Author: "Michelle Sam" - Searchworks@Jio Institute Digital Library Search Results

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38 results on '"Michelle Sam"'

1. An important case of atypical pneumonia

Author: Arvind Yerramilli, Michelle Sam, Aadith Ashok, and Eugene Athan
Subjects: General Medicine
Published: 2022

2. Genome-wide germline correlates of the epigenetic landscape of prostate cancer

Author: Michèle Orain, Lawrence E. Heisler, Alexander Gusev, Cindy Q. Yao, Matthew L. Freedman, Takafumi N. Yamaguchi, Ada Wong, Kathleen E. Houlahan, Vincent Huang, Ram Shankar Mani, Paul C. Boutros, Melvin L.K. Chua, Connor Bell, Thomas Kislinger, John Douglas Mcpherson, Lee Timms, Susmita G. Ramanand, Housheng Hansen He, Jiapei Yuan, Alain Bergeron, Hélène Hovington, Julie Livingstone, Mathieu Lupien, Shadrielle Melijah G. Espiritu, Yves Fradet, Mark Pomerantz, Edward P. O’Connor, Valérie Picard, Anamay Shetty, Alex Murison, Bogdan Pasaniuc, Bernard Têtu, Theodorus van der Kwast, Louis Lacombe, Yu Jia Shiah, Michelle Sam, Jeremy Johns, Alexandre Rouette, Michael Fraser, Ankit Sinha, Adrien Foucal, Robert G. Bristow, and Musaddeque Ahmed
Subjects: 0301 basic medicine, General Medicine, Methylation, Epigenome, Quantitative trait locus, Biology, medicine.disease, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Germline, 3. Good health, 03 medical and health sciences, Prostate cancer, 030104 developmental biology, 0302 clinical medicine, 030220 oncology & carcinogenesis, DNA methylation, Cancer research, medicine, Epigenetics, Carcinogenesis
Abstract: Oncogenesis is driven by germline, environmental and stochastic factors. It is unknown how these interact to produce the molecular phenotypes of tumors. We therefore quantified the influence of germline polymorphisms on the somatic epigenome of 589 localized prostate tumors. Predisposition risk loci influence a tumor’s epigenome, uncovering a mechanism for cancer susceptibility. We identified and validated 1,178 loci associated with altered methylation in tumoral but not nonmalignant tissue. These tumor methylation quantitative trait loci influence chromatin structure, as well as RNA and protein abundance. One prominent tumor methylation quantitative trait locus is associated with AKT1 expression and is predictive of relapse after definitive local therapy in both discovery and validation cohorts. These data reveal intricate crosstalk between the germ line and the epigenome of primary tumors, which may help identify germline biomarkers of aggressive disease to aid patient triage and optimize the use of more invasive or expensive diagnostic assays. Genetic variants in the germ line modulate DNA methylation in tumors and contribute to the aggressiveness of prostate cancer.
Published: 2019
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3. Cardiovascular Outcomes Associated With Hypoplastic Left Heart Syndrome Versus Other Types of Single Right Ventricle: A Multicenter Study

