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1.  ESICM LIVES 2016: part three 
Velasquez, T. | Mackey, G. | Lusk, J. | Kyle, U. G. | Fontenot, T. | Marshall, P. | Shekerdemian, L. S. | Coss-Bu, J. A. | Nishigaki, A. | Yatabe, T. | Tamura, T. | Yamashita, K. | Yokoyama, M. | Ruiz-Rodriguez, J. C. | Encina, B. | Belmonte, R. | Troncoso, I. | Tormos, P. | Riveiro, M. | Baena, J. | Sanchez, A. | Bañeras, J. | Cordón, J. | Duran, N. | Ruiz, A. | Caballero, J. | Nuvials, X. | Riera, J. | Serra, J. | Rutten, A. M. F. | van Ieperen, S. N. M. | Der Kinderen, E. P. H. M. | Van Logten, T. | Kovacikova, L. | Skrak, P. | Zahorec, M. | Kyle, U. G. | Akcan-Arikan, A. | Silva, J. C. | Mackey, G. | Lusk, J. | Goldsworthy, M. | Shekerdemian, L. S. | Coss-Bu, J. A. | Wood, D. | Harrison, D. | Parslow, R. | Davis, P. | Pappachan, J. | Goodwin, S. | Ramnarayan, P. | Chernyshuk, S. | Yemets, H. | Zhovnir, V. | Pulitano’, S. M. | De Rosa, S. | Mancino, A. | Villa, G. | Tosi, F. | Franchi, P. | Conti, G. | Patel, B. | Khine, H. | Shah, A. | Sung, D. | Singer, L. | Haghbin, S. | Inaloo, S. | Serati, Z. | Idei, M. | Nomura, T. | Yamamoto, N. | Sakai, Y. | Yoshida, T. | Matsuda, Y. | Yamaguchi, Y. | Takaki, S. | Yamaguchi, O. | Goto, T. | Longani, N. | Medar, S. | Abdel-Aal, I. R. | El Adawy, A. S. | Mohammed, H. M. E. H. | Mohamed, A. N. | Parry, S. M. | Knight, L. D. | Denehy, L. | De Morton, N. | Baldwin, C. E. | Sani, D. | Kayambu, G. | da Silva, V. Z. M. | Phongpagdi, P. | Puthucheary, Z. A. | Granger, C. L. | Rydingsward, J. E. | Horkan, C. M. | Christopher, K. B. | McWilliams, D. | Jones, C. | Reeves, E. | Atkins, G. | Snelson, C. | Aitken, L. M. | Rattray, J. | Kenardy, J. | Hull, A. M. | Ullman, A. | Le Brocque, R. | Mitchell, M. | Davis, C. | Macfarlane, B. | Azevedo, J. C. | Rocha, L. L. | De Freitas, F. F. M. | Cavalheiro, A. M. | Lucinio, N. M. | Lobato, M. S. | Ebeling, G. | Kraegpoeth, A. | Laerkner, E. | De Brito-Ashurst, I. | White, C. | Gregory, S. | Forni, L. G. | Flowers, E. | Curtis, A. | Wood, C. A. | Siu, K. | Venkatesan, K. | Muhammad, J. B. H. | Ng, L. | Seet, E. | Baptista, N. | Escoval, A. | Tomas, E. | Agrawal, R. | Mathew, R. | Varma, A. | Dima, E. | Charitidou, E. | Perivolioti, E. | Pratikaki, M. | Vrettou, C. | Giannopoulos, A. | Zakynthinos, S. | Routsi, C. | Atchade, E. | Houzé, S. | Jean-Baptiste, S. | Thabut, G. | Genève, C. | Tanaka, S. | Lortat-Jacob, B. | Augustin, P. | Desmard, M. | Montravers, P. | de Molina, F. J. González | Barbadillo, S. | Alejandro, R. | Álvarez-Lerma, F. | Vallés, J. | Catalán, R. M. | Palencia, E. | Jareño, A. | Granada, R. M. | Ignacio, M. L. | Cui, N. | Liu, D. | Wang, H. | Su, L. | Qiu, H. | Li, R. | Jaffal, K. | Rouzé, A. | Poissy, J. | Sendid, B. | Nseir, S. | Paramythiotou, E. | Rizos, M. | Frantzeskaki, F. | Antoniadou, A. | Vourli, S. | Zerva, L. | Armaganidis, A. | Riera, J. | Gottlieb, J. | Greer, M. | Wiesner, O. | Martínez, M. | Acuña, M. | Rello, J. | Welte, T. | Atchade, E. | Mignot, T. | Houzé, S. | Jean-Baptiste, S. | Thabut, G. | Lortat-Jacob, B. | Tanaka, S. | Augustin, P. | Desmard, M. | Montravers, P. | Soussi, S. | Dudoignon, E. | Ferry, A. | Chaussard, M. | Benyamina, M. | Alanio, A. | Touratier, S. | Chaouat, M. | Lafaurie, M. | Mimoun, M. | Mebazaa, A. | Legrand, M. | Sheils, M. A. | Patel, C. | Mohankumar, L. | Akhtar, N. | Noriega, S. K. Pacheco | Aldana, N. Navarrete | León, J. L. Ávila | Baquero, J. Durand | Bernal, F. Fernández | Ahmadnia, E. | Hadley, J. S. | Millar, M. | Hall, D. | Hewitt, H. | Yasuda, H. | Sanui, M. | Komuro, T. | Kawano, S. | Andoh, K. | Yamamoto, H. | Noda, E. | Hatakeyama, J. | Saitou, N. | Okamoto, H. | Kobayashi, A. | Takei, T. | Matsukubo, S. | Rotzel, H. B. | Lázaro, A. Serrano | Prada, D. Aguillón | Gimillo, M. Rodriguez | Barinas, O. Diaz | Cortes, M. L. Blasco | Franco, J. Ferreres | Roca, J. M. Segura | Carratalá, A. | Gonçalves, B. | Turon, R. | Mendes, A. | Miranda, F. | Mata, P. J. | Cavalcanti, D. | Melo, N. | Lacerda, P. | Kurtz, P. | Righy, C. | Rosario, L. E. de la Cruz | Lesmes, S. P. Gómez | Romero, J. C. García | Herrera, A. N. García | Pertuz, E. D. Díaz | Sánchez, M. J. Gómez | Sanz, E. Regidor | Hualde, J. Barado | Hernández, A. Ansotegui | Irazabal, J. M. Guergué | Spatenkova, V. | Bradac, O. | Suchomel, P. | Urli, T. | Lazzeri, E. Heusch | Aspide, R. | Zanello, M. | Perez-Borrero, L. | Garcia-Alvarez, J. M. | Arias-Verdu, M. D. | Aguilar-Alonso, E. | Rivera-Fernandez, R. | Mora-Ordoñez, J. | De La Fuente-Martos, C. | Castillo-Lorente, E. | Guerrero-Lopez, F. | Lesmes, S. P. Gómez | Rosario, L. E. De la Cruz | Pertuz, E. D. Díaz | Hernández, A. Ansotegui | Romero, J. C. García | Sánchez, M. J. Gómez | Herrera, A. N. García | Ramírez, J. Roldán | Sanz, E. Regidor | Hualde, J. Barado | León, J. P. Tirapu | Navarro-Guillamón, L. | Cordovilla-Guardia, S. | Iglesias-Santiago, A. | Guerrero-López, F. | Fernández-Mondéjar, E. | Vidal, A. | Perez, M. | Juez, A. | Arias, N. | Colino, L. | Perez, J. L. | Pérez, H. | Calpe, P. | Alcala, M. A. | Robaglia, D. | Perez, C. | Lan, S. K. | Cunha, M. M. | Moreira, T. | Santos, F. | Lafuente, E. | Fernandes, M. J. | Silva, J. G. | Rosario, L. E. de