49 results on '"Lygirou V"'
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2. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
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Brown, P, Zhou, Y, Tan, A, El-Esawi, M, Liehr, T, Blanck, O, Gladue, D, Almeida, G, Cernava, T, Sorzano, C, Yeung, A, Engel, M, Chandrasekaran, A, Muth, T, Staege, M, Daulatabad, S, Widera, D, Zhang, J, Meule, A, Honjo, K, Pourret, O, Yin, C, Zhang, Z, Cascella, M, Flegel, W, Goodyear, C, van Raaij, M, Bukowy-Bieryllo, Z, Campana, L, Kurniawan, N, Lalaouna, D, Huttner, F, Ammerman, B, Ehret, F, Cobine, P, Tan, E, Han, H, Xia, W, Mccrum, C, Dings, R, Marinello, F, Nilsson, H, Nixon, B, Voskarides, K, Yang, L, Costa, V, Bengtsson-Palme, J, Bradshaw, W, Grimm, D, Kumar, N, Martis, E, Prieto, D, Sabnis, S, Amer, S, Liew, A, Perco, P, Rahimi, F, Riva, G, Zhang, C, Devkota, H, Ogami, K, Basharat, Z, Fierz, W, Siebers, R, Tan, K, Boehme, K, Brenneisen, P, Brown, J, Dalrymple, B, Harvey, D, Ng, G, Werten, S, Bleackley, M, Dai, Z, Dhariwal, R, Gelfer, Y, Hartmann, M, Miotla, P, Tamaian, R, Govender, P, Gurney-Champion, O, Kauppila, J, Zhang, X, Echeverria, N, Subhash, S, Sallmon, H, Tofani, M, Bae, T, Bosch, O, Cuiv, P, Danchin, A, Diouf, B, Eerola, T, Evangelou, E, Filipp, F, Klump, H, Kurgan, L, Smith, S, Terrier, O, Tuttle, N, Ascher, D, Janga, S, Schulte, L, Becker, D, Browngardt, C, Bush, S, Gaullier, G, Ide, K, Meseko, C, Werner, G, Zaucha, J, Al-Farha, A, Greenwald, N, Popoola, S, Rahman, S, Xu, J, Yang, S, Hiroi, N, Alper, O, Baker, C, Bitzer, M, Chacko, G, Debrabant, B, Dixon, R, Forano, E, Gilliham, M, Kelly, S, Klempnauer, K, Lidbury, B, Lin, M, Lynch, I, Ma, W, Maibach, E, Mather, D, Nandakumar, K, Ohgami, R, Parchi, P, Tressoldi, P, Xue, Y, Armitage, C, Barraud, P, Chatzitheochari, S, Coelho, L, Diao, J, Doxey, A, Gobet, A, Hu, P, Kaiser, S, Mitchell, K, Salama, M, Shabalin, I, Song, H, Stevanovic, D, Yadollahpour, A, Zeng, E, Zinke, K, Alimba, C, Beyene, T, Cao, Z, Chan, S, Gatchell, M, Kleppe, A, Piotrowski, M, Torga, G, Woldesemayat, A, Cosacak, M, Haston, S, Ross, S, Williams, R, Wong, A, Abramowitz, M, Effiong, A, Lee, S, Abid, M, Agarabi, C, Alaux, C, Albrecht, D, Atkins, G, Beck, C, Bonvin, A, Bourke, E, Brand, T, Braun, R, Bull, J, Cardoso, P, Carter, D, Delahay, R, Ducommun, B, Duijf, P, Epp, T, Eskelinen, E, Fallah, M, Farber, D, Fernandez-Triana, J, Feyerabend, F, Florio, T, Friebe, M, Furuta, S, Gabrielsen, M, Gruber, J, Grybos, M, Han, Q, Heinrich, M, Helantera, H, Huber, M, Jeltsch, A, Jiang, F, Josse, C, Jurman, G, Kamiya, H, de Keersmaecker, K, Kristiansson, E, de Leeuw, F, Li, J, Liang, S, Lopez-Escamez, J, Lopez-Ruiz, F, Marchbank, K, Marschalek, R, Martin, C, Miele, A, Montagutelli, X, Morcillo, E, Nicoletti, R, Niehof, M, O'Toole, R, Ohtomo, T, Oster, H, Palma, J, Paterson, R, Peifer, M, Portilla, M, Portillo, M, Pritchard, A, Pusch, S, Raghava, G, Roberts, N, Ross, K, Schuele, B, Sergeant, K, Shen, J, Stella, A, Sukocheva, O, Uversky, V, Vanneste, S, Villet, M, Viveiros, M, Vorholt, J, Weinstock, C, Yamato, M, Zabetakis, I, Zhao, X, Ziegler, A, Aizat, W, Atlas, L, Bridges, K, Chakraborty, S, Deschodt, M, Domingues, H, Esfahlani, S, Falk, S, Guisado, J, Kane, N, Kueberuwa, G, Lau, C, Liang, D, Liu, E, Luu, A, Ma, C, Ma, L, Moyer, R, Norris, A, Panthee, S, Parsons, J, Peng, Y, Pinto, I, Reschke, C, Sillanpaa, E, Stewart, C, Uhle, F, Yang, H, Zhou, K, Zhu, S, Ashry, M, Bergsland, N, Berthold, M, Chen, C, Colella, V, Cuypers, M, Eskew, E, Fan, X, Gajda, M, Gonzalezlez-Prendes, R, Goodin, A, Graham, E, Groen, E, Gutierrez-Sacristan, A, Habes, M, Heffler, E, Higginbottom, D, Janzen, T, Jayaraman, J, Jibb, L, Jongen, S, Kinyanjui, T, Koleva-Kolarova, R, Li, Z, Liu, Y, Lund, B, Lussier, A, Mier, P, Moore, M, Nagler, K, Orme, M, Pearson, J, Prajapati, A, Saito, Y, Troder, S, Uchendu, F, Verloh, N, Voutchkova, D, Abu-Zaid, A, Bakkach, J, Baumert, P, Dono, M, Hanson, J, Herbelet, S, Hobbs, E, Kulkarni, A, Liu, S, Loft, N, Reddan, T, Senghore, T, Vindin, H, Xu, H, Bannon, R, Chen, B, Cheung, J, Cooper, J, Esnakula, A, Feghali, K, Ghelardi, E, Gnasso, A, Horbar, J, Lai, H, Ma, R, Pan, Z, Peres, M, Pranata, R, Seow, E, Sydes, M, Testoni, I, Westermair, A, Yang, Y, Afnan, M, Albiol, J, Albuquerque, L, Amir, S, Amiya, E, Amorim, R, An, Q, Andersen, S, Aplin, J, Argyropoulos, C, Asmann, Y, Assaeed, A, Atanasov, A, Atchison, D, Avery, S, Avillach, P, Baade, P, Backman, L, Badie, C, Baldi, A, Ball, E, Bardot, O, Barnett, A, Basner, M, Batra, J, Bazanova, O, Beale, A, Beddoe, T, Bell, M, Berezikov, E, Berners-Price, S, Bernhardt, P, Berry, E, Bessa, T, Billington, C, Birch, J, Blakely, R, Blaskovich, M, Blum, R, Boelaert, M, Bogdanos, D, Bosch, C, Bourgoin, T, Bouvard, D, Boykin, L, Bradley, G, Braun, D, Brownlie, J, Bruhl, A, Burt, A, Butler, L, Byrareddy, S, Byrne, H, Cabantous, S, Calatayud, S, Candal, E, Carlson, K, Casillas, S, Castelvetro, V, Caswell, P, Cavalli, G, Cerovsky, V, Chagoyen, M, Chen, D, Chen, H, Chen, J, Chen, Y, Cheng, C, Cheng, J, Chinapaw, M, Chinopoulos, C, Cho, W, Chong, L, Chowdhury, D, Chwalibog, A, Ciresi, A, Cockcroft, S, Conesa, A, Cook, P, Cooper, D, Coqueret, O, Corea, E, Costa, A, Costa, E, Coupland, C, Crawford, S, Cruz, A, Cui, H, Cui, Q, Culver, D, D'Angiulli, A, Dahms, T, Daigle, F, Dalgleish, R, Danielsen, H, Darras, S, Davidson, S, Day, D, Degirmenci, V, Demaison, L, Devriendt, K, Ding, J, Dogan, Y, Dong, X, Donner, C, Dressick, W, Drevon, C, Duan, H, Ducho, C, Dumaz, N, Dwarakanath, B, Ebell, M, Eisenhardt, S, Elkum, N, Engel, N, Erickson, T, Fairhead, M, Faville, M, Fejzo, M, Festa, F, Feteira, A, Flood-Page, P, Forsayeth, J, Fox, S, Franks, S, Frentiu, F, Frilander, M, Fu, X, Fujita, S, Galea, I, Galluzzi, L, Gani, F, Ganpule, A, Garcia-Alix, A, Gedye, K, Giordano, M, Giunta, C, Gleeson, P, Goarant, C, Gong, H, Gora, D, Gough, M, Goyal, R, Graham, K, Grande-Perez, A, Graves, P, Greidanus, H, Grice, D, Grunau, C, Gumulya, Y, Guo, Y, Gurevich, V, Gusev, O, Hacker, E, Hage, S, Hagen, G, Hahn, S, Haller, D, Hammerschmidt, S, Han, J, Han, R, Handfield, M, Hapuarachchi, H, Harder, T, Hardingham, J, Heck, M, Heers, M, Hew, K, Higuchi, Y, Hilaire, C, Hilton, R, Hodzic, E, Hone, A, Hongoh, Y, Hu, G, Huber, H, Hueso, L, Huirne, J, Hurt, L, Idborg, H, Ikeo, K, Ingley, E, Jakeman, P, Jensen, A, Jia, H, Jia, S, Jiang, J, Jiang, X, Jin, Y, Jo, D, Johnson, A, Johnston, M, Jonscher, K, Jorens, P, Jorgensen, J, Joubert, J, Jung, S, Junior, A, Kahan, T, Kamboj, S, Kang, Y, Karamanos, Y, Karp, N, Kelly, R, Kenna, R, Kennedy, J, Kersten, B, Khalaf, R, Khalid, J, Khatlani, T, Khider, T, Kijanka, G, King, S, Kluz, T, Knox, P, Kobayashi, T, Koch, K, Kohonen-Corish, M, Kong, X, Konkle-Parker, D, Korpela, K, Kostrikis, L, Kraiczy, P, Kratz, H, Krause, G, Krebsbach, P, Kristensen, S, Kumari, P, Kunimatsu, A, Kurdak, H, Kwon, Y, Lachat, C, Lagisz, M, Laky, B, Lammerding, J, Lange, M, Larrosa, M, Laslett, A, Laverman, G, Leclair, E, Lee, K, Lee, M, Li, G, Lieb, K, Lim, Y, Lindsey, M, Line, P, Liu, D, Liu, F, Liu, H, Lloyd, V, Lo, T, Locci, E, Loidl, J, Lorenzen, J, Lorkowski, S, Lovell, N, Lu, H, Lu, W, Lu, Z, Luengo, G, Lundh, L, Lysy, P, Mabb, A, Mack, H, Mackey, D, Mahdavi, S, Maher, P, Maher, T, Maity, S, Malgrange, B, Mamoulakis, C, Mangoni, A, Manke, T, Manstead, A, Mantalaris, A, Marsal, J, Marschall, H, Martin, F, Martinez-Raga, J, Martinez-Salas, E, Mathieu, D, Matsui, Y, Maza, E, Mccutcheon, J, Mckay, G, Mcmillan, B, Mcmillan, N, Meads, C, Medina, L, Merrick, B, Metzger, D, Meunier, F, Michaelis, M, Micheau, O, Mihara, H, Mintz, E, Mizukami, T, Moalic, Y, Mohapatra, D, Monteiro, A, Montes, M, Moran, J, Morozov, S, Mort, M, Murai, N, Murphy, D, Murphy, S, Murray, S, Naganawa, S, Nammi, S, Nasios, G, Natoli, R, Nguyen, F, Nicol, C, van Nieuwerburgh, F, Nilsen, E, Nobile, C, O'Mahony, M, Ohlsson, S, Olatunbosun, O, Olofsson, P, Ortiz, A, Ostrikov, K, Otto, S, Outeiro, T, Ouyang, S, Paganoni, S, Page, A, Palm, C, Paradies, Y, Parsons, M, Parsons, N, Pascal, P, Paul, E, Peckham, M, Pedemonte, N, Pellizzon, M, Petrelli, M, Pichugin, A, Pinto, C, Plevris, J, Pollesello, P, Polz, M, Ponti, G, Porcelli, P, Prince, M, Quinn, G, Quinn, T, Ramula, S, Rappsilber, J, Rehfeldt, F, Reiling, J, Remacle, C, Rezaei, M, Riddick, E, Ritter, U, Roach, N, Roberts, D, Robles, G, Rodrigues, T, Rodriguez, C, Roislien, J, Roobol, M, Rowe, A, Ruepp, A, van Ruitenbeek, J, Rust, P, Saad, S, Sack, G, Santos, M, Saudemont, A, Sava, G, Schrading, S, Schramm, A, Schreiber, M, Schuler, S, Schymkowitz, J, Sczyrba, A, Seib, K, Shi, H, Shimada, T, Shin, J, Shortt, C, Silveyra, P, Skinner, D, Small, I, Smeets, P, So, P, Solano, F, Sonenshine, D, Song, J, Southall, T, Speakman, J, Srinivasan, M, Stabile, L, Stasiak, A, Steadman, K, Stein, N, Stephens, A, Stewart, D, Stine, K, Storlazzi, C, Stoynova, N, Strzalka, W, Suarez, O, Sultana, T, Sumant, A, Summers, M, Sun, G, Tacon, P, Tanaka, K, Tang, H, Tanino, Y, Targett-Adams, P, Tayebi, M, Tayyem, R, Tebbe, C, Telfer, E, Tempel, W, Teodorczyk-Injeyan, J, Thijs, G, Thorne, S, Thrift, A, Tiffon, C, Tinnefeld, P, Tjahjono, D, Tolle, F, Toth, E, Del Tredici, A, Tsapas, A, Tsirigotis, K, Turak, A, Tzotzos, G, Udo, E, Utsumi, T, Vaidyanathan, S, Vaillant, M, Valsesia, A, Vandenbroucke, R, Veiga, F, Vendrell, M, Vesk, P, Vickers, P, Victor, V, Villemur, R, Vohl, M, Voolstra, C, Vuillemin, A, Wakelin, S, Waldron, L, Walsh, L, Wang, A, Wang, F, Wang, Y, Watanabe, Y, Weigert, A, Wen, J, Wham, C, White, E, Wiener, J, Wilharm, G, Wilkinson, S, Willmann, R, Wilson, C, Wirth, B, Wojan, T, Wolff, M, Wong, B, Wu, T, Wuerbel, H, Xiao, X, Xu, D, Xue, B, Yalcin, S, Yan, H, Yang, E, Yang, W, Ye, Y, Ye, Z, Yli-Kauhaluoma, J, Yoneyama, H, Yu, Y, Yuan, G, Yuh, C, Zaccolo, M, Zeng, C, Zevnik, B, Zhang, L, Zhang, Y, Zhao, Y, Zhou, M, Zuberbier, T, Aanei, C, Ahmad, R, Al-Lawama, M, Alanio, A, Allardyce, J, Alonso-Caneiro, D, Atack, J, Baier, D, Bansal, A, Benezeth, Y, Berbesque, C, Berrevoet, F, Biedermann, P, Bijleveld, E, Bittner, F, Blombach, F, van den Bos, W, Boudreau, S, Bramoweth, A, Braubach, O, Cai, Y, Campbell, M, Catry, T, Chen, X, Cheng, S, Chung, H, Chavez-Fumagalli, M, Conway, A, Costa, B, Cyr, N, Dean, L, Denzel, M, Dlamini, S, Dudley, K, Dufies, M, Ecke, T, Eckweiler, D, Eixarch, E, El-Adawy, H, Emmrich, J, Eustace, A, Falter-Wagner, C, Farhoudi, R, Fuss, J, Gao, J, Gill, M, Gloyn, L, Goggs, R, Govinden, U, Greene, G, Greiff, V, Grundle, D, Gruneberg, P, Gumede, N, Haore, G, Harrison, P, Hoenner, X, Hojsgaard, D, Hori, H, Ikonomopoulou, M, Jeurissen, P, Johnson, D, Kabra, D, Kamagata, K, Karmakar, C, Kasian, O, Kaye, L, Khan, M, Kim, Y, Kish, J, Kobold, S, Kohanbash, G, Kohls, G, Kugler, J, Kumar, G, Lacy-Colson, J, Latif, A, Lauschke, V, Li, B, Lim, C, Liu, X, Lu, J, Lu, Q, Mahavadi, P, Marzocchi, U, Mcgarrigle, C, van Meerten, T, Min, R, Moal, I, Molari, M, Molleman, L, Mondal, S, van de Mortel, T, Moss, W, Moultos, O, Mukherjee, M, Nakayama, K, Narayan, E, Navaratnarajah, Neumann, P, Nie, J, Nie, Y, Niemeyer, F, Nolan, F, Nwaiwu, O, Oldenmenger, W, Olumayede, E, Ou, J, Pallebage-Gamarallage, M, Pearce, S, Pelkonen, T, Pelleri, M, Pereira, J, Pheko, M, Pinto, K, Piovesan, A, Pluess, M, Podolsky, I, Prescott, J, Qi, D, Qi, X, Raikou, V, Ranft, A, Rhodes, J, Rotge, J, Saggar, M, Schuon, R, Shahid, S, Shalchyan, V, Shirvalkar, P, Shiryayev, O, Singh, J, Smout, M, Soares, A, Song, C, Srivastava, K, Srivastava, R, Sun, J, Szabo, A, Szymanski, W, Tai, C, Takeuchi, H, Tanadini-Lang, S, Tang, F, Tao, W, Theron, G, Tian, C, Tian, Y, Tuttle, L, Valenti, A, Verlot, P, Walker, M, Wang, J, Welter, D, Winslade, M, Wu, D, Wu, Y, Xiao, H, Xu, B, Xu, Z, Yang, D, Yang, M, Yankilevich, P, You, Y, Yu, C, Zhan, J, Zhang, G, Zhang, K, Zhang, T, Zhao, G, Zhao, J, Zhou, X, Zhu, Z, Ajani, P, Anazodo, U, Bagloee, S, Bail, K, Bar, I, Bathelt, J, Benkeser, D, Bernier, M, Blanchard, A, Boakye, D, Bonatsos, V, Boon, M, Bouboulis, G, Bromfield, E, Bul, K, Burton, K, Butkowski, E, Carroll, G, Chao, F, Charrier, E, Chenguang, Choi, J, Christoffersen, T, Comel, J, Cosse, C, Cui, Y, van Dessel, P, Dhaval, Diodato, D, Duffey, M, Dutt, A, Egea, L, El-Said, M, Faye, M, Fernandez-Fernandez, B, Foley, K, Founou, L, Fu, F, Gadelkareem, R, Galimov, E, Garip, G, Gemmill, A, Gouil, Q, Grey, J, Gridneva, Z, Grothe, M, Grebert, T, Guerrero, F, Guignard, L, Haenssgen, M, Hasler, D, Holgate, J, Huang, A, Hulse-Kemp, A, Jean-Quartier, C, Jeon, S, Jia, Y, Jutzeler, C, Kalatzis, P, Karim, M, Karsay, K, Keitel, A, Kempe, A, Keown, J, Khoo, C, Khwaja, N, Kievit, R, Kosanic, S, Koutoukidis, D, Kramer, P, Kumar, D, Kirag, N, Lanza, G, Le, T, Leem, J, Leightley, D, Leite, A, Lercher, L, Li, Y, Lim, R, Lima, L, Lin, L, Ling, T, Liu, Z, Lu, Y, Lum, F, Luo, H, Machhi, J, Macleod, A, Macwan, I, Madala, H, Madani, N, de