Author: Nabil Dib, Nancy Poirier, Michelle Samuel, Sewanou Hermann Honfo, Ali Zaidi, Alexander R. Opotowsky, François‐Pierre Mongeon, Blandine Mondésert, Joseph Kay, Reda Ibrahim, Robert M. Hamilton, Anne Fournier, Susan M. Jameson, Annie Dore, Stephen Cook, Scott Cohen, Marie‐A. Chaix, Craig S. Broberg, Jamil Aboulhosn, and Paul Khairy
Subjects: Fontan surgery, hypoplastic left heart syndrome, univentricular heart, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background The univentricular heart with a predominant right ventricle morphology (uRV) has been associated with a higher rate of adverse cardiovascular events. It remains to be determined whether the specific type of uRV influences outcomes. Methods and Results A North American multicenter retrospective cohort study was conducted by the Alliance for Adult Research in Congenital Cardiology on individuals with a uRV and total cavopulmonary connection Fontan. The incidence of a composite outcome consisting of all‐cause mortality, cardiac transplantation, atrial arrhythmias, or thromboembolic events was compared among patients with Fontan palliation who had hypoplastic left heart syndrome (HLHS) versus other forms of uRV (non‐HLHS). All components of the composite outcome were classified by a blinded adjudicating committee. Competing risks were taken into account in time‐to‐event analyses. A total of 171 patients with uRV of whom 76 (44.4%) had HLHS were followed for 10.2±5.7 years. The composite outcome occurred in 7.1 versus 2.1 cases per 100 person‐years in patients with HLHS versus non‐HLHS (P
Published: 2024
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4. Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Author: Bailey, Matthew H, Meyerson, William U, Dursi, Lewis Jonathan, Wang, Liang-Bo, Dong, Guanlan, Liang, Wen-Wei, Weerasinghe, Amila, Shantao, Li, Kelso, Sean, Saksena, Gordon, Ellrott, Kyle, Wendl, Michael C, Wheeler, David A, Getz, Gad, Simpson, Jared T, Gerstein, Mark B, Ding, Lirehan, Akbani, Pavana, Anur, Matthew, H Bailey, Alex, Buchanan, Kami, Chiotti, Kyle, Covington, Allison, Creason, Ding, Li, Kyle, Ellrott, Fan, Yu, Steven, Foltz, Gad, Getz, Walker, Hale, David, Haussler, Julian, M Hess, Carolyn, M Hutter, Cyriac, Kandoth, Katayoon, Kasaian, Melpomeni, Kasapi, Dave, Larson, Ignaty, Leshchiner, John, Letaw, Singer, Ma, Michael, D McLellan, Yifei, Men, Gordon, B Mills, Beifang, Niu, Myron, Peto, Amie, Radenbaugh, Sheila, M Reynolds, Gordon, Saksena, Heidi, Sofia, Chip, Stewart, Adam, J Struck, Joshua, M Stuart, Wenyi, Wang, John, N Weinstein, David, A Wheeler, Christopher, K Wong, Liu, Xi, Kai, Ye, Matthias, Bieg, Paul, C Boutros, Ivo, Buchhalter, Adam, P Butler, Ken, Chen, Zechen, Chong, Oliver, Drechsel, Lewis Jonathan Dursi, Roland, Eils, Shadrielle M, G Espiritu, Robert, S Fulton, Shengjie, Gao, Josep L, L Gelpi, Mark, B Gerstein, Santiago, Gonzalez, Ivo, G Gut, Faraz, Hach, Michael, C Heinold, Jonathan, Hinton, Taobo, Hu, Vincent, Huang, Huang, Yi, Barbara, Hutter, David, R Jones, Jongsun, Jung, Natalie, Jäger, Hyung-Lae, Kim, Kortine, Kleinheinz, Sushant, Kumar, Yogesh, Kumar, Christopher, M Lalansingh, Ivica, Letunic, Dimitri, Livitz, Eric, Z Ma, Yosef, E Maruvka, R Jay Mashl, Andrew, Menzies, Ana, Milovanovic, Morten Muhlig Nielsen, Stephan, Ossowski, Nagarajan, Paramasivam, Jakob Skou Pedersen, Marc, D Perry, Montserrat, Puiggròs, Keiran, M Raine, Esther, Rheinbay, Romina, Royo, S Cenk Sahinalp, Iman, Sarrafi, Matthias, Schlesner, Jared, T Simpson, Lucy, Stebbings, Miranda, D Stobbe, Jon, W Teague, Grace, Tiao, David, Torrents, Jeremiah, A Wala, Jiayin, Wang, Sebastian, M Waszak, Joachim, Weischenfeldt, Michael, C Wendl, Johannes, Werner, Zhenggang, Wu, Hong, Xue, Sergei, Yakneen, Takafumi, N Yamaguchi, Venkata, D Yellapantula, Christina, K Yung, Junjun, Zhang, Lauri, A Aaltonen, Federico, Abascal, Adam, Abeshouse, Hiroyuki, Aburatani, David, J Adams, Nishant, Agrawal, Keun Soo Ahn, Sung-Min, Ahn, Hiroshi, Aikata, Rehan, Akbani, Kadir, C Akdemir, Hikmat, Al-Ahmadie, Sultan, T Al-Sedairy, Fatima, Al-Shahrour, Malik, Alawi, Monique, Albert, Kenneth, Aldape, Ludmil, B Alexandrov, Adrian, Ally, Kathryn, Alsop, Eva, G Alvarez, Fernanda, Amary, Samirkumar, B Amin, Brice, Aminou, Ole, Ammerpohl, Matthew, J Anderson, Yeng, Ang, Davide, Antonello, Samuel, Aparicio, Elizabeth, L Appelbaum, Yasuhito, Arai, Axel, Aretz, Koji, Arihiro, Shun-Ichi, Ariizumi, Joshua, Armenia, Laurent, Arnould, Sylvia, Asa, Yassen, Assenov, Gurnit, Atwal, Sietse, Aukema, J Todd Auman, Miriam, R Aure, Philip, Awadalla, Marta, Aymerich, Gary, D Bader, Adrian, Baez-Ortega, Peter, J Bailey, Miruna, Balasundaram, Saianand, Balu, Pratiti, Bandopadhayay, Rosamonde, E Banks, Stefano, Barbi, Andrew, P Barbour, Jonathan, Barenboim, Jill, Barnholtz-Sloan, Hugh, Barr, Elisabet, Barrera, John, Bartlett, Javier, Bartolome, Bassi, Claudio, Oliver, F Bathe, Daniel, Baumhoer, Prashant, Bavi, Stephen, B Baylin, Wojciech, Bazant, Duncan, Beardsmore, Timothy, A Beck, Sam, Behjati, Andreas, Behren, Cindy, Bell, Sergi, Beltran, Christopher, Benz, Andrew, Berchuck, Anke, K Bergmann, Erik, N Bergstrom, Benjamin, P Berman, Daniel, M Berney, Stephan, H Bernhart, Rameen, Beroukhim, Mario, Berrios, Samantha, Bersani, Johanna, Bertl, Miguel, Betancourt, Vinayak, Bhandari, Shriram, G Bhosle, Andrew, V Biankin, Darell, Bigner, Hans, Binder, Ewan, Birney, Michael, Birrer, Nidhan, K Biswas, Bodil, Bjerkehagen, Tom, Bodenheimer, Lori, Boice, Giada, Bonizzato, Johann, S De Bono, Arnoud, Boot, Moiz, S Bootwalla, Ake, Borg, Arndt, Borkhardt, Keith, A Boroevich, Ivan, Borozan, Christoph, Borst, Marcus, Bosenberg, Mattia, Bosio, Jacqueline, Boultwood, Guillaume, Bourque, G Steven Bova, David, T Bowen, Reanne, Bowlby, David D, L Bowtell, Sandrine, Boyault, Rich, Boyce, Jeffrey, Boyd, Alvis, Brazma, Paul, Brennan, Daniel, S Brewer, Arie, B Brinkman, Robert, G Bristow, Russell, R Broaddus, Jane, E Brock, Malcolm, Brock, Annegien, Broeks, Angela, N Brooks, Denise, Brooks, Benedikt, Brors, Søren, Brunak, Timothy J, C Bruxner, Alicia, L Bruzos, Christiane, Buchholz, Susan, Bullman, Hazel, Burke, Birgit, Burkhardt, Kathleen, H Burns, John, Busanovich, Carlos, D Bustamante, Atul, J Butte, Niall, J Byrne, Anne-Lise, Børresen-Dale, Samantha, J Caesar-Johnson, Andy, Cafferkey, Declan, Cahill, Claudia, Calabrese, Carlos, Caldas, Fabien, Calvo, Niedzica, Camacho, Peter, J Campbell, Elias, Campo, Cinzia, Cantù, Shaolong, Cao, Thomas, E Carey, Joana, Carlevaro-Fita, Rebecca, Carlsen, Ivana, Cataldo, Mario, Cazzola, Jonathan, Cebon, Robert, Cerfolio, Dianne, E Chadwick, Dimple, Chakravarty, Don, Chalmers, Calvin Wing Yiu Chan, Kin, Chan, Michelle, Chan-Seng-Yue, Vishal, S Chandan, David, K Chang, Stephen, J Chanock, Lorraine, A Chantrill, Aurélien, Chateigner, Nilanjan, Chatterjee, Kazuaki, Chayama, Hsiao-Wei, Chen, Jieming, Chen, Yiwen, Chen, Zhaohong, Chen, Andrew, D Cherniack, Jeremy, Chien, Yoke-Eng, Chiew, Suet-Feung, Chin, Juok, Cho, Sunghoon, Cho, Jung Kyoon Choi, Wan, Choi, Christine, Chomienne, Su Pin Choo, Angela, Chou, Angelika, N Christ, Elizabeth, L Christie, Eric, Chuah, Carrie, Cibulskis, Kristian, Cibulskis, Sara, Cingarlini, Peter, Clapham, Alexander, Claviez, Sean, Cleary, Nicole, Cloonan, Marek, Cmero, Colin, C Collins, Ashton, A Connor, Susanna, L Cooke, Colin, S Cooper, Leslie, Cope, Corbo, Vincenzo, Matthew, G Cordes, Stephen, M Cordner, Isidro, Cortés-Ciriano, Prue, A Cowin, Brian, Craft, David, Craft, Chad, J Creighton, Yupeng, Cun, Erin, Curley, Ioana, Cutcutache, Karolina, Czajka, Bogdan, Czerniak, Rebecca, A Dagg, Ludmila, Danilova, Maria Vittoria Davi, Natalie, R Davidson, Helen, Davies, Ian, J Davis, Brandi, N Davis-Dusenbery, Kevin, J Dawson, Francisco, M De La Vega, Ricardo De Paoli-Iseppi, Timothy, Defreitas, Angelo, P Dei Tos, Olivier, Delaneau, John, A Demchok, Jonas, Demeulemeester, German, M Demidov, Deniz, Demircioğlu, Nening, M Dennis, Robert, E Denroche, Stefan, C Dentro, Nikita, Desai, Vikram, Deshpande, Amit, G Deshwar, Christine, Desmedt, Jordi, Deu-Pons, Noreen, Dhalla, Neesha, C Dhani, Priyanka, Dhingra, Rajiv, Dhir, Anthony, Dibiase, Klev, Diamanti, Shuai, Ding, Huy, Q Dinh, Luc, Dirix, Harshavardhan, Doddapaneni, Nilgun, Donmez, Michelle, T Dow, Ronny, Drapkin, Ruben, M Drews, Serge, Serge, Tim, Dudderidge, Ana, Dueso-Barroso, Andrew, J Dunford, Michael, Dunn, Fraser, R Duthie, Ken, Dutton-Regester, Jenna, Eagles, Douglas, F Easton, Stuart, Edmonds, Paul, A Edwards, Sandra, E Edwards, Rosalind, A Eeles, Anna, Ehinger, Juergen, Eils, Adel, El-Naggar, Matthew, Eldridge, Serap, Erkek, Georgia, Escaramis, Xavier, Estivill, Dariush, Etemadmoghadam, Jorunn, E Eyfjord, Bishoy, M Faltas, Daiming, Fan, William, C Faquin, Claudiu, Farcas, Matteo, Fassan, Aquila, Fatima, Francesco, Favero, Nodirjon, Fayzullaev, Ina, Felau, Sian, Fereday, Martin, L Ferguson, Vincent, Ferretti, Lars, Feuerbach, Matthew, A Field, J Lynn Fink, Gaetano, Finocchiaro, Cyril, Fisher, Matthew, W Fittall, Anna, Fitzgerald, Rebecca, C Fitzgerald, Adrienne, M Flanagan, Neil, E Fleshner, Paul, Flicek, John, A Foekens, Kwun, M Fong, Nuno, A Fonseca, Christopher, S Foster, Natalie, S Fox, Michael, Fraser, Scott, Frazer, Milana, Frenkel-Morgenstern, William, Friedman, Joan, Frigola, Catrina, C Fronick, Akihiro, Fujimoto, Masashi, Fujita, Masashi, Fukayama, Lucinda, A Fulton, Mayuko, Furuta, P Andrew Futreal, Anja, Füllgrabe, Stacey, B Gabriel, Steven, Gallinger, Carlo, Gambacorti-Passerini, Jianjiong, Gao, Levi, Garraway, Øystein, Garred, Erik, Garrison, Dale, W Garsed, Nils, Gehlenborg, Joshy, George, Daniela, S Gerhard, Clarissa, Gerhauser, Jeffrey, E Gershenwald, Moritz, Gerstung, Mohammed, Ghori, Ronald, Ghossein, Nasra, H Giama, Richard, A Gibbs, Anthony, J Gill, Pelvender, Gill, Dilip, D Giri, Dominik, Glodzik, Vincent, J Gnanapragasam, Maria Elisabeth Goebler, Mary, J Goldman, Carmen, Gomez, Abel, Gonzalez-Perez, Dmitry, A Gordenin, James, Gossage, Kunihito, Gotoh, Ramaswamy, Govindan, Dorthe, Grabau, Janet, S Graham, Robert, C Grant, Anthony, R Green, Eric, Green, Liliana, Greger, Nicola, Grehan, Sonia, Grimaldi, Sean, M Grimmond, Robert, L Grossman, Adam, Grundhoff, Gunes, Gundem, Qianyun, Guo, Manaswi, Gupta, Shailja, Gupta, Marta, Gut, Jonathan, Göke, Gavin, Ha, Andrea, Haake, David, Haan, Siegfried, Haas, Kerstin, Haase, James, E Haber, Nina, Habermann, Syed, Haider, Natsuko, Hama, Freddie, C Hamdy, Anne, Hamilton, Mark, P Hamilton, Leng, Han, George, B Hanna, Martin, Hansmann, Nicholas, J Haradhvala, Olivier, Harismendy, Ivon, Harliwong, Arif, O Harmanci, Eoghan, Harrington, Takanori, Hasegawa, Steve, Hawkins, Shinya, Hayami, Shuto, Hayashi, D Neil Hayes, Stephen, J Hayes, Nicholas, K Hayward, Steven, Hazell, Yao, He, Allison, P Heath, Simon, C Heath, David, Hedley, Apurva, M Hegde, David, I Heiman, Zachary, Heins, Lawrence, E Heisler, Eva, Hellstrom-Lindberg, Mohamed, Helmy, Seong Gu Heo, Austin, J Hepperla, José María Heredia-Genestar, Carl, Herrmann, Peter, Hersey, Holmfridur, Hilmarsdottir, Satoshi, Hirano, Nobuyoshi, Hiraoka, Katherine, A Hoadley, Asger, Hobolth, Ermin, Hodzic, Jessica, I Hoell, Steve, Hoffmann, Oliver, Hofmann, Andrea, Holbrook, Aliaksei, Z Holik, Michael, A Hollingsworth, Oliver, Holmes, Robert, A Holt, Chen, Hong, Eun Pyo Hong, Jongwhi, H Hong, Gerrit, K Hooijer, Henrik, Hornshøj, Fumie, Hosoda, Yong, Hou, Volker, Hovestadt, William, Howat, Alan, P Hoyle, Ralph, H Hruban, Jianhong, Hu, Xing, Hua, Kuan-Lin, Huang, Mei, Huang, Mi Ni Huang, Wolfgang, Huber, Thomas, J Hudson, Michael, Hummel, Jillian, A Hung, David, Huntsman, Ted, R Hupp, Jason, Huse, Matthew, R Huska, Daniel, Hübschmann, Christine, A Iacobuzio-Donahue, Charles David Imbusch, Marcin, Imielinski, Seiya, Imoto, William, B Isaacs, Keren, Isaev, Shumpei, Ishikawa, Murat, Iskar, M Ashiqul Islam, S, Michael, Ittmann, Sinisa, Ivkovic, Jose M, G Izarzugaza, Jocelyne, Jacquemier, Valerie, Jakrot, Nigel, B Jamieson, Gun Ho Jang, Se Jin Jang, Joy, C Jayaseelan, Reyka, Jayasinghe, Stuart, R Jefferys, Karine, Jegalian, Jennifer, L Jennings, Seung-Hyup, Jeon, Lara, Jerman, Yuan, Ji, Wei, Jiao, Peter, A Johansson, Amber, L Johns, Jeremy, Johns, Rory, Johnson, Todd, A Johnson, Clemency, Jolly, Yann, Joly, Jon, G Jonasson, Corbin, D Jones, David T, W Jones, Nic, Jones, Steven J, M Jones, Jos, Jonkers, Young Seok Ju, Hartmut, Juhl, Malene, Juul, Randi Istrup Juul, Sissel, Juul, Rolf, Kabbe, Andre, Kahles, Abdullah, Kahraman, Vera, B Kaiser, Hojabr, Kakavand, Sangeetha, Kalimuthu, Christof von Kalle, Koo Jeong Kang, Katalin, Karaszi, Beth, Karlan, Rosa, Karlić, Dennis, Karsch, Karin, S Kassahn, Hitoshi, Katai, Mamoru, Kato, Hiroto, Katoh, Yoshiiku, Kawakami, Jonathan, D Kay, Stephen, H Kazakoff, Marat, D Kazanov, Maria, Keays, Electron, Kebebew, Richard, F Kefford, Manolis, Kellis, James, G Kench, Catherine, J Kennedy, Jules N, A Kerssemakers, David, Khoo, Vincent, Khoo, Narong, Khuntikeo, Ekta, Khurana, Helena, Kilpinen, Hark Kyun Kim, Hyung-Yong, Kim, Hyunghwan, Kim, Jaegil, Kim, Jihoon, Kim, Jong, K Kim, Youngwook, Kim, Tari, A King, Wolfram, Klapper, Leszek, J Klimczak, Stian, Knappskog, Michael, Kneba, Bartha, M Knoppers, Youngil, Koh, Jan, Komorowski, Daisuke, Komura, Mitsuhiro, Komura, Kong, Gu, Marcel, Kool, Jan, O Korbel, Viktoriya, Korchina, Andrey, Korshunov, Michael, Koscher, Roelof, Koster, Zsofia, Kote-Jarai, Antonios, Koures, Milena, Kovacevic, Barbara, Kremeyer, Helene, Kretzmer, Markus, Kreuz, Savitri, Krishnamurthy, Dieter, Kube, Kiran, Kumar, Pardeep, Kumar, Ritika, Kundra, Kirsten, Kübler, Ralf, Küppers, Jesper, Lagergren, Phillip, H Lai, Peter, W Laird, Sunil, R Lakhani, Emilie, Lalonde, Fabien, C Lamaze, Adam, Lambert, Eric, Lander, Pablo, Landgraf, Landoni, Luca, Anita, Langerød, Andrés, Lanzós, Denis, Larsimont, Erik, Larsson, Mark, Lathrop, Loretta M, S Lau, Chris, Lawerenz, Rita, T Lawlor, Michael, S Lawrence, Alexander, J Lazar, Xuan, Le, Darlene, Lee, Donghoon, Lee, Eunjung Alice Lee, Hee Jin Lee, Jake June-Koo Lee, Jeong-Yeon, Lee, Juhee, Lee, Ming Ta Michael Lee, Henry, Lee-Six, Kjong-Van, Lehmann, Hans, Lehrach, Dido, Lenze, Conrad, R Leonard, Daniel, A Leongamornlert, Louis, Letourneau, Douglas, A Levine, Lora, Lewis, Tim, Ley, Chang, Li, Constance, H Li, Haiyan Irene Li, Jun, Li, Lin, Li, Siliang, Li, Xiaobo, Li, Xiaotong, Li, Xinyue, Li, Yilong, Li, Han, Liang, Sheng-Ben, Liang, Peter, Lichter, Pei, Lin, Ziao, Lin, M Linehan, W, Ole Christian Lingjærde, Dongbing, Liu, Eric Minwei Liu, Fei-Fei, Liu, Fenglin, Liu, Jia, Liu, Xingmin, Liu, Julie, Livingstone, Naomi, Livni, Lucas, Lochovsky, Markus, Loeffler, Georgina, V Long, Armando, Lopez-Guillermo, Shaoke, Lou, David, N Louis, Laurence, B Lovat, Yiling, Lu, Yong-Jie, Lu, Youyong, Lu, Luchini, Claudio, Ilinca, Lungu, Xuemei, Luo, Hayley, J Luxton, Andy, G Lynch, Lisa, Lype, Cristina, López, Carlos, López-Otín, Yussanne, Ma, Gaetan, Macgrogan, Shona, Macrae, Geoff, Macintyre, Tobias, Madsen, Kazuhiro, Maejima, Andrea, Mafficini, Dennis, T Maglinte, Arindam, Maitra, Partha, P Majumder, Luca, Malcovati, Salem, Malikic, Malleo, Giuseppe, Graham, J Mann, Luisa, Mantovani-Löffler, Kathleen, Marchal, Giovanni, Marchegiani, Elaine, R Mardis, Adam, A Margolin, Maximillian, G Marin, Florian, Markowetz, Julia, Markowski, Jeffrey, Marks, Tomas, Marques-Bonet, Marco, A Marra, Luke, Marsden, John W, M Martens, Sancha, Martin, Jose, I Martin-Subero, Iñigo, Martincorena, Alexander, Martinez-Fundichely, Charlie, E Massie, Thomas, J Matthew, Lucy, Matthews, Erik, Mayer, Simon, Mayes, Michael, Mayo, Faridah, Mbabaali, Karen, Mccune, Ultan, Mcdermott, Patrick, D McGillivray, John, D McPherson, John, R McPherson, Treasa, A McPherson, Samuel, R Meier, Alice, Meng, Shaowu, Meng, Neil, D Merrett, Sue, Merson, Matthew, Meyerson, William, U Meyerson, Piotr, A Mieczkowski, George, L Mihaiescu, Sanja, Mijalkovic, Ana Mijalkovic Mijalkovic-Lazic, Tom, Mikkelsen, Milella, Michele, Linda, Mileshkin, Christopher, A Miller, David, K Miller, Jessica, K Miller, Sarah, Minner, Marco, Miotto, Gisela Mir Arnau, Lisa, Mirabello, Chris, Mitchell, Thomas, J Mitchell, Satoru, Miyano, Naoki, Miyoshi, Shinichi, Mizuno, Fruzsina, Molnár-Gábor, Malcolm, J Moore, Richard, A Moore, Sandro, Morganella, Quaid, D Morris, Carl, Morrison, Lisle, E Mose, Catherine, D Moser, Ferran, Muiños, Loris, Mularoni, Andrew, J Mungall, Karen, Mungall, Elizabeth, A Musgrove, Ville, Mustonen, David, Mutch, Francesc, Muyas, Donna, M Muzny, Alfonso, Muñoz, Jerome, Myers, Ola, Myklebost, Peter, Möller, Genta, Nagae, Adnan, M Nagrial, Hardeep, K Nahal-Bose, Hitoshi, Nakagama, Hidewaki, Nakagawa, Hiromi, Nakamura, Toru, Nakamura, Kaoru, Nakano, Tannistha, Nandi, Jyoti, Nangalia, Mia, Nastic, Arcadi, Navarro, Fabio C, P Navarro, David, E Neal, Gerd, Nettekoven, Felicity, Newell, Steven, J Newhouse, Yulia, Newton, Alvin Wei Tian Ng, Anthony, Ng, Jonathan, Nicholson, David, Nicol, Yongzhan, Nie, G Petur Nielsen, Serena, Nik-Zainal, Michael, S Noble, Katia, Nones, Paul, A Northcott, Faiyaz, Notta, Brian, D O'Connor, Peter, O'Donnell, Maria, O'Donovan, Sarah, O'Meara, Brian Patrick O'Neill, J Robert O'Neill, David, Ocana, Angelica, Ochoa, Layla, Oesper, Christopher, Ogden, Hideki, Ohdan, Kazuhiro, Ohi, Lucila, Ohno-Machado, Karin, A Oien, Akinyemi, I Ojesina, Hidenori, Ojima, Takuji, Okusaka, Larsson, Omberg, Choon Kiat Ong, German, Ott, F Francis Ouellette, B, Christine, P'Ng, Marta, Paczkowska, Paiella, Salvatore, Chawalit, Pairojkul, Marina, Pajic, Qiang, Pan-Hammarström, Elli, Papaemmanuil, Irene, Papatheodorou, Ji Wan Park, Joong-Won, Park, Keunchil, Park, Kiejung, Park, Peter, J Park, Joel, S Parker, Simon, L Parsons, Harvey, Pass, Danielle, Pasternack, Alessandro, Pastore, Ann-Marie, Patch, Iris, Pauporté, Antonio, Pea, John, V Pearson, Chandra Sekhar Pedamallu, Paolo, Pederzoli, Martin, Peifer, Nathan, A Pennell, Charles, M Perou, Gloria, M Petersen, Nicholas, Petrelli, Robert, Petryszak, Stefan, M Pfister, Mark, Phillips, Oriol, Pich, Hilda, A Pickett, Todd, D Pihl, Nischalan, Pillay, Sarah, Pinder, Mark, Pinese, Andreia, V Pinho, Esa, Pitkänen, Xavier, Pivot, Elena, Piñeiro-Yáñez, Laura, Planko, Christoph, Plass, Paz, Polak, Tirso, Pons, Irinel, Popescu, Olga, Potapova, Aparna, Prasad, Shaun, R Preston, Manuel, Prinz, Antonia, L Pritchard, Stephenie, D Prokopec, Elena, Provenzano, Xose, S Puente, Sonia, Puig, Sergio, Pulido-Tamayo, Gulietta, M Pupo, Colin, A Purdie, Michael, C Quinn, Raquel, Rabionet, Janet, S Rader, Bernhard, Radlwimmer, Petar, Radovic, Benjamin, Raeder, Manasa, Ramakrishna, Kamna, Ramakrishnan, Suresh, Ramalingam, Benjamin, J Raphael, W Kimryn Rathmell, Tobias, Rausch, Guido, Reifenberger, Jüri, Reimand, Jorge, Reis-Filho, Victor, Reuter, Iker, Reyes-Salazar, Matthew, A Reyna, Yasser, Riazalhosseini, Andrea, L Richardson, Julia, Richter, Matthew, Ringel, Markus, Ringnér, Yasushi, Rino, Karsten, Rippe, Jeffrey, Roach, Lewis, R Roberts, Nicola, D Roberts, Steven, A Roberts, A Gordon Robertson, Alan, J Robertson, Javier Bartolomé Rodriguez, Bernardo, Rodriguez-Martin, F Germán Rodríguez-González, Michael H, A Roehrl, Marius, Rohde, Hirofumi, Rokutan, Gilles, Romieu, Ilse, Rooman, Tom, Roques, Daniel, Rosebrock, Mara, Rosenberg, Philip, C Rosenstiel, Andreas, Rosenwald, Edward, W Rowe, Steven, G Rozen, Yulia, Rubanova, Mark, A Rubin, Carlota, Rubio-Perez, Vasilisa, A Rudneva, Borislav, C Rusev, Ruzzenente, Andrea, Gunnar, Rätsch, Radhakrishnan, Sabarinathan, Veronica, Y Sabelnykova, Sara, Sadeghi, Natalie, Saini, Mihoko, Saito-Adachi, Adriana, Salcedo, Roberto, Salgado, Leonidas, Salichos, Richard, Sallari, Charles, Saller, Salvia, Roberto, 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T, Nakano, K, Nandi, T, Nangalia, J, Nastic, M, Navarro, A, Navarro, F, Neal, D, Nettekoven, G, Newell, F, Newhouse, S, Newton, Y, Ng, A, Nicholson, J, Nicol, D, Nie, Y, Nielsen, G, Nik-Zainal, S, Noble, M, Nones, K, Northcott, P, Notta, F, O'Connor, B, O'Donnell, P, O'Donovan, M, O'Meara, S, O'Neill, B, O'Neill, J, Ocana, D, Ochoa, A, Oesper, L, Ogden, C, Ohdan, H, Ohi, K, Ohno-Machado, L, Oien, K, Ojesina, A, Ojima, H, Okusaka, T, Omberg, L, Ong, C, Ott, G, Ouellette, B, P'Ng, C, Paczkowska, M, Paiella, S, Pairojkul, C, Pajic, M, Pan-Hammarstrom, Q, Papaemmanuil, E, Papatheodorou, I, Park, J, Park, K, Park, P, Parker, J, Parsons, S, Pass, H, Pasternack, D, Pastore, A, Patch, A, Pauporte, I, Pea, A, Pearson, J, Pedamallu, C, Pederzoli, P, Peifer, M, Pennell, N, Perou, C, Petersen, G, Petrelli, N, Petryszak, R, Pfister, S, Phillips, M, Pich, O, Pickett, H, Pihl, T, Pillay, N, Pinder, S, Pinese, M, Pinho, A, Pitkanen, E, Pivot, X, Pineiro-Yanez, E, Planko, L, Plass, C, Polak, P, Pons, T, Popescu, I, Potapova, O, Prasad, A, Preston, S, Prinz, M, Pritchard, A, Prokopec, S, Provenzano, E, Puente, X, Puig, S, Pulido-Tamayo, S, Pupo, G, Purdie, C, Quinn, M, Rabionet, R, Rader, J, Radlwimmer, B, Radovic, P, Raeder, B, Ramakrishna, M, Ramakrishnan, K, Ramalingam, S, Raphael, B, Rathmell, W, Rausch, T, Reifenberger, G, Reimand, J, Reis-Filho, J, Reuter, V, Reyes-Salazar, I, Reyna, M, Riazalhosseini, Y, Richardson, A, Richter, J, Ringel, M, Ringner, M, Rino, Y, Rippe, K, Roach, J, Roberts, L, Roberts, N, Roberts, S, Robertson, A, Rodriguez, J, Rodriguez-Martin, B, Rodriguez-Gonzalez, F, Roehrl, M, Rohde, M, Rokutan, H, Romieu, G, Rooman, I, Roques, T, Rosebrock, D, Rosenberg, M, Rosenstiel, P, Rosenwald, A, Rowe, E, Rozen, S, Rubanova, Y, Rubin, M, Rubio-Perez, C, Rudneva, V, Rusev, B, Ruzzenente, A, Ratsch, G, Sabarinathan, R, Sabelnykova, V, Sadeghi, S, Saini, N, Saito-Adachi, M, Salcedo, A, Salgado, R, Salichos, L, Sallari, R, Saller, C, Salvia, R, Sam, M, Samra, J, 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Yamamoto, S, Yamaue, H, Yang, F, Yang, H, Yang, J, Yang, L, Yang, S, Yang, T, Yang, Y, Yao, X, Yaspo, M, Yates, L, Yau, C, Ye, C, Yoon, C, Yoon, S, Yousif, F, Yu, J, Yu, K, Yu, W, Yu, Y, Yuan, K, Yuan, Y, Yuen, D, Zaikova, O, Zamora, J, Zapatka, M, Zenklusen, J, Zenz, T, Zeps, N, Zhang, C, Zhang, F, Zhang, H, Zhang, X, Zhang, Y, Zhang, Z, Zhao, Z, Zheng, L, Zheng, X, Zhou, W, Zhou, Y, Bin, Z, Zhu, H, Zhu, J, Zhu, S, Zou, L, Zou, X, Defazio, A, van As, N, van Deurzen, C, van de Vijver, M, van't Veer, L, von Mering, C, Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), Háskóli Íslands, University of Iceland, Tampere University, BioMediTech, TAYS Cancer Centre, University of St Andrews. Sir James Mackenzie Institute for Early Diagnosis, University of St Andrews. Cellular Medicine Division, University of St Andrews. Statistics, University of St Andrews. School of Medicine, University of Zurich, Gerstein, Mark B, Ding, Li, Bailey, Matthew H [0000-0003-4526-9727], Wheeler, David A [0000-0002-9056-6299], Gerstein, Mark B [0000-0002-9746-3719], Faculty of Economic and Social Sciences and Solvay Business School, Lauri Antti Aaltonen / Principal Investigator, Genome-Scale Biology (GSB) Research Program, Department of Medical and Clinical Genetics, Organismal and Evolutionary Biology Research Programme, Helsinki Institute for Information Technology, Institute of Biotechnology, Bioinformatics, Department of Computer Science, Faculty of Medicine, and HUS Helsinki and Uusimaa Hospital District
Subjects: VARIANTS, 0302 clinical medicine, 706/648/697/129/2043, Databases, Genetic, Cancer genomics, SOMATIC POINT MUTATIONS, Càncer, lcsh:Science, Exome, Exome sequencing, Cancer, Base Composition, Neoplasms -- genetics, 1184 Genetics, developmental biology, physiology, 3100 General Physics and Astronomy, 3. Good health, 030220 oncology & carcinogenesis, Science & Technology - Other Topics, Transformació genètica, Genetic databases, Erfðarannsóknir, Human, GENES, Science, 1600 General Chemistry, General Biochemistry, Genetics and Molecular Biology, RC0254, 03 medical and health sciences, Genetic, SDG 3 - Good Health and Well-being, 1300 General Biochemistry, Genetics and Molecular Biology, Exome Sequencing, Genetics, Humans, Author Correction, Retrospective Studies, Whole genome sequencing, Comparative genomics, Science & Technology, RC0254 Neoplasms. Tumors. Oncology (including Cancer), INSERTIONS, DNA, PERFORMANCE, Human genetics, Communication and replication, Cancérologie, 692/4028/67/69, Genòmica, 030104 developmental biology, Mutation, Genome mutation, Human genome, lcsh:Q, COMPREHENSIVE CHARACTERIZATION, Genètica, 0301 basic medicine, Medizin, General Physics and Astronomy, Genome, Whole Exome Sequencing, Genetic transformation, International Cancer Genome Consortium, Neoplasms, 631/114/2399, Genamengi, Medicine and Health Sciences, Medicine(all), Women's cancers Radboud Institute for Molecular Life Sciences [Radboudumc 17], Multidisciplinary, 318 Medical biotechnology, Exome -- genetics, article, Exons, Women's cancers Radboud Institute for Health Sciences [Radboudumc 17], Multidisciplinary Sciences, CAPTURE, 1181 Ecology, evolutionary biology, oncology, DNA, Intergenic, 139, Medical Genetics, Biotechnology, ICGC/TCGA Pan-Cancer Analysis, 3122 Cancers, 610 Medicine & health, 45/23, QH426 Genetics, Biology, MC3 Working Group, Databases, Germline mutation, PCAWG novel somatic mutation calling methods working group, Krabbameinsrannsóknir, Cancer Genome Atlas, Genome, Human -- genetics, ddc:610, QH426, Medicinsk genetik, Krabbamein, Intergenic, Whole Genome Sequencing, Genome, Human, Human Genome, PCAWG Consortium, DAS, General Chemistry, DELETIONS, Good Health and Well Being, 10032 Clinic for Oncology and Hematology, 3111 Biomedicine, 631/1647/2217/748
Abstract: MC3 Working Group: Rehan Akbani21, Pavana Anur22, Matthew H. Bailey1,2,3, Alex Buchanan9, Kami Chiotti9, Kyle Covington12,23, Allison Creason9, Li Ding1,2,3,20, Kyle Ellrott9, Yu Fan21, Steven Foltz1,2, Gad Getz8,14,15,16, Walker Hale12, David Haussler24,25, Julian M. Hess8,26, Carolyn M. Hutter27, Cyriac Kandoth28, Katayoon Kasaian29,30, Melpomeni Kasapi27, Dave Larson1 , Ignaty Leshchiner8, John Letaw31, Singer Ma32, Michael D. McLellan1,3,20, Yifei Men32, Gordon B. Mills33,34, Beifang Niu35, Myron Peto22, Amie Radenbaugh24, Sheila M. Reynolds36, Gordon Saksena8, Heidi Sofia27, Chip Stewart8, Adam J. Struck31, Joshua M. Stuart24,37, Wenyi Wang21, John N. Weinstein38, David A. Wheeler12,13, Christopher K. Wong24,39, Liu Xi12 & Kai Ye40,41 21Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 22Molecular and Medical Genetics, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 23Castle Biosciences Inc, Friendswood, TX 77546, USA. 24UC Santa Cruz Genomics Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 25Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 26Massachusetts General Hospital Center for Cancer Research, Charlestown, MA 02114, USA. 27National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20894, USA. 28Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. 29Ontario Institute for Cancer Research, Toronto, ON M5G 0A3, Canada. 30Canada’s Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, BC V5Z 4S6, Canada. 31Computational Biology Program, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA. 32DNAnexus Inc, Mountain View, CA 94040, USA. 33Department of Systems Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA. 34Precision Oncology, OHSU Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA. 35Computer Network Information Center, Chinese Academy of Sciences, Beijing, China. 36Institute for Systems Biology, Seattle, WA 98109, USA. 37Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 38Department of Bioinformatics and Computational Biology and Department of Systems Biology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. 39Biomolecular Engineering Department, University of California Santa Cruz, Santa Cruz, CA 95064, USA. 40School of Elect, PCAWG novel somatic mutation calling methods working group: Matthew H. Bailey1,2,3, Beifang Niu35, Matthias Bieg42,43, Paul C. Boutros6,44,45,46, Ivo Buchhalter43,47,48, Adam P. Butler49, Ken Chen50, Zechen Chong51, Li Ding1,2,3,20, Oliver Drechsel52,53, Lewis Jonathan Dursi6,7, Roland Eils47,48,54,55, Kyle Ellrott9, Shadrielle M. G. Espiritu6, Yu Fan21, Robert S. Fulton1,3,20, Shengjie Gao56, Josep L. l. Gelpi57,58, Mark B. Gerstein5,18,19, Gad Getz8,14,15,16, Santiago Gonzalez59,60, Ivo G. Gut52,61, Faraz Hach62,63, Michael C. Heinold47,48, Julian M. Hess8,26, Jonathan Hinton49, Taobo Hu64, Vincent Huang6, Yi Huang65,66, Barbara Hutter43,67,68, David R. Jones49, Jongsun Jung69, Natalie Jäger47, Hyung-Lae Kim70, Kortine Kleinheinz47,48, Sushant Kumar5,19, Yogesh Kumar64, Christopher M. Lalansingh6, Ignaty Leshchiner8, Ivica Letunic71, Dimitri Livitz8, Eric Z. Ma64, Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Michael D. McLellan1,3,20, Andrew Menzies49, Ana Milovanovic57, Morten Muhlig Nielsen73, Stephan Ossowski52,53,74, Nagarajan Paramasivam43,47, Jakob Skou Pedersen73,75, Marc D. Perry76,77, Montserrat Puiggròs57, Keiran M. Raine49, Esther Rheinbay8,14,72, Romina Royo57, S. Cenk Sahinalp62,78,79, Gordon Saksena8, Iman Sarrafi62,78, Matthias Schlesner47,80, Jared T. Simpson6,17, Lucy Stebbings49, Chip Stewart8, Miranda D. Stobbe52,61, Jon W. Teague49, Grace Tiao8, David Torrents57,81, Jeremiah A. Wala8,14,82, Jiayin Wang1,40,66, Wenyi Wang21, Sebastian M. Waszak60, Joachim Weischenfeldt60,83,84, Michael C. Wendl1,10,11, Johannes Werner47,85, Zhenggang Wu64, Hong Xue64, Sergei Yakneen60, Takafumi N. Yamaguchi6, Kai Ye40,41, Venkata D. Yellapantula20,86, Christina K. Yung76 & Junjun Zhang76, PCAWG Consortium: Lauri A. Aaltonen87, Federico Abascal49, Adam Abeshouse88, Hiroyuki Aburatani89, David J. Adams49, Nishant Agrawal90, Keun Soo Ahn91, Sung-Min Ahn92, Hiroshi Aikata93, Rehan Akbani21, Kadir C. Akdemir50, Hikmat Al-Ahmadie88, Sultan T. Al-Sedairy94, Fatima Al-Shahrour95, Malik Alawi96,97, Monique Albert98, Kenneth Aldape99,100, Ludmil B. Alexandrov49,101,102, Adrian Ally30, Kathryn Alsop103, Eva G. Alvarez104,105,106, Fernanda Amary107, Samirkumar B. Amin108,109,110, Brice Aminou76, Ole Ammerpohl111,112, Matthew J. Anderson113, Yeng Ang114, Davide Antonello115, Pavana Anur22, Samuel Aparicio116, Elizabeth L. Appelbaum1,117, Yasuhito Arai118, Axel Aretz119, Koji Arihiro93, Shun-ichi Ariizumi120, Joshua Armenia121, Laurent Arnould122, Sylvia Asa123,124, Yassen Assenov125, Gurnit Atwal6,126,127, Sietse Aukema112,128, J. Todd Auman129, Miriam R. Aure130, Philip Awadalla6,126, Marta Aymerich131, Gary D. Bader126, Adrian Baez-Ortega132, Matthew H. Bailey1,2,3, Peter J. Bailey133, Miruna Balasundaram30, Saianand Balu134, Pratiti Bandopadhayay8,135,136, Rosamonde E. Banks137, Stefano Barbi138, Andrew P. Barbour139,140, Jonathan Barenboim6, Jill Barnholtz-Sloan141,142, Hugh Barr143, Elisabet Barrera59, John Bartlett98,144, Javier Bartolome57, Claudio Bassi115, Oliver F. Bathe145,146, Daniel Baumhoer147, Prashant Bavi148, Stephen B. Baylin149,150, Wojciech Bazant59, Duncan Beardsmore151, Timothy A. Beck152,153, Sam Behjati49, Andreas Behren154, Beifang Niu35, Cindy Bell155, Sergi Beltran52,61, Christopher Benz156, Andrew Berchuck157, Anke K. Bergmann158, Erik N. Bergstrom101,102, Benjamin P. Berman159,160,161, Daniel M. Berney162, Stephan H. Bernhart163,164,165, Rameen Beroukhim8,14,82, Mario Berrios166, Samantha Bersani167, Johanna Bertl73,168, Miguel Betancourt169, Vinayak Bhandari6,44, Shriram G. Bhosle49, Andrew V. Biankin133,170,171,172, Matthias Bieg42,43, Darell Bigner173, Hans Binder163,164, Ewan Birney59, Michael Birrer72, Nidhan K. Biswas174, Bodil Bjerkehagen147,175, Tom Bodenheimer134, Lori Boice176, Giada Bonizzato177, Johann S. De Bono178, Arnoud Boot179,180, Moiz S. Bootwalla166, Ake Borg181, Arndt Borkhardt182, Keith A. Boroevich183,184, Ivan Borozan6, Christoph Borst185, Marcus Bosenberg186, Mattia Bosio52,53,57, Jacqueline Boultwood187, Guillaume Bourque188,189, Paul C. Boutros6,44,45,46, G. Steven Bova190, David T. Bowen49,191, Reanne Bowlby30, David D. L. Bowtell103, Sandrine Boyault192, Rich Boyce59, Jeffrey Boyd193, Alvis Brazma59, Paul Brennan194, Daniel S. Brewer195,196, Arie B. Brinkman197, Robert G. Bristow44,198,199,200,201, Russell R. Broaddus99, Jane E. Brock202, Malcolm Brock203, Annegien Broeks204, Angela N. Brooks8,24,37,82, Denise Brooks30, Benedikt Brors67,205,206, Søren Brunak207,208, Timothy J. C. Bruxner113,209, Alicia L. Bruzos104,105,106, Alex Buchanan9, Ivo Buchhalter43,47,48, Christiane Buchholz210, Susan Bullman8,82, Hazel Burke211, Birgit Burkhardt212, Kathleen H. Burns213,214, John Busanovich8,215, Carlos D. Bustamante216,217, Adam P. Butler49, Atul J. Butte218, Niall J. Byrne76, Anne-Lise Børresen-Dale130,219, Samantha J. Caesar-Johnson220, Andy Cafferkey59, Declan Cahill221, Claudia Calabrese59,60, Carlos Caldas222,223, Fabien Calvo224, Niedzica Camacho178, Peter J. Campbell49,225, Elias Campo226,227, Cinzia Cantù177, Shaolong Cao21, Thomas E. Carey228, Joana Carlevaro-Fita229,230,231, Rebecca Carlsen30, Ivana Cataldo167,177, Mario Cazzola232, Jonathan Cebon154, Robert Cerfolio233, Dianne E. Chadwick234, Dimple Chakravarty235, Don Chalmers236, Calvin Wing Yiu Chan47,237, Kin Chan238, Michelle Chan-Seng-Yue148, Vishal S. Chandan239, David K. Chang133,170, Stephen J. Chanock240, Lorraine A. Chantrill170,241, Aurélien Chateigner76,242, Nilanjan Chatterjee149,243, Kazuaki Chayama93, Hsiao-Wei Chen114,121, Jieming Chen218, Ken Chen50, Yiwen Chen21, Zhaohong Chen244, Andrew D. Cherniack8,82, Jeremy Chien245, Yoke-Eng Chiew246,247, Suet-Feung Chin222,223, Juok Cho8, Sunghoon Cho248, Jung Kyoon Choi249, Wan Choi250, Christine Chomienne251, Zechen Chong51, Su Pin Choo252, Angela Chou170,246, Angelika N. Christ113, Elizabeth L. Christie103, Eric Chuah30, Carrie Cibulskis8, Kristian Cibulskis8, Sara Cingarlini253, Peter Clapham49, Alexander Claviez254, Sean Cleary148,255, Nicole Cloonan256, Marek Cmero257,258,259, Colin C. Collins62, Ashton A. Connor255,260, Susanna L. Cooke133, Colin S. Cooper178,196,261, Leslie Cope149, Vincenzo Corbo138,177, Matthew G. Cordes1,262, Stephen M. Cordner263, Isidro Cortés-Ciriano264,265,266, Kyle Covington12,23, Prue A. Cowin267, Brian Craft24, David Craft8,268, Chad J. Creighton269, Yupeng Cun270, Erin Curley271, Ioana Cutcutache179,180, Karolina Czajka272, Bogdan Czerniak99,273, Rebecca A. Dagg274, Ludmila Danilova149, Maria Vittoria Davi275, Natalie R. Davidson276,277,278,279,280, Helen Davies49,281,282, Ian J. Davis283, Brandi N. Davis-Dusenbery284, Kevin J. Dawson49, Francisco M. De La Vega216,217,285, Ricardo De Paoli-Iseppi211, Timothy Defreitas8, Angelo P. Dei Tos286, Olivier Delaneau287,288,289, John A. Demchok220, Jonas Demeulemeester290,291, German M. Demidov52,53,74, Deniz Demircioğlu292,293, Nening M. Dennis221, Robert E. Denroche148, Stefan C. Dentro49,290,294, Nikita Desai76, Vikram Deshpande72, Amit G. Deshwar295, Christine Desmedt296,297, Jordi Deu-Pons298,299, Noreen Dhalla30, Neesha C. Dhani300, Priyanka Dhingra301,302, Rajiv Dhir303, Anthony DiBiase304, Klev Diamanti305, Li Ding1,2,3,20, Shuai Ding306, Huy Q. Dinh159, Luc Dirix307, HarshaVardhan Doddapaneni12, Nilgun Donmez62,78, Michelle T. Dow244, Ronny Drapkin308, Oliver Drechsel52,53, Ruben M. Drews223, Serge Serge49, Tim Dudderidge150,221, Ana Dueso-Barroso57, Andrew J. Dunford8, Michael Dunn309, Lewis Jonathan Dursi6,7, Fraser R. Duthie133,310, Ken Dutton-Regester311, Jenna Eagles272, Douglas F. Easton312,313, Stuart Edmonds314, Paul A. Edwards223,315, Sandra E. Edwards178, Rosalind A. Eeles178,221, Anna Ehinger316, Juergen Eils54,55, Roland Eils47,48,54,55, Adel El-Naggar99,273, Matthew Eldridge223, Kyle Ellrott9, Serap Erkek60, Georgia Escaramis53,317,318, Shadrielle M. G. Espiritu6, Xavier Estivill53,319, Dariush Etemadmoghadam103, Jorunn E. Eyfjord320, Bishoy M. Faltas280, Daiming Fan321, Yu Fan21, William C. Faquin72, Claudiu Farcas244, Matteo Fassan322, Aquila Fatima323, Francesco Favero324, Nodirjon Fayzullaev76, Ina Felau220, Sian Fereday103, Martin L. Ferguson325, Vincent Ferretti76,326, Lars Feuerbach205, Matthew A. Field327, J. Lynn Fink57,113, Gaetano Finocchiaro328, Cyril Fisher221, Matthew W. Fittall290, Anna Fitzgerald329, Rebecca C. Fitzgerald282, Adrienne M. Flanagan330, Neil E. Fleshner331, Paul Flicek59, John A. Foekens332, Kwun M. Fong333, Nuno A. Fonseca59,334, Christopher S. Foster335,336, Natalie S. Fox6, Michael Fraser6, Scott Frazer8, Milana Frenkel-Morgenstern337, William Friedman338, Joan Frigola298, Catrina C. Fronick1,262, Akihiro Fujimoto184, Masashi Fujita184, Masashi Fukayama339, Lucinda A. Fulton1 , Robert S. Fulton1,3,20, Mayuko Furuta184, P. Andrew Futreal340, Anja Füllgrabe59, Stacey B. Gabriel8, Steven Gallinger148,255,260, Carlo Gambacorti-Passerini341, Jianjiong Gao121, Shengjie Gao56, Levi Garraway82, Øystein Garred342, Erik Garrison49, Dale W. Garsed103, Nils Gehlenborg8,343, Josep L. l. Gelpi57,58, Joshy George110, Daniela S. Gerhard344, Clarissa Gerhauser345, Jeffrey E. Gershenwald346,347, Mark B. Gerstein5,18,19, Moritz Gerstung59,60, Gad Getz8,14,15,16, Mohammed Ghori49, Ronald Ghossein348, Nasra H. Giama349, Richard A. Gibbs12, Anthony J. Gill170,350, Pelvender Gill351, Dilip D. Giri348, Dominik Glodzik49, Vincent J. Gnanapragasam352,353, Maria Elisabeth Goebler354, Mary J. Goldman24, Carmen Gomez355, Santiago Gonzalez59,60, Abel Gonzalez-Perez298,299,356, Dmitry A. Gordenin357, James Gossage358, Kunihito Gotoh359, Ramaswamy Govindan3, Dorthe Grabau360, Janet S. Graham133,361, Robert C. Grant148,260, Anthony R. Green315, Eric Green27, Liliana Greger59, Nicola Grehan282, Sonia Grimaldi177, Sean M. Grimmond362, Robert L. Grossman363, Adam Grundhoff97,364, Gunes Gundem88, Qianyun Guo75, Manaswi Gupta8, Shailja Gupta365, Ivo G. Gut52,61, Marta Gut52,61, Jonathan Göke292,366, Gavin Ha8, Andrea Haake111, David Haan37, Siegfried Haas185, Kerstin Haase290, James E. Haber367, Nina Habermann60, Faraz Hach62,63, Syed Haider6, Natsuko Hama118, Freddie C. Hamdy351, Anne Hamilton267, Mark P. Hamilton368, Leng Han369, George B. Hanna370, Martin Hansmann371, Nicholas J. Haradhvala8,72, Olivier Harismendy102,372, Ivon Harliwong113, Arif O. Harmanci5,373, Eoghan Harrington374, Takanori Hasegawa375, David Haussler24,25, Steve Hawkins223, Shinya Hayami376, Shuto Hayashi375, D. Neil Hayes134,377,378, Stephen J. Hayes379,380, Nicholas K. Hayward211,311, Steven Hazell221, Yao He381, Allison P. Heath382, Simon C. Heath52,61, David Hedley300, Apurva M. Hegde38, David I. Heiman8, Michael C. Heinold47,48, Zachary Heins88, Lawrence E. Heisler152, Eva Hellstrom-Lindberg383, Mohamed Helmy384, Seong Gu Heo385, Austin J. Hepperla134, José María Heredia-Genestar386, Carl Herrmann47,48,387, Peter Hersey211, Julian M. Hess8,26, Holmfridur Hilmarsdottir320, Jonathan Hinton49, Satoshi Hirano388, Nobuyoshi Hiraoka389, Katherine A. Hoadley134,390, Asger Hobolth75,168, Ermin Hodzic78, Jessica I. Hoell182, Steve Hoffmann163,164,165,391, Oliver Hofmann392, Andrea Holbrook166, Aliaksei Z. Holik53, Michael A. Hollingsworth393, Oliver Holmes209,311, Robert A. Holt30, Chen Hong205,237, Eun Pyo Hong385, Jongwhi H. Hong394, Gerrit K. Hooijer395, Henrik Hornshøj73, Fumie Hosoda118, Yong Hou56,396, Volker Hovestadt397, William Howat352, Alan P. Hoyle134, Ralph H. Hruban149, Jianhong Hu12, Taobo Hu64, Xing Hua240, Kuan-lin Huang1,398, Mei Huang176, Mi Ni Huang179,180, Vincent Huang6, Yi Huang65,66, Wolfgang Huber60, Thomas J. Hudson272,399, Michael Hummel400, Jillian A. Hung246,247, David Huntsman401, Ted R. Hupp402, Jason Huse88, Matthew R. Huska403, Barbara Hutter43,67,68, Carolyn M. Hutter27, Daniel Hübschmann48,54,404,405,406, Christine A. Iacobuzio-Donahue348, Charles David Imbusch205, Marcin Imielinski407,408, Seiya Imoto375, William B. Isaacs409, Keren Isaev6,44, Shumpei Ishikawa410, Murat Iskar397, S. M. Ashiqul Islam244, Michael Ittmann411,412,413, Sinisa Ivkovic284, Jose M. G. Izarzugaza414, Jocelyne Jacquemier415, Valerie Jakrot211, Nigel B. Jamieson133,172,416, Gun Ho Jang148, Se Jin Jang417, Joy C. Jayaseelan12, Reyka Jayasinghe1 , Stuart R. Jefferys134, Karine Jegalian418, Jennifer L. Jennings419, Seung-Hyup Jeon250, Lara Jerman60,420, Yuan Ji421,422, Wei Jiao6, Peter A. Johansson311, Amber L. Johns170, Jeremy Johns272, Rory Johnson230,423, Todd A. Johnson183, Clemency Jolly290, Yann Joly424, Jon G. Jonasson320, Corbin D. Jones425, David R. Jones49, David T. W. Jones426,427, Nic Jones428, Steven J. M. Jones30, Jos Jonkers204, Young Seok Ju49,249, Hartmut Juhl429, Jongsun Jung69, Malene Juul73, Randi Istrup Juul73, Sissel Juul374, Natalie Jäger47, Rolf Kabbe47, Andre Kahles276,277,278,279,430, Abdullah Kahraman431,432,433, Vera B. Kaiser434, Hojabr Kakavand211, Sangeetha Kalimuthu148, Christof von Kalle405, Koo Jeong Kang91, Katalin Karaszi351, Beth Karlan435, Rosa Karlić436, Dennis Karsch437, Katayoon Kasaian29,30, Karin S. Kassahn113,438, Hitoshi Katai439, Mamoru Kato440, Hiroto Katoh410, Yoshiiku Kawakami93, Jonathan D. Kay117, Stephen H. Kazakoff209,311, Marat D. Kazanov441,442,443, Maria Keays59, Electron Kebebew444,445, Richard F. Kefford446, Manolis Kellis8,447, James G. Kench170,350,448, Catherine J. Kennedy246,247, Jules N. A. Kerssemakers47, David Khoo273, Vincent Khoo221, Narong Khuntikeo115,449, Ekta Khurana301,302,450,451, Helena Kilpinen117, Hark Kyun Kim452, Hyung-Lae Kim70, Hyung-Yong Kim415, Hyunghwan Kim250, Jaegil Kim8, Jihoon Kim453, Jong K. Kim454, Youngwook Kim455,456, Tari A. King457,458,459, Wolfram Klapper128, Kortine Kleinheinz47,48, Leszek J. Klimczak460, Stian Knappskog49,461, Michael Kneba437, Bartha M. Knoppers424, Youngil Koh462,463, Jan Komorowski305,464, Daisuke Komura410, Mitsuhiro Komura375, Gu Kong415, Marcel Kool426,465, Jan O. Korbel59,60, Viktoriya Korchina12, Andrey Korshunov465, Michael Koscher465, Roelof Koster466, Zsofia Kote-Jarai178, Antonios Koures244, Milena Kovacevic284, Barbara Kremeyer49, Helene Kretzmer164,165, Markus Kreuz467, Savitri Krishnamurthy99,468, Dieter Kube469, Kiran Kumar8, Pardeep Kumar221, Sushant Kumar5,19, Yogesh Kumar64, Ritika Kundra114,121, Kirsten Kübler8,14,72, Ralf Küppers470, Jesper Lagergren383,471, Phillip H. Lai166, Peter W. Laird472, Sunil R. Lakhani473, Christopher M. Lalansingh6, Emilie Lalonde6, Fabien C. Lamaze6, Adam Lambert351, Eric Lander8, Pablo Landgraf474,475, Luca Landoni115, Anita Langerød130, Andrés Lanzós230,231,423, Denis Larsimont476, Erik Larsson477, Mark Lathrop189, Loretta M. S. Lau478, Chris Lawerenz55, Rita T. Lawlor177, Michael S. Lawrence8,72,183, Alexander J. Lazar99,108, Xuan Le479, Darlene Lee30, Donghoon Lee5, Eunjung Alice Lee480, Hee Jin Lee417, Jake June-Koo Lee264,266, Jeong-Yeon Lee481, Juhee Lee482, Ming Ta Michael Lee340, Henry Lee-Six49, Kjong-Van Lehmann276,277,278,279,430, Hans Lehrach483, Dido Lenze400, Conrad R. Leonard209,311, Daniel A. Leongamornlert49,178, Ignaty Leshchiner8, Louis Letourneau484, Ivica Letunic71, Douglas A. Levine88,485, Lora Lewis12, Tim Ley486, Chang Li56,396, Constance H. Li6,44, Haiyan Irene Li30, Jun Li21, Lin Li56, Shantao Li5, Siliang Li56,396, Xiaobo Li56,396, Xiaotong Li5, Xinyue Li56, Yilong Li49, Han Liang21, Sheng-Ben Liang234, Peter Lichter68,397, Pei Lin8, Ziao Lin8,487, W. M. Linehan488, Ole Christian Lingjærde489, Dongbing Liu56,396, Eric Minwei Liu88,301,302, Fei-Fei Liu201,490, Fenglin Liu381,491, Jia Liu492, Xingmin Liu56,396, Julie Livingstone6, Dimitri Livitz8, Naomi Livni221, Lucas Lochovsky5,19,110, Markus Loeffler467, Georgina V. Long211, Armando Lopez-Guillermo493, Shaoke Lou5,19, David N. Louis72, Laurence B. Lovat117, Yiling Lu38, Yong-Jie Lu162,494, Youyong Lu495,496,497, Claudio Luchini167, Ilinca Lungu144,148, Xuemei Luo152, Hayley J. Luxton117, Andy G. Lynch223,315,498, Lisa Lype36, Cristina López111,112, Carlos López-Otín499, Eric Z. Ma64, Yussanne Ma30, Gaetan MacGrogan500, Shona MacRae501, Geoff Macintyre223, Tobias Madsen73, Kazuhiro Maejima184, Andrea Mafficini177, Dennis T. Maglinte166,502, Arindam Maitra174, Partha P. Majumder174, Luca Malcovati232, Salem Malikic62,78, Giuseppe Malleo115, Graham J. Mann211,246,503, Luisa Mantovani-Löffler504, Kathleen Marchal505,506, Giovanni Marchegiani115, Elaine R. Mardis1,193,507, Adam A. Margolin31, Maximillian G. Marin37, Florian Markowetz223,315, Julia Markowski403, Jeffrey Marks508, Tomas Marques-Bonet61,81,386,509, Marco A. Marra30, Luke Marsden351, John W. M. Martens332, Sancha Martin49,510, Jose I. Martin-Subero81,511, Iñigo Martincorena49, Alexander Martinez-Fundichely301,302,451 Yosef E. Maruvka8,26,72, R. Jay Mashl1,2, Charlie E. Massie223, Thomas J. Matthew37, Lucy Matthews178, Erik Mayer221,512, Simon Mayes513, Michael Mayo30, Faridah Mbabaali272, Karen McCune514, Ultan McDermott49, Patrick D. McGillivray19, Michael D. McLellan1,3,20, John D. McPherson148,272,515, John R. McPherson179,180, Treasa A. McPherson260, Samuel R. Meier8, Alice Meng516, Shaowu Meng134, Andrew Menzies49, Neil D. Merrett115,517, Sue Merson178, Matthew Meyerson8,14,82, William U. Meyerson4,5, Piotr A. Mieczkowski518, George L. Mihaiescu76, Sanja Mijalkovic284, Ana Mijalkovic Mijalkovic-Lazic284, Tom Mikkelsen519, Michele Milella253, Linda Mileshkin103, Christopher A. Miller1 , David K. Miller113,170, Jessica K. Miller272, Gordon B. Mills33,34, Ana Milovanovic57, Sarah Minner520, Marco Miotto115, Gisela Mir Arnau267, Lisa Mirabello240, Chris Mitchell103, Thomas J. Mitchell49,315,352, Satoru Miyano375, Naoki Miyoshi375, Shinichi Mizuno521, Fruzsina Molnár-Gábor522, Malcolm J. Moore300, Richard A. Moore30, Sandro Morganella49, Quaid D. Morris127,490, Carl Morrison523,524, Lisle E. Mose134, Catherine D. Moser349, Ferran Muiños298,299, Loris Mularoni298,299, Andrew J. Mungall30, Karen Mungall30, Elizabeth A. Musgrove133, Ville Mustonen525,526,527, David Mutch528, Francesc Muyas52,53,74, Donna M. Muzny12, Alfonso Muñoz59, Jerome Myers529, Ola Myklebost461, Peter Möller530, Genta Nagae89, Adnan M. Nagrial170, Hardeep K. Nahal-Bose76, Hitoshi Nakagama531, Hidewaki Nakagawa184, Hiromi Nakamura118, Toru Nakamura388, Kaoru Nakano184, Tannistha Nandi532, Jyoti Nangalia49, Mia Nastic284, Arcadi Navarro61,81,386, Fabio C. P. Navarro19, David E. Neal223,352, Gerd Nettekoven533, Felicity Newell209,311, Steven J. Newhouse59, Yulia Newton37, Alvin Wei Tian Ng534, Anthony Ng535, Jonathan Nicholson49, David Nicol221, Yongzhan Nie321,536, G. Petur Nielsen72, Morten Muhlig Nielsen73, Serena Nik-Zainal49,281,282,537, Michael S. Noble8, Katia Nones209,311, Paul A. Northcott538, Faiyaz Notta148,539, Brian D. O’Connor76,540, Peter O’Donnell541, Maria O’Donovan282, Sarah O’Meara49, Brian Patrick O’Neill542, J. Robert O’Neill543, David Ocana59, Angelica Ochoa88, Layla Oesper544, Christopher Ogden221, Hideki Ohdan93, Kazuhiro Ohi375, Lucila Ohno-Machado244, Karin A. Oien523,545, Akinyemi I. Ojesina546,547,548, Hidenori Ojima549, Takuji Okusaka550, Larsson Omberg551, Choon Kiat Ong552, Stephan Ossowski52,53,74, German Ott553, B. F. Francis Ouellette76,554, Christine P’ng6, Marta Paczkowska6, Salvatore Paiella115, Chawalit Pairojkul523, Marina Pajic170, Qiang Pan-Hammarström56,555, Elli Papaemmanuil49, Irene Papatheodorou59, Nagarajan Paramasivam43,47, Ji Wan Park385, Joong-Won Park556, Keunchil Park557,558, Kiejung Park559, Peter J. Park264,266, Joel S. Parker518, Simon L. Parsons124, Harvey Pass560, Danielle Pasternack272, Alessandro Pastore276, Ann-Marie Patch209,311, Iris Pauporté251, Antonio Pea115, John V. Pearson209,311, Chandra Sekhar Pedamallu8,14,82, Jakob Skou Pedersen73,75, Paolo Pederzoli115, Martin Peifer270, Nathan A. Pennell561, Charles M. Perou129,518, Marc D. Perry76,77, Gloria M. Petersen562, Myron Peto22, Nicholas Petrelli563, Robert Petryszak59, Stefan M. Pfister426,465,564, Mark Phillips424, Oriol Pich298,299, Hilda A. Pickett478, Todd D. Pihl565, Nischalan Pillay566, Sarah Pinder567, Mark Pinese170, Andreia V. Pinho568, Esa Pitkänen60, Xavier Pivot569, Elena Piñeiro-Yáñez95, Laura Planko533, Christoph Plass345, Paz Polak8,14,15, Tirso Pons570, Irinel Popescu571, Olga Potapova572, Aparna Prasad52, Shaun R. Preston573, Manuel Prinz47, Antonia L. Pritchard311, Stephenie D. Prokopec6, Elena Provenzano574, Xose S. Puente499, Sonia Puig176, Montserrat Puiggròs57, Sergio Pulido-Tamayo505,506, Gulietta M. Pupo246, Colin A. Purdie575, Michael C. Quinn209,311, Raquel Rabionet52,53,576, Janet S. Rader577, Bernhard Radlwimmer397, Petar Radovic284, Benjamin Raeder60, Keiran M. Raine49, Manasa Ramakrishna49, Kamna Ramakrishnan49, Suresh Ramalingam578, Benjamin J. Raphael579, W. Kimryn Rathmell580, Tobias Rausch60, Guido Reifenberger475, Jüri Reimand6,44, Jorge Reis-Filho348, Victor Reuter348, Iker Reyes-Salazar298, Matthew A. Reyna579, Sheila M. Reynolds36, Esther Rheinbay8,14,72, Yasser Riazalhosseini189, Andrea L. Richardson323, Julia Richter111,128, Matthew Ringel581, Markus Ringnér181, Yasushi Rino582, Karsten Rippe405, Jeffrey Roach583, Lewis R. Roberts349, Nicola D. Roberts49, Steven A. Roberts584, A. Gordon Robertson30, Alan J. Robertson113, Javier Bartolomé Rodriguez57, Bernardo Rodriguez-Martin104,105,106, F. Germán Rodríguez-González83,332, Michael H. A. Roehrl44,123,148,234,585,586, Marius Rohde587, Hirofumi Rokutan440, Gilles Romieu588, Ilse Rooman170, Tom Roques262, Daniel Rosebrock8, Mara Rosenberg8,72, Philip C. Rosenstiel589, Andreas Rosenwald590, Edward W. Rowe221,591, Romina Royo57, Steven G. Rozen179,180,592, Yulia Rubanova17,127, Mark A. Rubin423,593,594,595,596, Carlota Rubio-Perez298,299,597, Vasilisa A. Rudneva60, Borislav C. Rusev177, Andrea Ruzzenente598, Gunnar Rätsch276,277,278,279,280,430, Radhakrishnan Sabarinathan298,299,599, Veronica Y. Sabelnykova6, Sara Sadeghi30, S. Cenk Sahinalp62,78,79, Natalie Saini357, Mihoko Saito-Adachi440, Gordon Saksena8, Adriana Salcedo6, Roberto Salgado600, Leonidas Salichos5,19, Richard Sallari8, Charles Saller601, Roberto Salvia115, Michelle Sam272, Jaswinder S. Samra115,602, Francisco Sanchez-Vega114,121, Chris Sander276,603,604, Grant Sanders134, Rajiv Sarin605, Iman Sarrafi62,78, Aya Sasaki-Oku184, Torill Sauer489, Guido Sauter520, Robyn P. M. Saw211, Maria Scardoni167, Christopher J. Scarlett170,606, Aldo Scarpa177, Ghislaine Scelo194, Dirk Schadendorf68,607, Jacqueline E. Schein30, Markus B. Schilhabel589, Matthias Schlesner47,80, Thorsten Schlomm84,608, Heather K. Schmidt1 , Sarah-Jane Schramm246, Stefan Schreiber609, Nikolaus Schultz121, Steven E. Schumacher8,323, Roland F. Schwarz59,403,405,610, Richard A. Scolyer211,448,602, David Scott428, Ralph Scully611, Raja Seethala612, Ayellet V. Segre8,613, Iris Selander260, Colin A. Semple434, Yasin Senbabaoglu276, Subhajit Sengupta614, Elisabetta Sereni115, Stefano Serra585, Dennis C. Sgroi72, Mark Shackleton103, Nimish C. Shah352, Sagedeh Shahabi234, Catherine A. Shang329, Ping Shang211, Ofer Shapira8,323, Troy Shelton271, Ciyue Shen603,604, Hui Shen615, Rebecca Shepherd49, Ruian Shi490, Yan Shi134, Yu-Jia Shiah6, Tatsuhiro Shibata118,616, Juliann Shih8,82, Eigo Shimizu375, Kiyo Shimizu617, Seung Jun Shin618, Yuichi Shiraishi375, Tal Shmaya285, Ilya Shmulevich36, Solomon I. Shorser6, Charles Short59, Raunak Shrestha62, Suyash S. Shringarpure217, Craig Shriver619, Shimin Shuai6,126, Nikos Sidiropoulos83, Reiner Siebert112,620, Anieta M. Sieuwerts332, Lina Sieverling205,237, Sabina Signoretti202,621, Katarzyna O. Sikora177, Michele Simbolo138, Ronald Simon520, Janae V. Simons134, Jared T. Simpson6,17, Peter T. Simpson473, Samuel Singer115,458, Nasa Sinnott-Armstrong8,217, Payal Sipahimalani30, Tara J. Skelly390, Marcel Smid332, Jaclyn Smith622, Karen Smith-McCune514, Nicholas D. Socci276, Heidi J. Sofia27, Matthew G. Soloway134, Lei Song240, Anil K. Sood623,624,625, Sharmila Sothi626, Christos Sotiriou244, Cameron M. Soulette37, Paul N. Span627, Paul T. Spellman22, Nicola Sperandio177, Andrew J. Spillane211, Oliver Spiro8, Jonathan Spring628, Johan Staaf181, Peter F. Stadler163,164,165, Peter Staib629, Stefan G. Stark277,279,618,630, Lucy Stebbings49, Ólafur Andri Stefánsson631, Oliver Stegle59,60,632, Lincoln D. Stein6,126, Alasdair Stenhouse633, Chip Stewart8, Stephan Stilgenbauer634, Miranda D. Stobbe52,61, Michael R. Stratton49, Jonathan R. Stretch211, Adam J. Struck31, Joshua M. Stuart24,37, Henk G. Stunnenberg396,635, Hong Su56,396, Xiaoping Su99, Ren X. Sun6, Stephanie Sungalee60, Hana Susak52,53, Akihiro Suzuki89,636, Fred Sweep637, Monika Szczepanowski128, Holger Sültmann67,638, Takashi Yugawa617, Angela Tam30, David Tamborero298,299, Benita Kiat Tee Tan639, Donghui Tan518, Patrick Tan180,532,592,640, Hiroko Tanaka375, Hirokazu Taniguchi616, Tomas J. Tanskanen641, Maxime Tarabichi49,290, Roy Tarnuzzer220, Patrick Tarpey642, Morgan L. Taschuk152, Kenji Tatsuno89, Simon Tavaré223,643, Darrin F. Taylor113, Amaro Taylor-Weiner8, Jon W. Teague49, Bin Tean Teh180,592,640,644,645, Varsha Tembe246, Javier Temes104,105, Kevin Thai76, Sarah P. Thayer393, Nina Thiessen30, Gilles Thomas646, Sarah Thomas221, Alan Thompson221, Alastair M. Thompson633, John F. Thompson211, R. Houston Thompson647, Heather Thorne103, Leigh B. Thorne176, Adrian Thorogood424, Grace Tiao8, Nebojsa Tijanic284, Lee E. Timms272, Roberto Tirabosco648, Marta Tojo106, Stefania Tommasi649, Christopher W. Toon170, Umut H. Toprak48,650, David Torrents57,81, Giampaolo Tortora651,652, Jörg Tost653, Yasushi Totoki118, David Townend654, Nadia Traficante103, Isabelle Treilleux655,656, Jean-Rémi Trotta61, Lorenz H. P. Trümper469, Ming Tsao124,539, Tatsuhiko Tsunoda183,657,658,659, Jose M. C. Tubio104,105,106, Olga Tucker660, Richard Turkington661, Daniel J. Turner513, Andrew Tutt323, Masaki Ueno376, Naoto T. Ueno662, Christopher Umbricht151,213,663, Husen M. Umer305,664, Timothy J. Underwood665, Lara Urban59,60, Tomoko Urushidate616, Tetsuo Ushiku339, Liis Uusküla-Reimand666,667, Alfonso Valencia57,81, David J. Van Den Berg166, Steven Van Laere307, Peter Van Loo290,291, Erwin G. Van Meir668, Gert G. Van den Eynden307, Theodorus Van der Kwast123, Naveen Vasudev137, Miguel Vazquez57,669, Ravikiran Vedururu267, Umadevi Veluvolu518, Shankar Vembu490,670, Lieven P. C. Verbeke506,671, Peter Vermeulen307, Clare Verrill351,672, Alain Viari177, David Vicente57, Caterina Vicentini177, K. Vijay Raghavan365, Juris Viksna673, Ricardo E. Vilain674, Izar Villasante57, Anne Vincent-Salomon635, Tapio Visakorpi190, Douglas Voet8, Paresh Vyas311,351, Ignacio Vázquez-García49,86,675,676, Nick M. Waddell209, Nicola Waddell209,311, Claes Wadelius677, Lina Wadi6, Rabea Wagener111,112, Jeremiah A. Wala8,14,82, Jian Wang56, Jiayin Wang1,40,66, Linghua Wang12, Qi Wang465, Wenyi Wang21, Yumeng Wang21, Zhining Wang220, Paul M. Waring523, Hans-Jörg Warnatz483, Jonathan Warrell5,19, Anne Y. Warren352,678, Sebastian M. Waszak60, David C. Wedge49,294,679, Dieter Weichenhan345, Paul Weinberger680, John N. Weinstein38, Joachim Weischenfeldt60,83,84, Daniel J. Weisenberger166, Ian Welch681, Michael C. Wendl1,10,11, Johannes Werner47,85, Justin P. Whalley61,682, David A. Wheeler12,13, Hayley C. Whitaker117, Dennis Wigle683, Matthew D. Wilkerson518, Ashley Williams244, James S. Wilmott211, Gavin W. Wilson6,148, Julie M. Wilson148, Richard K. Wilson1,684, Boris Winterhoff685, Jeffrey A. Wintersinger17,127,384, Maciej Wiznerowicz686,687, Stephan Wolf688, Bernice H. Wong689, Tina Wong1,30, Winghing Wong690, Youngchoon Woo250, Scott Wood209,311, Bradly G. Wouters44, Adam J. Wright6, Derek W. Wright133,691, Mark H. Wright217, Chin-Lee Wu72, Dai-Ying Wu285, Guanming Wu692, Jianmin Wu170, Kui Wu56,396, Yang Wu179,180, Zhenggang Wu64, Liu Xi12, Tian Xia693, Qian Xiang76, Xiao Xiao66, Rui Xing497, Heng Xiong56,396, Qinying Xu209,311, Yanxun Xu694, Hong Xue64, Shinichi Yachida118,695, Sergei Yakneen60, Rui Yamaguchi375, Takafumi N. Yamaguchi6, Masakazu Yamamoto120, Shogo Yamamoto89, Hiroki Yamaue376, Fan Yang490, Huanming Yang56, Jean Y. Yang696, Liming Yang220, Lixing Yang697, Shanlin Yang306, Tsun-Po Yang270, Yang Yang369, Xiaotong Yao408,698, Marie-Laure Yaspo483, Lucy Yates49, Christina Yau156, Chen Ye56,396, Kai Ye40,41, Venkata D. Yellapantula20,86, Christopher J. Yoon249, Sung-Soo Yoon463, Fouad Yousif6, Jun Yu699, Kaixian Yu700, Willie Yu701, Yingyan Yu702, Ke Yuan223,510,703, Yuan Yuan21, Denis Yuen6, Takashi Yugawa617, Christina K. Yung76, Olga Zaikova704, Jorge Zamora49,104,105,106, Marc Zapatka397, Jean C. Zenklusen220, Thorsten Zenz67, Nikolajs Zeps705,706, Cheng-Zhong Zhang8,707, Fan Zhang381, Hailei Zhang8, Hongwei Zhang494, Hongxin Zhang121, Jiashan Zhang220, Jing Zhang5, Junjun Zhang76, Xiuqing Zhang56, Xuanping Zhang66,369, Yan Zhang5,708,709, Zemin Zhang381,710, Zhongming Zhao711, Liangtao Zheng381, Xiuqing Zheng381, Wanding Zhou615, Yong Zhou56, Bin Zhu240, Hongtu Zhu700,712, Jingchun Zhu24, Shida Zhu56,396, Lihua Zou713, Xueqing Zou49, Anna deFazio246,247,714, Nicholas van As221, Carolien H. M. van Deurzen715, Marc J. van de Vijver523, L. van’t Veer716 & Christian von Mering433,717, The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.
Published: 2020
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5. Comparative toxicoproteogenomics of mouse and rat liver identifies TCDD-resistance genes