la Cruz | Lesmes, S. P. Gómez | Herrera, A. N. García | Romero, J. C. García | Pertuz, E. D. Díaz | Sánchez, M. J. Gómez | Sanz, E. Regidor | Echeverría, J. G. Armando | Hernández, A. Ansotegui | Hualde, J. Barado | Podlepich, V. | Sokolova, E. | Alexandrova, E. | Lapteva, K. | Kurtz, P. | Shuinotsuka, C. | Rabello, L. | Vianna, G. | Reis, A. | Cairus, C. | Salluh, J. | Bozza, F. | Torres, J. C. Barrios | Araujo, N. J. Fernández | García-Olivares, P. | Keough, E. | Dalorzo, M. | Tang, L. K. | De Sousa, I. | Díaz, M. | Marcos-Zambrano, L. J. | Guerrero, J. E. | Gomez, S. E. Zamora | Lopez, G. D. Hernandez | Cuellar, A. I. Vazquez | Nieto, O. R. Perez | Gonzalez, J. A. Castanon | Bhasin, D. | Rai, S. | Singh, H. | Gupta, O. | Bhattal, M. K. | Sampley, S. | Sekhri, K. | Nandha, R. | Aliaga, F. A. | Olivares, F. | Appiani, F. | Farias, P. | Alberto, F. | Hernández, A. | Pons, S. | Sonneville, R. | Bouadma, L. | Neuville, M. | Mariotte, E. | Radjou, A. | Lebut, J. | Chemam, S. | Voiriot, G. | Dilly, M. P. | Mourvillier, B. | Dorent, R. | Nataf, P. | Wolff, M. | Timsit, J. F. | Ediboglu, O. | Ataman, S. | Ozkarakas, H. | Kirakli, C. | Vakalos, A. | Avramidis, V. | Obukhova, O. | Kurmukov, I. A. | Kashiya, S. | Golovnya, E. | Baikova, V. N. | Ageeva, T. | Haritydi, T. | Kulaga, E. V. | Rios-Toro, J. J. | Perez-Borrero, L. | Aguilar-Alonso, E. | Arias-Verdu, M. D. | Garcia-Alvarez, J. M. | Lopez-Caler, C. | De La Fuente-Martos, C. | Rodriguez-Fernandez, S. | Sanchez-Orézzoli, M. Gomez | Martin-Gallardo, F. | Nikhilesh, J. | Joshi, V. | Villarreal, E. | Ruiz, J. | Gordon, M. | Quinza, A. | Gimenez, J. | Piñol, M. | Castellanos, A. | Ramirez, P. | Jeon, Y. D. | Jeong, W. Y. | Kim, M. H. | Jeong, I. Y. | Ahn, M. Y. | Ahn, J. Y. | Han, S. H. | Choi, J. Y. | Song, Y. G. | Kim, J. M. | Ku, N. S. | Shah, H. | Kellner, F. | Rezai, F. | Mistry, N. | Yodice, P. | Ovnanian, V. | Fless, K. | Handler, E. | Alejos, R. Martínez | Romeu, J. D. Martí | Antón, D. González | Quinart, A. | Martí, A. Torres | Llaurado-Serra, M. | Lobo-Civico, A. | Ventura-Rosado, A. | Piñol-Tena, A. | Pi-Guerrero, M. | Paños-Espinosa, C. | Peralvo-Bernat, M. | Marine-Vidal, J. | Gonzalez-Engroba, R. | Montesinos-Cerro, N. | Treso-Geira, M. | Valeiras-Valero, A. | Martinez-Reyes, L. | Sandiumenge, A. | Jimenez-Herrera, M. F. | Helyar, S. | Riozzi, P. | Noon, A. | Hallows, G. | Cotton, H. | Keep, J. | Hopkins, P. A. | Taggu, A. | Renuka, S. | Sampath, S. | Rood, P. J. T. | Frenzel, T. | Verhage, R. | Bonn, M. | Pickkers, P. | van der Hoeven, J. G. | van den Boogaard, M. | Corradi, F. | Melnyk, L. | Moggia, F. | Pienovi, R. | Adriano, G. | Brusasco, C. | Mariotti, L. | Lattuada, M. | Bloomer, M. J. | Coombs, M. | Ranse, K. | Endacott, R. | Maertens, B. | Blot, K. | Blot, S. | Amerongen, M. P. van Nieuw | van der Heiden, E. S. | Twisk, J. W. R. | Girbes, A. R. J. | Spijkstra, J. J. | Riozzi, P. | Helyar, S. | Cotton, H. | Hallows, G. | Noon, A. | Bell, C. | Peters, K. | Feehan, A. | Keep, J. | Hopkins, P. A. | Churchill, K. | Hawkins, K. | Brook, R. | Paver, N. | Endacott, R. | Maistry, N. | van Wijk, A. | Rouw, N. | van Galen, T. | Evelein-Brugman, S. | Taggu, A. | Krishna, B. | Sampath, S. | Putzu, A. | Fang, M. | Berto, M. Boscolo | Belletti, A. | Cassina, T. | Cabrini, L. | Mistry, M. | Alhamdi, Y. | Welters, I. | Abrams, S. T. | Toh, C. H. | Han, H. S. | Gil, E. M. | Lee, D. S. | Park, C. M. | Winder-Rhodes, S. | Lotay, R. | Doyle, J. | Ke, M. W. | Huang, W. C. | Chiang, C. H. | Hung, W. T. | Cheng, C. C. | Lin, K. C. | Lin, S. C. | Chiou, K. R. | Wann, S. R. | Shu, C. W. | Kang, P. L. | Mar, G. Y. | Liu, C. P. | Dubó, S. | Aquevedo, A. | Jibaja, M. | Berrutti, D. | Labra, C. | Lagos, R. | García, M. F. | Ramirez, V. | Tobar, M. | Picoita, F. | Peláez, C. | Carpio, D. | Alegría, L. | Hidalgo, C. | Godoy, K. | Bakker, J. | Hernández, G. | Sadamoto, Y. | Katabami, K. | Wada, T. | Ono, Y. | Maekawa, K. | Hayakawa, M. | Sawamura, A. | Gando, S. | Marin-Mateos, H. | Perez-Vela, J. L. | Garcia-Gigorro, R. | Peiretti, M. A. Corres | Lopez-Gude, M. J. | Chacon-Alves, S. | Renes-Carreño, E. | Montejo-González, J. C. | Parlevliet, K. L. | Touw, H. R. W. | Beerepoot, M. | Boer, C. | Elbers, P. W. G. | Tuinman, P. R. | Abdelmonem, S. A. | Helmy, T. A. | El Sayed, I. | Ghazal, S. | Akhlagh, S. H. | Masjedi, M. | Hozhabri, K. | Kamali, E. | Zýková, I. | Paldusová, B. | Sedlák, P. | Morman, D. | Youn, A. M. | Ohta, Y. | Sakuma, M. | Bates, D. | Morimoto, T. | Su, P. L. | Chang, W. Y. | Lin, W. C. | Chen, C. W. | Facchin, F. | Zarantonello, F. | Panciera, G. | De Cassai, A. | Venrdramin, A. | Ballin, A. | Tonetti, T. | Persona, P. | Ori, C. | Del Sorbo, L. | Rossi, S. | Vergani, G. | Cressoni, M. | Chiumello, D. | Chiurazzi, C. | Brioni, M. | Algieri, I. | Tonetti, T. | Guanziroli, M. | Colombo, A. | Tomic, I. | Colombo, A. | Crimella, F. | Carlesso, E. | Gasparovic, V. | Gattinoni, L. | Neto, A. Serpa | Schmidt, M. | Pham, T. | Combes, A. | de