Maio, N, Makowiecki, K, Mallinson, D, Margelyte, R, Maria, C, Markonis, Y, Marsili, L, Mavoa, S, Mcwilliams, L, Megersa, M, Souto-Maior, C, Menichetti, J, Mercieca-Bebber, R, Miller, J, Minde, D, Minges, A, Mishra, E, Mishra, V, Moores, C, Morrice, N, Moskalensky, A, Navarin, N, Negera, E, Nolet, P, Nordberg, A, Norden, R, Nowicki, J, Olova, N, Olszewski, P, Onzima, R, Pan, C, Park, C, Park, D, Park, S, Patil, C, Pedro, S, Perry, S, Peter, J, Peterson, B, Pezzuolo, A, Pozdnyakov, I, Qian, S, Qin, L, Rafe, A, Raote, I, Raza, A, Rebl, H, Refai, O, Regan, T, Richa, T, Richardson, M, Robinson, K, Rossoni, L, Rouet, R, Safaei, S, Schneeberger, P, Schwotzer, D, Sebastian, A, Selinski, J, Seltmann, S, Sha, F, Shalev, N, Shang, J, Singer, J, Singh, M, Smith, T, Solomon-Moore, E, Song, L, Soraggi, S, Stanley, R, Steckhan, N, Strobl, F, Subissi, L, Supriyanto, I, Surve, C, Suzuki, T, Syme, C, Sorelius, K, Tang, Y, Tantawy, M, Tennakoon, S, Teseo, S, Toelzer, C, Tomov, N, Tovar, M, Tran, L, Tripathi, S, Tuladhar, A, Ukubuiwe, A, Ung, C, Valgepea, K, Vatanparast, H, Vidal, A, Wang, Q, Watari, R, Webster, R, Wei, J, Wibowo, D, Wingenbach, T, Xavier, R, Xiao, S, Xiong, P, Xu, S, Yao, R, Yao, W, Yin, Q, Zaitsu, M, Zeineb, Z, Zhan, X, Zhang, R, Zhang, W, Zheng, S, Zhou, B, Ahmad, H, Akinwumi, S, Albery, G, Alhowimel, A, Ali, J, Alshehri, M, 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A., van Meerten T., Min R., Moal I., Molari M., Molleman L., Mondal S. R., van de Mortel T., Moss W. N., Moultos O. A., Mukherjee M., Nakayama K., Narayan E., Neumann P. -A., Nie J., Nie Y., Niemeyer F., Nolan F., Nwaiwu O., Oldenmenger W. H., Olumayede E., Ou J., Pallebage-Gamarallage M., Pearce S. P., Pelkonen T., Pelleri M. C., Pereira J. L., Pheko M., Pinto K. A., Piovesan A., Pluess M., Podolsky I. M., Prescott J., Qi D., Qi X., Raikou V. D., Ranft A., Rhodes J., Rotge J. -Y., Rowe A. D., Saggar M., Schuon R. A., Shahid S., Shalchyan V., Shirvalkar P., Shiryayev O., Singh J., Smout M. J., Soares A., Song C., Srivastava K., Srivastava R. K., Sun J., Szabo A., Szymanski W., Tai C. N. P., Takeuchi H., Tanadini-Lang S., Tang F., Tao W., Theron G., Tian C. F., Tian Y. -S., Tuttle L. M., Valenti A., Verlot P., Walker M., Wang J., Welter D., Winslade M., Wu D., Wu Y. -R., Xiao H., Xu B., Xu Z., Yang D., Yang M., Yankilevich P., You Y., Yu C., Zhan J., Zhang G., Zhang K., Zhang T., Zhao G., Zhao J., Zhou X., Zhu Z., Ajani P. A., Anazodo U. C., Bagloee S. A., Bail K., Bar I., Bathelt J., Benkeser D., Bernier M. L., Blanchard A. M., Boakye D. W., Bonatsos V., Boon M. H., Bouboulis G., Bromfield E., Brown J., Bul K. C. M., Burton K. J., Butkowski E. G., Carroll G., Chao F., Charrier E. E., Chen Y. -C., Choi J. R., Christoffersen T., Comel J. C., Cosse C., Cui Y., van Dessel P., Diodato D., Duffey M., Dutt A., Egea L. G., El-Said M., Faye M., Fernandez-Fernandez B., Foley K. G., Founou L. L., Fu F., Gadelkareem R. A., Galimov E., Garip G., Gemmill A., Gouil Q., Grey J., Gridneva Z., Grothe M. J., Grebert T., Guerrero F., Guignard L., Haenssgen M. J., Hasler D., Holgate J. Y., Huang A., Hulse-Kemp A. M., Jean-Quartier C., Jeon S. -M., Jia Y., Jutzeler C., Kalatzis P., Karim M., Karsay K., Keitel A., Kempe A., Keown J. R., Khoo C. M., Khwaja N., Kievit R. A., Kosanic S., Koutoukidis D. A., Kramer P., Kumar D., Kirag N., Lanza G., Le T. D., Leem J. W., Leightley D., Leite A., Lercher L., Li Y., Lim R., Lima L. R. A., Lin L., Ling T., Liu Y., Liu Z., Lu Y., Lum F. M., Luo H., Machhi J., Macleod A., Macwan I., Madala H. R., Madani N., de Maio N., Makowiecki K., Mallinson D. J., Margelyte R., Maria C., Markonis Y., Marsili L., Mavoa S., McWilliams L., Megersa M., Souto-Maior C., Menichetti J., Mercieca-Bebber R., Miller J. J., Minde D. -P. M., Minges A., Mishra E., Mishra V. R., Moores C., Morrice N., Moskalensky A. E., Navarin N., Negera E., Nolet P., Nordberg A., Norden R., Nowicki J. P., Olova N., Olszewski P., Onzima R., Pan C. -L., Park C., Park D. I., Park S., Patil C. D., Pedro S. A., Perry S. R., Peter J., Peterson B. M., Pezzuolo A., Pozdnyakov I., Qian S., Qin L., Rafe A., Raote I., Raza A., Rebl H., Refai O., Regan T., Richa T., Richardson M. F., Robinson K. R., Rossoni L., Rouet R., Safaei S., Schneeberger P. H. H., Schwotzer D., Sebastian A., Selinski J., Seltmann S., Sha F., Shalev N., Shang J. -L., Singer J., Singh M., Smith T., Solomon-Moore E., Song L., Soraggi S., Stanley R., Steckhan N., Strobl F., Subissi L., Supriyanto I., Surve C. R., Suzuki T., Syme C., Sorelius K., Tang Y., Tantawy M., Tennakoon S., Teseo S., Toelzer C., Tomov N., Tovar M., Tran L., Tripathi S., Tuladhar A. M., Ukubuiwe A. C., Ung C. O. L., Valgepea K., Vatanparast H., Vidal A., Wang Q., Watari R., Webster R., Wei J., Wibowo D., Wingenbach T. S. H., Xavier R. M., Xiao S., Xiong P., Xu S., Yao R., Yao W., Yin Q., Zaitsu M., Zeineb Z., Zhan X. -Y., Zhang R., Zhang W., Zheng S., Zhou B., Ahmad H., Akinwumi S. A., Albery G. F., Alhowimel A., Ali J., Alshehri M., Alsuhaibani M., Anikin A., Azubuike S. O., Bach-Mortensen A., Baltiansky L., Bartas M., Belachew K. Y., Bhardwaj V., Binder K., Bland N. S., Boah M., Bullen B., Calabro G. E., Callahan T. J., Cao B., Chalmers K., Chang W., Che Z., Chen A. T. Y., Chen Z., Choi Y., Chowdhury M. A. K., Christensen M. R., Cooke R. S. C., Cottini M., Covington N. V., Cunningham C., Delarocque J., Devos L., Dhar A. R., Ding K. -F., Dong K., Dong Z., Dreyer N., Ekstrand C., Fardet T., Feleke B. E., Feurer T., Freitas A., Gao T., Giganti F., Grabowski P., Guerra-Mora J. R., Guo C., Guo X., Gupta H., He S., Heijne M., Heinemann S., Hogrebe A., Huang Z., Iskander-Rizk S., Iyer L. M., Jahan Y., James A. S., Joel E., Joffroy B., Jegousse C., Kambondo G., Karnati P., Kaya C., Ke A., Kelly D., Kickert R., Kidibule P. E., Kieselmann J. P., Kim H. J., Kitazawa T., Lamberts A., Liang H., Linn S. N., Litfin T., Liusuo W., Lygirou V., Mahato A. K., Mai Z. -M., Major R. W., Mali S., Mallis P., Mao W., Marvin-Dowle K., Mason L. D., Merideth B., Merino-Plaza M. 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X., Obeidat M., Oh D. -H., Owais M., Pace-Asciak P., Panwar A., Patterson C., Penagos-Tabaree F., Pianosi P. T., Pinzi V., Pridans C., Psaroulaki A., Pujala R. K., Pulido-Arjona L., Qi P. -F., Rahman P., Rai N. K., Rassaf T., Refardt J., Ricciardi W., Riess O., Rovas A., Sacks F. M., Saleh S., Sampson C., Schmutz A., Sepanski R., Sharma N., Spearman P., Subramaniapillai M., Swali R., Tan C. M., Tellechea J. I., Thomas L. -M., Tong X., Vavvas D. G., Veys R., Vitriol V., Wang H. -D., Waugh J., Webb S. A., Williams B. A., Workman A. D., Xiang T., Xie L. -X., Xu T., Yang C., Yoon J. G., Yuan C. M., Zaritsky A., Zhao H., Zuckerman H., Lyu R., and Pullan W.
- Abstract
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science.
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- 2019
3. Proteome-based classification of Nonmuscle Invasive Bladder Cancer
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Stroggilos, R. Mokou, M. Latosinska, A. Makridakis, M. Lygirou, V. Mavrogeorgis, E. Drekolias, D. Frantzi, M. Mullen, W. Fragkoulis, C. Stasinopoulos, K. Papadopoulos, G. Stathouros, G. Lazaris, A.C. Makrythanasis, P. Ntoumas, K. Mischak, H. Zoidakis, J. Vlahou, A.
- Abstract
DNA/RNA-based classification of bladder cancer (BC) supports the existence of multiple molecular subtypes, while investigations at the protein level are scarce. Here, we aimed to investigate if Nonmuscle Invasive Bladder Cancer (NMIBC) can be stratified to biologically meaningful groups based on the proteome. Tissue specimens from 117 patients at primary diagnosis (98 with NMIBC and 19 with MIBC), were processed for high-resolution proteomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteomics output was subjected to unsupervised consensus clustering, principal component analysis (PCA) and investigation of subtype-specific features, pathways, and gene sets. NMIBC patients were optimally stratified to three NMIBC proteomic subtypes (NPS), differing in size, clinicopathologic and molecular backgrounds: NPS1 (mostly high stage/grade/risk samples) was the smallest in size (17/98) and overexpressed proteins reflective of an immune/inflammatory phenotype, involved in cell proliferation, unfolded protein response and DNA damage response, whereas NPS2 (mixed stage/grade/risk composition) presented with an infiltrated/mesenchymal profile. NPS3 was rich in luminal/differentiation markers, in line with its pathological composition (mostly low stage/grade/risk samples). PCA revealed a close proximity of NPS1 and conversely, remoteness of NPS3 to the proteome of MIBC. Proteins distinguishing these two extreme subtypes were also found to consistently differ at the mRNA levels between high and low-risk subtypes of the UROMOL and LUND cohorts. Collectively, our study identifies three proteomic NMIBC subtypes and following a cross-omics validation in two independent cohorts, shortlists molecular features meriting further investigation for their biomarker or potentially therapeutic value. © 2019 UICC
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- 2020
4. A novel pipeline for drug repurposing for bladder cancer based on patients’ omics signatures
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Mokou, M. Lygirou, V. Angelioudaki, I. Paschalidis, N. Stroggilos, R. Frantzi, M. Latosinska, A. Bamias, A. Hoffmann, M.J. Mischak, H. Vlahou, A.
- Abstract
Multi-omics signatures of patients with bladder cancer (BC) can guide the identification of known de-risked therapeutic compounds through drug repurposing, an approach not extensively explored yet. In this study, we target drug repurposing in the context of BC, driven by tissue omics signatures. To identify compounds that can reverse aggressive high-risk Non-Muscle Invasive BC (NMIBC) to less aggressive low-risk molecular subtypes, the next generation Connectivity Map (CMap) was employed using as input previously published proteomics and transcriptomics respective signatures. Among the identified compounds, the ATP-competitive inhibitor of mTOR, WYE-354, showed a consistently very high score for reversing the aggressive BC molecular signatures. WYE-354 impact was assessed in a panel of eight multi-origin BC cell lines and included impaired colony growth and proliferation rate without any impact on apoptosis. Overall, with this study we introduce a promising pipeline for the repurposing of drugs for BC treatment, based on patients’ omics signatures. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.
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- 2020
5. Proteomics Analysis of Formalin Fixed Paraffin Embedded Tissues in the Investigation of Prostate Cancer
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Mantsiou, A. Makridakis, M. Fasoulakis, K. Katafigiotis, I. Constantinides, C.A. Zoidakis, J. Roubelakis, M.G. Vlahou, A. Lygirou, V.
- Abstract
Prostate cancer (PCa) is one of the leading causes of death in men worldwide. The molecular features, associated with the onset and progression of the disease, are under vigorous investigation. Formalin-fixed paraffin-embedded (FFPE) tissues are valuable resources for large-scale studies; however, their application in proteomics is limited due to protein cross-linking. In this study, the adjustment of a protocol for the proteomic analysis of FFPE tissues was performed which was followed by a pilot application on FFPE PCa clinical samples to investigate whether the optimized protocol can provide biologically relevant data for the investigation of PCa. For the optimization, FFPE mouse tissues were processed using seven protein extraction protocols including combinations of homogenization methods (beads, sonication, boiling) and buffers (SDS based and urea-thiourea based). The proteome extraction efficacy was then evaluated based on protein identifications and reproducibility using SDS electrophoresis and high resolution LC-MS/MS analysis. Comparison between the FFPE and matched fresh frozen (FF) tissues, using an optimized protocol involving protein extraction with an SDS-based buffer following beads homogenization and boiling, showed a substantial overlap in protein identifications with a strong correlation in relative abundances (rs = 0.819, p < 0.001). Next, FFPE tissues (3 sections, 15 μm each per sample) from 10 patients with PCa corresponding to tumor (GS = 6 or GS ≥ 8) and adjacent benign regions were processed with the optimized protocol. Extracted proteins were analyzed by GeLC-MS/MS followed by statistical and bioinformatics analysis. Proteins significantly deregulated between PCa GS ≥ 8 and PCa GS = 6 represented extracellular matrix organization, gluconeogenesis, and phosphorylation pathways. Proteins deregulated between cancerous and adjacent benign tissues, reflected increased translation, peptide synthesis, and protein metabolism in the former, which is consistent with the literature. In conclusion, the results support the relevance of the proteomic findings in the context of PCa and the reliability of the optimized protocol for proteomics analysis of FFPE material. Copyright © 2019 American Chemical Society.