Author: Stephenie D. Prokopec, Sandy Che Eun S. Lee, Amy X. Lu, Allan B. Okey, Rabah Soliymani, Cindy Q. Yao, John Douglas Mcpherson, Philip C. Zuzarte, John D. Watson, Michelle Sam, Raimo Pohjanvirta, Richard de Borja, Paul C. Boutros, Ren X. Sun, Ada Wong, Department of Biochemistry and Developmental Biology, Medicum, University of Helsinki, Helsinki One Health (HOH), Raimo Pohjanvirta / Principal Investigator, and Food Hygiene and Environmental Health
Subjects: 0301 basic medicine, Male, Proteomics, TCDD, Polychlorinated Dibenzodioxins, Health, Toxicology and Mutagenesis, Developmental toxicity, 010501 environmental sciences, Toxicology, 01 natural sciences, Transcriptome, Mice, BINDING, Basic Helix-Loop-Helix Transcription Factors, heterocyclic compounds, GENECHIP DATA, NONGENOMIC PATHWAY, AH RECEPTOR, biology, 1184 Genetics, developmental biology, physiology, General Medicine, Genomics, Phenotype, DEVELOPMENTAL TOXICITY, DIOXIN-RESPONSIVE ENHANCER, Liver, Mice, Inbred DBA, Toxicity, Environmental Pollutants, 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD, Genetically modified mouse, Gene isoform, Model organisms, ARYL-HYDROCARBON RECEPTOR, EXPRESSION, Mice, Transgenic, 03 medical and health sciences, Species Specificity, Animals, Rats, Long-Evans, RNA, Messenger, Rats, Wistar, Transcriptomics, Gene, 0105 earth and related environmental sciences, Whole-genome sequencing, Dose-Response Relationship, Drug, AhR, PROTEIN-DNA INTERACTIONS, Aryl hydrocarbon receptor, Molecular biology, Rats, Mice, Inbred C57BL, stomatognathic diseases, 030104 developmental biology, Receptors, Aryl Hydrocarbon, biology.protein, 3111 Biomedicine
Abstract: The aryl hydrocarbon receptor (AHR) mediates many toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, the AHR alone does not explain the widely different outcomes among organisms. To identify the other factors involved, we evaluated three transgenic mouse lines, each expressing a different rat AHR isoform (rWT, DEL, and INS) providing widely different resistance to TCDD toxicity, as well as C57BL/6 and DBA/2 mice which exhibit a similar to tenfold divergence in TCDD sensitivity (exposures of 5-1000 mu g/kg TCDD). We supplement these with whole-genome sequencing, together with transcriptomic and proteomic analyses of the corresponding rat models, Long-Evans (L-E) and Han/Wistar (H/W) rats (having a similar to 1000-fold difference in their TCDD sensitivities; 100 mu g/kg TCDD), to identify genes associated with TCDD-response phenotypes. Overall, we identified up to 50% of genes with altered mRNA abundance following TCDD exposure are associated with a single AHR isoform (33.8%, 11.7%, 5.2% and 0.3% of 3076 genes altered unique to rWT, DEL, C57BL/6 and INS respectively following 1000 mu g/kg TCDD). Hepatic Pxdc1 was significantly repressed in all three TCDD-sensitive animal models (C57BL/6 and rWT mice, and L-E rat) after TCDD exposure. Three genes, including Cxxc5, Sugp1 and Hgfac, demonstrated different AHRE-1 (full) motif occurrences within their promoter regions between rat strains, as well as different patterns of mRNA abundance. Several hepatic proteins showed parallel up- or downward alterations with their RNAs, with three genes (SNRK, IGTP and IMPA2) showing consistent, strain-dependent changes. These data show the value of integrating genomic, transcriptomic and proteomic evidence across multi-species models in toxicologic studies.
Published: 2019