Abreu, M. Gama | Pelosi, P. | Schultz, M. J. | Katira, B. H. | Engelberts, D. | Giesinger, R. E. | Ackerley, C. | Yoshida, T. | Zabini, D. | Otulakowski, G. | Post, M. | Kuebler, W. M. | McNamara, P. J. | Kavanagh, B. P. | Pirracchio, R. | Rigon, M. Resche | Carone, M. | Chevret, S. | Annane, D. | Eladawy, S. | El-Hamamsy, M. | Bazan, N. | Elgendy, M. | De Pascale, G. | Vallecoccia, M. S. | Cutuli, S. L. | Di Gravio, V. | Pennisi, M. A. | Conti, G. | Antonelli, M. | Andreis, D. T. | Khaliq, W. | Singer, M. | Hartmann, J. | Harm, S. | Carmona, S. Alcantara | Almudevar, P. Matia | Abellán, A. Naharro | Ramos, J. Veganzones | Pérez, L. Pérez | Valbuena, B. Lobo | Sanz, N. Martínez | Simón, I. Fernández | Arrigo, M. | Feliot, E. | Deye, N. | Cariou, A. | Guidet, B. | Jaber, S. | Leone, M. | Resche-Rigon, M. | Baron, A. Vieillard | Legrand, M. | Gayat, E. | Mebazaa, A. | Balik, M. | Kolnikova, I. | Maly, M. | Waldauf, P. | Tavazzi, G. | Kristof, J. | Herpain, A. | Su, F. | Post, E. | Taccone, F. | Vincent, J. L. | Creteur, J. | Lee, C. | Hatib, F. | Jian, Z. | Buddi, S. | Cannesson, M. | Fileković, S. | Turel, M. | Knafelj, R. | Gorjup, V. | Stanić, R. | Gradišek, P. | Cerović, O. | Mirković, T. | Noč, M. | Tirkkonen, J. | Hellevuo, H. | Olkkola, K. T. | Hoppu, S. | Lin, K. C. | Hung, W. T. | Chiang, C. C. | Huang, W. C. | Juan, W. C. | Lin, S. C. | Cheng, C. C. | Lin, P. H. | Fong, K. Y. | Hou, D. S. | Kang, P. L. | Wann, S. R. | Chen, Y. S. | Mar, G. Y. | Liu, C. P. | Paul, M. | Bougouin, W. | Geri, G. | Dumas, F. | Champigneulle, B. | Legriel, S. | Charpentier, J. | Mira, J. P. | Sandroni, C. | Cariou, A. | Zimmerman, J. | Sullivan, E. | Noursadeghi, M. | Fox, B. | Sampson, D. | McHugh, L. | Yager, T. | Cermelli, S. | Seldon, T. | Bhide, S. | Brandon, R. A. | Brandon, R. B. | Zwaag, J. | Beunders, R. | Pickkers, P. | Kox, M. | Gul, F. | Arslantas, M. K. | Genc, D. | Zibandah, N. | Topcu, L. | Akkoc, T. | Cinel, I. | Greco, E. | Lauretta, M. P. | Andreis, D. T. | Singer, M. | Garcia, I. Palacios | Cordero, M. | Martin, A. Diaz | Pallás, T. Aldabó | Montero, J. Garnacho | Rey, J. Revuelto | Malo, L. Roman | Montoya, A. A. Tanaka | Martinez, A. D. C. Amador | Ayala, L. Y. Delgado | Zepeda, E. Monares | Granillo, J. Franco | Sanchez, J. Aguirre | Alejo, G. Camarena | Cabrera, A. Rugerio | Montenegro, A. Pedraza | Pham, T. | Beduneau, G. | Schortgen, F. | Piquilloud, L. | Zogheib, E. | Jonas, M. | Grelon, F. | Runge, I. | Terzi, N. | Grangé, S. | Barberet, G. | Guitard, P. G. | Frat, J. P. | Constan, A. | Chrétien, J. M. | Mancebo, J. | Mercat, A. | Richard, J. C. M. | Brochard, L. | Soilemezi, E. | Koco, E. | Savvidou, S. | Nouris, C. | Matamis, D. | Di Mussi, R. | Spadaro, S. | Volta, C. A. | Mariani, M. | Colaprico, A. | Antonio, C. | Bruno, F. | Grasso, S. | Rodriguez, A. | Martín-Loeches, I. | Díaz, E. | Masclans, J. R. | Gordo, F. | Solé-Violán, J. | Bodí, M. | Avilés-Jurado, F. X. | Trefler, S. | Magret, M. | Reyes, L. F. | Marín-Corral, J. | Yebenes, J. C. | Esteban, A. | Anzueto, A. | Aliberti, S. | Restrepo, M. I. | Larsson, J. Skytte | Redfors, B. | Ricksten, S. E. | Haines, R. | Powell-Tuck, J. | Leonard, H. | Ostermann, M. | Berthelsen, R. E. | Itenov, T. S. | Perner, A. | Jensen, J. U. | Ibsen, M. | Jensen, A. E. K. | Bestle, M. H. | Bucknall, T. | Dixon, J. | Boa, F. | MacPhee, I. | Philips, B. J. | Doyle, J. | Saadat, F. | Samuels, T. | Huddart, S. | McCormick, B. | DeBrunnar, R. | Preece, J. | Swart, M. | Peden, C. | Richardson, S. | Forni, L. | Kalfon, P. | Baumstarck, K. | Estagnasie, P. | Geantot, M. A. | Berric, A. | Simon, G. | Floccard, B. | Signouret, T. | Boucekine, M. | Fromentin, M. | Nyunga, M. | Sossou, A. | Venot, M. | Robert, R. | Follin, A. | Renault, A. | Garrouste, M. | Collange, O. | Levrat, Q. | Villard, I. | Thévenin, D. | Pottecher, J. | Patrigeon, R. G. | Revel, N. | Vigne, C. | Mimoz, O. | Auquier, P. | Pawar, S. | Jacques, T. | Deshpande, K. | Pusapati, R. | Wood, B. | Pulham, R. A. | Wray, J. | Brown, K. | Pierce, C. | Nadel, S. | Ramnarayan, P. | Azevedo, J. R. | Montenegro, W. S. | Rodrigues, D. P. | Sousa, S. C. | Araujo, V. F. | Leitao, A. L. | Prazeres, P. H. | Mendonca, A. V. | Paula, M. P. | Das Neves, A. | Loudet, C. I. | Busico, M. | Vazquez, D. | Villalba, D. | Lischinsky, A. | Veronesi, M. | Emmerich, M. | Descotte, E. | Juliarena, A. | Bisso, M. Carboni | Grando, M. | Tapia, A. | Camargo, M. | Ulla, D. Villani | Corzo, L. | dos Santos, H. Placido | Ramos, A. | Doglia, J. A. | Estenssoro, E. | Carbonara, M. | Magnoni, S. | Donald, C. L. Mac | Shimony, J. S. | Conte, V. | Triulzi, F. | Stretti, F. | Macrì, M. | Snyder, A. Z. | Stocchetti, N. | Brody, D. L. | Podlepich, V. | Shimanskiy, V. | Savin, I. | Lapteva, K. | Chumaev, A. | Tjepkema-Cloostermans, M. C. | Hofmeijer, J. | Beishuizen, A. | Hom, H. | Blans, M. J. | van Putten, M. J. A. M. | Longhi, L. | Frigeni, B. | Curinga, M. | Mingone, D. | Beretta, S. | Patruno, A. | Gandini, L. | Vargiolu, A. | Ferri, F. | Ceriani, R. | Rottoli, M. R. | Lorini, L. | Citerio, G. | Pifferi, S. | Battistini, M. | Cordolcini, V. | Agarossi, A. | Di Rosso, R. | Ortolano, F. | Stocchetti, N. | Lourido, C. Mora | Cabrera, J. L. Santana | Santana, J. D. Martín | Alzola, L. Melián | del Rosario, C. García | Pérez, H. Rodríguez | Torrent, R. Lorenzo | Eslami, S. | Dalhuisen, A. | Fiks, T. | Schultz, M. J. | Hanna, A. Abu | Spronk, P. E. | Wood, M. | Maslove, D. | Muscedere, J. | Scott, S. H.
