vito , Turner, Bradley J. , Tuxworth, Richard I. , Unno, Rei , Urbé, Sylvie , Üstün, Şuayib , Vaccari, Thomas , Vakifahmetoglu-Norberg, Helin , Vanrell, María Cristina , Varano, Gabriele , Vavvas, Demetrios G. , Vega‐Naredo, Ignacio , Velotti, Francesca , Vessoni, Alexandre Teixeira , Vidal, Michel, Vierstra, Richard David , Vijayan, Vinoy, Vilar, Marçal , Villarroya, Francesc , Villarroya, Joan , Viscomi, Maria Teresa , Višnjić, Dora , Vitale, Ilio , Wade‐Martins, Richard , Walker, David W., Walker, Simon A. , Walter, Jochen , Wang, Chao-Yung, Wang, Dong , Wang, Fangyang , Wang, Feng , Wang, Guansong , Wang, Han, Wang, Hao , Wang, Jiou , Wang, Lianrong , Wang, Peipei , Wang, Ping, Wang, Qing Jun , Wang, Qing , Wang, Wuyang , Wang, Yan, Wang, Yen‐Yun , Wang, Yipeng , Warnes, Gary , Warnsmann, Verena , Watada, Hirotaka , Wei, Lei , Wells, Alan , Wen, Xin , Wheatley, Sally P. , Whitworth, Alexander J. , Willbold, Dieter , Williams, Roger L. , Winner, Beate , Witkin, Steven Sol , Wong, Esther S.P. , Wong, Jack Ho, Wu, Chengbiao , Wu, Jian Huang , Wu, Mian , Wu, Min , Wu, Shuyan , Wu, Xiaohong , Xiang, Jin, Xiang, Mingliang, Xiang, Wei, Xiao, Bin, Xu, Chuanshan , Xu, En, Xu, Haoxing , Xu, Jing , Xu, Wen , Yamaguchi, Osamu , Yan, Shian‐Jang , Yanagi, Yasuo , Yang, Huang‐Tian , Yang, Jin‐Ming , Yang, Pei‐Ming , Yang, Qian , Yang, Xuesong , Yang, Ying , Yao, Honghong , Yao, Shenggen , Yen, Paul M. , Ying, Meidan, Yoo, Young H., Yoshida, Kiyotsugu , Yoshii, Saori R. , Yousefi, Bahman , Yu, Jun Qing , Yu, Jun, Yu, Wai Haung , Yu, Zhou , Yuan, Shyng‐Shiou F. , Yun, Jeanho , Zarbalis, Konstantinos S. , Zhang, Bin , Zhang, Donna D. , Zhang, Hanlin , Zhang, Hong , Zhang, Hui , Zhang, Jianhua , Zhang, Lin , Zhang, Lisheng , Zhang, Wei , Zhang, Xiangnan, Zhang, Xu Dong , Zhang, Yang, Zhang, Yan‐Jin , Zhang, Yingmei , Zhang, Zhengguang , Zhang, Zhihai , Zhang, Zhiyong , Zhao, Xiao-Fan, Zhao, Ying, Zheng, Yi , Zhivotovsky, Boris , Zhou, Ao, Zhou, Hao , Zhou, Hong , Zhou, Jie , Zhou, Jing , Zhou, Jiyong , Zhou, Kailiang , Zhou, Shu‐Feng , Zhou, Zheng-Yu, Zhu, Hongxin, Zhu, Hua , Zhu, Wei‐Guo , Zientara‐Rytter, Katarzyna , Zimmermann, Christine M., Ziviani, Elena , Zwerschke, Werner , Brand‐Saberi, Beate , Li, Zuguo, Oshima, Shigeru , Rong, Yueguang , Devuyst, Olivier; https://orcid.org/0000-0003-3744-4767 , Xia, Zhengyuan , Netea, M. G.