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- 2020
6. Drug repurposing of bladder cancer driven by patients’ proteomic signatures
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Mokou, M, primary, Lygirou, V, additional, Angelioudaki, I, additional, Paschalidis, N, additional, Stroggilos, R, additional, Frantzi, M, additional, Latosinska, A, additional, Hoffmann, MJ, additional, Mischak, H, additional, and Vlahou, A, additional
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- 2020
- Full Text
- View/download PDF
7. High resolution analysis of the intracellular proteome of cervical cancer cell lines unveils novel regulators of cervical carcinogenesis
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Pappa, K.I. Lygirou, V. Kontostathi, G. Makridakis, M. Vougas, K. Sfakianakis, A. Daskalakis, G. Zoidakis, J. Anagnou, N.P.
- Abstract
Cervical cancer remains the fourth most common and most lethal type of cancer in women, despite the applied regular screening and prevention strategies, while the available treatment schemes still pose a threat to fertility. Substantial understanding of the underlying mechanisms and development of novel diagnostic, prognostic and therapeutic approaches are critical steps for improving cervical cancer management. Towards this goal, a comparative proteomic analysis was conducted between three cervical cancer cell lines (HeLa: HPV18+, SiHa: HPV16+, C33A: HPV-) and normal cervical keratinocytes (HCK1T). The total cell extract of each cell line was analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Differential expression analysis revealed 919, 826 and 1,370 deregulated proteins in the comparisons of HeLa, SiHa and C33A with HCK1T cell lines, respectively. Pathway enrichment analysis of the differentially expressed proteins highlighted common cancer characteristics such as high metabolic demands and increased cell turnover, confirming the validity of the proteomic results. Extensive literature mining of the consistently differentially expressed proteins that resulted from the three comparisons was performed leading to a shortlist of 21 proteins that are potentially involved in cervical malignancy. The criteria for this shortlisting were the association of the proteins with various types of cancer, while there is no study as yet associating their expression to cervical cancer. Moreover, the expression trend of two of the shortlisted proteins was validated using western blot analysis. The proteomic datasets generated in this study can be utilized to enrich the current knowledge on cervical cancer pathology and unveil key molecular mechanisms of carcinogenesis. In conclusion, the shortlist of consistently deregulated proteins between cervical cancer cell lines and normal cervical keratinocytes can be used for validation in clinical samples and in functional investigation experiments that could ultimately lead to the discovery of novel disease biomarkers and drug targets. © 2019 Spandidos Publications. All rights reserved.
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- 2019
8. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
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Brown, P. Zhou, Y. Tan, A.-C. El-Esawi, M.A. Liehr, T. Blanck, O. Gladue, D.P. Almeida, G.M.F. Cernava, T. Sorzano, C.O. Yeung, A.W.K. Engel, M.S. Chandrasekaran, A.R. Muth, T. Staege, M.S. Daulatabad, S.V. Widera, D. Zhang, J. Meule, A. Honjo, K. Pourret, O. Yin, C.-C. Zhang, Z. Cascella, M. Flegel, W.A. Goodyear, C.S. van Raaij, M.J. Bukowy-Bieryllo, Z. Campana, L.G. Kurniawan, N.A. Lalaouna, D. Hüttner, F.J. Ammerman, B.A. Ehret, F. Cobine, P.A. Tan, E.-C. Han, H. Xia, W. McCrum, C. Dings, R.P.M. Marinello, F. Nilsson, H. Nixon, B. Voskarides, K. Yang, L. Costa, V.D. Bengtsson-Palme, J. Bradshaw, W. Grimm, D.G. Kumar, N. Martis, E. Prieto, D. Sabnis, S.C. Amer, S.E.D.R. Liew, A.W.C. Perco, P. Rahimi, F. Riva, G. Zhang, C. Devkota, H.P. Ogami, K. Basharat, Z. Fierz, W. Siebers, R. Tan, K.H. Boehme, K.A. Brenneisen, P. Brown, J.A.L. Dalrymple, B.P. Harvey, D.J. Ng, G. Werten, S. Bleackley, M. Dai, Z. Dhariwal, R. Gelfer, Y. Hartmann, M.D. Miotla, P. Tamaian, R. Govender, P. Gurney-Champion, O.J. Kauppila, J.H. Zhang, X. Echeverría, N. Subhash, S. Sallmon, H. Tofani, M. Bae, T. Bosch, O. Cuív, P.O. Danchin, A. Diouf, B. Eerola, T. Evangelou, E. Filipp, F. Klump, H. Kurgan, L. Smith, S.S. Terrier, O. Tuttle, N. Ascher, D.B. Janga, S.C. Schulte, L.N. Becker, D. Browngardt, C. Bush, S.J. Gaullier, G. Ide, K. Meseko, C. Werner, G.D.A. Zaucha, J. Al-Farha, A.A. Greenwald, N.F. Popoola, S.I. Rahman, S. Xu, J. Yang, S.Y. Hiroi, N. Alper, O.M. Baker, C.I. Bitzer, M. Chacko, G. Debrabant, B. Dixon, R. Forano, E. Gilliham, M. Kelly, S. Klempnauer, K.-H. Lidbury, B.A. Lin, M.Z. Lynch, I. Ma, W. Maibach, E.W. Mather, D.E. Nandakumar, K.S. Ohgami, R.S. Parchi, P. Tressoldi, P. Xue, Y. Armitage, C. Barraud, P. Chatzitheochari, S. Coelho, L.P. Diao, J. Doxey, A.C. Gobet, A. Hu, P. Kaiser, S. Mitchell, K.M. Salama, M.F. Shabalin, I.G. Song, H. Stevanovic, D. Yadollahpour, A. Zeng, E. Zinke, K. Alimba, C.G. Beyene, T.J. Cao, Z. Chan, S.S. Gatchell, M. Kleppe, A. Piotrowski, M. Torga, G. Woldesemayat, A.A. Cosacak, M.I. Haston, S. Ross, S.A. Williams, R. Wong, A. Abramowitz, M.K. Effiong, A. Lee, S. Abid, M.B. Agarabi, C. Alaux, C. Albrecht, D.R. Atkins, G.J. Beck, C.R. Bonvin, A.M.J.J. Bourke, E. Brand, T. Braun, R.J. Bull, J.A. Cardoso, P. Carter, D. Delahay, R.M. Ducommun, B. Duijf, P.H.G. Epp, T. Eskelinen, E.-L. Fallah, M. Farber, D.B. Fernandez-Triana, J. Feyerabend, F. Florio, T. Friebe, M. Furuta, S. Gabrielsen, M. Gruber, J. Grybos, M. Han, Q. Heinrich, M. Helanterä, H. Huber, M. Jeltsch, A. Jiang, F. Josse, C. Jurman, G. Kamiya, H. de Keersmaecker, K. Kristiansson, E. de Leeuw, F.-E. Li, J. Liang, S. Lopez-Escamez, J.A. Lopez-Ruiz, F.J. Marchbank, K.J. Marschalek, R. Martín, C.S. Miele, A.E. Montagutelli, X. Morcillo, E. Nicoletti, R. Niehof, M. O'Toole, R. Ohtomo, T. Oster, H. Palma, J.-A. Paterson, R. Peifer, M. Portilla, M. Portillo, M.C. Pritchard, A.L. Pusch, S. Raghava, G.P.S. Roberts, N.J. Ross, K. Schuele, B. Sergeant, K. 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Zaritsky, A. Zhang, Y. Zhao, H. Zuckerman, H. Lyu, R. Pullan, W. RELISH Consortium
- Abstract
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science. © The Author(s) 2019. Published by Oxford University Press.
- Published
- 2019
9. P50 - Identification of markers for prostate cancer progression and aggressiveness through proteomic analysis of FFPE tissue samples
- Author
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Lygirou, V., Stroggilos, R., Fasoulakis, K., Makridakis, M., Latosinska, A., Frantzi, M., Katafigiotis, I., Alamanis, C., Stravodimos, K.G., Constantinides, C.A., Vlahou, A., and Zoidakis, J.
- Published
- 2022
- Full Text
- View/download PDF
10. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
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- Abstract
Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical science.
- Published
- 2019
11. Proteome-based classification of non-muscle invasive bladder cancer
- Author
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Fragkoulis, C., primary, Stroggilos, R., additional, Latosinska, A., additional, Makridakis, M., additional, Lygirou, V., additional, Mavrogeorgis, E., additional, Drekolias, D., additional, Frantzi, M., additional, Mullen, W., additional, Stasinopoulos, K., additional, Papadopoulos, G., additional, Stathouros, G., additional, Lazaris, A., additional, Makrythanasis, P., additional, Ntoumas, K., additional, Mischak, H., additional, Zoidakis, J., additional, and Vlahou, A., additional
- Published
- 2019
- Full Text
- View/download PDF
12. Preliminary proteomic analysis of F.F.P.E. tumor samples for predicting the response of bladder cancer patients to anti-PD-1/PDL-1 therapy
- Author
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Stroggilos, R., primary, Lygirou, V., additional, Makridakis, M., additional, Korkolopoulou, P., additional, Zakopoulou, R., additional, Termentzi, A., additional, Zoidakis, J., additional, Bamias, A., additional, and Vlahou, A., additional
- Published
- 2019
- Full Text
- View/download PDF
13. Cervical cancer cell line secretome highlights the roles of transforming growth factor-beta-induced protein ig-h3, peroxiredoxin-2, and NRF2 on cervical carcinogenesis
- Author
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Kontostathi, G. Zoidakis, J. Makridakis, M. Lygirou, V. Mermelekas, G. Papadopoulos, T. Vougas, K. Vlamis-Gardikas, A. Drakakis, P. Loutradis, D. Vlahou, A. Anagnou, N.P. Pappa, K.I.
- Abstract
Cancer cells acquire unique secretome compositions that contribute to tumor development and metastasis. The aim of our study was to elucidate the biological processes involved in cervical cancer, by performing a proteomic analysis of the secretome from the following informative cervical cell lines: SiHa (HPV16+), HeLa (HPV18+), C33A (HPV-), and HCK1T (normal). Proteins were analyzed by 2D gel electrophoresis coupled to MALDI-TOF-MS. Enrichment of secreted proteins with characteristic profiles for each cell line was followed by the identification of differentially expressed proteins. Particularly, transforming growth factor-beta-induced protein ig-h3 (Beta ig-h3) and peroxiredoxin-2 (PRDX2) overexpression in the secretome of cancer cell lines was detected and confirmed by Western blot. Bioinformatics analysis identified the transcription factor NRF2 as a regulator of differentially expressed proteins in the cervical cancer secretome. NRF2 levels were measured by both Western blot and Multiple Reaction Monitoring (MRM) in the total cell extract of the four cell lines. NRF2 was upregulated in SiHa and C33A compared to HCK1T. In conclusion, the secreted proteins identified in cervical cancer cell lines indicate that aberrant NRF2-mediated oxidative stress response (OSR) is a prominent feature of cervical carcinogenesis. © 2017 Georgia Kontostathi et al.
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- 2017
14. Proteomics analysis of bladder cancer invasion: Targeting EIF3D for therapeutic intervention
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Latosinska, A. Mokou, M. Makridakis, M. Mullen, W. Zoidakis, J. Lygirou, V. Frantzi, M. Katafigiotis, I. Stravodimos, K. Hupe, M.C. Dobrzynski, M. Kolch, W. Merseburger, A.S. Mischak, H. Roubelakis, M.G. Vlahou, A.
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Patients with advanced bladder cancer have poor outcomes, indicating a need for more efficient therapeutic approaches. This study characterizes proteomic changes underlying bladder cancer invasion aiming for the better understanding of disease pathophysiology and identification of drug targets. High resolution liquid chromatography coupled to tandem mass spectrometry analysis of tissue specimens from patients with non-muscle invasive (NMIBC, stage pTa) and muscle invasive bladder cancer (MIBC, stages pT2+) was conducted. Comparative analysis identified 144 differentially expressed proteins between analyzed groups. These included proteins previously associated with bladder cancer and also additional novel such as PGRMC1, FUCA1, BROX and PSMD12, which were further confirmed by immunohistochemistry. Pathway and interactome analysis predicted strong activation in muscle invasive bladder cancer of pathways associated with protein synthesis e.g. eIF2 and mTOR signaling. Knock-down of eukaryotic translation initiation factor 3 subunit D (EIF3D) (overexpressed in muscle invasive disease) in metastatic T24M bladder cancer cells inhibited cell proliferation, migration, and colony formation in vitro and decreased tumor growth in xenograft models. By contrast, knocking down GTP-binding protein Rheb (which is upstream of EIF3D) recapitulated the effects of EIF3D knockdown in vitro, but not in vivo. Collectively, this study represents a comprehensive analysis of NMIBC and MIBC providing a resource for future studies. The results highlight EIF3D as a potential therapeutic target. © Latosinska et al.
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- 2017
15. Proteomic analysis of normal and cancer cervical cell lines reveals deregulation of cytoskeleton-associated proteins
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Pappá, K.I. Lygirou, V. Kontostathi, G. Zoidakis, J. Makridakis, M. Vougas, K. Daskalakis, G. Polyzos, A. Anagnou, N.P.
- Abstract
Background: Both HPV-positive and -negative cervical cancers are primarily associated with features of cell cycle and cytoskeletal disruption; however, the actual biological processes affected remain elusive. To this end, we systematically characterized the intracellular proteomic profiles of four distinct and informative cervical cell lines. Materials and Methods: Cell extracts from a normal cervical (HCK1T) and three cervical cancer cell lines, one HPVnegative (C33A), and two HPV-positive, SiHa (HPV16+) and HeLa (HPV18+), were analyzed by 2-dimensional electrophoresis and differentially expressed proteins were identified by MALDI-TOF mass spectrometry, while differential expression was confirmed by western blot analysis. Results: In total, 133 proteins were found differentially expressed between the normal and the cervical cancer lines. Bioinformatics analysis revealed the actin cytoskeleton signaling pathway to be significantly affected, while up-regulation of cofilin-1, an actin depolymerizing factor, was documented and further validated by western blotting. Furthermore, two-way comparisons among the four cell lines, revealed a set of 18 informative differentially expressed proteins. Conclusion: These novel identified proteins provide the impetus for further functional studies to dissect the mechanisms operating in the two distinct pathways of cervical carcinogenesis.
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- 2017
16. Effect of Heme Oxygenase-1 Deficiency on Glomerular Proteomics
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Detsika, M.G. Lygirou, V. Frantzis, V. Zoidakis, J. Atsaves, V. Poulaki, E. Gakiopoulou, H. Vlahou, A. Lianos, E.A.
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urogenital system ,urologic and male genital diseases ,female genital diseases and pregnancy complications - Abstract
Background: The cytoprotective effect of heme oxygenase (HO)-1 in various forms of renal glomerular injury is established. However, little is known on the role of HO-1 in preserving glomerular structural/functional integrity in the absence of injury. The present study addressed this question in HO-1-deficient rats. Methods: HO-1-deficient rats were generated using zinc finger nuclease-mediated HO-1 gene ( Hmox1 ) disruption and studied. Glomeruli were isolated from HO-1-deficient ( Hmox1 -/- ) rats and their wild type (WT) littermates for proteomic analysis. Results: Glomerular lesions were characterized and differentially expressed proteins important for preserving integrity of the glomerular filtration barrier were identified. HO-1-deficient ( Hmox1 -/- ) rats developed albuminuria with decreased glomerular filtration rate. In albuminuric rats, there were lesions resembling focal and segmental glomerulosclerosis (FSGS). Western blot analysis of the integral slit diaphragm proteins, nephrin and podocin revealed a significant decrease in nephrin, with no change in podocin. Proteomic analysis of glomerular protein lysates from Hmox1 -/- and WT rats revealed differential expression of proteins previously linked with FSGS pathogenesis. Specifically, ?-actinin-4, actin related protein 3, cytokeratins and novel candidates including transgelin-2 and lamins. Bioinformatic analysis predicted the upregulation of pathways implicated in platelet aggregation and fibrin clot formation. Conclusion: HO-1 is a putative regulator of proteins important in preserving glomerular structural stability and integrity, and in minimizing the activity of proinflammatory pathways. © 2016 S. Karger AG, Basel.
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- 2016
17. Analytical performance of ELISA assays in Urine: One more bottleneck towards biomarker validation and clinical implementation
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Chatziharalambous, D. Lygirou, V. Latosinska, A. Stravodimos, K. Vlahou, A. Jankowski, V. Zoidakis, J.
- Abstract
ELISA is the main approach for the sensitive quantification of protein biomarkers in body fluids and is currently employed in clinical laboratories for the measurement of clinical markers. As such, it also constitutes the main methodological approach for biomarker validation and further qualification. For the latter, specific assay performance requirements have to be met, as described in respective guidelines of regulatory agencies. Even though many clinical ELISA assays in serum are regularly used, ELISA clinical applications in urine are significantly less. The scope of our study was to evaluate ELISA assay analytical performance in urine for a series of potential biomarkers for bladder cancer, as a first step towards their large scale clinical validation. Seven biomarkers (Secreted protein acidic and rich in cysteine, Survivin, Slit homolog 2 protein, NRC-Interacting Factor 1, Histone 2B, Proteinase-3 and Profilin-1) previously described in the literature as having differential expression in bladder cancer were included in the study. A total of 11 commercially available ELISA tests for these markers were tested by standard curve analysis, assay reproducibility, linearity and spiking experiments. The results show disappointing performance with coefficients of variation> 20% for the vast majority of the tests performed. Only 3 assays (for Secreted protein acidic and rich in cysteine, Survivin and Slit homolog 2 protein) passed the accuracy thresholds and were found suitable for further application in marker quantification. These results collectively reflect the difficulties in developing urine-based ELISA assays of sufficient analytical performance for clinical application, presumably attributed to the urine matrix itself and/or presence of markers in various isoforms. © Copyright 2016 Chatziharalambous et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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- 2016
18. Silencing of Profilin-1 suppresses cell adhesion and tumor growth via predicted alterations in integrin and Ca2+ signaling in T24M-based bladder cancer models
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Frantzi, M. Klimou, Z. Makridakis, M. Zoidakis, J. Latosinska, A. Borràs, D.M. Janssen, B. Giannopoulou, I. Lygirou, V. Lazaris, A.C. Anagnou, N.P. Mischak, H. Roubelakis, M.G. Vlahou, A.