doi:10.1186/s40635-016-0100-7
PMCID: PMC5042925
2.  Ultrafast 3D spin-echo acquisition improves Gadolinium-enhanced MRI signal contrast enhancement 
Scientific Reports  2014;4:5061.
Long scan times of 3D volumetric MR acquisitions usually necessitate ultrafast in vivo gradient-echo acquisitions, which are intrinsically susceptible to magnetic field inhomogeneities. This is especially problematic for contrast-enhanced (CE)-MRI applications, where non-negligible T2* effect of contrast agent deteriorates the positive signal contrast and limits the available range of MR acquisition parameters and injection doses. To overcome these shortcomings without degrading temporal resolution, ultrafast spin-echo acquisitions were implemented. Specifically, a multiplicative acceleration factor from multiple spin echoes (×32) and compressed sensing (CS) sampling (×8) allowed highly-accelerated 3D Multiple-Modulation-Multiple-Echo (MMME) acquisition. At the same time, the CE-MRI of kidney with Gd-DOTA showed significantly improved signal enhancement for CS-MMME acquisitions (×7) over that of corresponding FLASH acquisitions (×2). Increased positive contrast enhancement and highly accelerated acquisition of extended volume with reduced RF irradiations will be beneficial for oncological and nephrological applications, in which the accurate in vivo 3D quantification of contrast agent concentration is necessary with high temporal resolution.
doi:10.1038/srep05061
PMCID: PMC4034007  PMID: 24863102
3.  Menin mediates epigenetic regulation via histone H3 lysine 9 methylation 
Cell Death & Disease  2013;4(4):e583-.
Menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, is a tumor suppressor that leads to multiple endocrine tumors upon loss of its function. Menin functions as a transcriptional activator by tethering MLL complex to mediate histone H3 K4 methylation. It also functions as a repressor. However, the molecular mechanism of how menin contributes to the opposite outcome in gene expression is largely unknown. Here, we investigated the role of menin in the epigenetic regulation of transcription mediated by histone covalent modification. We show that the global methylation level of histone H3 K9, as well as H3 K4, was decreased in Men1−/− MEF cells. Consistently, menin was able to interact with the suppressor of variegation 3–9 homolog family protein, SUV39H1, to mediate H3 K9 methylation. This interaction decreased when patient-derived MEN1 mutation was introduced into the SUV39H1-interaction domain. We show that menin mediated different chromatin changes depending on target genes. Chromatin immunoprecipitation studies showed that menin directly associated with the GBX2 promoter and menin-dependent recruitment of SUV39H1 was essential for chromatin remodeling and transcriptional regulation. These results provide a molecular basis of how menin functions as a transcriptional repressor and suggest that menin-dependent integration of H3 K9 methylation might play an important role in preventing tumors.
doi:10.1038/cddis.2013.98
PMCID: PMC3668625  PMID: 23579270
menin; tumor suppressor; histone methylation; SUV39H1
4.  Underwater superoleophobicity, anti-oil and ultra-broadband enhanced absorption of metallic surfaces produced by a femtosecond laser inspired by fish and chameleons 
Scientific Reports  2016;6:36557.
Reported here is the bio-inspired and robust function of underwater superoleophobic, anti-oil metallic surfaces with ultra-broadband enhanced optical absorption obtained through femtosecond laser micromachining. Three distinct surface structures are fabricated using a wide variety of processing parameters. Underwater superoleophobic and anti-oil surfaces containing coral-like microstructures with nanoparticles and mount-like microstructures are achieved. These properties of the as-prepared surfaces exhibit good chemical stability when exposed to various types of oils and when immersed in water with a wide range of pH values. Moreover, coral-like microstructures with nanoparticle surfaces show strongly enhanced optical absorption over a broadband wavelength range from 0.2–25 μm. The potential mechanism for the excellent performance of the coral-like microstructures with a nanoparticle surface is also discussed. This multifunctional surface has potential applications in military submarines, amphibious military aircraft and tanks, and underwater anti-oil optical counter-reconnaissance devices.
doi:10.1038/srep36557
PMCID: PMC5098196  PMID: 27819287
6.  A miRNA-based signature predicts development of disease recurrence in HER2 positive breast cancer after adjuvant trastuzumab-based treatment 
Scientific Reports  2016;6:33825.
