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1.  5th International Symposium on Focused Ultrasound 
Zaaroor, Menashe | Sinai, Alon | Goldsher, Dorit | Eran, Ayelet | Nassar, Maria | Schlesinger, Ilana | Parker, Jonathon | Ravikumar, Vinod | Ghanouni, Pejman | Stein, Sherman | Halpern, Casey | Krishna, Vibhor | Hargrove, Amelia | Agrawal, Punit | Changizi, Barbara | Bourekas, Eric | Knopp, Michael | Rezai, Ali | Mead, Brian | Kim, Namho | Mastorakos, Panagiotis | Suk, Jung Soo | Miller, Wilson | Klibanov, Alexander | Hanes, Justin | Price, Richard | Wang, Shutao | Olumolade, Oluyemi | Kugelman, Tara | Jackson-Lewis, Vernice | Karakatsani, Maria Eleni (Marilena) | Han, Yang | Przedborski, Serge | Konofagou, Elisa | Hynynen, Kullervo | Aubert, Isabelle | Leinenga, Gerhard | Nisbet, Rebecca | Hatch, Robert | Van der Jeugd, Anneke | Evans, Harrison | Götz, Jürgen | Götz, Jürgen | Nisbet, Rebecca | Van der Jeugd, Ann | Evans, Harrison | Leinenga, Gerhard | Fishman, Paul | Yarowsky, Paul | Frenkel, Victor | Wei-Bin, Shen | Nguyen, Ben | Sanchez, Carlos Sierra | Acosta, Camilo | Chen, Cherry | Wu, Shih-Ying | Karakatsani, Maria Eleni (Marilena) | Konofagou, Elisa | Aryal, Muna | Papademetriou, Iason T. | Zhang, Yong-Zhi | Power, Chanikarn | McDannold, Nathan | Porter, Tyrone | Kovacs, Zsofia | Kim, Saejeong | Jikaria, Neekita | Qureshi, Farhan | Bresler, Michele | Frank, Joseph | Odéen, Henrik | Chiou, George | Snell, John | Todd, Nick | Madore, Bruno | Parker, Dennis | Pauly, Kim Butts | Marx, Mike | Ghanouni, Pejman | Jonathan, Sumeeth | Grissom, William | Arvanitis, Costas | McDannold, Nathan | Clement, Gregory | Parker, Dennis | de Bever, Joshua | Odéen, Henrik | Payne, Allison | Christensen, Douglas | Maimbourg, Guillaume | Santin, Mathieu David | Houdouin, Alexandre | Lehericy, Stéphane | Tanter, Mickael | Aubry, Jean Francois | Pauly, Kim Butts | Federau, Christian | Werner, Beat | Halpern, Casey | Ghanouni, Pejman | Paeng, Dong-Guk | Xu, Zhiyuan | Snell, John | Quigg, Anders | Eames, Matt | Jin, Changzhu | Everstine, Ashli | Sheehan, Jason | Lopes, M. Beatriz | Kassell, Neal | Snell, John | Quigg, Anders | Drake, James | Price, Karl | Lustgarten, Lior | Sin, Vivian | Mougenot, Charles | Donner, Elizabeth | Tam, Emily | Hodaie, Mojgan | Waspe, Adam | Looi, Thomas | Pichardo, Samuel | Lee, Wonhye | Chung, Yong An | Jung, Yujin | Song, In-Uk | Yoo, Seung-Schik | Lee, Wonhye | Kim, Hyun-Chul | Jung, Yujin | Chung, Yong An | Song, In-Uk | Lee, Jong-Hwan | Yoo, Seung-Schik | Caskey, Charles | Zinke, Wolf | Cosman, Josh | Shuman, Jillian | Schall, Jeffrey | Aurup, Christian | Wang, Shutao | Chen, Hong | Acosta, Camilo | Konofagou, Elisa | Kamimura, Hermes | Carneiro, Antonio | Todd, Nick | Sun, Tao | Zhang, Yong-Zhi | Power, Chanikarn | Nazai, Navid | Patz, Sam | Livingstone, Margaret | McDannold, Nathan | Mainprize, Todd | Huang, Yuexi | Alkins, Ryan | Chapman, Martin | Perry, James | Lipsman, Nir | Bethune, Allison | Sahgal, Arjun | Trudeau, Maureen | Hynynen, Kullervo | Liu, Hao-Li | Hsu, Po-Hung | Wei, Kuo-Chen | Sun, Tao | Power, Chanikarn | Zhang, Yong-Zhi | Sutton, Jonathan | Alexander, Phillip | Aryal, Muna | Miller, Eric | McDannold, Nathan | Kobus, Thiele | Zhang, Yong-Zhi | McDannold, Nathan | Carpentier, Alexandre | Canney, Michael | Vignot, Alexandre | Beccaria, Kevin | Leclercq, Delphine | Lafon, Cyril | Chapelon, Jean Yves | Hoang-Xuan, Khe | Delattre, Jean-Yves | Idbaih, Ahmed | Xu, Zhiyuan | Moore, David | Xu, Alexis | Schmitt, Paul | Snell, John | Foley, Jessica | Eames, Matt | Sheehan, Jason | Kassell, Neal | Sukovich, Jonathan | Cain, Charles | Xu, Zhiyuan | Pandey, Aditya | Snell, John | Chaudhary, Neeraj | Camelo-Piragua, Sandra | Allen, Steven | Paeng, Dong-Guk | Cannata, Jon | Teofilovic, Dejan | Bertolina, Jim | Kassell, Neal | Hall, Timothy | Xu, Zhen | Wu, Shih-Ying | Karakatsani, Maria Eleni (Marilena) | Grondin, Julien | Sanchez, Carlos Sierra | Ferrera, Vincent | Konofagou, Elisa | ter Haar, Gail | Mouratidis, Petros | Repasky, Elizabeth | Timbie, Kelsie | Badr, Lena | Campbell, Benjamin | McMichael, John | Buckner, Andrew | Prince, Jessica | Stevens, Aaron | Bullock, Timothy | Price, Richard | Skalina, Karin | Guha, Chandan | Orsi, Franco | Bonomo, Guido | Vigna, Paolo Della | Mauri, Giovanni | Varano, Gianluca | Schade, George | Wang, Yak-Nam | Pillarisetty, Venu | Hwang, Joo Ha | Khokhlova, Vera | Bailey, Michael | Khokhlova, Tatiana | Khokhlova, Vera | Sinilshchikov, Ilya | Yuldashev, Petr | Andriyakhina, Yulia | Kreider, Wayne | Maxwell, Adam | Khokhlova, Tatiana | Sapozhnikov, Oleg | Partanen, Ari | Lundt, Jonathan | Allen, Steven | Sukovich, Jonathan | Hall, Timothy | Cain, Charles | Xu, Zhen | Preusser, Tobias | Haase, Sabrina | Bezzi, Mario | Jenne, Jürgen | Langø, Thomas | Midiri, Massimo | Mueller, Michael | Sat, Giora | Tanner, Christine | Zangos, Stephan | Guenther, Matthias | Melzer, Andreas | Menciassi, Arianna | Tognarelli, Selene | Cafarelli, Andrea | Diodato, Alessandro | Ciuti, Gastone | Rothluebbers, Sven | Schwaab, Julia | Strehlow, Jan | Mihcin, Senay | Tanner, Christine | Tretbar, Steffen | Preusser, Tobias | Guenther, Matthias | Jenne, Jürgen | Payen, Thomas | Palermo, Carmine | Sastra, Steve | Chen, Hong | Han, Yang | Olive, Kenneth | Konofagou, Elisa | Adams, Matthew | Salgaonkar, Vasant | Scott, Serena | Sommer, Graham | Diederich, Chris | Vidal-Jove, Joan | Perich, Eloi | Ruiz, Antonio | Velat, Manuela | Melodelima, David | Dupre, Aurelien | Vincenot, Jeremy | Yao, Chen | Perol, David | Rivoire, Michel | Tucci, Samantha | Mahakian, Lisa | Fite, Brett | Ingham, Elizabeth | Tam, Sarah | Hwang, Chang-il | Tuveson, David | Ferrara, Katherine | Scionti, Stephen | Chen, Lili | Cvetkovic, Dusica | Chen, Xiaoming | Gupta, Roohi | Wang, Bin | Ma, Charlie | Bader, Kenneth | Haworth, Kevin | Maxwell, Adam | Holland, Christy | Sanghvi, Narendra | Carlson, Roy | Chen, Wohsing | Chaussy, Christian | Thueroff, Stefan | Cesana, Claudio | Bellorofonte, Carlo | Wang, Qingguo | Wang, Han | Wang, Shengping | Zhang, Junhai | Bazzocchi, Alberto | Napoli, Alessandro | Staruch, Robert | Bing, Chenchen | Shaikh, Sumbul | Nofiele, Joris | Szczepanski, Debra | Staruch, Michelle Wodzak | Williams, Noelle | Laetsch, Theodore | Chopra, Rajiv | Ghanouni, Pejman | Rosenberg, Jarrett | Bitton, Rachelle | Napoli, Alessandro | LeBlang, Suzanne | Meyer, Joshua | Hurwitz, Mark | Pauly, Kim Butts | Partanen, Ari | Yarmolenko, Pavel | Partanen, Ari | Celik, Haydar | Eranki, Avinash | Beskin, Viktoriya | Santos, Domiciano | Patel, Janish | Oetgen, Matthew | Kim, AeRang | Kim, Peter | Sharma, Karun | Chisholm, Alexander | Drake, James | Aleman, Dionne | Waspe, Adam | Looi, Thomas | Pichardo, Samuel | Napoli, Alessandro | Bazzocchi, Alberto | Scipione, Roberto | Temple, Michael | Waspe, Adam | Amaral, Joao Guilherme | Huang, Yuexi | Endre, Ruby | Lamberti-Pasculli, Maria | de Ruiter, Joost | Campbell, Fiona | Stimec, Jennifer | Gupta, Samit | Singh, Manoj | Mougenot, Charles | Hopyan, Sevan | Hynynen, Kullervo | Czarnota, Gregory | Drake, James | Brenin, David | Rochman, Carrie | Kovatcheva, Roussanka | Vlahov, Jordan | Zaletel, Katja | Stoinov, Julian | Han, Yang | Wang, Shutao | Konofagou, Elisa | Bucknor, Matthew | Rieke, Viola | Shim, Jenny | Staruch, Robert | Koral, Korgun | Chopra, Rajiv | Laetsch, Theodore | Lang, Brian | Wong, Carlos | Lam, Heather | Kovatcheva, Roussanka | Vlahov, Jordan | Zaletel, Katja | Stoinov, Julian | Shinkov, Alexander | Hu, Jim | Sharma, Karun | Zhang, Xi | Macoskey, Jonathan | Ives, Kimberly | Owens, Gabe | Gurm, Hitinder | Shi, Jiaqi | Pizzuto, Matthew | Cain, Charles | Xu, Zhen | Payne, Allison | Dillon, Christopher | Christofferson, Ivy | Hilas, Elaine | Shea, Jill | Greillier, Paul | Ankou, Bénédicte | Bessière, Francis | Zorgani, Ali | Pioche, Mathieu | Kwiecinski, Wojciech | Magat, Julie | Melot-Dusseau, Sandrine | Lacoste, Romain | Quesson, Bruno | Pernot, Mathieu | Catheline, Stefan | Chevalier, Philippe | Lafon, Cyril | Marquet, Fabrice | Bour, Pierre | Vaillant, Fanny | Amraoui, Sana | Dubois, Rémi | Ritter, Philippe | Haïssaguerre, Michel | Hocini, Mélèze | Bernus, Olivier | Quesson, Bruno | Tebebi, Pamela | Burks, Scott | Kim, Saejeong | Milo, Blerta | Frank, Joseph | Gertner, Michael | Zhang, Jimin | Wong, Andrew | Fite, Brett | Liu, Yu | Kheirolomoom, Azadeh | Seo, Jai | Watson, Katherine | Mahakian, Lisa | Tam, Sarah | Zhang, Hua | Foiret, Josquin | Borowsky, Alexander | Ferrara, Katherine | Xu, Doudou | Melzer, Andreas | Thanou, Maya | Centelles, Miguell | Wright, Mike | Amrahli, Maral | So, Po-Wah | Gedroyc, Wladyslaw | Centelles, Miguell | Wright, Mike | Gedroyc, Wladyslaw | Thanou, Maya | Kneepkens, Esther | Heijman, Edwin | Keupp, Jochen | Weiss, Steffen | Nicolay, Klaas | Grüll, Holger | Fite, Brett | Wong, Andrew | Liu, Yu | Kheirolomoom, Azadeh | Mahakian, Lisa | Tam, Sarah | Foiret, Josquin | Ferrara, Katherine | Burks, Scott | Nagle, Matthew | Kim, Saejeong | Milo, Blerta | Frank, Joseph | Sapozhnikov, Oleg | Nikolaeva, Anastasia V. | Terzi, Marina E. | Tsysar, Sergey A. | Maxwell, Adam | Cunitz, Bryan | Bailey, Michael | Mourad, Pierre | Downs, Matthew | Yang, Georgiana | Wang, Qi | Konofagou, Elisa | Burks, Scott | Nagle, Matthew | Nguyen, Ben | Bresler, Michele | Kim, Saejeong | Milo, Blerta | Frank, Joseph | Burks, Scott | Nagle, Matthew | Kim, Saejeong | Milo, Blerta | Frank, Joseph | Chen, Johnny | Farry, Justin | Dixon, Adam | Du, Zhongmin | Dhanaliwala, Ali | Hossack, John | Klibanov, Alexander | Ranjan, Ashish | Maples, Danny | Chopra, Rajiv | Bing, Chenchen | Staruch, Robert | Wardlow, Rachel | Staruch, Michelle Wodzak | Malayer, Jerry | Ramachandran, Akhilesh | Nofiele, Joris | Namba, Hirofumi | Kawasaki, Motohiro | Izumi, Masashi | Kiyasu, Katsuhito | Takemasa, Ryuichi | Ikeuchi, Masahiko | Ushida, Takahiro | Crake, Calum | Papademetriou, Iason T. | Zhang, Yong-Zhi | Porter, Tyrone | McDannold, Nathan | Kothapalli, Satya V. V. N. | Leighton, Wan | Wang, Zhaorui | Partanen, Ari | Gach, H. Michael | Straube, William | Altman, Michael | Chen, Hong | Kim, Young-sun | Lim, Hyo Keun | Rhim, Hyunchul | Kim, Young-sun | Lim, Hyo Keun | Rhim, Hyunchul | van Breugel, Johanna | Braat, Manon | Moonen, Chrit | van den Bosch, Maurice | Ries, Mario | Marrocchio, Cristina | Dababou, Susan | Bitton, Rachelle | Pauly, Kim Butts | Ghanouni, Pejman | Lee, Jae Young | Lee, Jae Young | Chung, Hyun Hoon | Kang, Soo Yeon | Kang, Kook Jin | Son, Keon Ho | Zhang, Dandan | Adams, Matthew | Salgaonkar, Vasant | Plata, Juan | Jones, Peter | Pascal-Tenorio, Aurea | Bouley, Donna | Sommer, Graham | Pauly, Kim Butts | Diederich, Chris | Bond, Aaron | Dallapiazza, Robert | Huss, Diane | Warren, Amy | Sperling, Scott | Gwinn, Ryder | Shah, Binit | Elias, W. Jeff | Curley, Colleen | Zhang, Ying | Negron, Karina | Miller, Wilson | Klibanov, Alexander | Abounader, Roger | Suk, Jung Soo | Hanes, Justin | Price, Richard | Karakatsani, Maria Eleni (Marilena) | Samiotaki, Gesthimani | Wang, Shutao | Kugelman, Tara | Acosta, Camilo | Konofagou, Elisa | Kovacs, Zsofia | Tu, Tsang-Wei | Papadakis, Georgios | Hammoud, Dima | Frank, Joseph | Silvestrini, Matthew | Wolfram, Frank | Güllmar, Daniel | Reichenbach, Juergen | Hofmann, Denis | Böttcher, Joachim | Schubert, Harald | Lesser, Thomas G. | Almquist, Scott | Parker, Dennis | Christensen, Douglas | Camarena, Francisco | Jiménez-Gambín, Sergio | Jiménez, Noé | Konofagou, Elisa | Chang, Jin Woo | Chaplin, Vandiver | Griesenauer, Rebekah | Miga, Michael | Caskey, Charles | Ellens, Nicholas | Airan, Raag | Quinones-Hinojosa, Alfredo | Farahani, Keyvan | Partanen, Ari | Feng, Xue | Fielden, Samuel | Zhao, Li | Miller, Wilson | Wintermark, Max | Pauly, Kim Butts | Meyer, Craig | Guo, Sijia | Lu, Xin | Zhuo, Jiachen | Xu, Su | Gullapalli, Rao | Gandhi, Dheeraj | Jin, Changzhu | Brokman, Omer | Eames, Matt | Snell, John | Paeng, Dong-Guk | Baek, Hongchae | Kim, Hyungmin | Leung, Steven | Webb, Taylor | Pauly, Kim Butts | McDannold, Nathan | Zhang, Yong-Zhi | Vykhodtseva, Natalia | Nguyen, Thai-Son | Sukovich, Jonathan | Hall, Timothy | Xu, Zhen | Cain, Charles | Park, Chang Kyu | Park, Sang Man | Jung, Na Young | Kim, Min Soo | Chang, Won Seok | Jung, Hyun Ho | Chang, Jin Woo | Pichardo, Samuel | Hynynen, Kullervo | Plaksin, Michael | Weissler, Yoni | Shoham, Shy | Kimmel, Eitan | Quigg, Anders | Snell, John | Paeng, Dong-Guk | Eames, Matt | Sapozhnikov, Oleg | Rosnitskiy, Pavel B. | Khokhlova, Vera | Shoham, Shy | Krupa, Steve | Hazan, Eilon | Naor, Omer | Levy, Yoav | Maimon, Noam | Brosh, Inbar | Kimmel, Eitan | Kahn, Itamar | Sukovich, Jonathan | Xu, Zhen | Hall, Timothy | Allen, Steven | Cain, Charles | Cahill, Jessica | Sun, Tao | Zhang, Yong-Zhi | Power, Chanikarn | Livingstone, Margaret | McDannold, Nathan | Todd, Nick | Colas, Elodie Constanciel | Wydra, Adrian | Waspe, Adam | Looi, Thomas | Maev, Roman | Pichardo, Samuel | Drake, James | Aly, Amirah | Sun, Tao | Zhang, Yong-Zhi | Sesenoglu-Laird, Ozge | Padegimas, Linas | Cooper, Mark | McDannold, Nathan | Waszczak, Barbara | Tehrani, Seruz | Miller, Wilson | Slingluff, Craig | Larner, James | Andarawewa, Kumari | Bucknor, Matthew | Ozhinsky, Eugene | Shah, Rutwik | Krug, Roland | Rieke, Viola | Deckers, Roel | Linn, Sabine | Suelmann, Britt | Braat, Manon | Witkamp, Arjen | Vaessen, Paul | van Diest, Paul | Bartels, Lambertus W. | Bos, Clemens | van den Bosch, Maurice | Borys, Nicolas | Storm, Gert | Van der Wall, Elsken | Moonen, Chrit | Farr, Navid | Alnazeer, Moez | Yarmolenko, Pavel | Katti, Prateek | Partanen, Ari | Eranki, Avinash | Kim, Peter | Wood, Bradford | Farrer, Alexis | Almquist, Scott | Dillon, Christopher | Parker, Dennis | Christensen, Douglas | Payne, Allison | Ferrer, Cyril | Bartels, Lambertus W. | de Senneville, Baudouin Denis | van Stralen, Marijn | Moonen, Chrit | Bos, Clemens | Liu, Yu | Liu, Jingfei | Fite, Brett | Foiret, Josquin | Leach, J. Kent | Ferrara, Katherine | Gupta, Roohi | Cvetkovic, Dusica | Ma, Charlie | Chen, Lili | Haase, Sabrina | Zidowitz, Stephan | Melzer, Andreas | Preusser, Tobias | Lee, Hsin-Lun | Hsu, Fang-Chi | Kuo, Chia-Chun | Jeng, Shiu-Chen | Chen, Tung-Ho | Yang, Nai-Yi | Chiou, Jeng-Fong | Jeng, Shiu-Chen | Kao, Yi-tzu | Pan, Chia-Hsin | Wu, Jing-Fu | Chen, Tung-Ho | Hsu, Fang-Chi | Lee, Hsin-Lun | Chiou, Jeng-Fong | Hsu, Fang-Chi | Tsai, Yi-Chieh | Lee, Hsin-Lun | Chiou, Jeng-Fong | Johnson, Sara | Parker, Dennis | Payne, Allison | Li, Dawei | He, Ye | Mihcin, Senay | Karakitsios, Ioannis | Strehlow, Jan | Schwenke, Michael | Haase, Sabrina | Demedts, Daniel | Levy, Yoav | Preusser, Tobias | Melzer, Andreas | Mihcin, Senay | Rothluebbers, Sven | Karakitsios, Ioannis | Xiao, Xu | Strehlow, Jan | Demedts, Daniel | Cavin, Ian | Sat, Giora | Preusser, Tobias | Melzer, Andreas | Minalga, Emilee | Payne, Allison | Merrill, Robb | Parker, Dennis | Hadley, Rock | Ramaekers, Pascal | Ries, Mario | Moonen, Chrit | de Greef, Martijn | Shahriari, Kian | Parvizi, Mohammad Hossein | Asadnia, Kiana | Chamanara, Marzieh | Kamrava, Seyed Kamran | Chabok, Hamid Reza | Schwenke, Michael | Strehlow, Jan | Demedts, Daniel | Tanner, Christine | Rothluebbers, Sven | Preusser, Tobias | Strehlow, Jan | Stein, Ruben | Demedts, Daniel | Schwenke, Michael | Rothluebbers, Sven | Preusser, Tobias | Demedts, Daniel | Haase, Sabrina | Muller, Sébastien | Strehlow, Jan | Langø, Thomas | Preusser, Tobias | Tan, Jeremy | Zachiu, Cornel | Ramaekers, Pascal | Moonen, Chrit | Ries, Mario | Wolfram, Frank | Güllmar, Daniel | Schubert, Harald | Lesser, Thomas G. | Erasmus, Hans-Peter | Colas, Elodie Constanciel | Waspe, Adam | Mougenot, Charles | Looi, Thomas | Van Arsdell, Glen | Benson, Lee | Drake, James | Jang, Kee W. | Tu, Tsang-Wei | Jikaria, Neekita | Nagle, Matthew | Angstadt, Mary | Lewis, Bobbi | Qureshi, Farhan | Burks, Scott | Frank, Joseph | McLean, Hailey | Payne, Allison | Hoogenboom, Martijn | Eikelenboom, Dylan | den Brok, Martijn | Wesseling, Pieter | Heerschap, Arend | Fütterer, Jurgen | Adema, Gosse | Wang, Kevin | Zhang, Ying | Zhong, Pei | Xiao, Xu | Joy, Joyce | McLeod, Helen | Melzer, Andreas | Bing, Chenchen | Staruch, Robert | Nofiele, Joris | Szczepanski, Debra | Staruch, Michelle Wodzak | Laetsch, Theodore | Chopra, Rajiv | Bing, Chenchen | Staruch, Robert | Yarmolenko, Pavel | Celik, Haydar | Nofiele, Joris | Szczepanski, Debra | Kim, Peter | Kim, Harry | Lewis, Matthew | Chopra, Rajiv | Shah, Rutwik | Ozhinsky, Eugene | Rieke, Viola | Bucknor, Matthew | Diederich, Chris | Salgaonkar, Vasant | Jones, Peter | Adams, Matthew | Ozilgen, Arda | Zahos, Peter | Coughlin, Dezba | Tang, Xinyan | Lotz, Jeff | Jedruszczuk, Kathleen | Gulati, Amitabh | Solomon, Stephen | Kaye, Elena | Fielden, Samuel | Mugler, John | Miller, Wilson | Pauly, Kim Butts | Meyer, Craig | Barbato, Gaetano | Scoarughi, Gian Luca | Corso, Cristiano | Gorgone, Alessandro | Migliore, Ilaria Giuseppina | Larrabee, Zachary | Hananel, Arik | Eames, Matt | Aubry, Jean-Francois | Eranki, Avinash | Farr, Navid | Partanen, Ari | Sharma, Karun | Yarmolenko, Pavel | Wood, Bradford | Kim, Peter | Farr, Navid | Kothapalli, Satya V. V. N. | Eranki, Avinash | Negussie, Ayele | Wilson, Emmanuel | Seifabadi, Reza | Kim, Peter | Chen, Hong | Wood, Bradford | Partanen, Ari | Moon, Hyungwon | Kang, Jeeun | Sim, Changbeom | Chang, Jin Ho | Kim, Hyuncheol | Lee, Hak Jong | Sasaki, Noboru | Takiguchi, Mitsuyoshi | Sebeke, Lukas | Luo, Xi | de Jager, Bram | Heemels, Maurice | Heijman, Edwin | Grüll, Holger | Strehlow, Jan | Schwenke, Michael | Demedts, Daniel | Preusser, Tobias
Journal of Therapeutic Ultrasound  2016;4(Suppl 1):1-113.