- Abstract
Bladder cancer (BC) is the second most common malignancy of the genitourinary system, characterized by the highest recurrence rate of all cancers. Treatment options are limited; thus a thorough understanding of the underlying molecular mechanisms is needed to guide the discovery of novel therapeutic targets. Profilins are actin binding proteins with attributed pleiotropic functions to cytoskeletal remodeling, cell adhesion, motility, even transcriptional regulation, not fully characterized yet. Earlier studies from our laboratory revealed that decreased tissue levels of Profilin-1 (PFN1) are correlated with BC progression to muscle invasive disease. Herein, we describe a comprehensive analysis of PFN1 silencing via shRNA, in vitro (by employing T24M cells) and in vivo [(with T24M xenografts in non-obese diabetic severe combined immunodeficient mice (NOD/SCID) mice]. A combination of phenotypic and molecular assays, including migration, proliferation, adhesion assays, flow cytometry and total mRNA sequencing, as well as immunohistochemistry for investigation of selected findings in human specimens were applied. A decrease in BC cell adhesion and tumor growth in vivo following PFN downregulation are observed, likely associated with the concomitant downregulation of Fibronectin receptor, Endothelin-1, and Actin polymerization. A decrease in the levels of multiple key members of the non-canonical Wnt/Ca2+ signaling pathway is also detected following PFN1 suppression, providing the groundwork for future studies, addressing the specific role of PFN1 in Ca2+ signaling, particularly in the muscle invasive disease.
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- 2016
19. O2 - Proteome-based classification of non-muscle invasive bladder cancer
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Fragkoulis, C., Stroggilos, R., Latosinska, A., Makridakis, M., Lygirou, V., Mavrogeorgis, E., Drekolias, D., Frantzi, M., Mullen, W., Stasinopoulos, K., Papadopoulos, G., Stathouros, G., Lazaris, A., Makrythanasis, P., Ntoumas, K., Mischak, H., Zoidakis, J., and Vlahou, A.
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- 2019
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20. O09 - Preliminary proteomic analysis of F.F.P.E. tumor samples for predicting the response of bladder cancer patients to anti-PD-1/PDL-1 therapy
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Stroggilos, R., Lygirou, V., Makridakis, M., Korkolopoulou, P., Zakopoulou, R., Termentzi, A., Zoidakis, J., Bamias, A., and Vlahou, A.
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- 2019
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21. Large expert-curated database for benchmarking document similarity detection in biomedical literature search
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Zeineb, Zian, Brown, Peter, Tan, Aik-Choon, El-Esawi, Mohamed A., Liehr, Thomas, Blanck, Oliver, Gladue, Douglas P., Almeida, Gabriel M. F., Cernava, Tomislav, Sorzano, Carlos O., Yeung, Andy W. K., Engel, Michael S., Chandrasekaran, Arun Richard, Muth, Thilo, Staege, Martin S., Daulatabad, Swapna V., Widera, Darius, Zhang, Junpeng, Meule, Adrian, Honjo, Ken, Pourret, Olivier, Yin, Cong-Cong, Zhang, Zhongheng, Cascella, Marco, Flegel, Willy A., Goodyear, Carl S., Raaij, Mark J. van, Bukowy-Bieryllo, Zuzanna, Campana, Luca G., Kurniawan, Nicholas A., Lalaouna, David, Hüttner, Felix J., Ammerman, Brooke A., Ehret, Felix, Cobine, Paul A., Tan, Ene-Choo, Han, Hyemin, Xia, Wenfeng, McCrum, Christopher, Dings, Ruud P. M., Marinello, Francesco, Nilsson, Henrik, Nixon, Brett, Voskarides, Konstantinos, Yang, Long, Costa, Vincent D., Bengtsson-Palme, Johan, Bradshaw, William, Grimm, Dominik G., Kumar, Nitin, Martis, Elvis, Prieto, Daniel, Sabnis, Sandeep C., Amer, Said E. D. R., Liew, Alan W. C., Perco, Paul, Rahimi, Farid, Riva, Giuseppe, Zhang, Chongxing, Devkota, Hari P., Ogami, Koichi, Basharat, Zarrin, Fierz, Walter, Siebers, Robert, Tan, Kok-Hian, Boehme, Karen A., Brenneisen, Peter, Brown, James A. L., Dalrymple, Brian P., Harvey, David J., Ng, Grace, Werten, Sebastiaan, Bleackley, Mark, Dai, Zhanwu, Dhariwal, Raman, Gelfer, Yael, Hartmann, Marcus D., Miotla, Pawel, Tamaian, Radu, Govender, Pragashnie, Gurney-Champion, Oliver J., Kauppila, Joonas H., Zhang, Xiaolei, Echeverría, Natalia, Subhash, Santhilal, Sallmon, Hannes, Tofani, Marco, Bae, Taeok, Bosch, Oliver, Cuív, Páraic O., Danchin, Antoine, Diouf, Barthelemy, Eerola, Tuomas, Evangelou, Evangelos, Filipp, Fabian V., Klump, Hannes, Kurgan, Lukasz, Smith, Simon S., Terrier, Olivier, Tuttle, Neil, Ascher, David B., Janga, Sarath C., Schulte, Leon N., Becker, Daniel, Browngardt, Christopher, Bush, Stephen J., Gaullier, Guillaume, Ide, Kazuki, Meseko, Clement, Werner, Gijsbert D. A., Zaucha, Jan, Al-Farha, Abd A., Greenwald, Noah F., Popoola, Segun I., Rahman, Md Shaifur, Xu, Jialin, Yang, Sunny Y., Hiroi, Noboru, Alper, Ozgul M., Baker, Chris I., Bitzer, Michael, Chacko, George, Debrabant, Birgit, Dixon, Ray, Forano, Evelyne, Gilliham, Matthew, Kelly, Sarah, Klempnauer, Karl-Heinz, Lidbury, Brett A., Lin, Michael Z., Lynch, Iseult, Ma, Wujun, Maibach, Edward W., Mather, Diane E., Nandakumar, Kutty S., Ohgami, Robert S., Parchi, Piero, Tressoldi, Patrizio, Xue, Yu, Armitage, Charles, Barraud, Pierre, Chatzitheochari, Stella, Coelho, Luis P., Diao, Jiajie, Doxey, Andrew C., Hu, Pingzhao, Kaiser, Stefan, Mitchell, Kate M., Salama, Mohamed F., Shabalin, Ivan G., Song, Haijun, Stevanovic, Dejan, Yadollahpour, Ali, Zeng, Erliang, Zinke, Katharina, Alimba, C. G., Beyene, Tariku J., Cao, Zehong, Chan, Sherwin S., Gatchell, Michael, Kleppe, Andreas, Piotrowski, Marcin, Torga, Gonzalo, Woldesemayat, Adugna A., Cosacak, Mehmet I., Haston, Scott, Ross, Stephanie A., Williams, Richard, Wong, Alvin, Abramowitz, Matthew K., Effiong, Andem, Lee, Senhong, Abid, Muhammad Bilal, Agarabi, Cyrus, Alaux, Cedric, Albrecht, Dirk R., Atkins, Gerald J., Beck, Charles R., Bonvin, A. M. J. J., Bourke, Emer, Brand, Thomas, Braun, Ralf J., Bull, James A., Cardoso, Pedro, Carter, Dee, Delahay, Robin M., Ducommun, Bernard, Duijf, Pascal H. G., Epp, Trevor, Eskelinen, Eeva-Liisa, Fallah, Mazyar, Farber, Debora B., Fernandez-Triana, Jose, Feyerabend, Frank, Florio, Tullio, Friebe, Michael, Furuta, Saori, Gabrielsen, Mads, Gruber, Jens, Grybos, Malgorzata, Han, Qian, Heinrich, Michael, Helanterä, Heikki, Huber, Michael, Jeltsch, Albert, Jiang, Fan, Josse, Claire, Jurman, Giuseppe, Kamiya, Haruyuki, Keersmaecker, Kim de, Kristiansson, Erik, Leeuw, Frank-Erik de, Li, Jiuyong, Liang, Shide, Lopez-Escamez, Jose A., Lopez-Ruiz, Francisco J., Marchbank, Kevin J., Marschalek, Rolf, Martín, Carmen S., Miele, Adriana E., Montagutelli, Xavier, Morcillo, Esteban, Nicoletti, Rosario, Niehof, Monika, O’Toole, Ronan, Ohtomo, Toshihiko, Oster, Henrik, Palma, Jose-Alberto, Paterson, Russell, Peifer, Mark, Portilla, Maribel, Portillo, M. C., Pritchard, Antonia L., Pusch, Stefan, Raghava, Gajendra P. S., Roberts, Nicola J., Ross, Kehinde, Schuele, Birgitt, Sergeant, Kjell, Shen, Jun, Stella, Alessandro, Sukocheva, Olga, Uversky, Vladimir N., Vanneste, Sven, Villet, Martin H., Viveiros, Miguel, Vorholt, Julia A., Weinstock, Christof, Yamato, Masayuki, Zabetakis, Ioannis, Zhao, Xin, Ziegler, Andreas, Aizat, Wan M., Atlas, Lauren, Bridges, Kristina M., Chakraborty, Sayan, Deschodt, Mieke, Domingues, Helena S., Esfahlani, Shabnam S., Falk, Sebastian, Guisado, J. L., Kane, Nolan C., Kueberuwa, Gray, Lau, Colleen L., Liang, Dai, Liu, Enwu, Luu, Andreas M., Ma, Chuang, Ma, Lisong, Moyer, Robert, Norris, Adam D., Panthee, Suresh, Parsons, Jerod R., Peng, Yousong, Pinto, Inês Mendes, Reschke, Cristina R., Sillanpää, Elina, Stewart, Christopher J., Uhle, Florian, Yang, Hui, Zhou, Kai, Zhu, Shu, Ashry, Mohamed, Bergsland, Niels, Berthold, Maximilian, Chen, Chang-Er, Colella, Vito, Cuypers, Maarten, Eskew, Evan A., Fan, Xiao, Gajda, Maksymilian, Gonzálezlez-Prendes, Rayner, Goodin, Amie, Graham, Emily B., Groen, Ewout J. N., Gutiérrez-Sacristán, Alba, Habes, Mohamad, Heffler, Enrico, Higginbottom, Daniel B., Janzen, Thijs, Jayaraman, Jayakumar, Jibb, Lindsay A., Jongen, Stefan, Kinyanjui, Timothy, Koleva-Kolarova, Rositsa G., Li, Zhixiu, Liu, Yu-Peng, Lund, Bjarte A., Lussier, Alexandre A., Ma, Liping, Mier, Pablo, Moore, Matthew D., Nagler, Katja, Orme, Mark W., Pearson, James A., Prajapati, Anilkumar S., Saito, Yu, Tröder, Simon E., Uchendu, Florence, Verloh, Niklas, Voutchkova, Denitza D., Abu-Zaid, Ahmed, Bakkach, Joaira, Baumert, Philipp, Dono, Marcos, Hanson, Jack, Herbelet, Sandrine, Hobbs, Emma, Kulkarni, Ameya, Kumar, Narendra, Liu, Siqi, Loft, Nikolai D., Reddan, Tristan, Senghore, Thomas, Vindin, Howard, Xu, Haotian, Bannon, Ross, Chen, Branson, Cheung, Johnny T. K., Cooper, Jeffrey, Esnakula, Ashwini K., Feghali, Karine A., Ghelardi, Emilia, Gnasso, Agostino, Horbar, Jeffrey, Lai, Hei M., Li, Jian, Ma, Lan, Ma, Ruiyan, Pan, Zihang, Peres, Marco A., Pranata, Raymond, Seow, Esmond, Sydes, Matthew, Testoni, Ines, Westermair, Anna L., Yang, Yongliang, Afnan, Masoud, Albiol, Joan, Albuquerque, Lucia G., Amiya, Eisuke, Amorim, Rogerio M., An, Qianli, Andersen, Stig U., Aplin, John D., Argyropoulos, Christos, Asmann, Yan W., Assaeed, Abdulaziz M., Atanasov, Atanas G., Atchison, David A., Avery, Simon V., Avillach, Paul, Baade, Peter D., Backman, Lars, Badie, Christophe, Baldi, Alfonso, Ball, Elizabeth, Bardot, Olivier, Barnett, Adrian G., Basner, Mathias, Batra, Jyotsna, Bazanova, O. M., Beale, Andrew, Beddoe, Travis, Bell, Melanie L., Berezikov, Eugene, Berners-Price, Sue, Bernhardt, Peter, Berry, Edward, Bessa, Theolis B., Billington, Craig, Birch, John, Blakely, Randy D., Blaskovich, Mark A. T., Blum, Robert, Boelaert, Marleen, Bogdanos, Dimitrios, Bosch, Carles, Bourgoin, Thierry, Bouvard, Daniel, Boykin, Laura M., Bradley, Graeme, Braun, Daniel, Brownlie, Jeremy, Brühl, Albert, Burt, Austin, Butler, Lisa M., Byrareddy, Siddappa N., Byrne, Hugh J., Cabantous, Stephanie, Calatayud, Sara, Candal, Eva, Carlson, Kimberly, Casillas, Sònia, Castelvetro, Valter, Caswell, Patrick T., Cavalli, Giacomo, Cerovsky, Vaclav, Chagoyen, Monica, Chen, Chang-Shi, Chen, Dong F., Chen, Hao, Chen, Hui, Chen, Jui-Tung, Chen, Yinglong, Cheng, Changxiu, Cheng, Jianlin, Chinapaw, Mai, Chinopoulos, Christos, Cho, William C. S., Chong, Lillian, Chowdhury, Debashish, Chwalibog, Andre, Ciresi, A., Cockcroft, Shamshad, Conesa, Ana, Cook, Penny A., Cooper, David N., Coqueret, Olivier, Corea, Enoka M., Costa, Elisio, Coupland, Carol, Crawford, Stephanie Y., Cruz, Aparecido D., Cui, Huijuan, Cui, Qiang, Culver, David C., D’Angiulli, Amedeo, Dahms, Tanya E. S., Daigle, France, Dalgleish, Raymond, Danielsen, Håvard E., Darras, Sébastien, Davidson, Sean M., Day, David A., Degirmenci, Volkan, Demaison, Luc, Devriendt, Koenraad, Ding, Jiandong, Dogan, Yunus, Dong, X. C., Donner, Claudio F., Dressick, Walter, Drevon, Christian A., Duan, Huiling, Ducho, Christian, Dumaz, Nicolas, Dwarakanath, Bilikere S., Ebell, Mark H., Eisenhardt, Steffen, Elkum, Naser, Engel, Nadja, Erickson, Timothy B., Fairhead, Michael, Faville, Marty J., Fejzo, Marlena S., Festa, Fernanda, Feteira, Antonio, Flood-Page, Patrick, Forsayeth, John, Fox, Simon A., Franks, Steven J., Frentiu, Francesca D., Frilander, Mikko J., Fu, Xinmiao, Fujita, Satoshi, Galea, Ian, Galluzzi, Luca, Gani, Federica, Ganpule, Arvind P., García-Alix, Antonio, Gedye, Kristene, Giordano, Maurizio, Giunta, Cecilia, Gleeson, Paul A., Goarant, Cyrille, Gong, Haipeng, Gora, Diop, Gough, Michael J., Goyal, Ravinder, Graham, Kathryn E., Grande-Pérez, Ana, Graves, Patricia M., Greidanus, Harm, Grice, Darren, Grunau, Christoph, Gumulya, Yosephine, Guo, Yabin, Gurevich, Vsevolod V., Gusev, Oleg, Hacker, Elke, Hage, Steffen R., Hagen, Guy, Hahn, Steven, Haller, Dagmar M., Hammerschmidt, Sven, Han, Jianwei, Han, Renzhi, Handfield, Martin, Hapuarachchi, Hapuarachchige C., Harder, Timm, Hardingham, Jennifer E., Heck, Michelle, Heers, Marcel, Hew, Khe F., Higuchi, Yohei, Hilaire, Cynthia St, Hilton, Rachel, Hodzic, Enisa, Hone, Andrew, Hongoh, Yuichi, Hu, Guoku, Huber, Heinz P., Hueso, Luis E., Huirne, Judith, Hurt, Lisa, Idborg, Helena, Ikeo, Kazuho, Ingley, Evan, Jakeman, Philip M., Jensen, Arne, Jia, Hong, Jia, Husen, Jia, Shuqin, Jiang, Jianping, Jiang, Xingyu, Jin, Yi, Jo, Daehyun, Johnson, Andrew M., Johnston, Marie, Jonscher, Karen R., Jorens, Philippe G., Jorgensen, Jens O. L., Joubert, Johan W., Jung, Sin-Ho, Junior, Antonio M., Kahan, Thomas, Kamboj, Sunjeev K., Kang, Yong-Kook, Karamanos, Yannis, Karp, Natasha A., Kelly, Ryan, Kenna, Ralph, Kennedy, Jonathan, Kersten, Birgit, Khalaf, Roy A., Khalid, Javaria M., Khatlani, T., Khider, Tarig, Kijanka, Gregor S., King, Sarah R. B., Kluz, Tomasz, Knox, Paul, Kobayashi, Tatsuya, Koch, Karl-Wilhelm, Kohonen-Corish, Maija R. J., Kong, Xiangpeng, Konkle-Parker, Deborah, Korpela, Kalevi M., Kostrikis, Leondios