6. Identifying TCDD-resistance genes via murine and rat comparative genomics and transcriptomics

Author: Amy X. Lu, Sandy Che Eun S. Lee, Allan B. Okey, Ada Wong, Stephenie D. Prokopec, Ren X. Sun, John Douglas Mcpherson, Philip C. Zuzarte, Richard de Borja, John D. Watson, Michelle Sam, Cindy Q. Yao, Raimo Pohjanvirta, and Paul C. Boutros
Subjects: Comparative genomics, Genetics, Genetically modified mouse, Gene isoform, 0303 health sciences, Biology, Aryl hydrocarbon receptor, Phenotype, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Gene expression, biology.protein, Gene, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract: The aryl hydrocarbon receptor (AHR) mediates many of the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). However, the AHR alone is insufficient to explain the widely different outcomes among organisms. Attempts to identify unknown factor(s) have been confounded by genetic variability of model organisms. Here, we evaluated three transgenic mouse lines, each expressing a different rat AHR isoform (rWT, DEL, and INS), as well as C57BL/6 and DBA/2 mice. We supplement these with whole-genome sequencing and transcriptomic analyses of the corresponding rat models: Long-Evans (L-E) and Han/Wistar (H/W) rats. These integrated multi-species genomic and transcriptomic data were used to identify genes associated with TCDD-response phenotypes.We identified several genes that show consistent transcriptional changes in both transgenic mice and rats. HepaticPxdc1was significantly repressed by TCDD in C57BL/6, rWT mice, and in L-E rat. Three genes demonstrated different AHRE-1 (full) motif occurrences within their promoter regions:Cxxc5had fewer occurrences in H/W, as compared with L-E;Sugp1andHgfac(in either L-E or H/W respectively). These genes also showed different patterns of mRNA abundance across strains.The AHR isoform explains much of the transcriptional variability: up to 50% of genes with altered mRNA abundance following TCDD exposure are associated with a single AHR isoform (30% and 10% unique to DEL and rWT respectively following 500 μg/kg TCDD). Genomic and transcriptomic evidence allowed identification of genes potentially involved in phenotypic outcomes:Pxdc1had differential mRNA abundance by phenotype;Cxxc5had altered AHR binding sites and differential mRNA abundance.Author SummaryEnvironmental contaminants such as dioxins cause many toxic responses, anything from chloracne (common in humans) to death. These toxic responses are mostly regulated by theAhr, a ligand-activated transcription factor with roles in drug metabolism and immune responses, however other contributing factors remain unclear. Studies are complicated by the underlying genetic heterogeneity of model organisms. Our team evaluated a number of mouse and rat models, including two strains of mouse, two strains of rat and three transgenic mouse lines which differ only at theAhrlocus, that present widely different sensitivities to the most potent dioxin: 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD). We identified a number of changes to gene expression that were associated with different toxic responses. We then contrasted these findings with results from whole-genome sequencing of the H/W and L-E rats and found some key genes, such asCxxc5andMafb, which might contribute to TCDD toxicity. These transcriptomic and genomic datasets will provide a valuable resource for future studies into the mechanisms of dioxin toxicities.
Published: 2019
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7. Genomic hallmarks of localized, non-indolent prostate cancer