Autophagy | March 24, 2021 | Volume: 17 | Issue: 1 | Pages: 1-382

10.1080/15548627.2020.1797280 | PMID 33634751 Get It

Abstract PD9-02: Personalized ctDNA as a predictive biomarker in high-risk early stage breast cancer (EBC) treated with neoadjuvant chemotherapy (NAC) with or without pembrolizumab (P)
Magbanua, Mark Jesus M. , Renner, Derrick , Shchegrova, Svetlana, Wu, Hsin-Ta, Kalashnikova, Ekaterina , Tin, Antony , Salari, Raheleh, Rodriguez, Angel , Aleshin, Alexey , Billings, Paul R. , Liu, Minetta C. , Nanda, Rita , Veer, Laura van ‘t , Investigators, I-SPY 2, Wolf, Denise M. , Swigart, Lamorna Brown , Yau, Christina , Hirst, Gillian L. , Delson, Amy , Yee, Douglas , DeMichele, Angela , Zimmermann, Bernhard G , Sethi, Himanshu , Esserman, Laura J. , Veer, Laura J. van’t , Investigators, I-SPY 2

Cancer Research | February 15, 2021 | Volume: 81 | Issue: 4_Supplement | Pages: PD9-02-PD9-02

10.1158/1538-7445.sabcs20-pd9-02 Get It

Abstract Background: In the I-SPY 2 TRIAL, the addition of P to standard NAC resulted in more than doubling of the pathologic complete response (pCR) rates for both hormone receptor-positive (HR+)/HER2- and triple-negative (TN) early breast cancer (EBC) patients (pts) compared to NAC only (Nanda et al, JAMA Oncol, 2020). At 3 years, distant recurrence-free survival (DRFS) rates in pts with pCR following NAC+P was >95%. We hypothesized that ctDNA can serve as a predictive biomarker of response and survival in pts treated with NAC. Methods: A personalized ctDNA test (Signatera) was performed on 511 serial plasma samples from 138 pts with high-risk HR+/HER2- (n=77) or TN (n=61) stage II/III EBC. Pts received P with paclitaxel (Tx) followed by AC (P arm, n=42) or standard NAC only (n=96), an exploratory subset of pts evaluated for P efficacy. Plasma was collected; pretreatment (T0), 3 weeks after treatment initiation (T1), between Tx+/-P and AC regimens (T2), and prior to surgery (T3). ctDNA was deemed positive with a minimum of 2 of the pt specific tumor mutation fragments detected in cfDNA. Association of ctDNA with response and survival was analyzed using logistic and Cox regressions with pCR and DRFS as endpoints. Median follow-up was 2.8 years. Results: Detection of ctDNA decreased over time (P arm: T0-81%, T1-50%, T2-19%, T3-3%) and NAC only: T0-82%, T1-65%, T2-26%, T3-10%). ctDNA data at T0 and T1 was available for 96% (132/138) of pts in P arm or NAC only (Table). Among ctDNA+ patients at baseline, clearance at T1 was significantly associated with pCR (OR=1.92, ctDNA+/-; OR=0.27, ctDNA+/+; LR p<0.001). This association remained significant after adjustment for HR status and treatment (LR p<0.001) and P arm or NAC only (P: LR p=0.03; NAC: LR p=0.01). ctDNA data at T0, T1, and T2 was available for 86% (118/138) pts. (Table). Among