doi:10.1186/s40349-016-0076-5
PMCID: PMC5123388
2.  Fish-T1K (Transcriptomes of 1,000 Fishes) Project: large-scale transcriptome data for fish evolution studies 
GigaScience  2016;5:18.
Ray-finned fishes (Actinopterygii) represent more than 50 % of extant vertebrates and are of great evolutionary, ecologic and economic significance, but they are relatively underrepresented in ‘omics studies. Increased availability of transcriptome data for these species will allow researchers to better understand changes in gene expression, and to carry out functional analyses. An international project known as the “Transcriptomes of 1,000 Fishes” (Fish-T1K) project has been established to generate RNA-seq transcriptome sequences for 1,000 diverse species of ray-finned fishes. The first phase of this project has produced transcriptomes from more than 180 ray-finned fishes, representing 142 species and covering 51 orders and 109 families. Here we provide an overview of the goals of this project and the work done so far.
Electronic supplementary material
The online version of this article (doi:10.1186/s13742-016-0124-7) contains supplementary material, which is available to authorized users.
doi:10.1186/s13742-016-0124-7
PMCID: PMC4853854  PMID: 27144000
Fish-T1K; Fish; Transcriptome; RNA; Database; Biodiversity
3.  The validation of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30) in pre-operative patients with brain tumor in China 
Background
Health related quality of life (HRQOL) has increasingly emphasized on cancer patients. The psychometric properties of the standard Chinese version of the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire 30 (EORTC QLQ-C30, version 3.0) in brain tumor patients wasn't proven, and there was no baseline HRQOL in brain tumor patients prior to surgery.
Methods
The questionnaire EORTC QLQ-C30 (version 3.0) was administered at three time points: T1, the first or the second day that patients were hospitalized after the brain tumor suspected or diagnosed by MRI or CT; T2, 1 to 2 days after T1, (T1 and T2 were both before surgery); T3, the day before discharge. Clinical variables included disease histologic types, cognitive function, and Karnofsky Performance Status.
Results
Cronbach's alpha coefficients for multi-item scales were greater than .70 and multitrait scaling analysis showed that most of the item-scale correlation coefficients met the standards of convergent and discriminant validity, except for the cognitive functioning scale. All scales and items exhibited construct validity. Score changes over peri-operation were observed in physical and role functioning scales. Compared with mixed cancer patients assessed after surgery but before adjuvant treatment, brain tumor patients assessed pre-surgery presented better function and fewer symptoms.
Conclusions
The standard Chinese version of the EORTC QLQ-C30 was overall a valid instrument to assess HRQOL in brain tumor patients in China. The baseline HRQOL in brain tumor patients pre-surgery was better than that in mixed cancer patients post-surgery. Future study should modify cognitive functioning scale and examine test-retest reliability and response validity.
doi:10.1186/1471-2288-11-56
PMCID: PMC3112193  PMID: 21513533
4.  Expression of human C9ORF72 hexanucleotide expansion reproduces RNA foci and dipeptide repeat proteins but not neurodegeneration in BAC transgenic mice 
Neuron  2015;88(5):902-909.
Summary
A non-coding hexanucleotide repeat expansion in the C9ORF72 gene is the most common mutation associated with familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Patients harboring this expansion develop several unique histopathological hallmarks, including intranuclear foci composed of either sense or antisense RNA transcripts from the expanded repeats and dipeptide repeat proteins generated by non-canonical translation of the expanded RNA transcripts. To further investigate the pathological role of C9ORF72 in these diseases, we generated a line of mice carrying a bacterial artificial chromosome containing exons 1 to 6 of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. The mice showed no overt behavioral phenotype but recapitulated distinctive histopathological features that are the hallmark of C9ORF72 ALS/FTD, including sense and antisense intranuclear RNA foci and poly(glycine-proline) dipeptides repeat proteins. Finally, using a synthetic microRNA that targets human C9ORF72 in cultures of primary cortical neurons from the C9BAC mice, we have attenuated expression of the C9BAC transgene and the poly(GP) dipeptides. The C9ORF72 BAC transgenic mice will be a valuable tool in the study of ALS/FTD pathobiology and therapy.
doi:10.1016/j.neuron.2015.11.018
PMCID: PMC4828340  PMID: 26637797
Amyotrophic lateral sclerosis (ALS); frontotemporal dementia (FTD); C9ORF72; transgenic mice; RNA foci; RAN translation; repeat expansions; neurodegeneration
5.  Genistein alleviates pressure overload‐induced cardiac dysfunction and interstitial fibrosis in mice 
British Journal of Pharmacology  2015;172(23):5559-5572.
Background and Purpose
Pressure overload‐induced cardiac interstitial fibrosis is viewed as a major cause of heart failure in patients with hypertension or aorta atherosclerosis. The purpose of this study was to investigate the effects and the underlying mechanisms of genistein, a natural phytoestrogen found in soy bean extract, on pressure overload‐induced cardiac fibrosis.
Experimental Approach
Genisten was administered to mice with pressure overload induced by transverse aortic constriction. Eight weeks later, its effects on cardiac dysfunction, hypertrophy and fibrosis were determined. Its effects on proliferation, collagen production and myofibroblast transformation of cardiac fibroblasts (CFs) and the signalling pathways were also assessed in vitro.
Key Results
Pressure overload‐induced cardiac dysfunction, hypertrophy and fibrosis were markedly attenuated by genistein. In cultured CFs, genistein inhibited TGFβ1‐induced proliferation, collagen production and myofibroblast transformation. Genistein suppressed TGFβ‐activated kinase 1 (TAK1) expression and produced anti‐fibrotic effects by blocking the TAK1/MKK4/JNK pathway. Further analysis indicated that it up‐regulated oestrogen‐dependent expression of metastasis‐associated gene 3 (MTA3), which was found to be a negative regulator of TAK1. Silencing MTA3 by siRNA, or inhibiting the activity of the MTA3‐NuRD complex with trichostatin A, abolished genistein's anti‐fibrotic effects.
Conclusions and Implications
Genistein improved cardiac function and inhibited cardiac fibrosis in response to pressure overload. The underlying mechanism may involve regulation of the MTA3/TAK1/MKK4/JNK signalling pathway. Genistein may have potential as a novel agent for prevention and therapy of cardiac disorders associated with fibrosis.