Author: Michèle Orain, Yu Jia Shiah, Ken Kron, Lawrence E. Heisler, Mathieu Lupien, Xuemei Luo, Andre P. Masella, Michelle Sam, Paul C. Boutros, Shaylan K. Govind, Daryl Waggott, Veronica Y. Sabelnykova, Natalie S. Fox, Musaddeque Ahmed, Julia F. Hopkins, Lee Timms, Clement Fung, Francis Nguyen, Zhiyuan Wang, Taryne Chong, Alain Bergeron, Julie Livingstone, Yves Fradet, Melvin L.K. Chua, Timothy Beck, Alexander Murison, Bernard Têtu, Ada Wong, Ren X. Sun, Constance H. Li, Kathleen E. Houlahan, John Douglas Mcpherson, Cenk Sahinalp, Housheng Hansen He, Junyan Zhang, Robert G. Bristow, Jeremy Johns, Neil E. Fleshner, Alejandro Berlin, Michelle Chan-Seng-Yue, Christine P'ng, Nicholas Buchner, Alister D'Costa, Richard de Borja, Xihui Lin, Louis Lacombe, Jeffrey Green, Hélène Hovington, Vincent Huang, Kenneth C. Chu, Haiying Kong, Emilie Lalonde, Nicholas J. Harding, Syed Haider, Esther Jung, Colin Collins, Shadrielle Melijah G. Espiritu, Takafumi N. Yamaguchi, Bryan Lo, Michael Xie, Valérie Picard, Michael Fraser, Stephenie D. Prokopec, Christopher I Cooper, Fouad Yousif, Theodorus van der Kwast, Robert E. Denroche, Alice Meng, Dominique Trudel, and Alan Dal Pra
Subjects: 0301 basic medicine, Male, DNA Copy Number Variations, Somatic hypermutation, Genomics, Disease, Biology, Bioinformatics, 03 medical and health sciences, Prostate cancer, Recurrence, medicine, Humans, Exome, Neoplasm Metastasis, 610 Medicine & health, Chromothripsis, Multidisciplinary, Genome, Human, Prostatic Neoplasms, Methylation, DNA Methylation, medicine.disease, Prognosis, Human genetics, Prostatic Neoplasms, Castration-Resistant, 030104 developmental biology, DNA methylation, Mutation, Cancer research
Abstract: Prostate tumours are highly variable in their response to therapies, but clinically available prognostic factors can explain only a fraction of this heterogeneity. Here we analysed 200 whole-genome sequences and 277 additional whole-exome sequences from localized, non-indolent prostate tumours with similar clinical risk profiles, and carried out RNA and methylation analyses in a subset. These tumours had a paucity of clinically actionable single nucleotide variants, unlike those seen in metastatic disease. Rather, a significant proportion of tumours harboured recurrent non-coding aberrations, large-scale genomic rearrangements, and alterations in which an inversion repressed transcription within its boundaries. Local hypermutation events were frequent, and correlated with specific genomic profiles. Numerous molecular aberrations were prognostic for disease recurrence, including several DNA methylation events, and a signature comprised of these aberrations outperformed well-described prognostic biomarkers. We suggest that intensified treatment of genomically aggressive localized prostate cancer may improve cure rates.
Published: 2017
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8. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes

Author: Conrad Leonard, Stefano Serra, Jeremy L. Humphris, J. Lynn Fink, Vincenzo Corbo, Deepa Pai, Ami Panchal, Jennifer Drummond, Anirban Maitra, Katia Nones, Mark J. Cowley, Nam Q. Nguyen, Marc D. Jones, David A. Largaespada, Karen M. Mann, Ralph H. Hruban, Nicole Cloonan, Timothy Beck, Marie-Claude Gingras, Sally E. Hodges, Darrin Taylor, Andrew V. Biankin, Angela Chou, Craig Nourse, Marina Pajic, Gloria M. Petersen, Kimberly Begley, Richard A. Morgan, Rita T. Lawlor, Senel Idrisoglu, Jessica A. Lovell, Lincoln Stein, Christina K. Yung, Lee Timms, Adnan Nagrial, Giampaolo Tortora, Shivangi Wani, Mark Pinese, Angelika N. Christ, Amanda Mawson, Neil D. Merrett, Maria Scardoni, Min Wang, Ann-Marie Patch, Steven Gallinger, Huyen Dinh, Richard A. Gibbs, John Douglas Mcpherson, Amber L. Johns, Nipun Kakkar, David A. Wheeler, Andrew Barbour, Patricia Shaw, Milena Gongora, Emily S. Humphrey, Christopher J. Scarlett, Matthew J. Anderson, Lodewyk F. A. Wessels, Andrew M.K. Brown, Christopher W. Toon, Felicity Newell, Margaret A. Tempero, Fengmei Zhao, Richard D. Schulick, Paola Capelli, Timothy J. C. Bruxner, Christine A. Iacobuzio-Donahue, Ivon Harliwong, Richard de Borja, Pedro A. Perez-Mancera, Jianmin Wu, Emily K. Colvin, Michelle Sam, Warren Kaplan, Debabrata Mukhopadhyay, John V. Pearson, Gabriel Kolle, Oliver Holmes, Lorraine A. Chantrill, Lora Lewis, Jaswinder S. Samra, Scott Wood, Lakshmi Muthuswamy, James R. Eshleman, Neal G. Copeland, Peter Wilson, David Miller, Anthony J. Gill, Qinying Xu, Nicola Waddell, Ming-Sound Tsao, Karin S. Kassahn, Venessa T. Chin, James G. Kench, David K. Chang, William E. Fisher, Kyle Chang, Aldo Scarpa, Christopher L. Wolfgang, Roger J. Daly, Alistair G. Rust, Ehsan Nourbakhsh, Jeffrey G. Reid, Nikolajs Zeps, Nicole Onetto, Donna M. Muzny, Brooke Gardiner, Robert E. Denroche, Yuan Qing Wu, Nancy A. Jenkins, Sean M. Grimmond, R. Scott Mead, David A. Tuveson, David J. Adams, Yi Han, F. Charles Brunicardi, Andreia V. Pinho, Elizabeth A. Musgrove, Sarah Song, Ilse Rooman, Thomas J. Hudson, Christian J. Buhay, Robert L. Sutherland, Suzanne Manning, Nicholas Buchner, Krishna Epari, Basic (bio-) Medical Sciences, and Laboratory for Medical and Molecular Oncology
Subjects: Exome sequencing, Gene Dosage, Copy number analysis, PDAC, KRAS, Kaplan-Meier Estimate, Biology, medicine.disease_cause, Mice, CDKN2A, Pancreatic cancer, medicine, Animals, Humans, Genetics, Mutation, Genome, Multidisciplinary, Proteins, Cancer, medicine.disease, Axons, Gene Expression Regulation, Neoplastic, Pancreatic Neoplasms, Cancer research, Carcinogenesis, Carcinoma, Pancreatic Ductal, Signal Transduction
Abstract: Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.
Published: 2012
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9. Expanded Perspectives on Social Transformation in Brazil

Author: Michelle Sampaio
Subjects: Theory of change, Decolonization, Good Living, Nature-Based solutions, Social sciences (General), H1-99
Abstract: This commentary presents a broader perspective on the paper Psychopolitical foresensing for social transformation (PFST): theoretical reflections for action research in Brazil towards the SDGs. It is generally accepted that the current path of capitalism is accelerating the planetary climate crisis and social inequality and is bringing an individual and collective feeling of frustration.Cimini and Homem’s brings in their paper a proposal in tackle this frustration feeling through advancing the theory of change (ToC) concept by creating a framework for an action research project based on awareness-based systems change (ABSC). I highlight three relevant contexts to Brazil to be considered in their action research project: i. Decolonization and good living: concepts in Brazil’s current transformation mindset; ii. Nature-based solutions: the value of socio-biocultural diversity in Brazil; and iii. Practical experience on building a participatory ToC for the Amazon. Cimini and Homem’s proposed journey on PFST aiming to expand on ToCs approach by adding ABSC methodologies using presence-sense-reconnection, seems to be a path to integrate inner and out change with social and cultural transformation. They have a great opportunity, combined with a challenge, to plant a seed in leaders and changemakers in expanding their views of how impact can be generated. They can be bold in the PFST journey by enhancing awareness and actions, going beyond the SDGs, and bringing light to Brazil’s position as a global leader in nature-based solutions to face climate change.
Published: 2023
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10. PARP inhibitors as first-line maintenance therapy in ovarian cancer: recommendations from an expert panel from Brazil

Author: Aknar FC Calabrich, Daniele Xavier Assad, Graziela Dal-Molin, Andreia C Melo, Angelica Nogueira-Rodrigues, Karime Kalil, Andrea PG Guimarães, Michelle Samora Almeida, Carla Rameri de Azevedo, Daniela de Freitas, Alessandra Menezes Morelle, Ana Carolina Leite, Marcela Crosara, João Soares Nunes, Poliana Signorini, Eduardo Cronemberger, Rachel Cossetti, Rodrigo Guindalini, Eduardo Paulino, and Fernando C Maluf
Subjects: carcinoma, ovarian epithelial, poly(adp-ribose) polymerase inhibitors, consensus, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Medicine
Abstract: To report consensus recommendations on the current role of poly(ADP-ribose) polymerase (PARP) inhibitors in the front-line management of patients with epithelial ovarian cancer (EOC) in the healthcare setting of Brazil. The expert panel convened in March 2021 and comprised 20 medical oncologists focus on gynecological oncology. The panel answered anonymously and based on scientific evidence a total of 67 questions. The panel reached consensus (at least 75% of votes for the same recommendation) or majority vote (50% to 74.9%) for the majority of questions that addressed: (1) who and when to test for BRCA mutations or homologous recombination deficiency (2) what test should be used; (3) when should maintenance PARP inhibitor therapy be indicated; (4) which PARP inhibitor should be used; (5) when should bevacizumab be combined; and (6) toxicity management. The current recommendations may help Brazilian practitioners to improve the use of PARP inhibitors in front-line management of EOC.
Published: 2023
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11. Spatial genomic heterogeneity within localized, multifocal prostate cancer

Author: Hanbo Chen, Julie Livingstone, Cherry Have, Thomas J. Hudson, Veronica Y. Sabelnykova, Ada Wong, Stephenie D. Prokopec, Timothy Beck, Shaylan K. Govind, Kenneth C. Chu, Gaetano Zafarana, Robert G. Bristow, Neil E. Fleshner, Alister D'Costa, Fouad Yousif, Jeremy Johns, James R. Hawley, Daryl Waggott, Lee Timms, John D. Watson, Colin Cooper, Paul C. Boutros, Bernard Têtu, Emilie Lalonde, Cenk Sahinalp, Dominique Trudel, Jenna Sykes, Esther Jung, David E. Neal, Trent T. Simmons, Faraz Hach, Michael Fraser, Christine P'ng, Robert E. Denroche, Lincoln Stein, Colin Collins, Xuemei Luo, Rosalind A. Eeles, Sohrab P. Shah, Melania Pintilie, Theodorus van der Kwast, Clement Fung, Francis Nguyen, Michelle Chan-Seng-Yue, Andrew M.K. Brown, John Douglas Mcpherson, Amin Zia, Alan Dal Pra, Nicholas J. Harding, Alice Meng, Lauren C. Chong, Philippe Lambin, Pablo H. Hennings-Yeomans, Richard de Borja, Nicholas Buchner, Andrew McPherson, Jianxin Wang, Yu Jia Shiah, Michelle Sam, Maud H.W. Starmans, Natalie S. Fox, Taryne Chong, Gregory M. Chen, Alejandro Berlin, Lakshmi Muthuswamy, Promovendi ODB, Radiotherapie, RS: GROW - Oncology, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
Subjects: Male, DNA Copy Number Variations, Genomics, Biology, Bioinformatics, Genome, Polymorphism, Single Nucleotide, DNA sequencing, Proto-Oncogene Proteins c-myc, Prostate cancer, Genetic Heterogeneity, Cell Line, Tumor, Genetics, medicine, Humans, Point Mutation, 610 Medicine & health, Gene, Genetic Association Studies, Genetic heterogeneity, Genome, Human, Point mutation, Cancer, Prostatic Neoplasms, Middle Aged, medicine.disease, Cancer research, Neoplasm Grading
Abstract: Herein we provide a detailed molecular analysis of the spatial heterogeneity of clinically localized, multifocal prostate cancer to delineate new oncogenes or tumor suppressors. We initially determined the copy number aberration (CNA) profiles of 74 patients with index tumors of Gleason score 7. Of these, 5 patients were subjected to whole-genome sequencing using DNA quantities achievable in diagnostic biopsies, with detailed spatial sampling of 23 distinct tumor regions to assess intraprostatic heterogeneity in focal genomics. Multifocal tumors are highly heterogeneous for single-nucleotide variants (SNVs), CNAs and genomic rearrangements. We identified and validated a new recurrent amplification of MYCL, which is associated with TP53 deletion and unique profiles of DNA damage and transcriptional dysregulation. Moreover, we demonstrate divergent tumor evolution in multifocal cancer and, in some cases, tumors of independent clonal origin. These data represent the first systematic relation of intraprostatic genomic heterogeneity to predicted clinical outcome and inform the development of novel biomarkers that reflect individual prognosis.
Published: 2014

12. CBD resistant Salmonella strains are susceptible to epsilon 34 phage tailspike protein

Author: Iddrisu Ibrahim, Joseph Atia Ayariga, Junhuan Xu, Ayomide Adebanjo, Boakai K. Robertson, Michelle Samuel-Foo, and Olufemi S. Ajayi
Subjects: cannabidiol, resistance, Salmonella, antibacterial agent, phage, Medicine (General), R5-920
Abstract: The rise of antimicrobial resistance is a global public health crisis that threatens the effective control and prevention of infections. Due to the emergence of pandrug-resistant bacteria, most antibiotics have lost their efficacy. Bacteriophages or their components are known to target bacterial cell walls, cell membranes, and lipopolysaccharides (LPS) and hydrolyze them. Bacteriophages being the natural predators of pathogenic bacteria, are inevitably categorized as “human friends”, thus fulfilling the adage that “the enemy of my enemy is my friend”. Leveraging on their lethal capabilities against pathogenic bacteria, researchers are searching for more ways to overcome the current antibiotic resistance challenge. In this study, we expressed and purified epsilon 34 phage tailspike protein (E34 TSP) from the E34 TSP gene, then assessed the ability of this bacteriophage protein in the killing of two CBD-resistant strains of Salmonella spp. We also assessed the ability of the tailspike protein to cause bacteria membrane disruption, and dehydrogenase depletion. We observed that the combined treatment of CBD-resistant strains of Salmonella with CBD and E34 TSP showed poor killing ability whereas the monotreatment with E34 TSP showed considerably higher killing efficiency. This study demonstrates that the inhibition of the bacteria by E34 TSP was due in part to membrane disruption, and dehydrogenase inactivation by the protein. The results of this work provides an interesting background to highlight the crucial role phage protein such as E34 TSP could play in pathogenic bacterial control.
Published: 2023
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13. Management of patients with recurrent/metastatic endometrial cancer: Consensus recommendations from an expert panel from Brazil

Author: Diocésio Alves Pinto de Andrade, Andréa Paiva Gadelha Guimarães, Andréia Cristina de Melo, Angélica Nogueira-Rodrigues, Larissa Müller Gomes, Mariana Scaranti, Joyce Maria Lisboa Maia, Alessandra Menezes Morelle, Candice Amorim de Araújo Lima Santos, Cristiano de Pádua Souza, Daniela de Freitas, Donato Callegaro Filho, Eduardo Paulino, Elge Werneck Araújo Júnior, Juliana Martins Pimenta, Marcela Bonalumi dos Santos, Michelle Samora de Almeida, Ronaldo Pereira Souza, Samantha Cabral, and Fernando Cotait Maluf
Subjects: endometrial cancer, consensus, Brazil, metastatic, recurrence, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: BackgroundEndometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting.MethodsThe panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to
Published: 2023
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14. Abstract A9: The pancreatic ductal adenocarcinoma project at the Ontario Institute for Cancer Research

Author: Carson Holt, Lynda Chin, Lee Timms, Patricia Shaw, Michelle Sam, Debabrata Mukhopadhyay, Thomas J. Hudson, John Douglas Mcpherson, Timothy Beck, Lakshmi Muthuswamy, Christina K. Yung, Alexei Protopopov, Steve Gallinger, Emin Ibrahimov, Kimberly Begley, Ming-Sound Tsao, Lincoln Stein, Gloria M. Petersen, and Sarah P. Thayer
Subjects: Pancreatic cancer, medicine, Cancer research, Cancer, Single-nucleotide polymorphism, Biology, medicine.disease, Exome, Genome, Primary tumor, Germline, Reference genome
Abstract: Pancreatic cancer is the fifth leading cause of cancer-related death with a poor prognosis and 5-year survival rates of less than 5%. As a contributing member of the International Cancer Genome Consortium (ICGC), the Ontario Institute for Cancer Research (OICR) has committed to generating a comprehensive catalogue of genomic abnormalities found in pancreatic ductal adenocarcinomas (PDAC). Using next-generation sequencing technologies, 375 independent pancreatic tumors and their matched controls will be characterized over a 3- to 5-year time span. Many of the samples also have derived matching xenografts and a few have cell lines derived from the xenograft tumors. To date, this project has collected 173 ICGC consented matched samples comprised of 85 PDAC tumor/reference and 21 xenograft/ reference pairs. 32 sample sets have matched tumor/xenograft/reference. In addition, there are 16 cell lines derived from some of these xenografts. Whole-genome and exome target-enrichment sequencing is currently performed using the HiSeq 2000 platform. For efficient variant calling, all whole-genome analyses used a minimal depth of 30x reference and 50x tumor/xeno/cell line and exome analyses used greater than 100x target coverage, with most samples exceeding these targets. Sequence alignment is primarily performed with Novoalign (Novocraft.com) and variants called with the Genome Analysis Toolkit (McKenna et al., Genome Res. 20:1297) to identify germline and somatic variants in all matched sample sets. On average 35 coding non-synonymous variants have been observed per primary tumor exome. Validation of the coding non-synonymous variants is ongoing with data deposited in the ICGC Data Coordinating Center (www.icgc. org). Initial data have been combined with PDAC data sets from the Australian ICGC effort (S. Grimmond and A. Biankin) and from sequencing efforts at the Baylor College of Medicine (R. Gibbs) to increase analytical power. Sequencing of primary tumors and xenografts was complicated by human and mouse stroma, respectively. Complete whole-genome sequencing of the host mouse strain was needed for removal of “interspecies SNP” observed due to alignment of both species to regions of similarity in the human reference sequence. The “SNPs” are falsely identified as somatic variants after subtracting the human germline SNP. Methods are under development to improve this removal process. Current sequencing is focusing on expanding the data set of matched normal and primary tumor pairs. It is anticipated that 150 exome pairs will be sequenced by 4th quarter 2012 with whole-genome sequencing following closely. Continued development of xenograft resources is ongoing in parallel. Whole genome sequences will be generated from selected xenografts. Collectively, the sequence data, xenografts, and cell line models will make a rich resource for studying PDAC. Citation Format: Kimberly N. Begley, Debabrata Mukhopadhyay, Gloria M. Petersen, Alexei Protopopov, Sarah Thayer, Lynda Chin, Emin Ibrahimov, Patricia Shaw, Thomas Hudson, Steve Gallinger, Ming-Sound Tsao, Lincoln Stein, John D. McPherson, Lakshmi Muthuswamy, Timothy Beck, Christina Yung, Michelle Sam, Lee Timms, Carson Holt. The pancreatic ductal adenocarcinoma project at the Ontario Institute for Cancer Research. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr A9.
Published: 2012
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15. Abstract B18: Genomic analysis of pancreatic ductal adenocarcinoma