all ctDNA+ pts at baseline, dynamics through T2 was associated with pCR (OR=1.44, ctDNA+/-/-; OR=0.33, ctDNA+/+/-, OR=0.12, ctDNA+/+/+; LR p=0.0011). This association remained significant when adjusted for HR status and treatment (LR p<0.001). Analysis within individual treatments showed significant association for NAC (LR p=0.040) and a non-significant trend in NAC+P (LR p=0.063), likely due to smaller sample size. All pts who achieved pCR were ctDNA- at T3 (n=34). Among those who failed to achieve pCR (n=81), DRFS was significantly better in ctDNA- (n=72/81; 20 in P and 52 in NAC) versus ctDNA+ pts (n=9/81; 1 in P and 8 in NAC) (adjusted HR 0.13; 95% CI 0.05-0.37). Conclusions: These exploratory results align with our previous findings that early clearance of ctDNA during NAC treatment was significantly associated with increased likelihood of achieving pCR. Additionally, we show that ctDNA clearance can be an early surrogate marker for therapy response assessment. Residual ctDNA after neoadjuvant treatment was a significant predictor of metastatic recurrence and death. Personalized monitoring of ctDNA during the course of NAC is feasible and provides information that can be combined with imaging and pathology, and may help to optimize decision making for de-escalation or escalation of therapy. Larger studies are ongoing. ctDNA dynamics and pCRctDNA status at T0 and T1 (n=132)ctDNA status at T0, T1, and T2 (n=118)ctDNA-/-ctDNA+/-ctDNA+/+ctDNA-/-/-ctDNA+/-/-ctDNA+/+/-ctDNA+/+/+Total, n (%)24 (18)28 (21)80 (61)22 (19)24 (20)43 (36)27 (23)pCR, n (%)9 (38)15 (54)11 (14)9 (41)12 (50)8 (19)2 (7)No pCR, n (%)15 (63)13 (46)69 (86)13 (59)12 (50)35 (81)25 (93) Citation Format: Mark Jesus M Magbanua, Denise Wolf, Derrick Renner, Svetlana Shchegrova, Lamorna Brown Swigart, Christina Yau, Gillian Hirst, Hsin-Ta Wu, Ekaterina Kalashnikova, Antony Tin, Amy Delson, Douglas Yee, Angela DeMichele, Raheleh Salari, Angel Rodriguez, Bernhard Zimmermann, Himanshu Sethi, Alexey Aleshin, Paul Billings, Laura Esserman, Minetta Liu, Rita Nanda, Laura van ‘t Veer, I-SPY 2 Investigators. Personalized ctDNA as a predictive biomarker in high-risk early stage breast cancer (EBC) treated with neoadjuvant chemotherapy (NAC) with or without pembrolizumab (P) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-02.
Tfeb Links MYC Signaling to Epigenetic Control of Acute Myeloid Leukemia Cell Death and Differentiation
Yu, Xiaoqing , Yang, Chunying , Hitosugi, Taro , Cheng, Chia‐Ho, Freischel, Audrey R. , Watson, G., Schaub, Franz X. , Vedder, Alexis , Cen, Ling , McGraw, Kathy L. , Yun, Seongseok , Vincelette, Nicole D. , Fernandez, Mario R. , Zhang, Ling , Li, Weimin , Hou, Hsin‐An , Murphy, Daniel J. , Ballabio, Andrea , Kaufmann, Scott H. , Berglund, Anders , Cleveland, John L.