G., Kraiczy, Peter, Kratz, Harald, Krause, Günter, Krebsbach, Paul H., Kristensen, Søren R., Kumari, Prerna, Kunimatsu, Akira, Kurdak, Hatice, Kwon, Young D., Lachat, Carl, Lagisz, Malgorzata, Laky, Brenda, Lammerding, Jan, Lange, Matthias, Larrosa, Mar, Laslett, Andrew L., LeClair, Elizabeth E., Lee, Kyung-Woo, Lee, Ming-Yih, Lee, Moon-Soo, Li, Genyuan, Li, Jiansheng, Lieb, Klaus, Lim, Yau Y., Lindsey, Merry L., Line, Paul-Dag, Liu, Dengcai, Liu, Fengbin, Liu, Haiyan, Liu, Hongde, Lloyd, Vett K., Lo, Te-Wen, Locci, Emanuela, Loidl, Josef, Lorenzen, Johan, Lorkowski, Stefan, Lovell, Nigel H., Lu, Hua, Lu, Wei, Lu, Zhiyong, Luengo, Gustavo S., Lundh, Lars-Gunnar, Lysy, Philippe A., Mabb, Angela, Mack, Heather G., Mackey, David A., Mahdavi, S. R., Maher, Pamela, Maher, Toby, Maity, Sankar N., Malgrange, Brigitte, Mamoulakis, Charalampos, Mangoni, Arduino A., Manke, Thomas, Manstead, Antony S. R., Mantalaris, Athanasios, Marsal, Jan, Marschall, Hanns-Ulrich, Martin, Francis L., Martinez-Raga, Jose, Martinez-Salas, Encarnacion, Mathieu, Daniel, Matsui, Yoichi, Maza, Elie, McCutcheon, James E., McKay, Gareth J., McMillan, Brian, McMillan, Nigel, Meads, Catherine, Medina, Loreta, Merrick, B. Alex, Metzger, Dennis W., Meunier, Frederic A., Michaelis, Martin, Micheau, Olivier, Mihara, Hisaaki, Mintz, Eric M., Mizukami, Takuo, Moalic, Yann, Mohapatra, D. P., Monteiro, Antonia, Montes, Matthieu, Moran, John V., Morozov, Sergey Y., Mort, Matthew, Murai, Noriyuki, Murphy, Denis J., Murphy, Susan K., Murray, Shauna A., Naganawa, Shinji, Nammi, Srinivas, Nasios, Grigorios, Natoli, Roman M., Nguyen, Frederique, Nicol, Christine, Nieuwerburgh, Filip van, Nilsen, Erlend B., Nobile, Clarissa J., O’Mahony, Margaret, Ohlsson, Sophie, Olatunbosun, Oluremi, Olofsson, Per, Ortiz, Alberto, Ostrikov, Kostya, Otto, Siegmar, Outeiro, Tiago F., Ouyang, Songying, Paganoni, Sabrina, Page, Andrew, Palm, Christoph, Paradies, Yin, Parsons, Michael H., Parsons, Nick, Pascal, Pigny, Paul, Elisabeth, Peckham, Michelle, Pedemonte, Nicoletta, Pellizzon, Michael A., Petrelli, M., Pichugin, Alexander, Pinto, Carlos J. C., Plevris, John N., Pollesello, Piero, Polz, Martin, Ponti, Giovanna, Porcelli, Piero, Prince, Martin, Quinn, Gwendolyn P., Quinn, Terence J., Ramula, Satu, Rappsilber, Juri, Rehfeldt, Florian, Reiling, Jan H., Remacle, Claire, Rezaei, Mohsen, Riddick, Eric W., Ritter, Uwe, Roach, Neil W., Roberts, David D., Robles, Guillermo, Rodrigues, Tiago, Rodriguez, Cesar, Roislien, Jo, Roobol, Monique J., Rowe, J. Alexandra, Ruepp, Andreas, Ruitenbeek, Jan van, Rust, Petra, Saad, Sonia, Sack, George H., Santos, Manuela, Saudemont, Aurore, Sava, Gianni, Schrading, Simone, Schramm, Alexander, Schreiber, Martin, Schuler, Sidney, Schymkowitz, Joost, Sczyrba, Alexander, Seib, Kate L., Shi, Han-Ping, Shimada, Tomohiro, Shin, Jeon-Soo, Shortt, Colette, Silveyra, Patricia, Skinner, Debra, Small, Ian, Smeets, Paul A. 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Mechanisms, Pediatric surgery, APH - Methodology, ACS - Atherosclerosis & ischemic syndromes, RELISH Consortium [Member of the MPIB: Lucas Molleman], Kostrikis, Leondios G. [0000-0002-5340-7109], Tan, AC, El-Esawi, MA, Gladue, DP, Almeida, GMF, Sorzano, CO, Yeung, AWK, Engel, MS, Chandrasekaran, AR, Staege, MS, Daulatabad, SV, Yin, CC, Flegel, WA, Goodyear, CS, van Raaij, MJ, Campana, LG, Kurniawan, NA, Huttner, FJ, Ammerman, BA, Cobine, PA, Tan, EC, Han, HM, Xia, WF, McCrum, C, Dings, RPM, Costa, VD, Grimm, DG, Sabnis, SC, Amer, SEDR, Liew, AWC, Zhang, CX, Devkota, HP, Tan, KH, Boehme, KA, Brown, JAL, Dalrymple, BP, Harvey, DJ, Dai, ZW, Hartmann, MD, Gurney-Champion, OJ, Kauppila, JH, Zhang, XL, Cuiv, PO, Filipp, FV, Smith, SS, Ascher, DB, Janga, SC, Schulte, LN, Bush, SJ, Werner, GDA, Al-Farha, AA, Greenwald, NF, Popoola, SI, Rahman, MS, Xu, JL, Yang, SY, Alper, OM, Baker, CI, Klempnauer, KH, Lidbury, BA, Lin, MZ, Ma, WJ, Maibach, EW, Mather, DE, Nandakumar, KS, Ohgami, RS, Coelho, LP, Doxey, AC, Hu, PZ, Mitchell, KM, Salama, MF, Shabalin, IG, Song, HJ, Zeng, EL, Alimba, CG, Beyene, TJ, Cao, ZH, Chan, SS, Woldesemayat, AA, Cosacak, MI, Ross, SA, Abramowitz, MK, Lee, SH, Abid, MB, Albrecht, DR, Atkins, GJ, Beck, CR, Bonvin, AMJJ, Braun, RJ, Bull, JA, Delahay, RM, Duijf, PHG, Eskelinen, EL, Farber, DB, Leeuw, FE, Lopez-Escamez, JA, Lopez-Ruiz, FJ, Marchbank, KJ, Martin, CS, Miele, AE, Palma, JA, Portillo, MC, Pritchard, AL, Raghava, GPS, Roberts, NJ, Uversky, VN, Villet, MH, Vorholt, JA, Aizat, WM, Bridges, KM, Domingues, HS, Esfahlani, SS, Guisado, JL, Kane, NC, Lau, CL, Luu, AM, Ma, LS, Norris, AD, Parsons, JR, Pinto, IM, Reschke, CR, Stewart, CJ, Chen, CE, Eskew, EA, Graham, EB, Groen, EJN, Higginbottom, DB, Jibb, LA, Koleva-Kolarova, RG, Liu, YP, Lund, BA, Lussier, AA, Moore, MD, Orme, MW, Pearson, JA, Prajapati, AS, Troder, SE, Voutchkova, DD, Liu, SQ, Loft, ND, Xu, HT, Cheung, JTK, Esnakula, AK, Feghali, KA, Lai, HM, Ma, RY, Pan, ZH, Peres, MA, Westermair, AL, Albuquerque, LG, Amorim, RM, Andersen, SU, Aplin, JD, Asmann, YW, Assaeed, AM, Atanasov, AG, Atchison, DA, Avery, SV, Baade, PD, Barnett, AG, Bazanova, OM, Bell, ML, Bessa, TB, Blakely, RD, Blaskovich, MAT, Boykin, LM, Butler, LM, Byrareddy, SN, Byrne, HJ, Caswell, PT, Chen, CS, Chen, DF, Chen, JT, Chen, YL, Cheng, CX, Cheng, JL, Cho, WCS, Cook, PA, Cooper, DN, Corea, EM, Crawford, SY, Cruz, AD, Cui, HJ, Culver, DC, Dahms, TES, Danielsen, HE, Davidson, SM, Day, DA, Dong, XC, Donner, CF, Drevon, CA, Duan, HL, Dwarakanath, BS, Ebell, MH, Erickson, TB, Faville, MJ, Fejzo, MS, Fox, SA, Franks, SJ, Frentiu, FD, Frilander, MJ, Fu, XM, Ganpule, AP, Gleeson, PA, Gong, HP, Gough, MJ, Graham, KE, Graves, PM, Guo, YB, Gurevich, VV, Hage, SR, Haller, DM, Han, JW, Hapuarachchi, HC, Hardingham, JE, Hew, KF, St Hilaire, C, Hu, GK, Huber, HP, Hueso, LE, Jakeman, PM, Jia, HS, Jia, SQ, Jiang, JP, Jiang, XY, Johnson, AM, Jonscher, KR, Jorens, PG, Jorgensen, JOL, Joubert, JW, Jung, SH, Junior, AM, Kamboj, SK, Kang, YK, Karp, NA, Khalaf, RA, Khalid, JM, Kijanka, GS, King, SRB, Koch, KW, Kohonen-Corish, MRJ, Korpela, KM, Kostrikis, LG, Krebsbach, PH, Kristensen, SR, Kwon, YD, Laslett, AL, LeClair, EE, Lee, KW, Lee, MY, Lee, MS, Li, GY, Li, JS, Lim, YY, Lindsey, ML, Line, PD, Liu, DC, Liu, FB, Liu, HY, Liu, HD, Lloyd, VK, Lo, TW, Lovell, NH, Lu, ZY, Luengo, GS, Lundh, LG, Lysy, PA, Mack, HG, Mackey, DA, Mahdavi, SR, Maity, SN, Mangoni, AA, Manstead, ASR, Marschall, HU, Martin, FL, McCutcheon, JE, Mckay, GJ, McMillan, B, McMillan, N, Merrick, BA, Metzger, DW, Meunier, FA, Mintz, EM, Mohapatra, DP, Moran, JV, Morozov, SY, Murphy, DJ, Murphy, SK, Murray, SA, Natoli, RM, Nilsen, EB, Nobile, CJ, Outeiro, TF, Parsons, MH, Pellizzon, MA, Pinto, CJC, Plevris, JN, Quinn, GP, Quinn, TJ, Reiling, JH, Riddick, EW, Roach, NW, Roberts, DD, Roobol, MJ, Rowe, JA, Sack, GH, Seib, KL, Shi, HP, Shin, JS, Smeets, PAM, So, PW, Sonenshine, DE, Song, JN, Speakman, JR, Srinivasan, MV, Stabile, LP, Steadman, KJ, Stephens, AW, Stewart, DI, Stoynova, NV, Suarez, OM, Sumant, AV, Summers, MJ, Tang, HX, Tebbe, CC, Telfer, EE, Teodorczyk-Injeyan, JA, Thrift, AG, Tjahjono, DH, del Tredici, AL, Udo, EE, Vandenbroucke, RE, Veiga, FH, Vesk, PA, Victor, VM, Vohl, MC, Voolstra, CR, Walsh, LJ, Wang, AY, Wen, JC, White, EP, Wojan, TR, Wong, BM, Wu, TW, Xiao, XS, Xu, JW, Xu, JP, Yang, EC, Yang, SQ, Ye, YZ, Ye, ZQ, Yuan, GC, Yuh, CH, Zhang, YK, Zhang, YS, Zhang, ZY, Aanei, CM, Atack, JM, Biedermann, PHW, den Bos, W, Boudreau, SA, Bramoweth, AD, Cao, ZX, Cheng, SQ, Chung, HJ, Chavez-Fumagalli, MA, Costa, BM, Dean, LT, Denzel, MS, Dlamini, SV, Dudley, KJ, Emmrich, JV, Eustace, AJ, Falter-Wagner, CM, Gao, JZ, Gill, MR, Grundle, DS, Ikonomopoulou, MP, Johnson, DM, Kaye, LK, Khan, MM, Kim, YM, Kish, JK, Kugler, JM, Lauschke, VM, Li, BL, Lim, CJ, Liu, XD, Lu, JJ, McGarrigle, CA, Mondal, SR, Van de Mortel, T, Moss, WN, Moultos, OA, Neumann, PA, Nie, JY, Nie, YJ, Oldenmenger, WH, Ou, JH, Pearce, SP, Pelleri, MC, Pereira, JL, Pinto, KA, Podolsky, IM, Qi, DC, Qi, XS, Raikou, VD, Rotge, JY, Rowe, AD, Schuon, RA, Smout, MJ, Song, CJ, Srivastava, RK, Tai, CNP, Tao, WY, Tian, CF, 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Univ Calif Irvine, Univ Hosp Leuven, Chongqing Med Univ, Childrens Hosp Kings Daughters, China Three Gorges Univ, and Xiangtan Univ
- Subjects
Technology and Engineering ,SCIENTIFIC SEARCH ,Expert-curated database ,Biokemia, solu- ja molekyylibiologia - Biochemistry, cell and molecular biology ,Databases ,RElevant LIterature SearcH consortium ,Medicine and Health Sciences ,Biomedical research ,benchmarking ,Biology ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,Settore MED/42 - IGIENE GENERALE E APPLICATA ,database ,Computer. Automation ,Science & Technology ,0804 Data Format ,relisch ,Scientific research in health sciences ,Mathematics and Statistics ,litearture search ,relisch , database ,biomedical research ,Biomedical literature ,Original Article ,RELISH ,Mathematical & Computational Biology ,RECOMMENDER-SYSTEMS ,Life Sciences & Biomedicine ,Mathematics ,0807 Library and Information Studies - Abstract
Made available in DSpace on 2020-12-11T01:57:28Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-10-29 Griffith University Gowonda HPC Cluster Queensland Cyber Infrastructure Foundation Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research. 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London, England La Trobe Univ, Anim Plant & Soil Sci, Melbourne, Vic, Australia Univ Arizona, Epidemiol & Biostat, Tucson, AZ USA Univ Groningen, Univ Med Ctr Groningen, ERIBA, Groningen, Netherlands Univ Gothenburg, Inst Clin Sci, Dept Radiat Phys, Gothenburg, Sweden SUNY Upstate Med Univ, Biochem & Mol Biol, Syracuse, NY 13210 USA Fundacao Oswaldo Cruz, Ctr Pesquisas Goncalo Moniz, Salvador, Bahia, Brazil Inst Environm Sci & Res ESR, Food Water & Environm Microbiol, Christchurch, New Zealand Univ Otago, Food Sci, Dunedin, New Zealand Florida Atlantic Univ, Biomed Sci, Boca Raton, FL 33431 USA Univ Queensland, Inst Mol Biosci, Brisbane, Qld, Australia Univ Hosp Wurzburg, Inst Clin Neurobiol, Wurzburg, Germany Inst Trop Med, Publ Hlth, Antwerp, Belgium Univ Thessaly, Sch Hlth Sci, Fac Med, Dept Rheumatol & Clin Immunol, Larisa, Greece Univ Basel, UZB Univ Ctr Dent Med, Dept Orthodont & Pediat Dent, Basel, Switzerland Sorbonne Univ, Museum Natl Hist Nat, Inst Systemat Evolut 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Montpellier, CNRS, Inst Human Genet, Montpellier, France Czech Acad Sci, Inst Organ Chem & Biochem, Prague, Czech Republic CSIC, Natl Ctr Biotechnol CNB, Computat Syst Biol Grp, Madrid, Spain Natl Cheng Kung Univ, Dept Biochem & Mol Biol, Tainan, Taiwan Harvard Med Sch, Schepens Eye Res Inst, Ophthalmol, Boston, MA 02115 USA Lanzhou Univ, Hosp 2, Dept Gen Surg, Lanzhou, Gansu, Peoples R China Univ Technol Sydney, Sch Life Sci, Sydney, NSW, Australia JT Chen Clin, Gynecol, Tokyo, Japan Univ Western Australia, Sch Agr & Environm, Perth, WA, Australia Beijing Normal Univ, Fac Geog Sci, Beijing, Peoples R China Univ Missouri, Elect Engn & Comp Sci, Columbia, MO USA Vrije Univ Amsterdam Med Ctr, Amsterdam Publ Hlth Res Inst, Dept Publ & Occupat Hlth, Amsterdam, Netherlands Semmelweis Univ, Med Biochem, Budapest, Hungary Queen Elizabeth Hosp, Dept Clin Oncol, Hong Kong, Peoples R China Univ Pittsburgh, Chem, Pittsburgh, PA USA GB Pant Inst Post Grad Med Educ & Res, Neurol, New Delhi, India Univ Copenhagen, Vet & Anim Sci, Copenhagen, Denmark Univ Palermo, Biomed Dept Internal & Specialist Med DIBIMIS, Sect Endocrinol, Palermo, Italy UCL, NPP, London, England Univ Florida, Microbiol & Cell Sci, Gainesville, FL USA Univ Salford, Sch Hlth Sci, Manchester, Lancs, England Cardiff Univ, Inst Med Genet, Cardiff, S Glam, Wales INSERM, ICO Canc Ctr, Angers, France Univ Colombo, Fac Med, Microbiol, Colombo, Sri Lanka Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China Univ Porto, Fac Pharm, Porto, Portugal Univ Nottingham, Div Primary Care, Nottingham, England Univ Illinois, Pharm Syst Outcomes & Policy, Chicago, IL USA Pontificia Univ Catolica Goias, Escola Ciencias Agr & Biol, Goiania, Go, Brazil China Japan Friendship Hosp, Dept Oncol, Beijing, Peoples R China Boston Univ, Chem, Boston, MA 02215 USA Amer Univ, Environm Sci, Washington, DC 20016 USA Carleton Univ, Neurosci, Ottawa, ON, Canada Univ Regina, Chem & Biochem, Regina, SK, Canada Univ Montreal, Microbiolgy, Montreal, PQ, Canada Univ Leicester, Dept Genet & Genome Biol, Leicester, Leics, England Univ Queensland, Sch Agr & Food Sci, Gatton, Qld, Australia CNRS, BIOM, Paris, France UCL, Hatter Cardiovasc Inst, London, England Flinders Univ S Australia, Sci & Engn, Adelaide, SA, Australia Univ Warwick, Engn, Coventry, W Midlands, England Katholieke Univ Leuven, Ctr Human Genet, Leuven, Belgium Fudan Univ, Dept Macromol Sci, Shanghai, Peoples R China Dokuz Eylul Univ, Biol