Approximately 20% of HER2 positive breast cancer develops disease recurrence after adjuvant trastuzumab treatment. This study aimed to develop a molecular prognostic model that can reliably stratify patients by risk of developing disease recurrence. Using miRNA microarrays, nine miRNAs that differentially expressed between the recurrent and non-recurrent patients were identified. Then, we validated the expression of these miRNAs using qRT-PCR in training set (n = 101), and generated a 2-miRNA (miR-4734 and miR-150-5p) based prognostic signature. The prognostic accuracy of this classifier was further confirmed in an internal testing set (n = 57), and an external independent testing set (n = 53). Besides, by comparing the ROC curves, we found the incorporation of this miRNA based classifier into TNM stage could improve the prognostic performance of TNM system. The results indicated the 2-miRNA based signature was a reliable prognostic biomarker for patients with HER2 positive breast cancer.
doi:10.1038/srep33825
PMCID: PMC5030658  PMID: 27650797
7.  Isolation of H5N6, H7N9 and H9N2 avian influenza A viruses from air sampled at live poultry markets in China, 2014 and 2015 
Zoonotic infections by avian influenza viruses occur at the human–poultry interface, but the modes of transmission have not been fully investigated. We assessed the potential for airborne and fomite transmission at live poultry markets in Guangzhou city and in Hong Kong Special Administrative Region (SAR), China, during 2014 and 2015. Viral genome and infectious avian influenza A viruses of H5N6, H7N9, and H9N2 subtypes were detected predominantly from particles larger or equal to 1 μm in diameter in the air sampled with cyclone-based bioaerosol samplers at the live poultry markets in Guangzhou. Influenza A(H9N2) viruses were ubiquitously isolated every month during the study period from air and environmental swabs, and different lineages of H9N2 virus were isolated from markets where chickens and minor land-based poultry were sold. The use of de-feathering devices increased the quantity of virus-laden airborne particles while market closure reduced the amount of such particles. The results highlight the possibility of airborne transmission of avian influenza viruses among poultry or from poultry to humans within such settings. This may explain epidemiological observations in which some patients with H7N9 infection reported being in markets but no direct contact with live poultry or poultry stalls.
doi:10.2807/1560-7917.ES.2016.21.35.30331
PMCID: PMC5015459  PMID: 27608369
8.  Substantial Underestimation of Post-Harvest Burning Emissions in the North China Plain Revealed by Multi-Species Space Observations 
Scientific Reports  2016;6:32307.
The large-scale burning of crop residues in the North China Plain (NCP), one of the most densely populated world regions, was recently recognized to cause severe air pollution and harmful health effects. A reliable quantification of the magnitude of these fires is needed to assess regional air quality. Here, we use an eight-year record (2005–2012) of formaldehyde measurements from space to constrain the emissions of volatile organic compounds (VOCs) in this region. Using inverse modelling, we derive that satellite-based post-harvest burning fluxes are, on average, at least a factor of 2 higher than state-of-the-art bottom-up statistical estimates, although with significant interannual variability. Crop burning is calculated to cause important increases in surface ozone (+7%) and fine aerosol concentrations (+18%) in the North China Plain in June. The impact of crop fires is also found in satellite observations of other species, glyoxal, nitrogen dioxide and methanol, and we show that those measurements validate the magnitude of the top-down fluxes. Our study indicates that the top-down crop burning fluxes of VOCs in June exceed by almost a factor of 2 the combined emissions from other anthropogenic activities in this region, underscoring the need for targeted actions towards changes in agricultural management practices.
doi:10.1038/srep32307
PMCID: PMC5006073  PMID: 27577535
9.  Long noncoding RNA related to periodontitis interacts with miR-182 to upregulate osteogenic differentiation in periodontal mesenchymal stem cells of periodontitis patients 
Wang, L | Wu, F | Song, Y | Li, X | Wu, Q | Duan, Y | Jin, Z
Cell Death & Disease  2016;7(8):e2327-.
Periodontitis impairs the osteogenic differentiation of human periodontal mesenchymal stem cells (hPDLSCs), but the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs (lncRNAs) have been demonstrated to have significant roles under both physiologic and pathological conditions. In this study, we performed comprehensive lncRNA profiling by lncRNA microarray analysis and identified a novel lncRNA, osteogenesis impairment-related lncRNA of PDLSCs from periodontitis patients (lncRNA-POIR), the expression of which was significantly decreased in PDLSCs from periodontitis patients (pPDLSCs) and was upregulated by osteogenic induction. To study the functions of lncRNA-POIR, we prepared cells with overexpression and knockdown of lncRNA-POIR and found that lncRNA-POIR positively regulated osteogenic differentiation of hPDLSCs and pPDLSCs both in vitro and in vivo. Using quantitative real-time PCRs (qPCRs) and luciferase reporter assays, we demonstrated that lncRNA-POIR may act as a competing endogenous RNA (ceRNA) for miR-182, leading to derepression of its target gene, FoxO1. In this process, lncRNA-POIR and miR-182 suppress each other and form a network to regulate FoxO1. FoxO1 increased bone formation of pPDLSCs by competing with TCF-4 for β-catenin and inhibiting the canonical Wnt pathway. Finally, inflammation increases miR-182 expression through the nuclear factor-κB pathway, and the miR-182 overexpression in the inflammatory microenvironment resulted in an imbalance in the lncRNA-POIR-miR-182 regulatory network. In conclusion, our results provide novel evidence that this lncRNA-miRNA (microRNA) regulatory network has a significant role in osteogenic differentiation of pPDLSCs and that it has potential as a therapeutic target in mesenchymal stem cells during inflammation.
doi:10.1038/cddis.2016.125
PMCID: PMC5108307  PMID: 27512949
10.  Ischemic postconditioning protects the heart against ischemia–reperfusion injury via neuronal nitric oxide synthase in the sarcoplasmic reticulum and mitochondria 
Hu, L | Wang, J | Zhu, H | Wu, X | Zhou, L | Song, Y | Zhu, S | Hao, M | Liu, C | Fan, Y | Wang, Y | Li, Q
Cell Death & Disease  2016;7(5):e2222-.
As a result of its spatial confinement in cardiomyocytes, neuronal nitric oxide synthase (nNOS) is thought to regulate mitochondrial and sarcoplasmic reticulum (SR) function by maintaining nitroso-redox balance and Ca2+ cycling. Thus, we hypothesize that ischemic postconditioning (IPostC) protects hearts against ischemic/reperfusion (I/R) injury through an nNOS-mediated pathway. Isolated mouse hearts were subjected to I/R injury in a Langendorff apparatus, H9C2 cells and primary neonatal rat cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) in vitro. IPostC, compared with I/R, decreased infarct size and improved cardiac function, and the selective nNOS inhibitors abolished these effects. IPostC recovered nNOS activity and arginase expression. IPostC also increased AMP kinase (AMPK) phosphorylation and alleviated oxidative stress, and nNOS and AMPK inhibition abolished these effects. IPostC increased nitrotyrosine production in the cytosol but decreased it in mitochondria. Enhanced phospholamban (PLB) phosphorylation, normalized SR function and decreased Ca2+ overload were observed following the recovery of nNOS activity, and nNOS inhibition abolished these effects. Similar effects of IPostC were demonstrated in cardiomyocytes in vitro. IPostC decreased oxidative stress partially by regulating uncoupled nNOS and the nNOS/AMPK/peroxisome proliferator-activated receptor gamma coactivator 1 alpha/superoxide dismutase axis, and improved SR function through increasing SR Ca2+ load. These results suggest that IPostC protected hearts against I/R injury via an nNOS-mediated pathway.
doi:10.1038/cddis.2016.108
PMCID: PMC4917647  PMID: 27171264
11.  Phosphoglycerate kinase-1 is a predictor of poor survival and a novel prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer 
Sun, S | Liang, X | Zhang, X | Liu, T | Shi, Q | Song, Y | Jiang, Y | Wu, H | Jiang, Y | Lu, X | Pang, D
British Journal of Cancer  2015;112(8):1332-1339.