Linked Articles
This article is part of a themed section on Chinese Innovation in Cardiovascular Drug Discovery. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-23
doi:10.1111/bph.13002
PMCID: PMC4667871  PMID: 25362897
6.  Mesenchymal Stem Cells and Cardiomyocytes Interplay to Prevent Myocardial Hypertrophy 
Stem Cells Translational Medicine  2015;4(12):1425-1435.
In this study, bone marrow-derived mesenchymal stem cells (BMSCs) were indirectly cocultured with neonatal rat ventricular cardiomyocytes in vitro or intramyocardially transplanted into hypertrophic hearts in vivo. The results showed that isoproterenol-induced typical hypertrophic characteristics of cardiomyocytes were prevented by BMSCs in the coculture model in vitro and after BMSC transplantation in vivo, providing the first evidence for the treatment of myocardial hypertrophy using BMSCs.
Bone marrow-derived mesenchymal stem cells (BMSCs) have emerged as a promising therapeutic strategy for cardiovascular disease. However, there is no evidence so far that BMSCs can heal pathological myocardial hypertrophy. In this study, BMSCs were indirectly cocultured with neonatal rat ventricular cardiomyocytes (NRVCs) in vitro or intramyocardially transplanted into hypertrophic hearts in vivo. The results showed that isoproterenol (ISO)-induced typical hypertrophic characteristics of cardiomyocytes were prevented by BMSCs in the coculture model in vitro and after BMSC transplantation in vivo. Furthermore, activation of the Ca2+/calcineurin/nuclear factor of activated T cells cytoplasmic 3 (NFATc3) hypertrophic pathway in NRVCs was abrogated in the presence of BMSCs both in vitro and in vivo. Interestingly, inhibition of vascular endothelial growth factor (VEGF) release from BMSCs, but not basic fibroblast growth factor and insulin-like growth factor 1, abolished the protective effects of BMSCs on cardiomyocyte hypertrophy. Consistently, VEGF administration attenuated ISO-induced enlargement of cellular size; the upregulation of atrial natriuretic peptide, brain natriuretic peptide, and β-myosin heavy chain expression; and the activation of Ca2+/calcineurin/NFATc3 hypertrophic pathways, and these pathways can be abrogated by blocking VEGFR-1 in cardiomyocytes, indicating that VEGF receptor 1 is involved in the antihypertrophic role of VEGF. We further found that the ample VEGF secretion contributing to the antihypertrophic effects of BMSCs originates from the crosstalk of BMSCs and cardiac cells but not BMSCs or cardiomyocytes alone. Interplay of mesenchymal stem cells with cardiomyocytes produced synergistic effects on VEGF release. In summary, crosstalk between mesenchymal stem cells and cardiomyocytes contributes to the inhibition of myocardial hypertrophy via inhibiting Ca2+/calcineurin/NFATc3 hypertrophic pathways in cardiac cells. These results provide the first evidence for the treatment of myocardial hypertrophy using BMSCs.
Significance
This study found that mesenchymal stem cells may crosstalk with cardiomyocytes, which causes a synergistic vascular endothelial growth factor (VEGF) release from both kinds of cells and then inhibits pathological cardiac remodeling following hypertrophic stimulation in cardiomyocytes in vitro and in vivo. Blockage of VEGF release from bone marrow-derived mesenchymal stem cells (BMSCs) abolishes the antihypertrophic actions of BMSCs in vitro and in vivo. On the contrary, VEGF administration attenuates hypertrophic signaling of calcineurin/ nuclear factor of activated T cell cytoplasmic 3 signal pathways. This study provides the first evidence for the treatment of myocardial hypertrophy using BMSCs.
doi:10.5966/sctm.2015-0032
PMCID: PMC4675503  PMID: 26586774
Mesenchymal stem cell; Cardiomyocyte; Crosstalk; Hypertrophy; Remodeling
7.  High-Pressure Water Swelling Sealant Injection Injury to the Hand: a Case Report and Review of the Literature 
The Indian Journal of Surgery  2015;77(6):508-511.
High-pressure injection injuries (HPII) caused by water swelling sealant are rare at present. The patient generally has small-sized skin lesions, and the misleadingly benign presentation may cause delayed treatment at the early stage of management. In addition, radiographic examination may be underestimated. Subsequently, the inadequate surgical intervention may cause tissue necrosis and poor prognosis. Furthermore, the early recognition of water swelling sealant injected into tissue and emergent surgical intervention are the key to successful management for the patient with HPII caused by injecting water swelling sealant to tissue.
doi:10.1007/s12262-015-1312-x
PMCID: PMC4744213  PMID: 26884659
High-pressure injection injuries; Water swelling sealant; Polyurethane; Debridement; Flap
8.  Efficacy and Safety of Propiverine Hydrochloride for Overactive Bladder in Adult: a Systematic Review and Meta-analysis 
The Indian Journal of Surgery  2015;77(Suppl 3):1369-1377.
We carried out a systematic review and meta-analysis to assess the efficacy and safety of propiverine for treating overactive bladder (OAB) in adult. A literature review was performed to identify all published randomized placebo-controlled trials (RCT) of propiverine for the treatment of OAB. The search included the following databases: PUBMED and EMBASE. The reference lists of retrieved studies were also investigated. A systematic review and meta-analysis were conducted. Ten publications involving nine different RCTs were used in the analysis. We found that propiverine was effective in treating OAB in our meta-analysis. The decrease in number of micturitions/24 h (P < 0.00001, the mean decrease was from 1.80 to 2.57) indicated that propiverine was more effective than the placebo. Propiverine also decrease the number of urgency, urgency incontinence, and nocturia and increase urine volume. However, the incidence of difficulty in voiding was higher with propiverine therapy compared with the placebo (P = 0.05, the mean percentage range from 0.34 to 4.93 %). The decrease of total international prostate symptom score (IPSS) (P < 0.0001, the mean decrease was from 12.5 to 16.1) indicated that propiverine add a1-adrenoceptor antagonist was more effective in decreasing the lower urinary tract symptom (LUTS). The combination therapy also decreases the voiding symptom and storage symptom scores and increases maximum flow rate. This meta-analysis shows that propiverine is a safe and effective treatment for OAB. The major adverse event associated with propiverine treatment was difficulty in voiding. Propiverine add a1-adrenoceptor antagonist was more effective in terms of decreasing difficulty in voiding.
doi:10.1007/s12262-015-1264-1
PMCID: PMC4775592  PMID: 27011567
Propiverine; Overactive bladder; Alpha-blockers; Meta-analysis; Randomized controlled trials
9.  Pseudomonas aeruginosa Inhibits the Growth of Cryptococcus Species 
Mycopathologia  2011;173(5-6):451-461.
Pseudomonas aeruginosa is a ubiquitous and opportunistic bacterium that inhibits the growth of different microorganisms, including Gram-positive bacteria and fungi such as Candida spp. and Aspergillus fumigatus. In this study, we investigated the interaction between P. aeruginosa and Cryptococcus spp. We found that P. aeruginosa PA14 and, to a lesser extent, PAO1 significantly inhibited the growth of Cryptococcus spp. The inhibition of growth was observed on solid medium by the visualization of a zone of inhibition of yeast growth and in liquid culture by viable cell counting. Interestingly, such inhibition was only observed when P. aeruginosa and Cryptococcus were co-cultured. Minimal inhibition was observed when cell–cell contact was prevented using a separation membrane, suggesting that cell contact is required for inhibition. Using mutant strains of Pseudomonas quinoline signaling, we showed that P. aeruginosa inhibited the growth of Cryptococcus spp. by producing antifungal molecules pyocyanin, a redox-active phenazine, and 2-heptyl-3,4-dihydroxyquinoline (PQS), an extracellular quorum-sensing signal. Because both P. aeruginosa and Cryptococcus neoformans are commonly found in lung infections of immunocompromised patients, this study may have important implication for the interaction of these microbes in both an ecological and a clinical point of view.
doi:10.1007/s11046-011-9494-7
PMCID: PMC5125078  PMID: 22076410
Cryptococcus spp.; Pseudomonas aeruginosa; Quorum sensing; 2-heptyl-3,4-dihydroxyquinoline; Pyocyanin
10.  Identification and expression analysis of an olfactory receptor gene family in green plant bug Apolygus lucorum (Meyer-Dür) 
Scientific Reports  2016;6:37870.