Educ, Izmir, Turkey Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA Mondo Med, Pulm Dis, Borgomanero, Italy US Naval, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC USA Univ Oslo, Inst Basic Med Sci, Dept Nutr, Oslo, Norway Peking Univ, Dept Mech & Engn Sci, Beijing, Peoples R China Saarland Univ, Dept Pharm Pharmaceut & Med Chem, Saarbrucken, Germany INSERM, Natl Inst Hlth & Med Res, Skin Res Inst, Paris, France Shanghai Proton & Heavy Ion Ctr, Res & Dev, Shanghai, Peoples R China Univ Georgia, Epidemiol, Athens, GA 30602 USA Univ Freiburg, Med Ctr, Dept Plast & Hand Surg, Freiburg, Germany Sidra Med, Res, Doha, Qatar Rostock Univ, Med Ctr, Dept Oral Maxillofacial & Plast Surg, Rostock, Germany Harvard Med Sch, Brigham & Womens Hosp, Emergency Med, Boston, MA 02115 USA AgResearch, Forage Sci, Palmerston North, New Zealand Univ Calif Los Angeles, Med, Los Angeles, CA USA Arizona State Univ, Biodesign Inst, Virginia G Piper Ctr Personalized Diagnost, Tempe, AZ USA Sheffield Hallam Univ, Res Inst, Mat & Engn, Sheffield, S Yorkshire, England Aneurin Bevan Univ Healthboard, Resp Med, Newport, Shrops, England Univ Calif San Francisco, Neurol Surg, San Francisco, CA 94143 USA Univ Western Australia, UWA Dent Sch, Perth, WA, Australia Fordham Univ, Biol Sci, Bronx, NY 10458 USA Univ Helsinki, Inst Biotechnol, Helsinki, Finland Fujian Normal Univ, Coll Life Sci, Fuzhou, Fujian, Peoples R China Univ Fukui, Dept Frontier Fiber Technol & Sci, Fukui, Japan Univ Southampton, Fac Med, Clin & Expt Sci, Southampton, Hants, England Univ Urbino, Dept Biomol Sci, Urbino, Italy Osped San Luigi, Allergol Unit, Turin, Italy Muljibhai Patel Urol Hosp, Dept Urol, Nadiad, Gujarat, India Univ Granada, Stratig & Paleontol, Granada, Spain Massey Univ, Sch Vet Sci, Auckland, New Zealand CNR, High Performance Comp & Networking Inst, Naples, Italy Univ Childrens Hosp Zurich, Div Metab, Zurich, Switzerland Univ Childrens Hosp Zurich, Childrens Res Ctr, Zurich, Switzerland Univ Melbourne, Biochem & Mol Biol, Parkville, Vic, Australia Inst Pasteur, Leptospirosis Res & Expertise Unit, Noumea, New Caledonia Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China Cheikh Anta Diop Univ UCAD, Sci Fac, Biol Anim Dept, Dakar, Senegal Providence Portland Med Ctr, Earle A Chiles Res Inst, Portland, OR USA Agr & Agri Food Canada, Lacombe Res & Dev Ctr, Lacombe, AB, Canada Alberta Innovates, Performance Management & Evaluat, Edmonton, AB, Canada Univ Malaga, CSIC, Inst Hortofruticultura Subtrop Mediterranea La Ma, IHSM,UMA, Malaga, Spain James Cook Univ, Coll Publ Hlth Med & Vet Sci, Cairns, Qld, Australia European Commiss, Joint Res Ctr, Ispra, Italy Univ Montpellier, Montpellier, France CSIRO, Floreat, WA, Australia Sun Yat Sen Univ, Sun Yat Sen Mem Hosp, Guangzhou, Guangdong, Peoples R China Vanderbilt Univ, Pharmacol, 221 Kirkland Hall, Nashville, TN 37235 USA RIKEN, KFU RIKEN Translat Genom Unit, Yokohama, Kanagawa, Japan Univ Tubingen, Neurobiol Vocal Commun, Tubingen, Germany Univ Colorado, UCCS Ctr Biofrontiers Inst, Colorado Springs, CO 80907 USA Fred Hutchinson Canc Ctr, Div Basic Sci, Seattle, WA USA Univ Geneva, Fac Med, Primary Care Unit, Geneva, Switzerland Ernst Moritz Arndt Univ Greifswald, Dept Mol Genet & Infect Biol, Greifswald, Germany East China Univ Sci & Technol, Dept Fine Chem, Shanghai, Peoples R China Ohio State Univ, Surg, Columbus, OH 43210 USA Oragenics, R&D, Tampa, FL USA Natl Environm Agcy, Environm Hlth Inst, Singapore, Singapore Friedrich Loeffler Inst, Inst Diagnost Virol, Greifswald, Germany Queen Elizabeth Hosp, Oncol, Woodville, SA, Australia USDA, Emerging Pests & Pathogens Res Unit, Ithaca, NY USA Univ Freiburg, Med Ctr, Dept Neurosurg, Epilepsy Ctr, Freiburg, Germany Univ Hong Kong, Fac Educ, Informat & Technol Studies, Hong Kong, Peoples R China Univ Tokyo, Grad Sch Agr & life Sci, Agr & Environm Biol, Tokyo, Japan Univ Pittsburgh, Dept Med, Pittsburgh Heart Lung & Blood Vasc Med Inst, Pittsburgh, PA USA Guys & St Thomas NHS Fdn Trust, Directorate Transplant Renal & Urol, London, England Univ Sarajevo, Clin Ctr, Clin Heart Blood Vessel & Rheumat Dis, Sarajevo, Bosnia & Herceg Univ Kent, Sch Math Stat & Actuarial Sci, Canterbury, Kent, England Tokyo Inst Technol, Dept Life Sci & Technol, Tokyo, Japan Univ Appl Sci Munich, Laser Ctr Dept Appl Sci & Mechatron, Munich, Germany CIC NanoGUNE, Nanodevices, San Sebastian, Spain Vrije Univ Amsterdam Med Ctr, Gynaecol, Amsterdam, Netherlands Cardiff Univ, Med Sch, Div Populat Med, Cardiff, S Glam, Wales Karolinska Inst, Dept Med, Solna, Sweden Natl Inst Genet, Ctr Informat Biol, Mishima, Shizuoka, Japan Murdoch Univ, Harry Perkins Inst Med Res, Perth, WA, Australia Univ Limerick, Phys Educ & Sport Sci, Limerick, Ireland Ruhr Univ Bochum, Campus Clin Gynecol, Univ Str, Bochum, Germany Southwest Med Univ, Sch Publ Hlth, Epidemiol & Biostat, Luzhou, Sichuan, Peoples R China Beijing Canc Hosp, Minist Educ Beijing, Key Lab Carcinogenesis & Translat Res, Ctr Mol Diagnost, Beijing, Peoples R China Chinese Acad Sci, Chengdu Inst Biol, Herpetol Dept, Chengdu, Sichuan, Peoples R China Key Lab Nano Biol Effects & Safety, Beijing, Peoples R China NIBR, PK Sci, Basel, Switzerland Daejeon St Marys Hosp, Pain Ctr, Daejeon, South Korea Univ Western Ontario, Sch Hlth Studies, London, ON, Canada Univ Aberdeen, Hlth Psychol Grp, Aberdeen, Scotland Univ Colorado, Anesthesiol, Anschutz Med Campus, Boulder, CO 80309 USA Univ Antwerp, UZA Antwerp Univ Hosp, Crit 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Res Ctr, Stem Cell & Regenerat Med, Riyadh, Saudi Arabia Univ Bahri, Ind Pulp & Paper, Khartoum, Sudan Univ Queensland, Mater Med Res Inst, Mater Res Inst, Brisbane, Qld, Australia Colorado State Univ, NREL, Ft Collins, CO 80523 USA Rzeszow Univ Hosp, Ob Gyn Dept, Rzeszow, Poland Univ Leeds, Fac Biol Sci, Leeds, W Yorkshire, England Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA Carl von Ossietzky Univ Oldenburg, Neurosci, Oldenburg, Germany UNSW, St George & Sutherland Clin Sch, Microbiome Res Ctr, Sydney, NSW, Australia NYU, Sch Med, Dept Biochem, New York, NY 10016 USA NYU, Sch Med, Dept Mol Pharmacol, New York, NY USA Univ Mississippi, Med Ctr, Med Infect Dis, Jackson, MS 39216 USA Tampere Univ, Fac Social Sci Psychol, Tampere, Finland Univ Cyprus, Dept Biol Sci, Nicosia, Cyprus Goethe Univ, Inst Med Microbiol & Infect Control, Frankfurt, Germany Charite Med Univ Berlin, Inst Radiol, Berlin, Germany Univ Cologne, Univ Hosp Cologne, Internal Med 1, Cologne, Germany Univ Calif Los Angeles, Sch Dent, Sect Periodont, Los Angeles, CA 90024 USA Aalborg Univ Hosp, Dept Clin Biochem, Aalborg, Denmark Manipal Acad Higher Educ, Pharm Practice, Manipal, Karnataka, India Univ Tokyo, Inst Med Sci, Dept Radiol, Tokyo, Japan Cukurova Univ, Family Med, Fac Med, Adana, Turkey Catholic Univ Korea, Coll Med, Dept Humanities & Social Med, Seoul, South Korea Univ Ghent, Food Technol Safety & Hlth, Ghent, Belgium UNSW Sydney, Sch Biol Earth & Environm Sci BEES, Sydney, NSW, Australia St Vincent Shoulder & Sports Clin, Res Unit, Vienna, Austria Cornell Univ, Biomed Engn, Ithaca, NY USA Leibniz Inst Plant Genet & Crop Plant Res IPK, Res Grp Bioinformat & Informat Technol, Gatersleben, Germany Univ Europea Madrid, Sch Doctoral Studies, Madrid, Spain CSIRO Mfg, Biomed Mfg, Melbourne, Vic, Australia Depaul Univ, Biol Sci, Chicago, IL 60604 USA Konkuk Univ, Dept Anim Sci & Technol, Seoul, South Korea Chang Gung Univ, Grad Inst Med Mechatron, Taoyuan, Taiwan Korea Univ, Coll Med, Psychiat, Seoul, South Korea Princeton Univ, Chem, Princeton, NJ 08544 USA Henan Univ Chinese Med, Henan Key Lab Chinese Med Resp Dis, Zhengzhou, Henan, Peoples R China Univ Med Ctr Mainz, Dept Psychiat & Psychotherapy, Mainz, Germany Monash Univ Malaysia, Sch Sci, Selangor, Malaysia Univ Mississippi, Med Ctr, Physiol & Biophys, Jackson, MS 39216 USA Univ Oslo, Dept Transplantat Med, Oslo, Norway Sichuan Agr Univ, Triticeae Res Inst, Yaan, Sichuan, Peoples R China Guangzhou Univ Chinese Med, Gastroenterol, Guangzhou, Guangdong, Peoples R China Southeast Univ, Sch Biol Sci & Med Engn, Suzhou, Jiangsu, Peoples R China Mt Allison Univ, Biol, Sackville, NB, Canada Ithaca Coll, Biol, Ithaca, NY 14850 USA Univ Cagliari, Dept Med Sci & Publ Hlth, Monserrato, Italy Univ Vienna, Chromosome Biol, Vienna, Austria Univ Zurich, Nephrol, Zurich, Switzerland Friedrich Schiller Univ, Inst Nutr Sci, Jena, Germany UNSW Sydney, Grad Sch Biomed Engn, Sydney, NSW, Australia Tulane Univ, Sch Med, Biochem & Mol Biol, 1430 Tulane Ave, New Orleans, LA 70112 USA NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA NIH, NCBI, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA LOreal Res & Innovat, Aulnay Sous Bois, France Lund Univ, Dept Psychol, Malmo, Sweden Catholic Univ Louvain, Inst Rech Expt & Clin, Brussels, Belgium Georgia State Univ, Neurosci Inst, Atlanta, GA 30303 USA Univ Melbourne, Ophthalmol, Surg, Parkville, Vic, Australia Univ Western Australia, Ctr Ophthalmol & Visual Sci, Perth, WA, Australia Iran Univ Med Sci, Med Phys, Fac Med, Tehran, Iran Salk Inst Biol Studies, Cellular Neurobiol, La Jolla, CA USA Imperial Coll London, Fibrosis Res Grp, London, England Univ Texas MD Anderson Canc Ctr, Genitourinary Med Oncol, Houston, TX 77030 USA Univ Liege, GIGA Neurosci, Liege, Belgium Univ Crete, Sch Med, Urol, Iraklion, Greece Flinders Univ S Australia, Flinders Med Ctr, Dept Clin Pharmacol, Adelaide, SA, Australia Max Planck Inst Immunobiol & Epigenet, Bioinformat, Breisgau, Germany Cardiff Univ, Sch Psychol, Cardiff, S Glam, Wales Imperial Coll London, Chem Engn, London, England Lund Univ, Skane Univ Hosp, Clin Sci, Malmo, Sweden Sahlgrens Acad, Inst Clin Sci, Dept Mol & Clin Med, Gothenburg, Sweden Univ Cent Lancashire, Sch Pharm & Biomed Sci, Preston, Lancs, England Hosp Univ Doctor Peset, Psychiat & Clin Psychol, Valencia, Spain Ctr Biol Mol Severo Ochoa, Genome Dynam & Funct, Madrid, Spain Unvivers Hosp Lille, Dept Intens Care, Lille, France Kansai Med Univ, Surg, Osaka, Japan Univ Toulouse, Inst Natl Polytech Toulouse, Ecole Natl Super Agron Toulouse, Lab Genom & Biotechnol Fruit, Toulouse, France UiT Arctic Univ Norway, Inst Psychol, Tromsto, Norway Queens Univ, Ctr Publ Hlth, Belfast, Antrim, North Ireland Univ Manchester, Ctr Primary Care & Hlth Serv Res, Manchester, Lancs, England Griffith Univ, Menzies Hlth Inst, Gold Coast, Qld, Australia Anglia Ruskin Univ, FHSCE, Cambridge, England Univ Lleida, Dept Expt Med, Lleida, Spain NIEHS, Biomol Screening Branch, Div Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA Albany Med Coll, Immunol & Microbial Dis, Albany, NY 12208 USA Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia Univ Kent, Sch Biosci, Canterbury, Kent, England Univ Bourgogne Franche Comte, INSERM, LNC, UMR 1231, Besancon, France Ritsumeikan Univ, Coll Life Sci, Dept Biotechnol, Shiga, Japan Kent State Univ, Biol Sci, Kent, OH 44242 USA Natl Inst Infect Dis, Dept Safety Res Blood & Biol Prod, Tokyo, Japan European Inst Marine Studies, Lab Microbiol Extreme Environm, Plouzane, France Univ Iowa, Dept Pharmacol, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA Natl Univ Singapore, Biol Sci, Singapore, Singapore Conservatoire Natl Arts & Metiers, Lab GBA, EA4627, Paris, France Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA Lomonosov Moscow State Univ, Belozersky Inst Physicochem Biol, Moscow, Russia Jikei Univ, Sch Med, Dept Mol Biol, Tokyo, Japan Univ South Wales, Genom & Computat Biol, Treforest, Wales Duke Univ, Med Ctr, Obstet & Gynecol, Durham, NC USA Univ Technol Sydney, Climate Change Cluster, Sydney, NSW, Australia Nagoya Univ, Grad Sch Med, Dept Radiol, Nagoya, Aichi, Japan Western Sydney Univ, Sch Sci & Hlth, Sydney, NSW, Australia TEI Epirus, Dept Speech & Language Therapy, Ioannina, Greece Indiana Univ Purdue Univ, Orthopaed Surg, Indianapolis, IN 46202 USA Oniris, Vet Pathol, Nantes, France Royal Vet Coll, Pathobiol & Populat Sci, Hatfield, Herts, England Univ Ghent, Lab Pharmaceut Biotechnol, Ghent, Belgium Norwegian Inst Nat Res, Terr Ecol, Trondheim, Norway Univ Calif Merced, Mol & Cell Biol, Merced, CA USA Univ Dublin, Trinity Coll Dublin, Sch Engn, Ctr Transport Res, Dublin, Ireland Lund Univ, Inst Clin Sci, Nephrol, Malmo, Sweden Univ Birmingham, Mech Engn, Birmingham, W Midlands, England Lund Univ, Inst Clin Sci, OB GYN, Lund, Sweden Fdn Jimenez Diaz Hosp, Nephrol & Hypertens, Madrid, Spain Queensland Univ Technol, Sch Chem Phys & Mech Engn, Brisbane, Qld, Australia Otto von Guericke Univ, Psychol, Magdeburg, Germany Univ Med Ctr Gottingen, Dept Expt Neurodegenerat, Gottingen, Germany Harvard Med Sch, Spaulding Rehabil Hosp, Phys Med & Rehabil, Boston, MA 02115 USA Quadram Inst Biosci, Sci Operat, Norwich, Norfolk, England Ostbayer Tech Hsch Regensburg OTH Regensburg, Regensburg Med Image Comp ReMIC, Regensburg, Germany Deakin Univ, Fac Arts & Educ, Melbourne, Vic, Australia Univ Warwick, Warwick Med Sch, Coventry, W