Background:
Phosphoglycerate kinase-1 (PGK1) has been recently documented in various malignancies; however, the molecular mechanisms of the variable PGK1 expression and its clinical significance in terms of survival status remain unclear.
Methods:
Real-time quantitative PCR (real-time qPCR) and western blotting were used to verify PGK1 expression in 46 fresh breast cancer tissues and matched normal tissues. A tissue microarray (TMA) comprising 401 breast cancer tissues and 123 matched normal tissues was investigated by immunohistochemistry for PGK1 expression. Then, the correlation between PGK1 expression and the clinicopathologic features was analysed.
Results:
PGK1 mRNA and protein expression were significantly increased in breast cancer tissues compared with that in normal breast tissues. High PGK1 expression was significantly associated with higher histologic grade (P=0.009) and positive status of ER (P=0.004), Her-2 (P=0.026) and P53 (P=0.012). High levels of PGK1 expression were associated with worse overall survival (OS, P=0.02). Furthermore, patients who underwent paclitaxel chemotherapy with high levels PGK1 expression had shorter OS than did those with low levels of PGK1 expression (P<0.001). Multivariate analysis indicated that PGK1 (P=0.001) was an independent predictor in the patients treated with paclitaxel.
Conclusions:
PGK1 is a prognostic biomarker of chemoresistance to paclitaxel treatment in breast cancer.
doi:10.1038/bjc.2015.114
PMCID: PMC4402453  PMID: 25867275
PGK1; breast cancer; prognosis; paclitaxel
12.  Metagenomic analysis of bloodstream infections in patients with acute leukemia and therapy-induced neutropenia 
Scientific Reports  2016;6:23532.
Leukemic patients are often immunocompromised due to underlying conditions, comorbidities and the effects of chemotherapy, and thus at risk for developing systemic infections. Bloodstream infection (BSI) is a severe complication in neutropenic patients, and is associated with increased mortality. BSI is routinely diagnosed with blood culture, which only detects culturable pathogens. We analyzed 27 blood samples from 9 patients with acute leukemia and suspected BSI at different time points of their antimicrobial treatment using shotgun metagenomics sequencing in order to detect unculturable and non-bacterial pathogens. Our findings confirm the presence of bacterial, fungal and viral pathogens alongside antimicrobial resistance genes. Decreased white blood cell (WBC) counts were associated with the presence of microbial DNA, and was inversely proportional to the number of sequencing reads. This study could indicate the use of high-throughput sequencing for personalized antimicrobial treatments in BSIs.
doi:10.1038/srep23532
PMCID: PMC4800731  PMID: 26996149
13.  The economic value of screening haemodialysis patients for methicillinresistant Staphylococcus aureus in the USA 
Methicillin-resistant Staphylococcus aureus (MRSA) can cause severe infections in patients undergoing haemodialysis. Routine periodic testing of haemodialysis patients and attempting to decolonize those who test positive may be a strategy to prevent MRSA infections. The economic value of such a strategy has not yet been estimated. We constructed a Markov computer simulation model to evaluate the economic value of employing routine testing (agar-based or PCR) at different MRSA prevalence, spontaneous clearance, costs of decolonization and decolonization success rates, performed every 3, 6 or 12 months. The model showed periodic MRSA surveillance with either test to be cost-effective (incremental cost-effectiveness ratio ≤$50 000/quality-adjusted life-year) for all conditions tested. Agar surveillance was dominant (i.e. less costly and more effective) at an MRSA prevalence ≥10% and a decolonization success rate ≥25% for all decolonization treatment costs tested with no spontaneous clearance. PCR surveillance was dominant when the MRSA prevalence was ≥20% and decolonization success rate was ≥75% with no spontaneous clearance. Routine periodic testing and decolonization of haemodialysis patients for MRSA may be a cost-effective strategy over a wide range of MRSA prevalences, decolonization success rates, and testing intervals.
doi:10.1111/j.1469-0691.2011.03525.x
PMCID: PMC4745896  PMID: 21595796
Cost-effectiveness; economics; haemodialysis; methicillin-resistant Staphylococcus aureus; surveillance
15.  Congenital hydrocephalus and hemivertebrae associated with de novo partial monosomy 6q (6q25.3→qter) 
This study was conducted to describe a prenatal case of congenital hydrocephalus and hemivertebrae with a 6q terminal deletion and to investigate the possible correlation between the genotype and phenotype of the proband. We performed an array-based comparative genomic hybridization (aCGH) analysis on a fetus diagnosed with congenital hydrocephalus and hemivertebrae. The deletion, spanning 10.06 Mb from 6q25.3 to 6qter, was detected in this fetus. The results of aCGH, karyotype and fluorescent in situ hybridization (FISH) analyses in the healthy parents were normal, which confirmed that the proband’s copy-number variant (CNV) was de novo. This deleted region encompassed 97 genes, including 28 OMIM genes. We discussed four genes (TBP, PSMB1, QKI and Pacrg) that may be responsible for hydrocephalus while the T gene may have a role in hemivertebra. We speculate that five genes in the 6q terminal deletion region were potentially associated with hemivertebrae and hydrocephalus in the proband.
doi:10.1515/bjmg-2015-0009
PMCID: PMC4768829  PMID: 26929909
Genotype; Hemivertebrae; Hydrocephalus; Phenotype; 6q Terminal deletion
16.  Creating Sub-50 nm Nanofluidic Junctions in PDMS Microchip via Self-Assembly Process of Colloidal Silica Beads for Electrokinetic Concentration of Biomolecules 
Lab on a chip  2014;14(23):4455-4460.
In this work we describe a novel and simple self-assembly of colloidal silica beads to create nanofluidic junction between two microchannels. The nanoporous membrane was used to induce ion concentration polarization inside the microchannel and this electrokinetic preconcentration system allowed rapid concentration of DNA samples by ∼1700 times and protein samples by ∼100 times within 5 minutes.
doi:10.1039/c4lc00895b
PMCID: PMC4213239  PMID: 25254651
17.  Urinary concentrations of bisphenol A and phthalate metabolites and weight change: a prospective investigation in US women 
OBJECTIVE
Both bisphenol A (BPA) and phthalates are known endocrine-disrupting chemicals for which there is widespread general population exposure. Human exposure occurs through dietary and non-dietary routes. Although animal studies have suggested a potential role of these chemicals in obesity, evidence from human studies is sparse and inconsistent, and prospective evidence is lacking. This study evaluated urinary concentrations of BPA and major phthalate metabolites in relation to prospective weight change.