Blood | February 8, 2021 | Volume: 136 | Issue: Supplement 1 | Pages: 12-13

10.1182/blood-2020-137209 Get It

MYC gene amplification and somatic mutations are frequent in both adult and pediatric AML although how MYC drives and contributes to the development and maintenance of AML has not been resolved. Transcription factor EB (TFEB) is a master regulator of genes that control autophagy and lysosome biogenesis, a central catabolic recycling pathway that regulates cell survival. Given the oncogenic effects of MYC in AML and that the induction of autophagy compromises AML cell growth and survival, we tested if the oncogenic effect of MYC depends on its suppression of TFEB transcription programs in AML. In support of this hypothesis, inducible MYC expression in K562 and THP-1 leukemia cells was sufficient to suppress expression of TFEB and its target genes. Further and conversely, MYC knockdown in NB4 AML cells provoked increased expression of TFEB mRNA and protein, as well as increased expression of TFEB target genes. Notably, dose response studies demonstrated that expression of TFEBS211A, constitutively nuclear form of TFEB that is refractory to control by mTORC1 signaling, dramatically impairs proliferation of HL60, OCI-AML2 and OCI-AML3 AML cells. In addition, induction of TFEBS211A provoked rampant apoptosis. Of important, overexpression of TFEBS211A in HL-60 and OCI-AML3 cells was also sufficient to promote monocytic and granulocytic differentiation, as judged by morphological changes and the acquisition of mature monocytic and granulocytic markers including CD11b, Gr1, and CD15. To identify TFEB targets that might contribute to myeloid/granulocytic differentiation, we performed RNA-seq analysis of HL60 leukemia cells engineered to inducibly express the TFEBS211A transgene. Using a cut-off of fold change>4 with q<0.01, a total of 1152 genes were differentially regulated following the induction of TFEBS211A in HL60 cells. As expected, this included the robust induction of nearly all TFEB target genes associated with the autophagy-lysosome pathway, but also of STAT1, KLF4, KLF6, CEBPB, CSF1 and GATA2 genes that are necessary and/or sufficient to provoke terminal monocytic and granulocytic differentiation of AML cells. Surprisingly, among genes induced by TFEB in HL60 cells is IDH1, which catalyzes the production of α-ketoglutarate (α-KG), a required substrate of the TET family of dioxygenases that convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC). In particular, TFEBS211A expression provoked increases in levels of α-KG and significant increases in global levels of 5hmC in genomic DNA of HL60 leukemia cells both ex vivo and in vivo. Furthermore, TFEB-mediated induction of IDH1/2 mRNA and protein, and of IDH1 promoter activity, was antagonized by inducible expression of MYC. To assess the global effects of TFEB on 5mC/5hmC landscapes, we performed paired reduced representation bisulfite (BS)- and oxidation bisulfite (oxBS)-sequencing. As predicted, TFEBS211A induced both loss and gains of 5mC, but there were more losses (n = 722) than gains (n = 459) across all 22 chromosomes. Quite remarkably, and consistent with TFEB-provoked increases of 5hmC signals, TFEBS211A exclusively induced 5hmC gains (in a total of 863 genes), and 37% and 36% of these 5hmC gains occurred in promoter regions and CpG islands, and across all 22 chromosomes. Comparison of BS- and oxBS-seq versus RNA-seq analyses of HL60 cells expressing TFEB revealed significant changes in mRNA levels and concomitant differential changes in 5mC and 5hmC marks in KLF4, KLF6, STAT3, TP73, andFOXO1 that have pivotal roles in controlling myeloid cell differentiation and death. Collectively, these findings demonstrate that MYC suppresses TFEB expression and function in AML cells, and that TFEB functions as a tumor suppressor that provokes AML cell differentiation and death. Strikingly, these responses rely on epigenetic control, where TFEB directly induces the transcription of IDH1 and IDH2 to provoke global hydroxylation of 5-methylcytosine and the expression of genes that drive terminal differentiation and apoptosis. Thus, a MYC-TFEB-IDH1/2-TET2 circuit controls AML cell fate. Disclosures Murphy: Merck: Research Funding; Puma Biotech: Research Funding. Ballabio:CASMA Therapeutics: Other: Co-Founder. Kaufmann:Takeda Pharmaceuticals: Research Funding.
TFEB Links MYC Signaling to Epigenetic Control of Myeloid Differentiation and Acute Myeloid Leukemia
Yun, Seongseok , Yu, Xiaoqing , Watson, G., Fernandez, Mario R. , Yang, Chunying , Hitosugi, Taro , Cheng, Chia‐Ho, Freischel, Audrey R. , Schaub, Franz X. , Vedder, Alexis , Cen, Ling , McGraw, Kathy L. , Moon, Jungwon , Murphy, Daniel J. , Berglund, Anders , Kaufmann, Scott H , Berglund, Anders E , Yun, Seongseok , Murphy, Daniel J , Vincelette, Nicole D. , Zhang, Ling , Li, Weimin , Hou, Hsin‐An , Ballabio, Andrea , Kaufmann, Scott H. , Cleveland, John L.