Midlands, England INSERM, Natl Inst Hlth & Med Res, Biochem & Mol Biol, Paris, France Univ Liege, Tax Inst, Liege, Belgium Univ Leeds, Sch Mol & Cellular Biol, Leeds, W Yorkshire, England IRCCS Ist Giannina Gaslini, UOC Genet Med, Genoa, Italy Res Diets Inc, Sci, New Brunswick, NJ USA Univ Perugia, Dept Phys & Geol, Perugia, Italy Walter Reed Natl Mil Med Ctr, Cellular Immunol, Bethesda, MD USA Univ Fed Santa Catarina, Biol Sci Ctr, Microbiol Immunol & Parasitol Dept, Florianopolis, SC, Brazil Univ Edinburgh, Royal Infirm, Ctr Liver & Digest Disorders, Edinburgh, Midlothian, Scotland Orion Pharma, Crit Care Proprietary Prod Div, Espoo, Finland MIT, Dept Civil & Environm Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA Univ Turin, Dept Vet Sci, Turin, Italy Univ G dAnnunzio, Dept Psychol Hlth & Territorial Sci, Chieti, Italy NYU, Sch Med, OB GYN, New York, NY USA Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland Univ Turku, Dept Biol, Turku, Finland Tech Univ Berlin, Bioanalyt, Berlin, Germany Univ Goettingen, Inst Phys Biophys 3, Gottingen, Germany Univ Texas MD Anderson Canc Ctr, Inst Appl Canc Sci, Translat Res Adv Therapeut & Innovat Oncol TRACTI, Houston, TX 77030 USA Univ Liege, Life Sci, Liege, Belgium Tarbiat Modares Univ, Fac Med Sci, Dept Toxicol, Tehran, Iran ARS, USDA, Stoneville, MS USA Univ Regensburg, RCI Regensburg Ctr Intervent Immunol, Regensburg, Germany Univ Nottingham, Sch Psychol, Nottingham, England NIH, Pathol Lab, Bethesda, MD 20892 USA Univ Carlos III Madrid, Elect Engn, Madrid, Spain Inst Med Mol, Chem Biol, Lisbon, Portugal Univ Costa Rica, CIET, San Jose, Costa Rica Univ Stavanger, Fac Hlth Sci, Stavanger, Norway Erasmus MC, Urol, Rotterdam, Netherlands Univ Edinburgh, Sch Biol Sci, Edinburgh, Midlothian, Scotland German Res Ctr Environm Hlth GmbH, Helmholtz Zentrum Munchen, Inst Bioinformat & Syst Biol IBIS, Ingolstadter Landstr 1, D-85764 Neuherberg, Germany Leiden Univ, Huygens Kamerlingh Onnes Lab, Leiden, Netherlands Univ Vienna, Nutr Sci, Vienna, Austria Kolling Inst Med Res, Med, St Leonards, NSW, Australia Johns Hopkins Sch Med, Biol Chem, Baltimore, MD USA Univ Montreal, Med Nutr & Microbiome Lab, Montreal, PQ, Canada GlaxoSmithKline, Cell & Gene Therapy, Stevenage, Herts, England Univ Trieste, Life Sci, Trieste, Italy Rhein Westfal TH Aachen, Dept Radiol, Aachen, Germany Univ Duisburg Essen, Univ Hosp Essen, West German Canc Ctr, Dept Med Oncol, Essen, Germany Med Univ Vienna, Obstet & Gynecol, Vienna, Austria FHI 360, Social & Behav Hlth Sci Div, Washington, DC USA KU Leuven VIB, Switch Lab, Leuven, Belgium Bielefeld Univ, Fac Technol, Bielefeld, Germany Capital Med Univ, Beijing Shijitan Hosp, Dept Clin Nutr, Dept Gastrointestinal Surg, Beijing, Peoples R China Meiji Univ, Dept Agr Chem, Kawasaki, Japan Yonsei Univ, Coll Med, Microbiol, Seoul, South Korea Johnson & Johnson EAME, Maidenhead, Berks, England Penn State Coll Med, Pediat, Hershey, PA USA Univ N Carolina, Dept Social Med, Chapel Hill, NC 27515 USA Univ Western Australia, ARC CoE Plant Energy Biol, Perth, WA, Australia Wageningen Univ, Div Human Nutr & Hlth, Wageningen, Netherlands Kings Coll London, Dept Neuroimaging, London, England Univ Murcia, Biochem & Mol Biol, Murcia, Spain Old Dominion Univ, Dept Biol Sci, Norfolk, VA 23529 USA Monash Univ, Biochem & Mol Biol, Melbourne, Vic, Australia Chinese Acad Sci, Inst Genet & Dev Biol, Beijing, Peoples R China Univ Pittsburgh, Pharmacol & Chem Biol, Pittsburgh, PA USA Univ Lausanne, Ctr Integrat Genom, Lausanne, Switzerland Univ Queensland, Sch Pharm, Brisbane, Qld, Australia Leibniz Inst Plant Genet & Crop Plant Res IPK Gat, Genebank, Gatersleben, Germany Piramal Imaging, Res & Dev, Berlin, Germany Univ Leeds, Civil Engn, Leeds, W Yorkshire, England Univ Missouri, Chem & Biochem, St Louis, MO 63121 USA US Geol Survey, Coastal & Marine Geol Program, Pacific Coastal & Marine Sci Ctr, Santa Cruz, CA USA Ajinomoto Genet Res Inst, Moscow, Russia Jagiellonian Univ, Fac Biochem Biophys & Biotechnol, Dept Plant Biotechnol, Krakow, Poland Univ Puerto Rico, Engn Sci & Mat, Mayaguez, PR USA Univ Regina, Dept Chem & Biochem, Regina, SK, Canada Argonne Natl Lab, Ctr Nanoscale Mat, 9700 S Cass Ave, Argonne, IL 60439 USA Univ Sunshine Coast, Sunshine Coast Mind & Neurosci Thompson Inst, Sippy Downs, Qld, Australia Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing, Peoples R China Griffith Univ, Griffith Ctr Social & Cultural Res, Gold Coast, Qld, Australia Tohoku Univ, Inst Dev Aging Canc, Dept Mol Oncol, Sendai, Miyagi, Japan Indiana Univ, Comp Sci, Bloomington, IN USA Fukushima Med Univ, Sch Med, Dept Pulm Med, Fukushima, Japan MEDIVIR AB, Biol, Huddinge, Sweden Western Sydney Univ, Neuroimmunol, Sydney, NSW, Australia Univ Jordan, Nutr & Food Technol, Amman, Jordan Thunen Inst Forest Genet, Fed Res Ctr Rura Areas Forestry & Fisheries, Inst Biodivers, Grosshansdorf, Germany Univ Edinburgh, Inst Cell Biol, Edinburgh, Midlothian, Scotland Univ Edinburgh, Ctr Integrat Physiol, Edinburgh, Midlothian, Scotland Univ Toronto, Struct Genom Consortium, Toronto, ON, Canada Canadian Mem Chiropract Coll, Grad Educ & Res, Toronto, ON, Canada Agilent Technol, R&D, Leuven, Belgium Univ British Columbia, Sch Nursing, Vancouver, BC, Canada Monash Univ, Monash Hlth, Sch Clin Sci, Stroke & Ageing Res,Dept Med, Melbourne, Vic, Australia French Natl Canc Inst, Innovat, Transfer, Biol, Boulogne, France Ludwig Maximilians Univ Munchen, Phys Chem, NanoBioSci, Munich, Germany Bandung Inst Technol, Sch Pharm, Med Chem, Bandung, Indonesia Univ Luxembourg, Life Sci Res Unit, Luxembourg, Luxembourg Lund Univ, Skane Univ Hosp, Dept Gastroenterol, Malmo, Sweden Millennium Hlth, Translat Genet, San Diego, CA USA Aristotle Univ Thessaloniki, Med Dept 2, Clin Res & Evidence Based Med Unit, Thessaloniki, Greece Jan Kochanowski Univ Humanities & Sci, Piotrkow Trybunalski Branch, Dept Psychol, Kielce, Poland McMaster Univ, Engn Phys, Hamilton, ON, Canada Marche Polytech Univ, Dept Agr Food & Environm Sci, Ancona, Italy Kuwait Univ, Fac Med, Microbiol, Kuwait, Kuwait Fujita Hlth Univ, Dept Breast Surg, Toyoake, Aich, Japan North West Reg Spinal Injuries Ctr, Spinal Injuries Ctr, Southport, Merseyside, England Luxembourg Inst Hlth, Competence Ctr Methodol & Stat, Luxembourg, Luxembourg Nestle Inst Hlth Sci SA, Metab Hlth, Ecublens, Vaud, Switzerland Ctr Inflammat Res VIB, Ghent, Belgium Univ Ghent, Dept Biomed Mol Biol, Ghent, Belgium Univ Lisbon, Inst Educ, Curriculo Formacao Prof & Tecnol, Lisbon, Portugal Univ Edinburgh, Ctr Inflammat Res, Edinburgh, Midlothian, Scotland Univ Melbourne, Sch BioSci, Parkville, Vic, Australia Northumbria Univ, Comp & Informat Sci, Newcastle Upon Tyne, Tyne & Wear, England Univ Valencia, Endocrinol, Valencia, Spain INRS, Inst Armand Frappier, Laval, PQ, Canada Univ Laval, INAF, Sch Nutr, Quebec City, PQ, Canada Univ Konstanz, Dept Biol, Constance, Germany Univ Cote dAzur, LAMHESS, Nice, France Scion, Syst Ecol, Christchurch, New Zealand CUNY, Grad Sch Publ Hlth & Hlth Policy, Epidemiol & Biostat, New York, NY 10021 USA Univ Queensland, Sch Dent, Brisbane, Qld, Australia George Inst Global Hlth, Renal & Metab Div, Sydney, NSW, Australia Wuhan Univ, Coll Chem & Mol Sci, Wuhan, Hubei, Peoples R China Griffith Univ, Sch Environm & Sci, Gold Coast, Qld, Australia Univ Minnesota, Radiat Oncol, Minneapolis, MN USA Goethe Univ, Fac Med, Frankfurt, Germany Natl Yunlin Univ Sci & Technol, Dept & Grad Sch Safety & Environm Engn, Touliu, Yunlin, Taiwan Massey Univ, Sch Sport Exercise & Nutr, Auckland, New Zealand Univ Florida, Wildlife Ecol & Conservat, Gainesville, FL USA Bournemouth Univ, Dept Psychol, Poole, Dorset, England Robert Koch Inst, Project Grp P2, Berlin, Germany Univ Edinburgh, MRC Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland Univ Basel, Biozentrum, Basel, Switzerland Univ Wollongong, Sch Med, Wollongong, NSW, Australia Univ Cologne, Inst Human Genet, Cologne, Germany Rural Econ Branch, Econ Res Serv, Washington, DC USA Uivers Bordeaux, CNRS, Inst Neurosci Cognit & Integrat Aquitaine, Bordeaux, France Univ Calif Riverside, Dept Chem & Environm Engn, Riverside, CA 92521 USA Univ Calif Riverside, Mat Sci & Engn Program, Riverside, CA 92521 USA Mackay Med Coll, Dept Med, New Taipei, Taiwan Univ Bern, Div Anim Welf, Bern, Switzerland Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Med Sci, Shanghai, Peoples R China McMaster Univ, Biol, Hamilton, ON, Canada Univ S Florida, Dept Cell Biol Microbiol & Mol Biol, Tampa, FL USA Hacettepe Univ, Inst Canc, Med Oncol, Ankara, Turkey City Univ Hong Kong, Dept Elect Engn, Hong Kong, Peoples R China Natl Taiwan Univ, Dept Entomol, Taipei, Taiwan Chinese Acad Agr Sci, Inst Environm & Sustainable Dev Agr, Ecol Secur, Beijing, Peoples R China Florida State Univ, Inst Mol Biophys, Chem & Biochem, Tallahassee, FL USA Peking Univ, Shenzhen Grad Sch, State Key Lab Chem Oncogen, Lab Computat Chem & Drug Design, Shenzhen, Peoples R China Univ Helsinki, Fac Pharm, Div Pharmaceut Chem & Technol, Drug Res Program, Helsinki, Finland Tohoku Univ, Microbial Biotechnol, Sendai, Miyagi, Japan Tianjin Med Univ, Sch Basical Med Sci, Dept Pharmacol, Tianjin, Peoples R China Dana Farber Canc Inst, Biostat & Computat Biol, Boston, MA 02115 USA Natl Hlth Res Inst, Inst Mol & Genom Med, Zhunan, Taiwan 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Neuropsychiat Genet & Genom, Cardiff, S Glam, Wales Zurich Univ Appl Sci, Social Work, Zurich, Switzerland Jawaharlal Nehru Univ, Sch Life Sci, New Delhi, India Univ Burgundy Franche Comte, LE2I, Dijon, France Univ Roehampton, Life Sci, London, England Ghent Univ Hosp, Gen & HPB Surg, Ghent, Belgium Univ Wurzburg, Insect Fungus Symbiosis Lab, Wurzburg, Germany Radboud Univ Nijmegen, Behav Sci Inst, Nijmegen, Netherlands Fraunhofer WKI, Applicat Ctr HOFZET, Hannover, Germany UCL, Struct & Mol Biol, London, England Univ Amsterdam, Dev Psychol, Amsterdam, Netherlands Aalborg Univ, Hlth Sci & Technol, CNAP, SMI, Aalborg, Denmark VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA Cedars Sinai Med Ctr, Neurosurg, Los Angeles, CA 90048 USA Sun Yat Sen Univ, Sch Data & Comp Sci, Guangzhou, Guangdong, Peoples R China Dezhou Univ, Shandong Prov Key Lab Biophys, Guangzhou, Guangdong, Peoples R China Maison Teledetection, Inst Rech Dev, UMR Espace DEv, Montpellier, France Xiamen Univ, Sch Life Sci, Xiamen, Fujian, Peoples R China Nanjing Univ, Sch Med, Jinling Hosp, Natl Clin Res Ctr Kidney Dis,Dept Med Imaging, Nanjing, Jiangsu, Peoples R China Univ Kent, Sch Social Policy Sociol & Social Res, Canterbury, Kent, England Univ Fed Minas Gerais, Infect Dis & Trop Med, Belo Horizonte, MG, Brazil Univ Minho, Sch Med, Life & Hlth Sci Res Inst ICVS, Braga, Portugal Univ Montreal, Biochim & Med Mol, Montreal, PQ, Canada Johns Hopkins Bloomberg Sch Publ Hlth, Epidemiol, Baltimore, MD USA Max Planck Inst Biol Ageing, Metab & Genet Regulat Ageing, Cologne, Germany Univ Swaziland, Hlth Sci, Kwaluseni, Eswatini Queensland Univ Technol, Inst Future Environm, Brisbane, Qld, Australia Ctr Sci Monaco, Dept Biol Med, Monaco, Monaco HELIOS Hosp, Urol, Bad Saarow Pieskow, Germany Tech Univ Carolo Wilhelmina Braunschweig, Inst Microbiol, Braunschweig, Germany Univ Barcelona, Barcelona Ctr Maternal Fetal & Neonatal Med, Fetal i D Fetal Med Res Ctr, IDIBAPS BCNatal,Hosp Clin, Barcelona, Spain Univ Barcelona, Hosp St Joan de Deu, Barcelona, Spain Friedrich Loeffler Inst, Inst Bacterial Infect & Zoonoses, Jena, Germany Charite Med Univ Berlin, Neurol, Berlin, Germany Dublin City Univ, Natl Inst Cellular Biotechnol, Mol Therapeut Canc Ireland, Dublin, Ireland Schoen Clin Roseneck, Prien Am Chiemsee, Germany Univ Med Ctr Hamburg Eppendorf, Inst Sex Res & Forens Psychiat, Hamburg, Germany Nankai Univ, Sch Math Sci, Tianjin, Peoples R China Nankai Univ, LPMC, Tianjin, Peoples R China Univ Oxford, Oncol, Oxford, England Royal Holloway Univ London, Class, Egham, Surrey, England Cornell Univ, Clin Sci, Ithaca, NY USA Univ KwaZulu Natal, Pharmaceut Chem, Westville Campus, Durban, South Africa Royal Coll Surgeons Ireland, Med, Dublin, Ireland Univ Oslo, Dept Immunol, Oslo, Norway Bermuda Inst Ocean Sci, Marine Nitrogen Cycling Lab, St Georges, Bermuda Kanazawa Univ, Inst Liberal Arts & Sci, Kanazawa, Ishikawa, Japan World Hlth Org Reg Off Africa, Brazzaville, Rep Congo Univ Hosp BesanCon, Infect Control Dept, Besancon, France Galapagos NV, Clin Dev, Mechelen, Belgium Univ Tasmania, Integrated Marine Observing Syst, Hobart, Tas, Australia Georg August Univ Gottingen, Albrecht von Haller Inst Plant Sci, Dept Systemat Biodivers & Evolut Plants, Gottingen, Germany Univ Occupat & Environm Hlth, Dept Psychiat, Fukuoka, Fukuoka, Japan IMDEA Food, Program Precis Nutr & Aging, Madrid, Spain Radboud Univ Nijmegen, Med Sch, IQHealthcare, Nijmegen, Netherlands Maastricht Univ, Dept Cardiovasc Surg, Maastricht, Netherlands German Diabet Ctr, Inst Clin