Olfactory receptors are believed to play a central role in insects host-seeking, mating, and ovipositing. On the basis of male and female antennal transcriptome of adult Apolygus lucorum, a total of 110 candidate A. lucorum odorant receptors (AlucOR) were identified in this study including five previously annotated AlucORs. All the sequences were validated by cloning and sequencing. Tissue expression profiles analysis by RT-PCR indicated most AlucORs were antennal highly expressed genes. The qPCR measurements further revealed 40 AlucORs were significantly higher in the antennae. One AlucOR was primarily expressed in the female antennae, while nine AlucORs exhibited male-biased expression patterns. Additionally, both the RPKM value and RT-qPCR analysis showed AlucOR83 and AlucOR21 were much higher abundant in male antennae than in female antennae, suggesting their different roles in chemoreception of gender. Phylogenetic analysis of ORs from several Hemipteran species demonstrated that most AlucORs had orthologous genes, and five AlucOR-specific clades were defined. In addition, a sub-clade of potential male-based sex pheromone receptors were also identified in the phylogenetic tree of AlucORs. Our results will facilitate the functional studies of AlucORs, and thereby provide a foundation for novel pest management approaches based on these genes.
doi:10.1038/srep37870
PMCID: PMC5124970  PMID: 27892490
11.  Regulatory Roles of Rpl22 in Hematopoiesis: An Old Dog With New Tricks 
Critical reviews in immunology  2015;35(5):379-400.
Ribosomal proteins have long been known to serve critical roles in facilitating the biogenesis of the ribosome and its ability to synthesize proteins. However, evidence is emerging that suggests ribosomal proteins are also capable of performing tissue-restricted, regulatory functions that impact normal development and pathological conditions, including cancer. The challenge in studying such regulatory functions is that elimination of many ribosomal proteins also disrupts ribosome biogenesis and/or function, preventing one from unambiguously determining whether developmental abnormalities resulting from ablation of a ribosomal protein result from loss of core ribosome functions or from loss of the regulatory function of the ribosomal protein. Rpl22, a ribosomal protein component of the large 60S subunit, provides insight into this conundrum, as Rpl22 is dispensable for both ribosome biogenesis and protein synthesis, yet its ablation causes tissue-restricted disruptions in development. Here we review evidence supporting the regulatory functions of Rpl22 and other ribosomal proteins.
PMCID: PMC5111805  PMID: 26853850
12.  One-and-a-half nostril endoscopic transsphenoidal approach for pituitary adenomas—a technical report 
Background
Binostril endoscopic transsphenoidal approach (BETA) provides sufficient manipulation space and wide endoscopic vision, although it increases the trauma of nose. Mononostril endoscopic transsphenoidal approach (META) has minimal trauma of nose, at the expense of space within the operation. We describe a one-and-a-half nostril endoscopic transsphenoidal approach (OETA) that combines the advantages of BETA and META.
Methods
We introduced OETA for pituitary adenomas with a detailed technical description. A retrospective analysis was also performed on 57 consecutive patients who underwent one-and-a-half nostril endoscopic transsphenoidal surgery between March 2014 and June 2015 at Jinling hospital.
Results
The gross total resection rate was 79%. The gross complete resection rate of Knosp grade 3 tumors were 63.6, and 27.3% in grade 4 tumors. Postoperative hormone remission was achieved in 14 out of 18 (77.8%) patients with secreting adenomas. Postoperative abnormal visual function improvement was achieved in 23 out of 32 patients (73%) with preoperative visual dysfunction. The overall intra-operative CSF leak was 17.5%, with the postoperative CSF leak decreased to 3.5% after the sellar reconstruction with the unilateral “rescue” nasoseptal flap procedure. The main sinonasal complaints 2 weeks after surgery were: loss of sense of smell (28%), decrease in sense of taste (4%), trouble breathing during the day (18%), thick nasal discharge (36%), post nasal discharge (8%), dried nasal material (6%), and headache (6%). Three months after surgery, there were no reports of decrease of taste, post nasal discharge, or dried nasal material. Other complaints were decreased significantly. Six months after surgery, the main complaints of sinonasal quality of life were negligible, and overall health status was near complete recovery to preoperative status.
Conclusions
The one-and-a-half nostril endoscopic transsphenoidal approach for pituitary adenomas is a simple and reliable technique. It provides not only a sufficient surgical corridor for a 2-surgeon/4 or 3-hands technique, but also ensures minimal invasion of the nasal canal.
doi:10.1186/s40463-016-0174-y
PMCID: PMC5111234  PMID: 27846864
One-and-a-half nostril; Endonasal endoscopic transsphenoidal approach; The “rescue” nasoseptal flap; Trauma of nose; Manipulation space
13.  Noninvasive monitoring of early antiangiogenic therapy response in human nasopharyngeal carcinoma xenograft model using MRI with RGD-conjugated ultrasmall superparamagnetic iron oxide nanoparticles 
Purpose
Arginine-glycine-aspartic acid (RGD)-based nanoprobes allow specific imaging of integrin αvβ3, a protein overexpressed during angiogenesis. Therefore, this study applied a novel RGD-coupled, polyacrylic acid (PAA)-coated ultrasmall superparamagnetic iron oxide (USPIO) (referred to as RGD-PAA-USPIO) in order to detect tumor angiogenesis and assess the early response to antiangiogenic treatment in human nasopharyngeal carcinoma (NPC) xenograft model by magnetic resonance imaging (MRI).
Materials and methods
The binding specificity of RGD-PAA-USPIO with human umbilical vein endothelial cells (HUVECs) was confirmed by Prussian blue staining and transmission electron microscopy in vitro. The tumor targeting of RGD-PAA-USPIO was evaluated in the NPC xenograft model. Later, mice bearing NPC underwent MRI at baseline and after 4 and 14 days of consecutive treatment with Endostar or phosphate-buffered saline (n=10 per group).
Results
The specific uptake of the RGD-PAA-USPIO nanoparticles was mainly dependent on the interaction between RGD and integrin αvβ3 of HUVECs. The tumor targeting of RGD-PAA-USPIO was observed in the NPC xenograft model. Moreover, the T2 relaxation time of mice in the Endostar-treated group decreased significantly compared with those in the control group both on days 4 and 14, consistent with the immunofluorescence results of CD31 and CD61 (P<0.05).
Conclusion
This study demonstrated that the magnetic resonance molecular nanoprobes, RGD-PAA-USPIOs, allow noninvasive in vivo imaging of tumor angiogenesis and assessment of the early response to antiangiogenic treatment in NPC xenograft model, favoring its potential clinical translation.
doi:10.2147/IJN.S115357
PMCID: PMC5117895  PMID: 27895477
magnetic resonance imaging; ultrasmall superparamagnetic iron oxide; integrin αvβ3; antiangiogenic therapy; Endostar; nasopharyngeal carcinoma
14.  Fish gut-liver immunity during homeostasis or inflammation revealed by integrative transcriptome and proteome studies 
Scientific Reports  2016;6:36048.