Blood Cancer Discovery | December 22, 2020 | Volume: 2 | Issue: 2 | Pages: 162-185

10.1158/2643-3230.bcd-20-0029 | PMID 33860275 Get It

Abstract MYC oncoproteins regulate transcription of genes directing cell proliferation, metabolism, and tumorigenesis. A variety of alterations drive MYC expression in acute myeloid leukemia (AML), and enforced MYC expression in hematopoietic progenitors is sufficient to induce AML. Here we report that AML and myeloid progenitor cell growth and survival rely on MYC-directed suppression of Transcription Factor EB (TFEB), a master regulator of the autophagy–lysosome pathway. Notably, although originally identified as an oncogene, TFEB functions as a tumor suppressor in AML, where it provokes AML cell differentiation and death. These responses reflect TFEB control of myeloid epigenetic programs by inducing expression of isocitrate dehydrogenase-1 (IDH1) and IDH2, resulting in global hydroxylation of 5-methycytosine. Finally, activating the TFEB–IDH1/IDH2–TET2 axis is revealed as a targetable vulnerability in AML. Thus, epigenetic control by an MYC–TFEB circuit dictates myeloid cell fate and is essential for maintenance of AML. Significance: Alterations in epigenetic control are a hallmark of AML. This study establishes that a MYC–TFEB circuit controls AML differentiation and epigenetic programs by inducing IDH1/IDH2 and hydroxylation of 5-methylcytosine, that TFEB functions as a tumor suppressor in AML, and that this circuit is a targetable vulnerability in AML. See related commentary by Wu and Eisenman, p. 116.
Abstract 3215: ClinGen somatic cancer working group: Disseminating standardized cancer molecular diagnostic data and evidence through global collaboration and expert curation
Ritter, Deborah , Danos, Arpad , Raca, Gordana , Roy, Angshumoy , Lin, Wan‐Hsin , Wang, Jue , Hosseini, Seyed Ali, Kanagal-Shamana, Rashmi, Xu, Xinjie , Merker, Jason D. , Kulkarni, Shashikant , Madhavan, Subha , Rao, Shruti , Krysiak, Kilannin , Barnell, Erica K. , McCoy, Matthew , Pitel, Beth A. , Sonkin, Dmitriy , Selvarajah, Shamini , King, Ian F. G. , Warner, Jeremy L. , Meric‐Bernstam, Funda , Li, Marilyn M , Wagner, Alex H. , Griffith, Malachi , Griffith, Obi L.

Cancer Research | September 4, 2020 | Volume: 80 | Issue: 16_Supplement | Pages: 3215-3215