METHODS
The study population was from the controls in a prospective case-control study of type 2 diabetes in the Nurses’ Health Study (NHS) and NHSII. A total of 977 participants provided first-morning-void urine samples in 1996–2002. Urinary concentrations of BPA and nine phthalate metabolites were measured using liquid chromatography–mass spectrometry. Body weights were self-reported at baseline and updated biennially thereafter for 10 years.
RESULTS
On average, the women gained 2.09 kg (95% confidence interval (CI), − 2.27 to 6.80 kg) during the 10-year follow-up. In multivariate analysis with adjustment of lifestyle and dietary factors, in comparison with women in the lowest quartile of BPA concentration, those in the highest quartile had 0.23 kg per year (95% CI, 0.07–0.38 kg per year) greater weight gain during the 10-year follow-up (P-trend = 0.02). Several phthalate metabolites, including phthalic acid, MBzP and monobutyl phthalate, were also associated with faster prospective weight gain in a dose-response fashion (P-trend < 0.01), whereas other phthalates metabolites, including MEP and monoethylhexyl phthalate, were not monotonically associated with body weight change.
CONCLUSIONS
These data suggest urinary concentrations of BPA and certain individual phthalate metabolites that were associated with modestly greater weight gain in a dose-response fashion. These data are consistent with a potential role of BPA and phthalates in obesity, although more prospective data are needed to corroborate these observations.
doi:10.1038/ijo.2014.63
PMCID: PMC4481130  PMID: 24722546
bisphenol A; phthalate; endocrine-disrupting chemicals
18.  Distinct roles of RIP1–RIP3 hetero- and RIP3–RIP3 homo-interaction in mediating necroptosis 
Cell Death and Differentiation  2014;21(11):1709-1720.
Necroptosis is mediated by a signaling complex called necrosome, containing receptor-interacting protein (RIP)1, RIP3, and mixed-lineage kinase domain-like (MLKL). It is known that RIP1 and RIP3 form heterodimeric filamentous scaffold in necrosomes through their RIP homotypic interaction motif (RHIM) domain-mediated oligomerization, but the signaling events based on this scaffold has not been fully addressed. By using inducible dimer systems we found that RIP1–RIP1 interaction is dispensable for necroptosis; RIP1–RIP3 interaction is required for necroptosis signaling, but there is no necroptosis if no additional RIP3 protein is recruited to the RIP1–RIP3 heterodimer, and the interaction with RIP1 promotes the RIP3 to recruit other RIP3; RIP3–RIP3 interaction is required for necroptosis and RIP3–RIP3 dimerization is sufficient to induce necroptosis; and RIP3 dimer-induced necroptosis requires MLKL. We further show that RIP3 oligomer is not more potent than RIP3 dimer in triggering necroptosis, suggesting that RIP3 homo-interaction in the complex, rather than whether RIP3 has formed homo polymer, is important for necroptosis. RIP3 dimerization leads to RIP3 intramolecule autophosphorylation, which is required for the recruitment of MLKL. Interestingly, phosphorylation of one of RIP3 in the dimer is sufficient to induce necroptosis. As RIP1–RIP3 heterodimer itself cannot induce necroptosis, the RIP1–RIP3 heterodimeric amyloid fibril is unlikely to directly propagate necroptosis. We propose that the signaling events after the RIP1–RIP3 amyloid complex assembly are the recruitment of free RIP3 by the RIP3 in the amyloid scaffold followed by autophosphorylation of RIP3 and subsequent recruitment of MLKL by RIP3 to execute necroptosis.
doi:10.1038/cdd.2014.77
PMCID: PMC4211369  PMID: 24902902
19.  Force-induced Adrb2 in Periodontal Ligament Cells Promotes Tooth Movement 
Journal of Dental Research  2014;93(11):1163-1169.
The sympathetic nervous system (SNS) regulates bone resorption through β-2 adrenergic receptor (Adrb2). In orthodontic tooth movement (OTM), mechanical force induces and regulates alveolar bone remodeling. Compressive force-associated osteoclast differentiation and alveolar bone resorption are the rate-limiting steps of tooth movement. However, whether mechanical force can activate Adrb2 and thus contribute to OTM remains unknown. In this study, orthodontic nickel-titanium springs were applied to the upper first molars of rats and Adrb1/2-/- mice to confirm the role of SNS and Adrb2 in OTM. The results showed that blockage of SNS activity in the jawbones of rats by means of superior cervical ganglion ectomy reduced OTM distance from 860 to 540 μm after 14 d of force application. In addition, the injection of nonselective Adrb2 agonist isoproterenol activated the downstream signaling of SNS to accelerate OTM from 300 to 540 μm after 7 d of force application. Adrb1/2-/- mice showed significantly reduced OTM distance (19.5 μm) compared with the wild-type mice (107.6 μm) after 7 d of force application. Histopathologic analysis showed that the number of Adrb2-positive cells increased in the compressive region of periodontal ligament after orthodontic force was applied on rats. Mechanistically, mechanical compressive force upregulated Adrb2 expression in primary-cultured human periodontal ligament cells (PDLCs) through the elevation of intracellular Ca2+ concentration. Activation of Adrb2 in PDLCs increased the RANKL/OPG ratio and promoted the peripheral blood mononuclear cell differentiation to osteoclasts in the cocultured system. Upregulation of Adrb2 in PDLCs promoted osteoclastogenesis, which accelerated OTM through Adrb2-enhanced bone resorption. In summary, this study suggests that mechanical force-induced Adrb2 activation in PDLCs contributes to SNS-regulated OTM.
doi:10.1177/0022034514551769
PMCID: PMC4293769  PMID: 25252876
orthodontics; biomechanical phenomena; beta-2 adrenergic receptors; sympathetic nervous system; bone remodeling; osteoclast
20.  Subtypes of major depression: latent class analysis in depressed Han Chinese women 
Psychological medicine  2014;44(15):3275-3288.
Background
Despite substantial research, uncertainty remains about the clinical and etiological heterogeneity of major depression (MD). Can meaningful and valid subtypes be identified and would they be stable cross-culturally?
Method
Symptoms at their lifetime worst depressive episode were assessed at structured psychiatric interview in 6008 women of Han Chinese descent, age ≥30 years, with recurrent DSM-IV MD. Latent class analysis (LCA) was performed in Mplus.
Results
Using the nine DSM-IV MD symptomatic A criteria, the 14 disaggregated DSM-IV criteria and all independently assessed depressive symptoms (n=27), the best LCA model identified respectively three, four and six classes. A severe and non-suicidal class was seen in all solutions, as was a mild/moderate subtype. An atypical class emerged once bidirectional neurovegetative symptoms were included. The non-suicidal class demonstrated low levels of worthlessness/guilt and hopelessness. Patterns of co-morbidity, family history, personality, environmental precipitants, recurrence and body mass index (BMI) differed meaningfully across subtypes, with the atypical class standing out as particularly distinct.