Author: Richard de Borja, Christine Ouellete, Michelle Sam, Lee Timms, Timothy Beck, Carson Holt, Rob Denroche, John Douglas Mcpherson, Lakshmi Muthuswamy, Kimberly Begley, Thomas J. Hudson, Lincoln Stein, Fouad Yousif, Christina K. Yung, Niloofar Arshadi, and Z. Zha
Subjects: Genetics, Candidate gene, Mutation, Pancreatic cancer, medicine, Cancer, KRAS, Ion semiconductor sequencing, Biology, medicine.disease, medicine.disease_cause, Exome, Deep sequencing
Abstract: Pancreatic cancer is the fifth leading cause of cancer deaths. Five-year survival rate is In our initial screen, whole-exome sequencing of 33 primary PDAC tumors and matched controls has been performed on the Illumina HiSeq 2000. Sequence alignment and variant calling have been performed using Novoalign and GATK, respectively. After manual review and validation on the Ion Torrent platform, we have identified 648 somatic mutations, 471 of which are non-silent mutations that impact 444 genes. Our results confirm several known mutations in PDAC such as KRAS, p53 and SMAD4. However, their mutation frequencies are lower than expected due to tumor cellularity. We have also screened for copy number alterations (CNAs) using Illumina Omni1-Quad BeadChip. Analysis was performed using Genome Studio, KSseg and PennCNV. In the 33 primary tumors, a median of 90 regions with copy number gain, copy number loss, or copy-neutral LOH have been detected per sample. Median genomic lengths are 19Mb and 20Mb in regions with copy number gain and loss, respectively. Annotation of the altered regions has identified 9152 protein-coding genes, miRNA and non-coding RNA that are altered in 4 or more tumors. To identify the pathways that contribute to PDAC, we have analyzed the genes with somatic mutations or CNAs by means of a functional interaction (FI) network. The FI network consists of curated pathways from Reactome and other databases and a high confidence set of functional interactions predicted by machine learning techniques. A PDAC-specific subnetwork is constructed by projecting the altered genes onto the FI network, and subsequently analyzed by a community clustering algorithm to identify network modules. These modules have been identified as KRAS, p53, TGFβ, Hedgehog, Integrin, Cadherin, Wnt, Rho GTPase and G-protein signaling pathways. While our effort in identifying driver mutations is ongoing, our initial screen has identified candidate genes that will be targeted for deep sequencing in all primary tumors. We will continue to perform whole-exome sequencing of other primary tumors along with xenografts derived from some of the primaries and cell lines derived from some of the xenografts. In addition, whole-genome sequencing of selected specimens is being performed to complement the exome data. The wealth of data will help to characterize the genomic abnormalities in PDAC. Citation Format: Christina K. Yung, Christine Ouellete, Lee Timms, Michelle Sam, Kimberly Begley, Thomas J. Hudson, John D. McPherson, Lincoln D. Stein, Timothy Beck, Lakshmi Muthuswamy, Richard De Borja, Carson Holt, Rob Denroche, Fouad Yousif, Zheng Zha, Niloofar Arshadi. Genomic analysis of pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B18.
Published: 2012
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16. Abstract B13: Whole-genome mutation landscape in pancreatic ductal adenocarcinoma

Author: Richard de Borja, Tim Beck, Lakshmi Muthuswamy, Carson Holt, Kimberly Begley, Lee Timms, Christina K. Yung, Irinia Kalatskaya, Niloofar Arshadi, Robert E. Denroche, John Douglas Mcpherson, Lincoln Stein, Christine Ouelltt, Michelle Sam, Bojan Losic, Fouad Yousif, and Thomas J. Hudson
Subjects: Whole genome sequencing, Genetics, Mutation, Pancreatic cancer, DNA methylation, medicine, Biology, medicine.disease, medicine.disease_cause, Genome, Gene, Primary tumor, Deep sequencing
Abstract: Pancreatic ductal adenocarcinoma (PDAC) is a rare cancer with a very high mortality rate. Because it is extremely difficult to detect at an early stage; PDAC tumors often spread to regional lymph nodes or distant metastases by the time they are diagnosed. Published reports have already identified a number of chromosomal alterations at many genomic levels; however PDAC still lacks a comprehensive catalogue for the whole genome mutation spectrum. The goal of our study is to annotate all types of identifiable genomic aberrations based on whole genome sequencing of 5 PDAC tumors. It is a common knowledge that surgical primary tissues of PDAC have very low tumor content. Hence, for our study all five primary tumors have been modeled as xenografts using NOD-SCID mice to enrich for tumor cells. Here, we report on the cancer-specific genome alterations in 5 PDAC tumors and show that xenograft models do represent genomic landscape of primary tumors. All samples were whole-genome sequenced using Illumina HiSeq to give a minimum coverage of 30X. We have developed an analysis pipeline to identify somatic single nucleotide variations (SNVs) using The Genome Analysis Tool Kit (GATK), copy number alterations (CNAs) using KSseg (in-house CNV algorithm) and structural variations using Geometric Analysis of Structural Variants (GASV). A number of filters have been implemented to separate germline variants and mouse derived contamination from the cancer specific somatic variation. Our analysis has identified an average of 1527 SNVs, 1555 INDELs, and 53 CNAs per PDAC genome (combined for primary and xenograft). All somatic SNVs were verified using Ion Torrent based sequencing technology with a verification rate of 93%. CNAs were verified using Nimblegen 2.1M Array-based Comparative Genome Hybridization technology, and produced a verification rate of greater than 98% for losses and 60-97% for gains. We also observed a high level of overlap between primary tumor and xenograft samples, with 84% of total primary tumor SNVs and 61% of INDELS (called across all samples) being found in the correlating xenograft genome. After verification of SNVs by deep sequencing, we observe an additional 50% of SNVs that were called only in the xenograft samples validate in the primary sample. Our results show that the somatic single nucleotide mutation rate is in the range of 1 - 4 SNVs/Mb and there is a statistically significant increase in the G>T transversions. It is well known that methylated CpG dinucleotides are the preferred sites for G > T transversions and we are investigating the role played by DNA methylation alterations. All somatic variants were annotated using an in-house software package based on Sequence Ontology classification of variant effects to integrate different types of variations and provide a functional interpretation. Our analysis has identified 290 genes that are functionally impacted in 4 or more genomes by any type of mutation. They include 6 known oncogenes, 10 protein kinases, 9 cell differentiation markers, 17 transcription factors and 6 cytokines and growth factors. Functional enrichment analysis on this gene set using MSigDB v3.0 database shows important cancer-related pathways including the NK cells pathway, the Adherens junctions interactions pathway, and the axon guidance signaling pathway. Citation Format: Carson Holt, Fouad Yousif, Lee Timms, Michelle Sam, Kimberly Begley, Thomas Hudson, John D. McPherson, Lincoln D. Stein, Lakshmi B. Muthuswamy, Christina Yung, Tim Beck, Bojan Losic, Niloofar Arshadi, Christine Ouelltt, Irinia Kalatskaya, Richard de Borja, Robert Denroche. Whole-genome mutation landscape in pancreatic ductal adenocarcinoma. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Progress and Challenges; Jun 18-21, 2012; Lake Tahoe, NV. Philadelphia (PA): AACR; Cancer Res 2012;72(12 Suppl):Abstract nr B13.
Published: 2012
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17. Elevated coding mutation rate during the reprogramming of human somatic cells into induced pluripotent stem cells

Author: Quang M. Trinh, Vivek Sharma, Siemon Ng, Junfeng Ji, Samer M.I. Hussein, Andras Nagy, Dante Neculai, George M. Church, John Douglas Mcpherson, Michelle Sam, and Nizar N. Batada
Subjects: Genome instability, Mutation rate, Somatic cell, DNA Mutational Analysis, Genetic Vectors, Induced Pluripotent Stem Cells, Kruppel-Like Transcription Factors, Biology, medicine.disease_cause, Proto-Oncogene Proteins c-myc, Kruppel-Like Factor 4, Open Reading Frames, medicine, Humans, Point Mutation, Induced pluripotent stem cell, Cells, Cultured, Mutation, Point mutation, SOXB1 Transcription Factors, Cell Biology, Cell Dedifferentiation, Fibroblasts, Recombinant Proteins, Retroviridae, Mutagenesis, Cancer research, Molecular Medicine, Stem cell, Reprogramming, Octamer Transcription Factor-3, Developmental Biology
Abstract: Mutations in human induced pluripotent stem cells (iPSCs) pose a risk for their clinical use due to preferential reprogramming of mutated founder cell and selection of mutations during maintenance of iPSCs in cell culture. It is unknown, however, if mutations in iPSCs are due to stress associated with oncogene expression during reprogramming. We performed whole exome sequencing of human foreskin fibroblasts and their derived iPSCs at two different passages. We found that in vitro passaging contributed 7% to the iPSC coding point mutation load, and ultradeep amplicon sequencing revealed that 19% of the mutations preexist as rare mutations in the parental fibroblasts suggesting that the remaining 74% of the mutations were acquired during cellular reprogramming. Simulation suggests that the mutation intensity during reprogramming is ninefold higher than the background mutation rate in culture. Thus the factor induced reprogramming stress contributes to a significant proportion of the mutation load of iPSCs.
Published: 2011

18. Effect of Perindopril on Atrial Fibrillation Recurrence and Burden: Results of the Canadian Trial of Atrial Fibrillation (CTAF)-2

Author: Lena Rivard, MD, MSc, Michelle Samuel, MPH, PhD, Annik Fortier, MSc, Marie-Claude Guertin, PhD, Paul Khairy, MD, PhD, Denis Roy, MD, Mario Talajic, MD, and Jean-Claude Tardif, MD
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Hypertension is a risk factor for the development and exacerbation of atrial fibrillation (AF). Angiotensin-converting enzyme inhibitors are a standard-of-care treatment option for patients with hypertension; however, there is conflicting evidence about their effects on AF recurrence. Therefore, our objective was to assess the efficacy of perindopril, compared with placebo, to reduce AF recurrence in patients with hypertension and AF. Methods: In a multicenter, double-blind, placebo-controlled trial, patients with hypertension and symptomatic AF were randomly assigned (1:1) to perindopril or placebo based on a stratification factor of antiarrhythmic drug use. Patients with terminated AF were followed up from 30 days after randomization to 7 to 13 months. The primary endpoint was AF recurrence. Secondary endpoints included AF hospitalization, cardioversion, and blood pressure control. Recurrent events, AF burden, and safety endpoints were also investigated. Results: A total of 315 patients were randomly assigned, and 301 patients were included in the modified intent-to-treat analysis (155 vs 146 patients in the perindopril and placebo groups, respectively). The mean follow-up was 336 ± 70 days, and 91.1% of patients were compliant to the treatment medication throughout the study. After adjustment for baseline antiarrhythmic drugs, there was no statistically significant difference in the hazards of AF recurrence (hazard ratio, 1.22; 95% confidence interval, 0.92-1.61), with similar blood pressure. The incidence of secondary endpoints and adverse events also did not differ between treatment arms. Conclusions: Perindopril does not reduce recurrence or the number of AF episodes in patients with hypertension and AF. RÉSUMÉ: Introduction: L'hypertension est un facteur de risque de l'apparition et de l'exacerbation de la fibrillation auriculaire (FA). Les inhibiteurs de l'enzyme de conversion de l'angiotensine représentent une option de traitement qui répond à la norme de soins à prescrire aux patients hypertendus. Toutefois, les données probantes concernant leurs répercussions sur la récurrence de la FA sont contradictoires. Par conséquent, notre objectif était de comparer l'efficacité du périndopril au placebo dans la réduction de la récurrence de la FA chez les patients hypertendus atteints de FA. Méthodes: Dans un essai multicentrique en double aveugle contre placebo, nous avons réparti de façon aléatoire (1:1) les patients hypertendus atteints de FA symptomatique au périndopril ou au placebo en fonction d'un facteur de stratification de l'utilisation de médicaments antiarythmiques. Nous avons suivi les patients, dont la FA a cessé, du 30e jour après la répartition aléatoire jusqu'au 7e au 13e mois. Le critère d’évaluation principal était la récurrence de la FA. Les critères secondaires étaient les suivants : l'hospitalisation en raison de la FA, la cardioversion et la maîtrise de la pression artérielle. Nous avons aussi examiné les critères suivants : événements récurrents, fardeau de la FA et innocuité. Résultats: Parmi les 315 patients répartis de façon aléatoire, nous avons sélectionné 301 patients pour l'analyse en intention de traiter modifiée (155 vs 146 patients, et ce respectivement, dans le groupe du périndopril et le groupe du placebo). Le suivi moyen a été de 336 ± 70 jours, et 91,1 % de patients ont suivi fidèlement le traitement médicamenteux durant toute la durée de l’étude. Après l'ajustement initial des médicaments antiarythmiques, il n'y a eu aucune différence significative sur le plan statistique dans les risques de récurrence de la FA (ratio d'incidence approché 1,22 [intervalle de confiance à 95 %, 0,92-1,61]) en présence d'une pression artérielle similaire. La fréquence des critères secondaires et des événements indésirables n'a également pas différé entre les bras de traitement. Conclusions: Le périndopril ne contribue pas à la réduction de la récurrence ou du nombre d’épisodes de FA chez les patients hypertendus atteints de FA.
Published: 2021
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19. Abstract 2966: The mutational landscape of localized gleason 6 and 7 prostate cancer

Author: Alice Meng, Xuemei Luo, Robert G. Bristow, Dominique Trudel, Lee Timms, Yves Fradet, Colin Collins, Shaylan K. Govind, Clement Fung, Francis Nguyen, Paul C. Boutros, Hélène Hovington, Alejandro Berlin, Junyan Zhang, Stephenie D. Prokopec, Michael Fraser, Haiying Kong, Louis Lacombe, Ada Wong, Vincent Huang, Julie Livingstone, Christopher I Cooper, Andre P. Masella, Michelle Sam, Taryne Chong, Veronica Y. Sabelnykova, Kathleen E. Houlahan, John Douglas Mcpherson, Nicholas J. Harding, Takafumi N. Yamaguchi, Michèle Orain, Lawrence E. Heisler, Nicholas Buchner, Jeremy Johns, Natalie S. Fox, Alister D'Costa, Fouad Yousif, Xihui Lin, Richard de Borja, Bryan Lo, Christine P'ng, Kenneth C. Chu, Emilie Lalonde, Theodorus H. van der Kwast, Timothy E. Beck, Thomas J. Hudson, Michael Xie, Robert E. Denroche, Bernard Têtu, and Valérie Picard
Subjects: Oncology, Genetics, Cancer Research, medicine.medical_specialty, Chromothripsis, business.industry, medicine.disease, Prostate cancer, Prostate tumours, medicine.anatomical_structure, Prostate, Kataegis, Localized disease, Internal medicine, medicine, business
Abstract: Prostate cancer (CaP) remains the most common male malignancy worldwide, leading to over 300,000 deaths per year. In Western countries, most prostate tumours are diagnosed while they are confined to the prostate and have relatively indolent histology, as assessed by the Gleason Score (GS). CaP is a C-class tumour, characterized by large number of driver copy-number aberrations and genomic rearrangements. Therefore, while previous sequencing studies have focused largely on the coding regions of late-stage disease, herein we comprehensively characterized the copy-number profiles of 250 localized prostate cancers and analyzed the whole genomes of 124 matched tumour/normal pairs derived from patients with GS6 and GS7 prostate cancer. Using this – the largest whole-genome sequencing dataset of prostate cancer to date – we confirm the C-class character of the disease and identify strong genomic subtypes that stretch across multiple types of somatic alteration, including SNVs, CNAs and genomic rearrangements. We provide the first assessments of localized hyper-mutation phenomena (chromothripsis and kataegis) in prostate cancer, and identify specific genes driving higher levels of these hyper-mutations. We identify unexpected biases in the location and role of both non-coding SNVs and genomic rearrangements, including clear association with epigenetic processes, and with genome-wide profiling of methylation in 92 samples. Finally, we demonstrate a stark paucity of clinically-actionable mutations in localized GS6 and GS7 disease, even lacking those common in high-risk localized disease, indicating that novel therapeutic development against the recurrent targets identified here will be key to allowing less-aggressive, targeted treatment of early-stage disease. Citation Format: Michael E. Fraser, Veronica Y. Sabelnykova, Takafumi N. Yamaguchi, Alice Meng, Lawrence E. Heisler, Junyan Zhang, Julie Livingstone, Vincent Huang, Andre P. Masella, Fouad Yousif, Michael Xie, Nicholas J. Harding, Xihui Lin, Haiying Kong, Stephenie D. Prokopec, Alejandro Berlin, Dominique Trudel, Xuemei Luo, Timothy E. Beck, Richard de Borja, Alister D'Costa, Robert E. Denroche, Natalie S. Fox, Emilie Lalonde, Ada Wong, Taryne Chong, Michelle Sam, Jeremy Johns, Lee Timms, Nicholas Buchner, Michele Orain, Valerie Picard, Helene Hovington, Kenneth C. Chu, Christine P'ng, Bryan Lo, Francis Nguyen, Kathleen E. Houlahan, Christopher Cooper, Shaylan K. Govind, Clement Fung, Louis Lacombe, Colin C. Collins, Yves Fradet, Bernard Tetu, Theodorus van der Kwast, John McPherson, Thomas J. Hudson, Rob G. Bristow, Paul Boutros. The mutational landscape of localized gleason 6 and 7 prostate cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2966. doi:10.1158/1538-7445.AM2015-2966
Published: 2015
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20. Population-Level Sex Differences and Predictors for Treatment With Catheter Ablation in Patients With Atrial Fibrillation and Heart Failure

Author: Michelle Samuel, MPH, PhD, Michal Abrahamowicz, PhD, Jacqueline Joza, MD, Vidal Essebag, MD, PhD, and Louise Pilote, MD, MPH, PhD
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Current guidelines are relatively general regarding the type of patient with heart failure (HF) who should be considered for catheter ablation (CA) of atrial fibrillation (AF). The aim of the present study was to identify clinical predictors and sex differences for treatment with CA in the AF-HF population. Methods: A population-based AF-HF cohort was created using the Quebec administrative data (2000-2017). Patients were followed from the date of diagnosis of both diseases to the date of CA or death. Predictors for CA, represented by time-varying covariates, were assessed in a multivariable Cox model that accounted for the competing risk of death. Results: Among 101,931 patients with AF-HF with medication information (median age, 80.7 years; interquartile range [IQR], 73.9-86.3; 51.4% were female, median CHA2DS2-VASc, 4; IQR, 3-4), only 432 (0.4%) underwent CA after a median of 0.8 years (IQR, 0.1-2.7). Independent of multiple comorbidities and advanced age, which were associated with a lower likelihood of CA, women were approximately half as likely to undergo a CA (26% were women; adjusted hazard ratio, 0.6; 95% confidence interval, 0.4-0.7). Prior use of direct-acting oral anticoagulants and antiarrhythmics, and the presence of an implantable cardioverter-defibrillator were also predictors for CA treatment (P < 0.05 for all). Conclusion: In a real-world population, CA was infrequently used to treat AF among patients with HF, and the likelihood of CA was further reduced in women. Because patients with CA had few comorbidities, future studies need to be conducted to determine whether CA can be beneficial in subjects whose clinical characteristics are more representative of the AF-HF population. Résumé: Contexte: Les lignes directrices actuelles abordent de façon relativement générale les cas d’insuffisance cardiaque (IC) où les patients devraient être considérés comme des candidats à l’ablation par cathéter (AC) pour le traitement de la fibrillation auriculaire (FA). La présente étude visait à cerner les prédicteurs cliniques et les différences entre les sexes dans le contexte de l’AC au sein de la population atteinte de FA et d’IC. Méthodologie: Une cohorte populationnelle de patients atteints de FA et d’IC a été constituée à partir de données administratives du Québec (2000-2017). Le suivi des patients allait de la date du diagnostic des deux affections à la date de l’AC ou du décès. Les prédicteurs d’AC, représentés par des covariables temporalisées, ont été évalués dans un modèle de Cox multivarié tenant compte du risque concurrent de décès. Résultats: Sur 101 931 patients atteints de FA et d’IC dont la médication était documentée (âge médian : 80,7 ans; intervalle interquartile [IIQ] : 73,9-86,3; proportion de patients de sexe féminin : 51,4 %; score CHA2DS2-VASc médian : 4; IIQ : 3-4), seulement 432 (0,4 %) ont subi une AC au bout d’un laps de temps médian de 0,8 an (IIQ : 0,1-2,7). Indépendamment des maladies concomitantes multiples et de l’âge avancé, associés à une moindre probabilité d’AC, les femmes étaient environ deux fois moins susceptibles de subir une AC (proportion de patients de sexe féminin : 26 %; rapport des risques instantanés corrigé : 0,6; intervalle de confiance à 95 % : de 0,4 à 0,7). Les antécédents de traitement par des anticoagulants oraux à action directe et des antiarythmiques, ainsi que la présence d’un défibrillateur cardioverteur implantable étaient également des prédicteurs d’AC (p < 0,05 dans tous les cas). Conclusion: Au sein d’une population en contexte réel, l’AC a été rarement pratiquée pour traiter la FA chez des patients atteints d’IC. En outre, la probabilité d’une AC était moindre chez les femmes. Étant donné que les patients ayant subi une AC présentaient peu de maladies concomitantes, d’autres études devront être menées pour déterminer si l’AC peut être salutaire chez les personnes présentant des caractéristiques cliniques plus représentatives de la population atteinte de FA et d’IC.
Published: 2020
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21. Abstract B129: Clinical implications of inter- and intra- prostatic heterogeneity