10.1158/1538-7445.am2020-3215 Get It

Abstract The Clinical Genome (ClinGen) Resource is a US National Human Genome Research Institute (NHGRI)-funded program dedicated to building an expert curated and freely available central resource that defines the clinical relevance of genes and variants for use in precision medicine. Teams of experts in various clinical domains come together as working groups within ClinGen to facilitate the interpretation, annotation and utilization of genes-variants for clinical application. Somatic Cancer is one such ClinGen Clinical Domain Working Group (CDWG) that consists of over 90 members worldwide, including clinicians, clinical laboratory diagnosticians, genomic scientists and bioinformaticians. Members of this CDWG identify high priority somatic variants in different cancer types that require expert curation and consensus in their clinical interpretation. In order to accurately implement practice guidelines/standards for variant interpretation, the Somatic Cancer CDWG recently established a somatic Variant Curation Expert Panel (VCEP) approval process. Based on their interest and clinical domain expertise, a subset of the CDWG members formed somatic VCEPs to perform authoritative curation on the shortlisted genes-somatic variants within the context of a disease, therapeutic indication or biological pathway. Expert curation within these VCEPs is performed by utilizing guidelines such as those recommended by AMP/ASCO/CAP (Li et al. 2017) and the Somatic Cancer CDWG (Ritter et al. 2016). Wherever necessary, the somatic VCEPs will develop: 1) gene- and disease-specific modifications to address gaps in existing variant assessment guidelines, 2) quantitative approaches for variant interpretation, and 3) implement standardized protocols for annotating somatic variants in genes for a specific disease, drug or biological pathway. Furthermore, ClinGen recently formed the Cancer Variant Interpretation (CVI) committee to provide support, review and feedback on the provisional somatic variant interpretation proposals developed by the VCEPs. The CVI provides somatic VCEPs with a preliminary approval before the final approval by the ClinGen CDWG oversight committee and ultimately ‘expert panel' status in ClinVar, an NCBI-maintained database of clinically relevant gene variants. NTRK fusions in cancer is the first Somatic VCEP going through the ClinGen Somatic Expert Panel approval process. Alterations in the FGFR pathway in GU cancers is the second somatic VCEP under consideration. The Somatic CDWG uses the CIViC (Clinical Interpretation of Variants in Cancer) platform for curation of somatic variants. To date, the CDWG has curated 268 evidence items relating to cancer variants in CIViC, 6 assertions, and 33 evidence source suggestions. The ultimate goal of the Somatic CDWG is to enhance the usability, dissemination and implementation of cancer somatic changes in the ClinGen resource and other cancer variant knowledgebases. Citation Format: Shruti Rao, Deborah Ritter, Arpad Danos, Gordana Raca, Angshumoy Roy, Kilannin Krysiak, Wan-Hsin Lin, Erica Barnell, Matthew McCoy, Beth Pitel, Dmitriy Sonkin, Jue Wang, Seyed Ali Hosseini, Shamini Selvarajah, Ian King, Rashmi Kanagal-Shamana, Xinjie Xu, Jeremy L. Warner, Funda Meric-Bernstam, Jason D. Merker, Marilyn Li, Alex H. Wagner, Malachi Griffith, Obi L. Griffith, Shashikant Kulkarni, Subha Madhavan. ClinGen somatic cancer working group: Disseminating standardized cancer molecular diagnostic data and evidence through global collaboration and expert curation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3215.
Abstract A58: Curation of pediatric cancer variants within the Clinical Genome Resource (ClinGen)
Church, Alanna J. , Ritter, Deborah , Danos, Arpad , Krysiak, Kilann, Hiemenz, Matthew , Janeway, Katherine A. , Ji, Jianling , Laetsch, Theodore W. , Schmidt, Ryan J. , Sund, Kristen L. , Lin, Wan‐Hsin , Kulkarni, Shashikant , Madhavan, Subha , Roy, Angshumoy , Raca, Gordana , Rao, Shruti , Corson, Laura , Fisher, Kevin E. , Kesserwan, Chimene A. , Parsons, D. Williams , Griffith, Malachi , Griffith, Obi L.

Cancer Research | August 12, 2020 | Volume: 80 | Issue: 14_Supplement | Pages: A58-A58