Conclusions
MD is a clinically complex syndrome with several detectable subtypes with distinct clinical and demographic correlates. Three subtypes were most consistently identified in our analyses: severe, atypical and non-suicidal. Severe and atypical MD have been identified in multiple prior studies in samples of European ethnicity. Our non-suicidal subtype, with low levels of guilt and hopelessness, may represent a pathoplastic variant reflecting Chinese cultural influences.
doi:10.1017/S0033291714000749
PMCID: PMC4180813  PMID: 25065911
Atypical depression; China; depression; latent class analysis; melancholia; suicidal ideation
21.  Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder 
Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.
doi:10.1590/1414-431X20154550
PMCID: PMC4671523  PMID: 26375446
Bipolar disorder; Plasma; Proteomic; Carbonic anhydrase 1; Apolipoprotein
22.  Metadherin regulates proliferation and metastasis via actin cytoskeletal remodelling in non-small cell lung cancer 
Yao, Y | Gu, X | Liu, H | Wu, G | Yuan, D | Yang, X | Song, Y
British Journal of Cancer  2014;111(2):355-364.
Background:
Metaderin (MTDH) protein is a novel component part of tight junction complex. The aim of this study was to investigate the correlation between MTDH and prognosis of patients and to explore the role of MTDH on NSCLC development and metastasis.
Methods:
Relative mRNA expression was evaluated by quantitative real-time PCR, and protein expression was detected using immunohistochemistry staining. The role of MTDH in cancer cell proliferation, migration and invasion was studied by modulation of MTDH expression in NSCLC cell lines. These functions of MTDH were further confirmed in vivo.
Results:
In NSCLC, low MTDH protein expression was correlated with lymph node metastasis, TNM stage and decreased OS (P=0.001, 0.011 and 0.013, respectively). Overexpression of MTDH reduced anchorage-independent and -dependent growth through arresting cell cycle, inhibited migration and invasion in vitro and further suppressed tumorigenesis, tumour growth and metastasis in vivo. Knockdown of MTDH expression increased cell invasiveness. MTDH overexpression reversed pro-metastatic actin cytoskeleton remodelling and inhibited EMT, supporting that MTDH has a key role on cancer proliferation and metastasis.
Conclusions:
MTDH has an important role in NSCLC proliferation and metastasis and provides potential in predicting metastasis and prognosis for patients with NSCLC.
doi:10.1038/bjc.2014.267
PMCID: PMC4102939  PMID: 24918821
non-small cell lung cancer; metadherin; epithelial–mesenchymal transition; metastasis; proliferation
23.  Risk and prognosis of ovarian cancer in women with endometriosis: a meta-analysis 
British Journal of Cancer  2014;110(7):1878-1890.
Background:
The risk and prognosis of ovarian cancer have not been well established in women with endometriosis. Thus, we investigated the impact of endometriosis on the risk and prognosis for ovarian cancer, and evaluated clinicopathologic characteristics of endometriosis-associated ovarian cancer (EAOC) in comparison with non-EAOC.
Methods:
After we searched an electronic search to identify relevant studies published online between January 1990 and December 2012, we found 20 case–control and 15 cohort studies including 444 255 patients from 1 625 potentially relevant studies. In the meta-analysis, ovarian cancer risk by endometriosis and clinicopathologic characteristics were evaluated using risk ratio (RR) or standard incidence ratio (SIR), and prognosis was investigated using hazard ratio (HR) with 95% confidence interval (CI). Heterogeneity was evaluated using Higgins I2 to select fixed-effect (I2 ⩽50%) or random effects models (I2>50%), and found no publication bias using funnel plots with Egger's test (P>0.05). Furthermore, we performed subgroup analyses based on study design, assessment of endometriosis, histology, disease status, quality of study and adjustment for potential confounding factors to minimise bias.
Results:
Endometriosis increased ovarian cancer risk in case–control or two-arm cohort studies (RR, 1.265; 95% CI, 1.214–1.318) and single-arm cohort studies (SIR, 1.797; 95% CI, 1.276–2.531), which were similar in subgroup analyses. Although progression-free survival was not different between EAOC and non-EAOC (HR, 1.023; 95% CI, 0.712–1.470), EAOC was associated with better overall survival than non-EAOC in crude analyses (HR, 0.778; 95% CI, 0.655–0.925). However, progression-free survival and overall survival were not different between the two groups in subgroup analyses. Stage I–II disease, grade 1 disease and nulliparity were more common in EAOC (RRs, 1.959, 1.319 and 1.327; 95% CIs, 1.367–2.807, 1.149–1.514 and 1.245–1.415), whereas probability of optimal debulking surgery was not different between the two groups (RR, 1.403; 95% CI, 0.915–2.152). Furthermore, endometrioid and clear cell carcinomas were more common in EAOC (RRs, 1.759 and 2.606; 95% CIs, 1.551–1.995 and 2.225–3.053), whereas serous carcinoma was less frequent in EAOC than in non-EAOC (RR, 0.733; 95% CI, 0.617–0.871), and there was no difference in the risk of mucinous carcinoma between the two groups (RR, 0.805; 95% CI, 0.584–1.109). These clinicopathologic characteristics were also similar in subgroup analyses.
Conclusions:
Endometriosis is strongly associated with the increased risk of ovarian cancer, and EAOC shows favourable characteristics including early-stage disease, low-grade disease and a specific histology such as endometrioid or clear cell carcinoma. However, endometriosis may not affect disease progression after the onset of ovarian cancer.
doi:10.1038/bjc.2014.29
PMCID: PMC3974076  PMID: 24518590
endometriosis; ovarian cancer; risk; prognosis; meta-analysis
24.  Low rate of total hip replacement as reflected by a low prevalence of hip osteoarthritis in South Korea 
Summary
Objective
We attempted to estimate the rate of total hip replacement (THR) using a national database and the prevalence of hip osteoarthritis (OA) from the reading of intravenous pyelograms (IVPs) in a Korean population.
Materials
Reimbursement records from all hospitals in South Korea were extracted from the Health Insurance Review Agency (HIRA) database. Records with both the procedure code corresponding to THR and containing the diagnosis code for hip OA were selected. We estimated the age- and sex-specific rates of THR from 2002 to 2006. Hip joints from 580 subjects older than 70 years old who underwent an IVP were assessed for the presence of OA.
Results
The rate of THR increased with age, reaching a peak over the age of 65–69 years, with the age-standardized risk ratios in women vs men of approximately 1.5. Although the rate of THR increased over the 5-year study period, it was significantly lower than that of total knee replacement (TKR) in Korean population (THR vs TKR 1:15.9). The prevalence of hip OA in the IVP cohort was 1.2% (1.7% for men and 0.7% for women).
Conclusion
The rate of THR was significantly lower than that of TKR in Korean population. Hip OA prevalence among the IVP subjects was 1.2%. Further studies on factors that account for the low prevalence of hip OA among Asians need to be conducted.
doi:10.1016/j.joca.2008.04.024
PMCID: PMC4373077  PMID: 18558502
Hip; Osteoarthritis; Arthroplasty; Replacement; Prevalence

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