The gut-associated lymphoid tissue, connected with liver via bile and blood, constructs a local immune environment of both defense and tolerance. The gut-liver immunity has been well-studied in mammals, yet in fish remains largely unknown, even though enteritis as well as liver and gallbladder syndrome emerged as a limitation in aquaculture. In this study, we performed integrative bioinformatic analysis for both transcriptomic (gut and liver) and proteomic (intestinal mucus and bile) data, in both healthy and infected tilapias. We found more categories of immune transcripts in gut than liver, as well as more adaptive immune in gut meanwhile more innate in liver. Interestingly reduced differential immune transcripts between gut and liver upon inflammation were also revealed. In addition, more immune proteins in bile than intestinal mucus were identified. And bile probably providing immune effectors to intestinal mucus upon inflammation was deduced. Specifically, many key immune transcripts in gut or liver as well as key immune proteins in mucus or bile were demonstrated. Accordingly, we proposed a hypothesized profile of fish gut-liver immunity, during either homeostasis or inflammation. Current data suggested that fish gut and liver may collaborate immunologically while keep homeostasis using own strategies, including potential unique mechanisms.
doi:10.1038/srep36048
PMCID: PMC5093735  PMID: 27808112
15.  Gradual Changes of Gut Microbiota in Weaned Miniature Piglets 
Colonization of gut microbiota in mammals during the early life is vital to host health. The miniature piglet has recently been considered as an optimal infant model. However, less is known about the development of gut microbiota in miniature piglets. Here, this study was conducted to explore how the gut microbiota develops in weaned Congjiang miniature piglets. In contrast to the relatively stabilized gut fungal community, gut bacterial community showed a marked drop in alpha diversity, accompanied by significant alterations in taxonomic compositions. The relative abundances of 24 bacterial genera significantly declined, whereas the relative abundances of 7 bacterial genera (Fibrobacter, Collinsella, Roseburia, Prevotella, Dorea, Howardella, and Blautia) significantly increased with the age of weaned piglets. Fungal taxonomic analysis showed that the relative abundances of two genera (Kazachstania and Aureobasidium) significantly decreased, whereas the relative abundances of four genera (Aspergillus, Cladosporium, Simplicillium, and Candida) significantly increased as the piglets aged. Kazachstania telluris was the signature species predominated in gut fungal communities of weaned miniature piglets. The functional maturation of the gut bacterial community was characterized by the significantly increased digestive system, glycan biosynthesis and metabolism, and vitamin B biosynthesis as the piglets aged. These findings suggest that marked gut microbial changes in Congjiang miniature piglets may contribute to understand the potential gut microbiota development of weaned infants.
doi:10.3389/fmicb.2016.01727
PMCID: PMC5090779  PMID: 27853453
Gut microbiota; Congjiang miniature piglet; Lactobacillus coleohominis; Eubacterium hallii; PICRUSt
16.  Genome-Wide Association of Stem Water Soluble Carbohydrates in Bread Wheat 
PLoS ONE  2016;11(11):e0164293.
Water soluble carbohydrates (WSC) in stems play an important role in buffering grain yield in wheat against biotic and abiotic stresses; however, knowledge of genes controlling WSC is very limited. We conducted a genome-wide association study (GWAS) using a high-density 90K SNP array to better understand the genetic basis underlying WSC, and to explore marker-based breeding approaches. WSC was evaluated in an association panel comprising 166 Chinese bread wheat cultivars planted in four environments. Fifty two marker-trait associations (MTAs) distributed across 23 loci were identified for phenotypic best linear unbiased estimates (BLUEs), and 11 MTAs were identified in two or more environments. Liner regression showed a clear dependence of WSC BLUE scores on numbers of favorable (increasing WSC content) and unfavorable alleles (decreasing WSC), indicating that genotypes with higher numbers of favorable or lower numbers of unfavorable alleles had higher WSC content. In silico analysis of flanking sequences of trait-associated SNPs revealed eight candidate genes related to WSC content grouped into two categories based on the type of encoding proteins, namely, defense response proteins and proteins triggered by environmental stresses. The identified SNPs and candidate genes related to WSC provide opportunities for breeding higher WSC wheat cultivars.
doi:10.1371/journal.pone.0164293
PMCID: PMC5089554  PMID: 27802269
17.  Activation of serotonin 5-HT2C receptor suppresses behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice 
Neuroscience letters  2015;607:23-28.
Abuse and dependence to heroin has evolved into a global epidemic as a significant clinical and societal problem with devastating consequences. Repeated exposure to heroin can induce long-lasting behavioral sensitization and withdrawal. Pharmacological activation of 5-HT2C receptors (5-HT2CRs) suppresses psychostimulant-induced drug-seeking and behavioral sensitization. The present study examined the effect of a selective 5-HT2CR agonist lorcaserin on behavioral sensitization and naloxone-precipitated withdrawal symptoms in heroin-treated mice. Male mice received heroin (1.0 mg/kg, s.c.) twice a day for 3 days and then drug treatment was suspended for 5 days. On day 9, a challenge dose of heroin (1.0 mg/kg) was administered to examine the expression of behavioral sensitization. Lorcaserin administered during the development, withdrawal or expression stage suppressed heroin-induced behavioral sensitization on day 9. Another cohort of mice received increasing doses of heroin over a 4.5-day period. Lorcaserin, or the positive control clonidine (an α2-adrenoceptor agonist) suppressed naloxone-precipitated withdrawal symptoms in heroin-treated mice. These findings suggest that activation of 5-HT2CRs suppresses behavioral sensitization and withdrawal in heroin-treated mice. Thus, pharmacological activation of 5-HT2CRs may represent a new avenue for the treatment of heroin addiction.
doi:10.1016/j.neulet.2015.09.013
PMCID: PMC4631619  PMID: 26375926
serotonin; 5-HT2C receptor; heroin; behavioral sensitization; withdrawal
19.  The effectiveness and safety of amisulpride in Chinese patients with schizophrenia: An 8‐week, prospective, open‐label, multicenter, single‐arm study 
Asia-Pacific Psychiatry  2016;8(3):241-244.
Abstract
Introduction
This study evaluated the effectiveness and safety of amisulpride in Chinese schizophrenia patients.
Methods
A multicenter, single‐arm Phase IV study (NCT01795183). Chinese patients with schizophrenia received amisulpride for 8 weeks. The primary endpoint was ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8.
Results
A total of 316 patients were enrolled; 295 were included in the effectiveness analysis; 66.8% (197/295) achieved ≥50% decrease in Positive and Negative Syndrome Scale total score from Baseline to Week 8. Nine patients discontinued treatment because of adverse events.
Discussion
Amisulpride had clinical effectiveness and was relatively well tolerated in Chinese patients with schizophrenia.
doi:10.1111/appy.12238
PMCID: PMC5071681  PMID: 27020720
amisulpride; antipsychotic agents/adverse effects; antipsychotic agents/therapeutic use; Chinese; Schizophrenia
20.  Melatonin improves age-induced fertility decline and attenuates ovarian mitochondrial oxidative stress in mice 
Scientific Reports  2016;6:35165.
Increasing evidence shows that melatonin protected against age-related mitochondrial oxidative damage. However, the protective effects of melatonin against ovarian aging has not been explored. Young Kunming females (aged 2–3 months) were fed with melatonin added to drinking water for 6 or 12 months (mo). We found that long-term (12 mo) melatonin treatment significantly reduced ovarian aging, as indicated by substantial increases in litter size, pool of follicles, and telomere length as well as oocyte quantity and quality. Melatonin treatment suppressed ovarian mitochondrial oxidative damage by decreasing mitochondrial reactive oxygen species (mROS) generation, inhibiting apoptosis, repressing collapse of mitochondrial membrane potential and preserving respiratory chain complex activities. Female mice fed with melatonin had enhanced mitochondrial antioxidant activities, thus reducing the risk of mitochondrial oxidative damage cause by free radicals. Notably, melatonin treatment enhanced SIRT3 activity but not the protein expression level, and increased the binding affinity of FoxO3a to the promoters of both superoxide dismutase 2 (SOD2) and catalase (CAT). In conclusion, melatonin exerted protection against aging-induced fertility decline and maintenance of mitochondrial redox balance.
doi:10.1038/srep35165
PMCID: PMC5059725  PMID: 27731402
21.  Experimental Evidence Shows the Importance of Behavioural Plasticity and Body Size under Competition in Waterfowl 
PLoS ONE  2016;11(10):e0164606.