10.1158/1538-7445.pedca19-a58 Get It

Abstract Introduction: The Clinical Genome Resource (ClinGen) Somatic Working Group (sWG) is a multi-institution team engaged in developing processes, resources, and standards to support accurate classification of somatic variants in cancer. Existing decision support resources in cancer knowledgebases are heavily skewed towards genes and variants relevant in adult cancers; however, information to support variant interpretation in childhood cancers is limited. Here we report on the goals and progress of the Pediatric Cancer Taskforce, created within the ClinGen sWG, to lead curation efforts of actionable alterations in childhood cancers. Methods: The ClinGen sWG Pediatric Cancer Taskforce (PCT) consists of a core group of twelve members comprising geneticists, pathologists, and oncologists with expertise in different pediatric cancers and with representation from 9 leading pediatric institutions. The taskforce has a total of 35 members including volunteer-curators who work under guidance of the expert members. Curation of childhood cancer variants is conducted in collaboration with the Clinical Interpretation of Variants in Cancer (CIViC) team at Washington University in Saint Louis, using the CIViC knowledgebase (civicdb.org) and the ClinVar database as open-access curation and data-sharing platforms. Diagnostic, prognostic, and therapeutic evidence is tiered according to the AMP/ASCO/CAP guidelines for the clinical interpretation of somatic variants. PCT members are assigned specific genetic variant-tumor type associations for curation, which are then reviewed in monthly conferences to finalize assertions in CIViC. Results: The PCT has prioritized 40 genetic alterations relevant to pediatric cancer for curation based on their clinical relevance and the lack of sufficient existing curated evidence in clinical knowledgebases. To date, 4 assertions have been created and added to the database: HEY1-NCOA2 fusion in mesenchymal chondrosarcoma, KIAA1549-BRAF fusion and ACVR1 p.G328V variant in pediatric glioma, and EBF1-PDGFRB fusion in pediatric B-cell precursor acute lymphoblastic leukemia. Active curation has been initiated for NTRK fusions agnostic of tissue histology, targetable kinase fusions in Ph-like B-lymphoblastic leukemia, and common variants in selected pediatric sarcomas and brain tumors, focusing heavily on driver gene fusions in childhood cancers. 119 evidence items have been created in CIViC by the members. The PCT also works to implement more standardized and accurate classification of pediatric cancers in CIViC and other cancer resources, and to enhance search for pediatric-specific data through appropriate tagging of evidence using ontology terms. Conclusions: As molecular alterations are increasingly relevant to the care of children with cancer, the ClinGen PCT will work to develop standards, processes, and resources for efficient and accurate determination of clinical relevance of pediatric cancer variants. Citation Format: Alanna J. Church, Shruti Rao, Deborah Ritter, Arpad Danos, Kilann Krysiak, Laura B. Corson, Kevin E. Fisher, Matthew Hiemenz, Katherine A. Janeway, Jianling Ji, Chimene A. Kesserwan, Theodore W. Laetsch, Donald W. Parsons, Ryan J. Schmidt, Kristen L. Sund, Wan-Hsin Lin, Malachi Griffith, Obi L. Griffith, Shashikant Kulkarni, Subha Madhavan, Angshumoy Roy, Gordana Raca. Curation of pediatric cancer variants within the Clinical Genome Resource (ClinGen) [abstract]. In: Proceedings of the AACR Special Conference on the Advances in Pediatric Cancer Research; 2019 Sep 17-20; Montreal, QC, Canada. Philadelphia (PA): AACR; Cancer Res 2020;80(14 Suppl):Abstract nr A58.
Building the vertebrate codex using the gene breaking protein trap library
Ichino, Noriko , Serres, MaKayla R., Urban, Rhianna , Urban, Mark D. , Treichel, Anthony J. , Schaefbauer, Kyle, Tallant, Lauren , Varshney, Gaurav K. , Skuster, Kimberly J., McNulty, Melissa S. , Daby, Camden L. , Wáng, Ying , Liao, Hsin‐Kai, El‐Rass, Suzan , Liu, Weibin , Anderson, Jennifer L. , Wishman, Mark , Sabharwal, Ankit , Schimmenti, Lisa A. , Sivasubbu, Sridhar , Balciunas, Darius , Hammerschmidt, Matthias , Farber, Steven , Wen, Xiao‐Yan , McGrail, Maura , Burgess, Shawn M. , Ekker, Stephen C. , Urban, Rhianna M , Schaefbauer, Kyle J., Tallant, Lauren E., Ding, Yonghe , Wishman, Mark D, Sabharwal, Ankit , Balciunas, Darius , Hammerschmidt, Matthias , Farber, Steven Arthur , Lin, Xueying , McGrail, Maura , Essner, Jeffrey , Burgess, Shawn M , Clark, Karl J , Ekker, Stephen C , Wen, Xiao-Yan , Schimmenti, Lisa A , Treichel, Anthony J , Ichino, Noriko , Xu, Xiaolei , Essner, Jeffrey J. , Clark, Karl J.

eLife | August 11, 2020 | Volume: 9 | Issue: No issue available | Pages: No page available