Author: Lee Timms, Nicholas Buchner, Dominique Trudel, Sohrab P. Shah, Thomas J. Hudson, Richard de Borja, Jianxin Wang, Amin Zia, Cenk Sahinalp, Natalie S. Fox, Paul C. Boutros, Alice Meng, Pablo H. Hennings-Yeomans, Andrew McPherson, Taryne Chong, Timothy Beck, Emilie Lalonde, Robert G. Bristow, Michael Fraser, John Douglas Mcpherson, Nicholas J. Harding, Theodorus van der Kwast, Michelle Sam, and Jeremy Johns
Subjects: Genetics, Oncology, Biochemical recurrence, Cancer Research, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Genetic heterogeneity, Disease, medicine.disease, Prostate cancer, medicine.anatomical_structure, Prostate, Internal medicine, Biopsy, medicine, SNP, Personalized medicine, business
Abstract: Men with localized prostate cancer vary widely in clinical outcome, with a 30-50% failure rate after primary treatment. There is thus significant interest in developing genomically refined prognostic groups. We sought to evaluate the extent of genetic heterogeneity, both between patients (inter-prostate) and within individual prostate glands (intra-prostate) to assess the impact of genetic heterogeneity on risk stratification within a tight clinical cohort. Copy number aberrations (CNAs) from 75 Gleason 7 patients were determined by OncoScan SNP microarrays. We measure the percentage of genome involved in a CNA, termed percent genome aberration (PGA), a proxy for genomic instability. Additionally, whole genome sequencing was applied to 10 intermediate-risk prostate tumours and matched blood, including multiple manually macro-dissected regions from 5 of the prostates (range 2 to 9). Somatic single nucleotide variants (SNVs) and genomic rearrangements (GR) were extracted from each patient. We find a high degree of inter-prostatic heterogeneity between the 75 Gleason 7 patients, with the number of CNAs per patient ranging from 0 to 929, corresponding to PGA 0 to 16.7%. Known prognostic markers can differentiate between patients at higher risk for biochemical recurrence, but only account for a fraction of the cohort. Notably, when these prognostic genes are examined within multiple regions of five independent tumours, they differ in copy number between cancerous regions of the same prostate. For example, TP53 is deleted in 1/2, 1/3, 4/9, 0/4, and 4/5 prostate regions. Indeed, phylogenetic analysis of geographically distinct regions revealed multi-clonal disease in two of the five patients; separate analyses based on SNVs, CNAs, and GRs all concluded that these patient have two genetically distinct cancers within their prostate. We demonstrate dramatic levels of inter- and intra- prostate genetic heterogeneity within pathologically identical or similar cancers. The observed intra-prostatic genomic heterogeneity, both in terms of multi-focal and multi-clonal disease, has critical implications for clinical management. Prognostic information obtained by biopsy may be inconsistent depending on the site of biopsy, and applying personalized medicine to prostate cancer will be challenging. This study highlights the need for further evaluation of how intra-prostatic heterogeneity is related to patient prognosis. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B129. Citation Format: Emilie Lalonde, Paul C. Boutros, Michael Fraser, Richard de Borja, Nicholas J. Harding, Dominique Trudel, Alice Meng, Pablo H. Hennings-Yeomans, Andrew McPherson, Amin Zia, Jianxin Wang, Timothy Beck, Natalie S. Fox, Taryne Chong, Michelle Sam, Jeremy Johns, Lee Timms, Nicholas Buchner, Sohrab Shah, Cenk Sahinalp, Thomas J. Hudson, John D. McPherson, Theodorus van der Kwast, Robert G. Bristow. Clinical implications of inter- and intra- prostatic heterogeneity. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B129.
Published: 2013
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22. Abstract 2003: A molecular portrait of potentially curable prostate cancer

Author: Michelle Chan-Seng-Yue, Amin Zia, Francis Nguyen, Thomas J. Hudson, Gaetano Zafarana, Natalie S. Fox, Fouad Yousif, Lee Timms, Hanbert Chen, Paul C. Boutros, Shaylan K. Govind, Maud H.W. Starmans, Lincoln Stein, Melania Pintilie, Michael Fraser, Rob Denroche, Theodorus van der Kwast, Stanislav Volik, Jeremy Johns, Andrew M.K. Brown, Nicholas J. Harding, Colin Collins, Alice Meng, Ada Wong, Pablo H. Hennings-Yeomans, Nicholas Buchner, Timothy Beck, Michelle Sam, Emilie Lalonde, Taryne Chong, Lakshmi Muthuswamy, Neil Fleshner, John Douglas Mcpherson, Richard de Borja, Jianxin Wang, Dominique Trudel, and Robert G. Bristow
Subjects: Oncology, Cancer Research, medicine.medical_specialty, Pathology, business.industry, Prostatectomy, Genetic heterogeneity, medicine.medical_treatment, Concordance, Cancer, medicine.disease, Prostate cancer, genomic DNA, Internal medicine, medicine, Personalized medicine, business, SNP array
Abstract: Intermediate risk prostate cancer (CaP) with Gleason score (GS) of 7 show up to 100x variability in genetic instability. As CaP is multifocal and likely multiclonal, there is a need to characterize heterogeneity for patient stratification, which would increase the ability to act on genomic information by adding adjuvant therapies to offset systemic occult metastases that currently limit cure in ∼30% of patients. Individual genetic portraits could be used to improve cure on combined clinical-molecular staging criteria. We undertook a pilot study to assess the genetic heterogeneity of potentially curable GS=7 CaP. We selected 10 men with GS=7 CaP; 5 treated with external beam radiotherapy (frozen pre-treatment biopsies) and 5 treated with radical prostatectomy (RadP, frozen tumour). Additionally, DNA from 18 distinct formalin-fixed, paraffin-embedded (FFPE) foci from the 5 RadP were analysed. Each of these 28 foci were subjected to whole-genome sequencing (WGS) and OncoScan SNP arrays to yield comprehensive genetic profiles. mRNA expression was evaluated on frozen RadP by microarray. Germline DNA from whole-blood was also analysed. Following independent pathology reviews and manual macro-dissection of tumour areas of ≥70% cellularity, WGS (≥50x tumour, ≥30x germline) was performed on as little as 50 ng genomic DNA, and OncoScan arrays were performed using as little as 30ng DNA using either amplified or innate genomic DNA. Regions of CaP in FFPE RadP were recorded using a tissue map to identify independent malignant foci, and ERG immunostaining was performed to assist in the identification. In cases where ERG-positive and -negative foci were adjacent, ERG staining was repeated on an un-stained slide to confirm separate foci based on 3D multi-section analyses. ERG fusion status was also assessed in frozen samples by aCGH or IHC. Validation of SNVs via SNP array and deep-resequencing showed ∼99% accuracy. Tumour cellularity was estimated using Qpure and was >60% for all samples. Phylogenetic techniques were used to demonstrate clear multi-clonality in two tumours. Across all tumours, ∼50% of SNVs were specific to an individual tumour-region. Phylogenies were confirmed with both SNVs and CNAs, but CNAs generally exhibited greater concordance amongst different regions of the same tumour. Some previously observed recurrent mutations were previously identified as recurrent in CaP (e.g. SPOP), and the overall mutation rate for intermediate-risk CaP was only somewhat below that reported for castrate-resistant disease (11,230 somatic SNVs per tumour). Our studies support the concept that a complete characterization of inter- and intra-CaP heterogeneity is possible in fresh and archival tissues; the latter is important for correlations to clinical outcome. These approaches can then be streamlined for high-throughput analyses within personalized medicine laboratories leading to “point of care” molecular tests and individualization of therapy. Citation Format: Michael E. Fraser, Richard de Borja, Dominique Trudel, Nicholas J. Harding, Pablo H. Hennings-Yeomans, Alice Meng, Emilie R. Lalonde, Andrew Brown, Natalie S. Fox, Taryne Chong, Amin Zia, Michelle Sam, Jianxin Wang, Michelle A. Chan-Seng-Yue, Jeremy Johns, Lee Timms, Nicholas Buchner, Ada Wong, Fouad Yousif, Rob Denroche, Gaetano Zafarana, Maud HW Starmans, Hanbert Chen, Shaylan Govind, Francis Nguyen, Melania Pintilie, Neil Fleshner, Stanislav Volik, Lakshmi Muthuswamy, Colin C. Collins, Thomas J. Hudson, Lincoln D. Stein, Timothy Beck, John D. McPherson, Theodorus van der Kwast, Paul C. Boutros, Rob G. Bristow. A molecular portrait of potentially curable prostate cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2003. doi:10.1158/1538-7445.AM2013-2003
Published: 2013
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23. Abstract 3184: Whole genome sequencing of low-input fresh frozen prostate cancer biopsies

Author: Lee Timms, Maud H.W. Starmans, John Douglas Mcpherson, Michelle Chan-Seng-Yue, Amin Zia, Timothy Beck, Lakshmi Muthuswamy, Michelle Sam, Theodorus van der Kwast, Alice Meng, Pablo H. Hennings-Yeomans, Jeremy Johns, Neil Fleshner, Emilie Lalonde, Robert G. Bristow, Lincoln Stein, Thomas J. Hudson, Fouad Yousif, Rob Denroche, Richard de Borja, Jianxin Wang, Melania Pintilie, Gaetano Zafarana, Michael Fraser, Colin Collins, Paul C. Boutros, and Taryne Chong
Subjects: Whole genome sequencing, Oncology, Cancer Research, medicine.medical_specialty, medicine.diagnostic_test, business.industry, Cancer, Bioinformatics, medicine.disease, Malignancy, Genome, Prostate cancer, medicine.anatomical_structure, Prostate, Internal medicine, Biopsy, Medicine, business, Genotyping
Abstract: Prostate cancer is the most commonly diagnosed malignancy among men in the United States. Due to an aging population, prostate cancer incidence has been increasing, with an estimated 200,000 men being diagnosed in 2010 and more than 32,000 deaths resulting from this disease. Better predictors of patient prognosis and treatment outcome are required to individualize prostate cancer treatment. High-throughput genomic sequence-based approaches offer a unique opportunity to identify biomarkers of disease-progression, thereby enabling more individualized therapy. The Canadian Prostate Cancer Genome Network (CPC-GENE) is an outcomes-based initiative that will sequence 500 specimens from 350 prostate cancer patients over a 5-year time span. Previously, whole genome sequencing efforts from biopsy specimens have been hindered by insufficient quantities of extracted DNA required as input for sequencing library construction. As a proof of concept to demonstrate the ability to sequence low input amounts of DNA from prostate biopsies, whole genome sequencing has been initiated for 50 prostate tumor biopsy samples along with their matched blood-derived reference sample. An on-bead sample preparation protocol was optimized using decreasing quantities of input DNA and used to construct sequencing libraries from as low as 100ng of DNA derived from macrodissected fresh frozen prostate biopsies (>70% cellularity). Sequencing is performed on the Illumina HiSeq 2000 platform to generate coverage depths of 50x for tumor samples and 30x for reference samples. Following alignment using NovoAlign and variant-calling using GATK, we compared our results to genotyping-array results generated using the Affymetrix OncoScan platform. Single-nucleotide variants detected using arrays were validated >99% of the time by sequence data, confirming that the use of a low-input library did not hinder mutation detection. Sequencing does not exhibit significant genome-wide coverage biases, and CNV calls were compared between the genotyping arrays and the next-generation sequencing data. Outcomes from the sequencing and analysis of the initial 50 sample sets will similarly be applied over a 5-year period to characterize an additional 450 prostate specimens. The ability to whole genome sequence specimens where minimal amounts of extracted DNA exist presents new opportunities to sequence many samples previously deemed unusable, while also providing encouraging prospects for whole genome sequencing applications for future studies using biopsy specimens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3184. doi:1538-7445.AM2012-3184
Published: 2012
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24. Incidence and Predictors of Intracardiac Thrombus on Pre-electrophysiological Procedure Transesophageal Echocardiography

Author: Mohamed Al Rawahi, MD, Michelle Samuel, MPH, Christos Galatas, MD, Jacqueline Joza, MD, Pedro Y. Lima, MD, Rodrigo Barbosa, MD, George Thanassoulis, MD, Martin L. Bernier, MD, Thao Huynh, MD, PhD, and Vidal Essebag, MD, PhD
Subjects: Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Background: Cerebral thromboembolism is a potentially devastating complication of atrial fibrillation (AF) and atrial flutter (AFl). The use of transesophageal echocardiogram (TEE) before electrophysiological procedures in anticoagulated patients is variable. Our objective was to determine the incidence and identify predictors of intracardiac left atrial appendage (LAA) thrombus on TEE in patients with AF/AFl before electrical cardioversion or ablation. Methods: We reviewed TEEs of 401 patients undergoing an electrical cardioversion, AF, or AFl ablation from April 2013 to September 2015 at the McGill University Health Center. Clinical and echocardiographic variables were collected at the time of the TEE and follow-up visits. Multivariate logistic regression was used to determine predictors of LAA thrombus. Results: Of 401 patients, 11.2% had LAA thrombus on TEE. The majority (87%) of patients were anticoagulated for at least 3 weeks before the TEE. The incidence of LAA thrombus was 21% (23/110) in patients taking warfarin vs 6.4% (15/236) in patients taking direct oral anticoagulants. Multivariate analysis identified prior stroke (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.1-6.9) and heart failure (OR, 2.2; 95% CI, 1.0-4.7) as predictors of thrombus, whereas direct oral anticoagulant use (OR, 0.4; 95% CI, 0.2-0.8) was associated with reduced odds of thrombus. Conclusions: LAA thrombus was identified in a significant proportion of patients undergoing TEE before cardioversion or ablation of AF/AFl despite preprocedural anticoagulation. Patients at increased risk of LAA thrombus (heart failure and prior stroke) may benefit from TEE before cardioversion, AF, or AFl ablation. Résumé: Introduction: La thromboembolie cérébrale est une complication potentiellement dévastatrice de la fibrillation auriculaire (FA) et du flutter auriculaire. L’utilisation de l’échocardiographie transœsophagienne (ETO) avant les interventions en électrophysiologie chez les patients anticoagulés est variable. Notre objectif était de déterminer la fréquence et les prédicteurs des thrombi intracardiaques dans l’appendice auriculaire gauche (AAG) à l’ETO chez les patients atteints de FA ou de flutter auriculaire avant de procéder à une cardioversion électrique ou à une ablation. Méthodes: Nous avons passé en revue les ETO de 401 patients qui avaient subi une cardioversion électrique, ou une ablation de la FA ou du flutter auriculaire entre avril 2013 et septembre 2015 au Centre universitaire de santé McGill. Nous avons recueilli les variables cliniques et échocardiographiques au moment de l’ETO et des visites de suivi. Nous avons utilisé la régression logistique multivariée pour déterminer les prédicteurs de thrombus dans l’AAG. Résultats: Parmi les 401 patients, 11,2 % avaient un thrombus dans l’AAG à l’ETO. La majorité (87 %) des patients étaient anticoagulés au moins 3 semaines avant l’ETO. La fréquence des thrombus dans l’AAG était de 21 % (23/110) chez les patients qui prenaient de la warfarine vs 6,4 % (15/236) chez les patients qui prenaient des anticoagulants oraux directs. L’analyse multivariée a permis d’établir que l’accident vasculaire cérébral (AVC) antérieur (ratio d’incidence approché [RIA], 2,7; intervalle de confiance [IC] à 95 %, 1,1-6,9) et l’insuffisance cardiaque (RIA, 2,2; IC à 95 %, 1,0-4,7) étaient des prédicteurs de thrombus, alors que l’utilisation d’anticoagulants oraux directs (RIA, 0,4; IC à 95 %, 0,2-0,8) était associée une probabilité moindre de thrombus. Conclusions: Une proportion importante de patients qui avaient subi l’ETO avant la cardioversion, ou l’ablation de la FA ou du flutter auriculaire avaient un thrombus dans l’AAG en dépit de l’anticoagulation avant l’intervention. Les patients exposés à un risque accru de thrombus dans l’AAG (insuffisance cardiaque et AVC antérieur) peuvent bénéficier de l’ETO avant la cardioversion, ou l’ablation de la FA ou du flutter auriculaire.
Published: 2019
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25. Cannabis sativa CBD Extract Exhibits Synergy with Broad-Spectrum Antibiotics against Salmonella enterica subsp. Enterica serovar typhimurium

Author: Logan Gildea, Joseph Atia Ayariga, Junhuan Xu, Robert Villafane, Boakai K. Robertson, Michelle Samuel-Foo, and Olufemi S. Ajayi
Subjects: Salmonella, novel antibacterial agents, cannabidiol, co-therapy, cell-membrane integrity, Biology (General), QH301-705.5
Abstract: New generation antibiotics are needed to combat the development of resistance to antimicrobials. One of the most promising new classes of antibiotics is cannabidiol (CBD). It is a non-toxic and low-resistance chemical that can be used to treat bacterial infections. The antibacterial activity of Cannabis sativa L. byproducts, specifically CBD, has been of growing interest in the field of novel therapeutics. As research continues to define and characterize the antibacterial activity that CBD possesses against a wide variety of bacterial species, it is important to examine potential interactions between CBD and common therapeutics such as broad-spectrum antibiotics. In this study it is demonstrated that CBD-antibiotic (combination of CBD and antibiotic) co-therapy can effectively fight Salmonella typhimurium (S. typhimurium) via membrane integrity disruption. This research serves to examine the potential synergy between CBD and three broad-spectrum antibiotics (ampicillin, kanamycin, and polymyxin B) for potential CBD-antibiotic co-therapy. In this study, it is revealed that S. typhimurium growth is inhibited at very low dosages of CBD-antibiotic. This interesting finding demonstrates that CBD and CBD-antibiotic co-therapies are viable novel alternatives to combating S. typhimurium.
Published: 2022
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26. Evaluation of propensity score used in cardiovascular research: a cross-sectional survey and guidance document

Author: Joanne Kim, Robert W Platt, James M Brophy, Michelle Samuel, Brice Batomen, Julie Rouette, and Jay S Kaufman
Subjects: Medicine
Abstract: Background Propensity score (PS) methods are frequently used in cardiovascular clinical research. Previous evaluations revealed poor reporting of PS methods, however a comprehensive and current evaluation of PS use and reporting is lacking. The objectives of the present survey were to (1) evaluate the quality of PS methods in cardiovascular publications, (2) summarise PS methods and (3) propose key reporting elements for PS publications.Methods A PubMed search for cardiovascular PS articles published between 2010 and 2017 in high-impact general medical (top five by impact factor) and cardiovascular (top three by impact factor) journals was performed. Articles were evaluated for the reporting of PS techniques and methods. Data extraction elements were identified from the PS literature and extraction forms were pilot tested.Results Of the 306 PS articles identified, most were published in Journal of the American College of Cardiology (29%; n=88), and Circulation (27%, n=81), followed by European Heart Journal (15%; n=47). PS matching was performed most often, followed by direct adjustment, inverse probability of treatment weighting and stratification. Most studies (77%; n=193) selected variables to include in the PS model a priori. A total of 38% (n=116) of studies did not report standardised mean differences, but instead relied on hypothesis testing. For matching, 92% (n=193) of articles presented the balance of covariates. Overall, interpretations of the effect estimates corresponded to the PS method conducted or described in 49% (n=150) of the reviewed articles.Discussion Although PS methods are frequently used in high-impact medical journals, reporting of methodological details has been inconsistent. Improved reporting of PS results is warranted and these proposals should aid both researchers and consumers in the presentation and interpretation of PS methods.
Published: 2020
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27. Cannabis sativa CBD Extract Shows Promising Antibacterial Activity against Salmonella typhimurium and S. newington

Author: Logan Gildea, Joseph Atia Ayariga, Olufemi S. Ajayi, Junhuan Xu, Robert Villafane, and Michelle Samuel-Foo
Subjects: Salmonella, novel antibacterial agents, membrane disruption, cannabidiol, Organic chemistry, QD241-441
Abstract: Products derived from Cannabis sativa L. have gained increased interest and popularity. As these products become common amongst the public, the health and potential therapeutic values associated with hemp have become a premier focus of research. While the psychoactive and medicinal properties of Cannabis products have been extensively highlighted in the literature, the antibacterial properties of cannabidiol (CBD) have not been explored in depth. This research serves to examine the antibacterial potential of CBD against Salmonella newington and S. typhimurium. In this study, we observed bacterial response to CBD exposure through biological assays, bacterial kinetics, and fluorescence microscopy. Additionally, comparative studies between CBD and ampicillin were conducted against S. typhimurium and S. newington to determine comparative efficacy. Furthermore, we observed potential resistance development of our Salmonella spp. against CBD treatment.
Published: 2022
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28. Hemp Pest Spectrum and Potential Relationship between Helicoverpa zea Infestation and Hemp Production in the United States in the Face of Climate Change

Author: Olufemi S. Ajayi and Michelle Samuel-Foo
Subjects: industrial hemp, Cannabis sativa, climate change, pests, beneficials, corn earworm, Science
Abstract: There has been a resurgence in the cultivation of industrial hemp, Cannabis sativa L., in the United States since its recent legalization. This may facilitate increased populations of arthropods associated with the plant. Hemp pests target highly marketable parts of the plant, such as flowers, stalks, and leaves, which ultimately results in a decline in the quality. Industrial hemp can be used for several purposes including production of fiber, grain, and cannabidiol. Thus, proper management of pests is essential to achieve a substantial yield of hemp in the face of climate change. In this review, we provide updates on various arthropods associated with industrial hemp in the United States and examine the potential impact of climate change on corn earworm (CEW) Helicoverpa zea Boddie, a major hemp pest. For example, temperature and photoperiod affect the development and diapause process in CEW. Additionally, drought can lead to a reduction in hemp growth. Host plant diversity of CEW may prevent populations of the pest from reaching outbreak levels. It is suggested that hemp varieties resistant to drought, high soil salinity, cold, heat, humidity, and common pests and diseases should be selected. Ongoing research on effective management of CEW in hemp is critical.
Published: 2021
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29. Alpha-enolase (ENO1) controls alpha v/beta 3 integrin expression and regulates pancreatic cancer adhesion, invasion, and metastasis