When differently sized species feed on the same resources, interference competition may occur, which may negatively affect their food intake rate. It is expected that competition between species also alters behaviour and feeding patch selection. To assess these changes in behaviour and patch selection, we applied an experimental approach using captive birds of three differently sized Anatidae species: wigeon (Anas penelope) (~600 g), swan goose (Anser cygnoides) (~2700 g) and bean goose (Anser fabalis) (~3200 g). We quantified the functional response for each species and then recorded their behaviour and patch selection with and without potential competitors, using different species combinations. Our results showed that all three species acquired the highest nitrogen intake at relatively tall swards (6, 9 cm) when foraging in single species flocks in the functional response experiment. Goose species were offered foraging patches differing in sward height with and without competitors, and we tested for the effect of competition on foraging behaviour. The mean percentage of time spent feeding and being vigilant did not change under competition for all species. However, all species utilized strategies that increased their peck rate on patches across different sward heights, resulting in the same instantaneous and nitrogen intake rate. Our results suggest that variation in peck rate over different swards height permits Anatidae herbivores to compensate for the loss of intake under competition, illustrating the importance of behavioural plasticity in heterogeneous environments when competing with other species for resources.
doi:10.1371/journal.pone.0164606
PMCID: PMC5058547  PMID: 27727315
22.  Local anesthesia for pain control during transrectal ultrasound-guided prostate biopsy: a systematic review and meta-analysis 
Journal of Pain Research  2016;9:787-796.
Background
A meta-analysis was performed to evaluate the efficacy and safety of intrarectal local anesthestic (IRLA), periprostatic nerve block (PPNB), and the combined modalities in alleviating the pain during transrectal ultrasound (TRUS)-guided prostate biopsy.
Materials and methods
A literature review was performed to identify all published randomized controlled trials (RCTs) about IRLA vs no anesthesia or placebo gel; PPNB vs no injection, periprostatic placebo injection, or IRLA; combined PPNB and IRLA vs PPNB alone; and combined PPNB and intraprostatic nerve block (IPNB) vs PPNB alone before TRUS-guided biopsy. Sources included MEDILINE, EMBASE, and Cochrane Library from 1980 to 2016. The main outcomes were biopsy pain score, probe manipulation pain score, and anesthetic infiltration pain score assessed by the visual pain scale.
Results
A total of 26 articles involving 36 RCTs were used in this analysis: Although IRLA can lead to pain reduction, the result was not statistically significant when compared with no anesthesia or placebo gel (weighted mean difference [WMD]: −0.22, 95% CI: −0.45 to 0, P=0.06). PPNB can lead to significantly lower biopsy pain scores when compared with no analgesia (WMD: −1.32, 95% CI: −1.68 to −0.95, P<0.00001), placebo injection (WMD: −2.62, 95% CI: −3.16 to −2.07, P<0.00001), or IRLA (WMD: −1.31, 95% CI: −1.40 to −1.22, P<0.00001). PPNB + IRLA can lead to significantly lower biopsy pain scores when compared with PPNB alone (WMD: −0.45, 95% CI: −0.62 to −0.28, P<0.00001). PPNB + IPNB can lead to significantly lower biopsy pain scores when compared with PPNB alone (WMD: −0.73, 95% CI: −0.92 to −0.55, P<0.00001). There were no severe reported general or local complications related to local anesthesia.
Conclusion
This meta-analysis indicates that a combination of PPNB and IRLA/IPNB is effective and safe in alleviating the pain during TRUS-guided prostate biopsy. Further high-quality RCTs are needed to validate this result.
doi:10.2147/JPR.S117451
PMCID: PMC5067058  PMID: 27785093
local anesthesia; biopsy; meta-analysis; pain control; prostate
23.  The anti-hyperglycemic efficacy of a lipid-lowering drug Daming capsule and the underlying signaling mechanisms in a rat model of diabetes mellitus 
Scientific Reports  2016;6:34284.
Diabetes mellitus (DM) is a metabolic disorder manifested by hyperglycemia. Daming Capsule (DMC), a combination of traditional Chinese herbs, is used clinically as a lipid-lowering drug. This study was designed to evaluate if DMC possesses an anti-hyperglycemic effect and to elucidate the underlying mechanisms. Compared to diabetic rats, the rats received DMC (200 mg/kg/d) had significantly lower blood lipid and glucose levels. DMC markedly restored the decreased secretion of GLP-1 and GIP as well as the coding gene GCG and GIP in ileum. Moreover, DMC normalized depressed GCG and GIP transcription by significantly enhancing the GSK-3β/β-catenin signaling pathway and expression of TCF7L2, a transactivator of GCG and GIP in diabetic rats. DMC possesses an anti-hyperglycemic property characterized by preservation/stimulation of GLP-1 and GIP secretion in DM rats. Here, we proposed DMC → GSK-3β/β-catenin↑ → TCF7L2↑ → GLP-1, GIP secretion↑ → blood glucose↓ as a regulatory pathway of blood glucose homeostasis. Our findings suggest DMC as a promising therapeutic drug in the clinical treatment of diabetes.
doi:10.1038/srep34284
PMCID: PMC5056381  PMID: 27721485
24.  Formation of diploid and triploid hybrid groupers (hybridization of Epinephelus coioides ♀ × Epinephelus lanceolatus ♂) and their 5S gene analysis 
BMC Genetics  2016;17:136.
Background
Interspecies hybridization is widely used to achieve heterosis or hybrid vigor, which has been observed and harnessed by breeders for centuries. Natural allopolyploid hybrids generally exhibit more superior heterosis than both the diploid progenies and their parental species. However, polyploid formation processes have been long ignored, the genetic basis of heterosis in polyploids remains elusive.
Results
In the present study, triploid hybrids had been demonstrated to contain two sets of chromosomes from mother species and one set from father species. Cellular polyploidization process in the embryos had been traced. The triploid hybrids might be formed by failure formation of the second polarized genome during the second meiosis stage. Four spindle centers were observed in anaphase stage of the first cell division. Three spindle centers were observed in side of cell plate after the first cell division.
The 5S rDNA genes of four types of groupers were cloned and analyzed. The diploid and triploid hybrids had been proved to contain the tandem chimera structures which were recombined by maternal and paternal monomer units. The results indicated that genome re-fusion had occurred in the hybrid progenies.
To further elucidate the genetic patterns of diploid and triploid hybrids, fluorescence chromosome location had been carried out, maternal 5S gene (M-386) were used as the probe. The triploid hybrids contained fewer fluorescence loci numbers than the maternal species. The results indicated that participation of paternal 5S gene in the triploid hybrid genome had degraded the match rates of M-386 probe.
Conclusions
Our study is the first to investigate the cellular formation processes of natural allopolyploids in hybrid fish, the cellular polyploidization process may be caused by failure formation of the second polarized genome during the meiosis, and our results will provide the molecular basis of hybrid vigor in interspecies hybridization.
Electronic supplementary material
The online version of this article (doi:10.1186/s12863-016-0443-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12863-016-0443-9
PMCID: PMC5054551  PMID: 27717311
Natural polyploidization; Embryo development; Grouper; 5S gene; Heterosis
25.  Efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung squamous cell carcinoma 
Medicine  2016;95(40):e5077.
Abstract
Introduction:
Currently, the options are limited for the treatment of patients who have failed 2 lines of chemotherapy for advanced lung squamous cell carcinoma (SCC). Recently, nivolumab, a fully human IgG4 programmed death 1 immune checkpoint inhibitor antibody, was approved to treat patients with advanced stage, relapsed/refractory lung SCC. Although nivolumab has demonstrated antitumor activity with survival benefit in Caucasian patients, its efficacy in Asian patients is unknown.
Case Report:
In this report, we describe a Chinese patient with relapsed advanced stage lung SCC who had an excellent response to nivolumab after only 2 doses without any adverse effects. Immunohistochemical analysis indicated the tumor was stained positive for programmed death-ligand 1.
Conclusion:
To our knowledge, this is the first report of satisfactory efficacy of short-term nivolumab treatment in a Chinese patient with relapsed advanced-stage lung SCC. Further clinical trials in Asian countries are needed to test whether nivolumab immunotherapy is a safe and effective treatment for Asian patients with lung SCC.
doi:10.1097/MD.0000000000005077
PMCID: PMC5059083  PMID: 27749580
lung squamous cell carcinoma; nivolumab; PD-L1; relapsed; short-term

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