10.7554/elife.54572 | PMID 32779569 Get It

One key bottleneck in understanding the human genome is the relative under-characterization of 90% of protein coding regions. We report a collection of 1200 transgenic zebrafish strains made with the gene-break transposon (GBT) protein trap to simultaneously report and reversibly knockdown the tagged genes. Protein trap-associated mRFP expression shows previously undocumented expression of 35% and 90% of cloned genes at 2 and 4 days post-fertilization, respectively. Further, investigated alleles regularly show 99% gene-specific mRNA knockdown. Homozygous GBT animals in ryr1b , fras1 , tnnt2a , edar and hmcn1 phenocopied established mutants. 204 cloned lines trapped diverse proteins, including 64 orthologs of human disease-associated genes with 40 as potential new disease models. Severely reduced skeletal muscle Ca 2+ transients in GBT ryr1b homozygous animals validated the ability to explore molecular mechanisms of genetic diseases. This GBT system facilitates novel functional genome annotation towards understanding cellular and molecular underpinnings of vertebrate biology and human disease.
Multicenter Study on the Diagnostic Performance of Native-T1 Cardiac Magnetic Resonance of Chronic Myocardial Infarctions at 3T
Wang, Guan , Yang, Qi , Sadras, Vignesh , Patel, Suraj , Yang, Hsin‐Jung , Sharif, Behzad , Kali, Avinash , Cokic, Ivan, Xie, Guoxi , Tighiouart, Mourad , Li, Debiao , Berman, Daniel S. , Chang, Hyuk‐Jae , Collins, Jeremy, Chang, Hyuk-Jae , Li, Debiao , Lee, Sang‐Eun , Collins, Jeremy D. , Dharmakumar, Rohan

Circulation: Cardiovascular Imaging | June 8, 2020 | Volume: 13 | Issue: 6 | Pages: No page available

10.1161/circimaging.119.009894 | PMID 32507020 Get It

Background: Preclinical studies and pilot patient studies have shown that chronic infarctions can be detected and characterized from cardiac magnetic resonance without gadolinium-based contrast agents using native-T1 maps at 3T. We aimed to investigate the diagnostic capacity of this approach for characterizing chronic myocardial infarctions (MIs) in a multi-center setting. Methods: Patients with a prior MI (n=105) were recruited at 3 different medical centers and were imaged with native-T1 mapping and late gadolinium enhancement (LGE) at 3T. Infarct location, size, and transmurality were determined from native-T1 maps and LGE. Sensitivity, specificity, receiver-operating characteristic metrics, and inter- and intraobserver variabilities were assessed relative to LGE. Results: Across all subjects, T1 of MI territory was 1621±110 ms, and remote territory was 1225±75 ms. Sensitivity, specificity, and area under curve for detecting MI location based on native-T1 mapping relative to LGE were 88%, 92%, and 0.93, respectively. Native-T1 maps were not different for measuring infarct size (native-T1 maps: 12.1±7.5%; LGE: 11.8±7.2%, P =0.82) and were in agreement with LGE ( R 2 =0.92, bias, 0.09±2.6%). Corresponding inter- and intraobserver assessments were also highly correlated (interobserver: R 2 =0.90, bias, 0.18±2.4%; and intraobserver: R 2 =0.91, bias, 0.28±2.1%). Native T1 maps were not different for measuring MI transmurality (native-T1 maps: 49.1±15.8%; LGE: 47.2±19.0%, P =0.56) and showed agreement ( R 2 =0.71; bias, 1.32±10.2%). Corresponding inter- and intraobserver assessments were also in agreement (interobserver: R 2 =0.81, bias, 0.1±9.4%; and intraobserver: R 2 =0.91, bias, 0.28±2.1%, respectively). While the overall accuracy for detecting MI with native-T1 maps at 3T was high, logistic regression analysis showed that MI location was a prominent confounder. Conclusions: Native-T1 mapping can be used to image chronic MI with high degree of accuracy, and as such, it is a viable alternative for scar imaging in patients with chronic MI who are contraindicated for LGE. Technical advancements may be needed to overcome the imaging confounders that currently limit native-T1 mapping from reaching equivalent detection levels as LGE.