Author: Moitza Principe, Simone Borgoni, Mariafrancesca Cascione, Michelle Samuel Chattaragada, Sammy Ferri-Borgogno, Michela Capello, Sara Bulfamante, Jennifer Chapelle, Francesca Di Modugno, Paola Defilippi, Paola Nisticò, Paola Cappello, Chiara Riganti, Stefano Leporatti, and Francesco Novelli
Subjects: Pancreatic cancer, ENO1, Integrin, Atomic force microscopy, Invasion, Diseases of the blood and blood-forming organs, RC633-647.5, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background We have previously shown that in pancreatic ductal adenocarcinoma (PDA) cells, the glycolytic enzyme alpha-enolase (ENO1) also acts as a plasminogen receptor and promotes invasion and metastasis formation. Moreover, ENO1 silencing in PDA cells induces oxidative stress, senescence and profoundly modifies PDA cell metabolism. Although anti-ENO1 antibody inhibits PDA cell migration and invasion, little is known about the role of ENO1 in regulating cell-cell and cell-matrix contacts. We therefore investigated the effect of ENO1 silencing on the modulation of cell morphology, adhesion to matrix substrates, cell invasiveness, and metastatic ability. Methods The membrane and cytoskeleton modifications that occurred in ENO1-silenced (shENO1) PDA cells were investigated by a combination of confocal microscopy and atomic force microscopy (AFM). The effect of ENO1 silencing was then evaluated by phenotypic and functional experiments to identify the role of ENO1 in adhesion, migration, and invasion, as well as in senescence and apoptosis. The experimental results were then validated in a mouse model. Results We observed a significant increase in the roughness of the cell membrane due to ENO1 silencing, a feature associated with an impaired ability to migrate and invade, along with a significant downregulation of proteins involved in cell-cell and cell-matrix adhesion, including alpha v/beta 3 integrin in shENO1 PDA cells. These changes impaired the ability of shENO1 cells to adhere to Collagen I and IV and Fibronectin and caused an increase in RGD-independent adhesion to vitronectin (VN) via urokinase plasminogen activator receptor (uPAR). Binding of uPAR to VN triggers integrin-mediated signals, which result in ERK1-2 and RAC activation, accumulation of ROS, and senescence. In shENO1 cancer cells, the use of an anti-uPAR antibody caused significant reduction of ROS production and senescence. Overall, a decrease of in vitro and in vivo cell migration and invasion of shENO1 PDA cells was observed. Conclusion These data demonstrate that ENO1 promotes PDA survival, migration, and metastasis through cooperation with integrins and uPAR.
Published: 2017
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30. Influência de diferentes tipos de respiração na resposta cardíaca durante o exercício de força

Author: Fabiana Nascimento Bracarense, Hugo Ribeiro Zanetti, Alexandre Gonçalves, Michelle Samora Almeida, and Leandro Teixeira Paranhos Lopes
Subjects: exercício, manobra de valsalva, pressão arterial, frequência cardíaca, Sports medicine, RC1200-1245
Abstract: Objetivo: Analisar a resposta cardiovascular, usando como parâmetro a frequência cardíaca (FC), pressão arterial sistólica (PAS) e duplo-produto (DP), em três diferentes tipos de respiração, definidos em respiração ativa (RA), respiração passiva (RP) e Manobra de Valsalva (MV). Métodos: Foram recrutados 15 voluntários, com idade entre 18 e 26 anos, todos saudáveis e com experiência mínima de 6 meses com exercícios de força. O protocolo de exercício foi composto por três séries de 12 repetições máximas no aparelho Leg Press 45º. Foi utilizado o teste de Wilcoxon para comparar as variáveis hemodinâmicas, no final de cada série e entre os tipos de respiração. Resultados: Houve diferença significativa de PAS, FC e DP entre o momento pré (repouso) e todas as séries posteriores em todos os tipos de respiração. A MV apresentou maiores valores de PAS, FC e DP quando comparado a outros tipos de respiração em todas as três séries do exercício. Conclusão: A MV acarreta maior sobrecarga cardíaca quando comparado a outros tipos de respiração. ABSTRACT Influence of different types of breathing in cardiac response during resistance exercise Purpose: To analyze the cardiovascular response, using as parameter the heart rate (HR), systolic blood pressure (SBP) and double-product (DP) in three different types of breathing, defined in active breathing (AB), passive breathing (PB) and Valsalva maneuver (VM). Methods: 15 volunteers were recruited, aged 18 and 26, all healthy and with minimum experience of 6 months with strength exercises. The exercise protocol consisted of three sets of 12 repetitions maximum in leg press machine 45. The Wilcoxon test was used to compare the hemodynamic variable at the end of each series and between breath types. Results: There was significant difference in SBP, HR and DP between the time Pre (rest) and all subsequent series in all types of breathing. The MV showed higher SBP, HR and DP compared to other types of breathing in all three series of the year. Conclusion: MV entails greater cardiac overload when compared to other types of breathing.
Published: 2016

31. A serviço da Coroa: Política e administração do vice-rei D. Vasco Mascarenhas na América Portuguesa (1663-1667).

Author: Michelle Samuel Silva
Subjects: Anthropology, GN1-890, Social sciences (General), H1-99
Abstract: O presente artigo visa analisar a administração do vice-rei D. Vasco Mascarenhas, 1º conde de Óbidos, que governou o Estado do Brasil entre 1663 a 1667. A análise pautará especificamente nas capitanias do Rio de Janeiro e de Pernambuco no período posterior à Restauração Bragantina. Pretende-se compreender suas práticas governativas e sua relação política com os governadores dessas capitanias em um momento de ascensão e consolidação da dinastia Bragantina. A atuação do vice-rei D. Vasco Mascarenhas foi fundamental no sentido de aprofundar o controle do governo-geral, que se afrouxara no decurso da guerra holandesa. Os capitães-mores que administravam as capitanias menores passaram a ser diretamente sujeitos ao governo-geral na Bahia.
Published: 2017
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32. The Decisions, Interventions, and Goals in ImplaNtable Cardioverter‐DefIbrillator TherapY (DIGNITY) Pilot Study

Author: Daniel B. Kramer, Daniel Habtemariam, Yaw Adjei‐Poku, Michelle Samuel, Diane Engorn, Matthew R. Reynolds, and Susan L. Mitchell
Subjects: end‐of‐life care, health services research, implantable cardioverter‐defibrillator, outcomes research, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: BackgroundImplantable cardioverter‐defibrillators (ICDs) are commonly implanted in older patients, including those with multiple comorbidities. There are few prospective studies assessing the clinical course and end‐of‐life circumstances for these patients. Methods and ResultsWe prospectively followed 51 patients with ICDs for up to 18 months to longitudinally assess in terms of (1) advance care planning, (2) health status, (3) healthcare utilization, and (4) end‐of‐life circumstances through quarterly phone interviews and electronic medical record review. The mean age was 71.1±8.3, 74.5% were men, and 19.6% were non‐white. Congestive heart failure was predominant (82.4%), as was chronic kidney disease (92%). At baseline, a total of 12% of subjects met criteria for major depression, and 78.4% met criteria for mild cognitive impairment. From this initial study cohort, 76% survived to 18 months and completed all follow‐up interviews, 18% died, and 19% withdrew or were lost to follow‐up. Though living will completion and healthcare proxy assignment were common (cumulative outcome at 18 months 88% and 98%, respectively), discussions of prognosis were uncommon (baseline, 9.8%; by 18 months, 22.7%), as were conversations regarding ICD deactivation (baseline, 15.7%; by 18 months, 25.5%). Five decedents with available data received shocks in the days immediately prior to death, including 3 of whom ultimately had their ICDs deactivated prior to death. ConclusionsWe demonstrated the feasibility of prospective enrollment and follow‐up of older, vulnerable ICD patients. Early findings suggest a high burden of cognitive and psychological impairment, poor communication with providers, and frequent shocks at the end of life. These findings will inform the design of a larger cohort study designed to further explore the experiences of living and dying with an ICD in this important patient population.
Published: 2017
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33. Myasthenia as a paraneoplastic manifestation of ovarian Cancer

Author: Marcelo Simonsen, Marcos Minamoto Miyabe, Helio Toshio Ouki, Antônio Cezar Ribeiro Galvão, Denise Leite, Bárbara Alencar Rolim Murayama, Fabio Martins Laginha, and Michelle Samora
Subjects: Gynecology and obstetrics, RG1-991, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: We describe the first case of myasthenia gravis as a possible paraneoplastic manifestation of ovarian cancer preceding its diagnosis. Keywords: Myasthenia gravis, Ovarian neoplasm, Paraneoplastic disorders, Diagnosis, Treatment
Published: 2018
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34. CAPACITAÇÃO PROFISSIONAL SOBRE PROTOCOLO DE ACOLHIMENTO COM CLASSIFICAÇÃO DE RISCO EM PEDIATRIA

Author: Francisca Elisângela Teixeira Lima, Fernanda Jorge Magalhães, Alline Falconieri de Moura, Ana Paula Oliveira Queiroz, Diliane Paiva de Melo Matos, and Michelle Sampaio Bezerra
Subjects: Nursing, RT1-120
Abstract: El protocolo de acogida con Clasificación de Riesgo en pediatría posibilita la clasificación del niño según su gravedad. El objetivo fue relatar la experiencia de capacitación del equipo multiprofesional para la implementación del protocolo de con Clasificación de Riesgo en pediatría. Relato de experiencia de un curso de capacitación del equipo multiprofesional para la implementación del protocolo en un hospital pediátrico municipal de Fortaleza-Ceará-Brasil. El curso fue dividido en tres etapas expuestas a continuación: 1a) Apertura y Presentación del protocolo; 2a) Actividades de dispersión; y 3a) Discusiones y clausura del curso. Por lo tanto, se cree que la utilización de la estrategia de capacitación de los profesionales para la implementación del protocolo fue satisfactoria, ya que los participantes verbalizaron la comprensión del protocolo y el interés en implementarlo, pues posibilita mejoría en la atención y favorece el cuidado holístico, humanizado y eficaz.
Published: 2012

35. International network of cancer genome projects

Author: Thomas J, Hudson, Warwick, Anderson, Axel, Artez, Anna D, Barker, Cindy, Bell, Rosa R, Bernabé, M K, Bhan, Fabien, Calvo, Iiro, Eerola, Daniela S, Gerhard, Alan, Guttmacher, Mark, Guyer, Fiona M, Hemsley, Jennifer L, Jennings, David, Kerr, Peter, Klatt, Patrik, Kolar, Jun, Kusada, David P, Lane, Frank, Laplace, Lu, Youyong, Gerd, Nettekoven, Brad, Ozenberger, Jane, Peterson, T S, Rao, Jacques, Remacle, Alan J, Schafer, Tatsuhiro, Shibata, Michael R, Stratton, Joseph G, Vockley, Koichi, Watanabe, Huanming, Yang, Matthew M F, Yuen, Bartha M, Knoppers, Martin, Bobrow, Anne, Cambon-Thomsen, Lynn G, Dressler, Stephanie O M, Dyke, Yann, Joly, Kazuto, Kato, Karen L, Kennedy, Pilar, Nicolás, Michael J, Parker, Emmanuelle, Rial-Sebbag, Carlos M, Romeo-Casabona, Kenna M, Shaw, Susan, Wallace, Georgia L, Wiesner, Nikolajs, Zeps, Peter, Lichter, Andrew V, Biankin, Christian, Chabannon, Lynda, Chin, Bruno, Clément, Enrique, de Alava, Françoise, Degos, Martin L, Ferguson, Peter, Geary, D Neil, Hayes, Amber L, Johns, Arek, Kasprzyk, Hidewaki, Nakagawa, Robert, Penny, Miguel A, Piris, Rajiv, Sarin, Aldo, Scarpa, Marc, van de Vijver, P Andrew, Futreal, Hiroyuki, Aburatani, Mónica, Bayés, David D L, Botwell, Peter J, Campbell, Xavier, Estivill, Sean M, Grimmond, Ivo, Gut, Martin, Hirst, Carlos, López-Otín, Partha, Majumder, Marco, Marra, John D, McPherson, Zemin, Ning, Xose S, Puente, Yijun, Ruan, Hendrik G, Stunnenberg, Harold, Swerdlow, Victor E, Velculescu, Richard K, Wilson, Hong H, Xue, Liu, Yang, Paul T, Spellman, Gary D, Bader, Paul C, Boutros, Paul, Flicek, Gad, Getz, Roderic, Guigó, Guangwu, Guo, David, Haussler, Simon, Heath, Tim J, Hubbard, Tao, Jiang, Steven M, Jones, Qibin, Li, Nuria, López-Bigas, Ruibang, Luo, Lakshmi, Muthuswamy, B F Francis, Ouellette, John V, Pearson, Victor, Quesada, Benjamin J, Raphael, Chris, Sander, Terence P, Speed, Lincoln D, Stein, Joshua M, Stuart, Jon W, Teague, Yasushi, Totoki, Tatsuhiko, Tsunoda, Alfonso, Valencia, David A, Wheeler, Honglong, Wu, Shancen, Zhao, Guangyu, Zhou, Mark, Lathrop, Gilles, Thomas, Teruhiko, Yoshida, Myles, Axton, Chris, Gunter, Linda J, Miller, Junjun, Zhang, Syed A, Haider, Jianxin, Wang, Christina K, Yung, Anthony, Cros, Anthony, Cross, Yong, Liang, Saravanamuttu, Gnaneshan, Jonathan, Guberman, Jack, Hsu, Don R C, Chalmers, Karl W, Hasel, Terry S H, Kaan, William W, Lowrance, Tohru, Masui, Laura Lyman, Rodriguez, Catherine, Vergely, David D L, Bowtell, Nicole, Cloonan, Anna, deFazio, James R, Eshleman, Dariush, Etemadmoghadam, Brooke B, Gardiner, Brooke A, Gardiner, James G, Kench, Robert L, Sutherland, Margaret A, Tempero, Nicola J, Waddell, Peter J, Wilson, Steve, Gallinger, Ming-Sound, Tsao, Patricia A, Shaw, Gloria M, Petersen, Debabrata, Mukhopadhyay, Ronald A, DePinho, Sarah, Thayer, Kamran, Shazand, Timothy, Beck, Michelle, Sam, Lee, Timms, Vanessa, Ballin, Youyong, Lu, Jiafu, Ji, Xiuqing, Zhang, Feng, Chen, Xueda, Hu, Qi, Yang, Geng, Tian, Lianhai, Zhang, Xiaofang, Xing, Xianghong, Li, Zhenggang, Zhu, Yingyan, Yu, Jun, Yu, Jörg, Tost, Paul, Brennan, Ivana, Holcatova, David, Zaridze, Alvis, Brazma, Lars, Egevard, Egor, Prokhortchouk, Rosamonde Elizabeth, Banks, Mathias, Uhlén, Juris, Viksna, Fredrik, Ponten, Konstantin, Skryabin, Ewan, Birney, Ake, Borg, Anne-Lise, Børresen-Dale, Carlos, Caldas, John A, Foekens, Sancha, Martin, Jorge S, Reis-Filho, Andrea L, Richardson, Christos, Sotiriou, Giles, Thoms, Laura, van't Veer, Daniel, Birnbaum, Hélène, Blanche, Pascal, Boucher, Sandrine, Boyault, Jocelyne D, Masson-Jacquemier, Iris, Pauporté, Xavier, Pivot, Anne, Vincent-Salomon, Eric, Tabone, Charles, Theillet, Isabelle, Treilleux, Paulette, Bioulac-Sage, Thomas, Decaens, Dominique, Franco, Marta, Gut, Didier, Samuel, Jessica, Zucman-Rossi, Roland, Eils, Benedikt, Brors, Jan O, Korbel, Andrey, Korshunov, Pablo, Landgraf, Hans, Lehrach, Stefan, Pfister, Bernhard, Radlwimmer, Guido, Reifenberger, Michael D, Taylor, Christof, von Kalle, Partha P, Majumder, Paolo, Pederzoli, Rita A, Lawlor, Massimo, Delledonne, Alberto, Bardelli, Thomas, Gress, David, Klimstra, Giuseppe, Zamboni, Yusuke, Nakamura, Satoru, Miyano, Akihiro, Fujimoto, Elias, Campo, Silvia, de Sanjosé, Emili, Montserrat, Marcos, González-Díaz, Pedro, Jares, Heinz, Himmelbauer, Heinz, Himmelbaue, Silvia, Bea, Samuel, Aparicio, Douglas F, Easton, Francis S, Collins, Carolyn C, Compton, Eric S, Lander, Wylie, Burke, Anthony R, Green, Stanley R, Hamilton, Olli P, Kallioniemi, Timothy J, Ley, Edison T, Liu, Brandon J, Wainwright, CCA -Cancer Center Amsterdam, Pathology, Other departments, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universitat de Barcelona, The International Cancer Genome Consortium, and Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
Subjects: Cancer therapy, Carcinogenesis, Genetics, Medical, International Cooperation, Systems biology, DNA Mutational Analysis, education, Genomics, Biology, Genome, Article, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Oncogènesi, Neoplasms, Databases, Genetic, medicine, Cancer genomics, Humans, Càncer, Molecular Biology, Cancer, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, Genome, Human, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, DNA Methylation, medicine.disease, Intellectual Property, Human genetics, 3. Good health, Cancer Genome Project, 030220 oncology & carcinogenesis, Mutation, cancer genome projects, Human genome, Genes, Neoplasm
Abstract: International audience; The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumors from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of over 25,000 cancer genomes at the genomic, epigenomic, and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically-relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
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36. Professional training on of the protocol of reception with risk classification in pediatrics

Author: Francisca Elisângela Teixeira Lima, Fernanda Jorge Magalhães, Alline Falconieri de Moura, Ana Paula Oliveira Queiroz, Diliane Paiva de Melo Matos, and Michelle Sampaio Bezerra
Subjects: Welcoming, humanization of assistance, pediatric nursin, Nursing, RT1-120
Abstract: The protocol of reception with risk evaluation and classification (RREC) in pediatrics enables the classification of children according to severity. The aim of this research was to report the experience of training a multidisciplinary team to implement the protocol RREC in pediatrics. This is an experience report of a training course of the multidisciplinary team to implement the protocol in a municipal pediatric hospital in Fortaleza, Ceará, Brazil. The project was approved by the Ethics Committee under protocol No. 80/09. The course was conducted in three stages: 1st) Opening and Presentation of the Protocol; 2nd) Activities of dispersion, and 3rd) Discussion and closure of the course. Therefore, it is believed that the use of the strategy of management training for implementation of the protocol was satisfactory, since the participants voiced an understanding of the protocol and the need to implement it because it allows for improvement in care and promotes holistic, humanized and effective care.
Published: 2012

37. Disparities in cancer epidemiology and care delivery among Brazilian indigenous populations

Author: Pedro Nazareth Aguiar Jr., Gustavo Trautman Stock, Gilberto de Lima Lopes Jr., Michelle Samora de Almeida, Hakaru Tadokoro, Bárbara de Souza Gutierres, and Douglas Antônio Rodrigues
Subjects: Epidemiology, Public health, Ethnicity and health, Neoplasms, Health services accessibility, Brazil, Medicine
Abstract: ABSTRACT Objective: To assess aspects related to cancer in indigenous population. Methods: This is a retrospective study developed in a public university hospital. We included patients with 18 or more years of age, diagnosed with solid tumors, and followed between 2005 and 2015. Clinical features were assessed by descriptive statistics, and survival was evaluated by Kaplan-Meier curves and multivariate Cox regression. Results: Fifty patients were included. The cancer incidence was 15.73 per 100,000. The mean age at diagnosis was 54 years and most patients were female (58%). Cancer of the cervix (28%) and prostate (16%) were the most common. The mean time between the onset of symptoms and the diagnosis was 9 months and from diagnosis to the treatment was 3.4 months. Disease diagnosed at stage IV (17%) had worse overall survival (HR: 11.4; p
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38. Improving trends estimates for specific work-related ill-health conditions when excess zeros are present in a voluntary health reporting scheme.

Author: Gittins M, Carder M, Seed MJ, Iskandar I, Daniels SAM, and van Tongeren M
Subjects: Humans, Incidence, Models, Statistical, Occupational Diseases epidemiology, Asthma, Dermatitis, Contact
Abstract: Background: Trends in occupational disease incidence are estimated in voluntary reporting schemes such as The Health and Occupational Reporting (THOR) Network in the UK. Voluntary reporting schemes request responses even if no cases are observed to reduce uncertainty in non-response. This may result in false zeros that bias trends estimates. Analysis using zero-inflated models is unsuitable for specific health outcomes due to overestimates of the excess zeros. Here, we attempt to account for excess zeros while investigating condition-specific trends., Methods: Zero-inflated negative binomial (ZINB) models were fitted to three THOR work-related ill health surveillance schemes Occupational Skin Disease Surveillance (437 reporters between 1996 and 2019), Occupational Physicians Reporting Activity (1094 between 1996 and 2019) and Surveillance of Work-Related and Occupational Respiratory Disease (878 between 1999 and 2019). The probability associated with a response being a false zero was estimated and applied in weighted negative binomial (wgt-NB) models fitted to specific ill-heath conditions. Three ill-health conditions from the three THOR schemes were considered; contact dermatitis, musculoskeletal and asthma, respectively., Results: Wgt-NB models approximately estimated the incidence rate ratios reported by the ZINB models (eg, EPIDERM; ZINB=0.969, NB=0.963, wgt-NB=0.968) for all health outcome annual trends. This was consistent for specific health outcomes which also tended towards the null (eg, contact dermatitis; NB=0.964, wgt-NB=0.969), indicating potentially overestimated downward trends. Though as the ratio of excess zeros to true zeros decreased in rarer health outcomes, the influence on trends also decreased., Conclusions: Through weighting, we were able to adjust for excess zeros in health outcome-specific trends estimates. Though uncertainty is still present in underlying reporter behaviour meaning caution should be applied with interpretation of any results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2023
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