Biochem & Pathobiochem, Dusseldorf, Germany Juntendo Univ, Grad Sch Med, Dept Radiol, Tokyo, Japan Deakin Univ, Sch Informat Technol, Melbourne, Vic, Australia Max Planck Inst Eusenforschung, Dept Interface Chem & Surface Sci, Dusseldorf, Germany Edge Hill Univ, Dept Psychol, Ormskirk, England Aga Khan Univ, Psychiat, Karachi, Pakistan KRIBB, Korean Bioinformat Ctr, Seoul, South Korea Cardinal Hlth Specialty Solut, Hlth Econ & Outcomes Res, Dallas, TX USA Klinikum Univ Munchen, Div Clin Pharmacol, Munich, Germany Univ Pittsburgh, Neurol Surg, Pittsburgh, PA USA Rhein Westfal TH Aachen, Dept Child & Adolescent Psychiat Psychosomat & Ps, Aachen, Germany Univ Copenhagen, Inst Mol & Cellular Biol, Copenhagen, Denmark St Jude Childrens Res Hosp, Struct Biol, 332 N Lauderdale St, Memphis, TN 38105 USA Royal Shrewsbury Hosp, Colorectal Surg, Shrewsbury, Salop, England Univ Nottingham, Fac Med & Hlth Sci, Nottingham, England Karolinska Inst, Dept Physiol & Pharmacol, Solna, Sweden Chinese Acad Sci, Changchun Inst Appl Chem, State Key Lab Electroanalyt Chem, Jilin, Jilin, Peoples R China Univ British Columbia, Pediat, Vancouver, BC, Canada Chinese Acad Agr Sci, State Key Lab Cotton Biol, Res Base Anyang Inst Technol, Cotton Germplasm Resources,Inst Cotton Res, Beijing, Peoples R China Chinese Univ Hong Kong, Anaesthesia & Intens Care, Hong Kong, Peoples R China Univ Macau, ICMS, 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Cytotechnol Educ, Omaha, NE USA Shinko Mem Hosp, Dept Cardiovasc Med, Kobe, Hyogo, Japan Imperial Coll London, Mat, London, England Tech Univ Munich, Dept Surg, Munich, Germany Chinese Acad Agr Sci, Res Inst Pomol, Minist Agr, Lab Qual & Safety Risk Assessment Fruit Xingcheng, Shenyang, Liaoning, Peoples R China James Madison Univ, Commun Sci & Disorders, Harrisonburg, VA 22807 USA Univ Hosp Ulm, Inst Orthopaed Res & Biomech, Ulm, Germany Univ Essex, Sch Hlth & Social Care, Colchester, Essex, England Alpha Altis, Res Serv, Nottingham, England Erasmus MC, Med Oncol, Rotterdam, Netherlands Fed Univ Oye, Dept Ind Chem, Ekiti, Nigeria Duke Univ, Med Ctr, Cell Biol, Durham, NC USA Univ Oxford, Nuffield Dept Clin Neurosci, Oxford, England Univ Manchester, Canc Res UK Manchester Inst, Manchester, Lancs, England Helsinki Univ Hosp, Childrens Hosp, Helsinki, Finland Univ Aveiro, CESAM Ctr Environm & Marine Studies, Dept Biol, Aveiro, Portugal Univ Botswana, Psychol, Gaborone, Botswana Univ Fed Bahia, Nursing Sch, Salvador, BA, Brazil Queen Mary Univ London, Biol & Expt Psychol, London, England Natl Univ Pharm, Med Chem Dept, Kharkov, Ukraine Univ Bolton, Dept Educ & Psychol, Bolton, England La Trobe Univ, Dept Chem & Phys, Melbourne, Vic, Australia Gen Hosp Northern Theater Command, Dept Gastroenterol, Shenyang, Liaoning, Peoples R China Doctors Hosp, Dept Nephrol, Athens, Greece Univ Hosp Essen, Pediat 3, Essen, Germany Imperial Coll London, Infect Dis Epidemiol, London, England Sorbonne Univ, Dept Psychiat, Paris, France UNSW Sydney, Educ, Sydney, NSW, Australia Stanford Univ, Dept Psychiat & Behav Sci, Palo Alto, CA 94304 USA Hannover Med Sch, Clin Laryngol Rhinol & Otol, Hannover, Germany Curtin Univ, Ctr Aboriginal Studies, Perth, WA, Australia Iran Univ Sci & Technol, Biomed Engn Dept, Tehran, Iran Univ Calif San Francisco, Anesthesiol, San Francisco, CA 94143 USA Khalifa Univ Sci & Technol, Mech Engn, Abu Dhabi, U Arab Emirates Univ Florida, Hort Sci, Gainesville, FL USA James Cook Univ, Australian Inst Trop Hlth & Med, Ctr Biodiscovery & Mol Dev Therapeut, Cairns, Qld, Australia Univ Porto, Fac Med, CINTESIS, Porto, Portugal Shaoxing Peoples Hosp, Med Res Ctr, Shaoxing, Zhejiang, Peoples R China NIH, Dept Transfus Med, Bethesda, MD 20892 USA AIIMS, Dept Biotechnol, New Delhi, India Univ Ottawa, Biochem Microbiol & Immunol, Ottawa, ON, Canada Univ Oslo, Inst Clin Med, Div Mental Hlth & Addict, Oslo, Norway Univ Groningen, Univ Med Ctr Groningen, Dept Radiol, Groningen, Netherlands Univ Hong Kong, Sch Nursing, Hong Kong, Peoples R China Tokyo Med Univ, Ibaraki Med Ctr, Urol, Tokyo, Japan Univ Hosp Zurich, Dept Radiat Oncol, Zurich, Switzerland Univ Maryland, Inst Human Virol, Div Immunotherapy, Baltimore, MD 21201 USA Univ Maryland, Dept Surg, Baltimore, MD 21201 USA Stellenbosch Univ, Fac Med & Hlth Sci, Div Mol Biol & Human Genet, Stellenbosch, South Africa China Agr Univ, Coll Biol Sci, Beijing, Peoples R China Osaka Univ, Grad Sch Pharmaceut Sci, Suita, Osaka, Japan Univ Washington, Biochem, Seattle, WA 98195 USA Natl Res Council Italy, Inst Biosci & BioResources, Naples, Italy Univ Lyon, Phys, Lyon, France Univ Basel, Fac Psychol, Ctr Social Psychol, Basel, Switzerland Queen Mary Univ London, Barts Canc Inst, Ctr Mol Oncol, London, England EBI, EMBL, Samples Phenotypes & Ontol Team, Cambridge, England Charles Sturt Univ, Fac Arts & Educ, Bathurst, NSW, Australia Shandong Univ, Helmholtz Inst Biotechnol, Sch Life Sci, State Key Lab Microbial Technol, Jinan, Shandong, Peoples R China Shantou Univ, Dept Biol, Shantou, Guangdong, Peoples R China Shanxi Univ, Inst Biomed Sci, Taiyuan, Shanxi, Peoples R China St Jude Childrens Res Hosp, Computat Biol, 332 N Lauderdale St, Memphis, TN 38105 USA Harbin Med Univ, Coll Bioinformat Sci & Technol, Harbin, Heilongjiang, Peoples R China NIH, Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA Georgia Inst Technol, Dept Biol Sci, Atlanta, GA 30332 USA XtalPi Inc, Cambridge, MA USA Consejo Nacl Invest Cient & Tecn, Partner Inst Max Planck Soc, Inst Invest Biomed Buenos Aires IBioBA, Bioinformat, Buenos Aires, DF, Argentina Univ Sydney, Save Sight Inst, Sydney, NSW, Australia Univ South Australia, Canc Res Inst, Australian Ctr Precis Hlth, Adelaide, SA, Australia Jinan Univ, Inst Life & Hlth Engn, Guangdong Higher Educ Inst, Key Lab Funct Prot Res, Guangzhou, Guangdong, Peoples R China Univ Texas Hlth Sci Ctr Houston, Epidemiol Human Genet & Environm Sci, Houston, TX 77030 USA Weill Cornell Med, Dept Microbiol & Immunol, New York, NY USA Guangdong Inst Appl Biol Resources, Biotechnol Lab, Guangzhou, Guangdong, Peoples R China Shandong Normal Univ, Coll Life Sci, Jinan, Shandong, Peoples R China Shandong Univ, Life Sci Dept, Jinan, Shandong, Peoples R China South China Agr Univ, Integrat Microbiol Res Ctr, Guangzhou, Guangdong, Peoples R China Liaoning Acad Agr Sci, Crop Mol Improving Lab, Shenyang, Liaoning, Peoples R China Lawson Hlth Res Inst, Med Biophys, London, ON, Canada Univ Melbourne, Infrastruct Engn, Parkville, Vic, Australia Univ Canberra, Fac Hlth, Canberra, ACT, Australia Univ Cambridge, MRC Cognit & Brain Sci Unit, Cambridge, England Emory Univ, Biostat & Bioinformat, Atlanta, GA 30322 USA Johns Hopkins Sch Med, Anesthesiol & Crit Care Med, Baltimore, MD USA Nottingham Trent Univ, Sch Anim Rural & Environm Sci, Nottingham, England Univ Exeter, Biosci, Exeter, Devon, England Hillingdon Hosp NHS Fdn Trust, London, England Univ Glasgow, MRC CSO Social & Publ Hlth Sci Unit, Glasgow, Lanark, Scotland Natl & Kapodistrian Univ Athens, Evaggelismos Athens Hosp, ICU, Athens, Greece Univ Newcastle, Biol Sci, Callaghan, NSW, Australia Coventry Univ, Fac Hlth & Life Sci, Ctr Innovat Res Life Course, Coventry, W Midlands, England Lausanne Univ Hosp, Serv Endocrinol Diabet & Metab, Lausanne, Switzerland Charles Sturt Univ, Sch Community Hlth, Bathurst, NSW, Australia Queens Univ Belfast, Inst Global Food Secur, Belfast, Antrim, North Ireland Natl Univ Singapore, Inst Policy Studies, Singapore, Singapore Univ Penn, Intitute Med & Engn, Philadelphia, PA 19104 USA Cold Spring Harbor Lab, POB 100, Cold Spring Harbor, NY 11724 USA Univ Michigan, EECS, Ann Arbor, MI 48109 USA Univ British Columbia, Ctr Blood Res, Vancouver, BC, Canada UiT Arctic Univ Norway, Dept Hlth & Care Sci, Fac Hlth Sci, Tromso, Norway Hosp Clin Porto Alegre, Physiotherapy, Porto Alegre, RS, Brazil Univ Paris 05, Med Sch, Paris, France Chinese Acad Agr Sci, Inst Crop Sci, Natl Key Facil Crop Gene Resources & Genet Improv, Beijing, Peoples R China Univ Ghent, Expt Clin & Hlth Psychol, Ghent, Belgium Indian Inst Adv Res, Bioinformat & Struct Biol, Gandhinagar, Gujart, India Bambino Ges Childrens Res Hosp, Lab Mol Med, Rome, Italy Heidelberg Univ, Ctr Infect Dis Parasitol, Heidelberg, Germany Stanford Univ, Elect Engn, Palo Alto, CA 94304 USA Univ Cadiz, Biol, Andalucia, Spain Mansoura Univ Hosp, Gen Surg, Mansoura, Egypt Inst Pasteur, Virol Pole, Dakar, Senegal Cardiff Univ, Div Canc & Genet, Cardiff, S Glam, Wales Ctr Expertise & Biol Diagnost Cameroon, Food Safety & Environm Microbiol, Yaounde, Cameroon Swiss Fed Labs Mat Sci & Technol, Lab Thin Films & Photovolta, Dubendorf, Switzerland Assiut Univ, Assiut Urol & Nephrol Hosp, Fac Med, Assiut, Egypt UCL, GEE, London, England UCL, IHA, London, England Univ Derby, Univ Derby Online Learning, Derby, England SUNY Stony Brook, Family Populat & Prevent Med, Stony Brook, NY 11794 USA Walter & Eliza Hall Inst Med Res, Mol Med Div, Melbourne, Vic, Australia Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne, Tyne & Wear, England German Ctr Neurodegenerat Dis, Clin Dementia Res, Bonn, Germany Sorbonne Univ, CNRS, UMR 7144, Stn Biol, Paris, France Univ Barcelona, Odontoestomatol, Barcelona, Spain Janelia Res Campus, Comp Sci, Ashburn, VA USA Univ Oxford, Ctr Trop Med & Global Hlth, Oxford, England Univ Bern, ARTORG Ctr Biomed Engn Res, Bern, Switzerland Australian Natl Univ, Eccles Inst Neurosci, John Curtain Sch Med Res, Canberra, ACT, Australia John Innes Ctr, Metab Biol, Norwich, Norfolk, England USDA ARS, Genom & Bioinformat Res Unit, Raleigh, NC 27695 USA Med Univ Graz, Inst Med Informat Stat & Documentat, Holzinger Grp, Graz, Austria Ajou Univ, Pharm, Suwon, South Korea City Univ Hong Kong, Sch Energy & Environm, Hong Kong, Peoples R China Univ British Columbia, Sch Kinseiol, Vancouver, BC, Canada Univ Copenhagen, Marine Biol Sect, Dept Biol, Copenhagen, Denmark Univ Vienna, Dept Commun, Vienna, Austria Univ Dundee, Sch Social Sci, Dundee, Scotland Tech Univ Dresden, Inst Bot, Dresden, Germany Univ Oxford, Div Struct Biol, Oxford, England Natl Univ Hlth Syst, Med, Singapore, Singapore Univ Canterbury, Sch Biol Sci, Christchurch, New Zealand Univ Hosp Southern Denmark, Focused Res Unit Mol Diagnost & Clin Res, Odense, Denmark Univ Oxford, Primary Care Hlth Sci, Oxford, England Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA Adnan Menderes Univ Aydin, Fac Nursing, Dept Publ Hlth Nursing, Aydin, Turkey Oasi Res Inst IRCCS, Dept Neurol IC, Troina, Italy Purdue Univ, Weldon Sch Biomed Engn, W Lafayette, IN 47907 USA Kings Coll London, Kings Ctr Mil Hlth Res, London, England LSHTM, Dept Infect Dis Epidemiol, London, England Leibniz Univ Hannover, BMWZ Organ Chem, Hannover, Germany Xi An Jiao Tong Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Xian, Shaanxi, Peoples R China Univ South Australia, Sch Pharm & Med Sci, Adelaide, SA, Australia Univ Fed Santa Catarina, Dept Phys Educ, Florianopolis, SC, Brazil Southern Med Univ, Nanfang Hosp, Dept Oncol, Guangzhou, Guangdong, Peoples R China Stanford Univ, Hansen Expt Phys Lab, Palo Alto, CA 94304 USA Shenzhen Univ, Affiliated Hosp 1, Shenzhen Peoples Hosp 2, Inst Translat Med, Shenzhen, Guangdong, Peoples R China Univ Hong Kong, Dept Stat & Actuarial Sci, Hong Kong, Peoples R China UCL, Dept Mech Engn, London, England ASTAR, Singapore Immunol Network, Lab Microbial Immun, Singapore, Singapore Cent South Univ, State Key Lab Powder Met, Changsha, Hunan, Peoples R China Univ Aberdeen, Inst Appl Hlth Sci, Aberdeen, Scotland Univ Bridgeport, Biomed Engn, Bridgeport, CT 06601 USA Texas Tech Univ, Hlth Sci Ctr, Pharmaceut Sci, Lubbock, TX 79430 USA Univ Montana, Ecosyst & Conservat Sci, Missoula, MT 59812 USA Univ Goettingen, Dept Syst Neurosci, Gottingen, Germany NHLBI, Lab Syst Genet, Bldg 10, Bethesda, MD 20892 USA Cleveland Clin, Lou Ruvo Ctr Brain Hlth, Imaging, Las Vegas, NV USA Flinders Univ S Australia, Coll Nursing & Hlth Sci, Nutr & Dietet, Adelaide, SA, Australia Univ Padua, Dept Math, Padua, Italy Lund Univ, Fac Law, Lund, Sweden Univ Gothenburg, Dept Microbiol & Immunol, Gothenburg, Sweden NARO, Kachwekano Zardi, Entebbe, Uganda Natl Yunlin Univ Sci & Technol, Bachelor Program Interdisciplinary Studies, Touliu, Yunlin, Taiwan Aarhus Univ, Dept Biomed, Danish Res Inst Translat Neurosci DANDRITE, Aarhus, Denmark Eduardo Mondlane Univ, Math & Comp Sci, Maputo, Mozambique Univ Bern, Dept Old Age Psychiat & Psychotherapy, Bern, Switzerland RAS, Inst Cytol, Lab Cytol Unicellular Organisms, St Petersburg, Russia Beijing Inst Technol, Sch Chem & Chem Engn, Beijing, Peoples R China Univ Queensland, Queensland Alliance Agr & Food Innovat, Brisbane, Qld, Australia Fraunhofer Inst Toxicol & Expt Med ITEM, Inhalat Toxicol, Hannover, Germany Univ Hong Kong, Publ Hlth, Hong Kong, Peoples R China Univ Hlth Network, Anesthesia & Pain Med, Toronto, ON, Canada Univ Toronto, Toronto, ON, Canada Univ Bath, Dept Hlth, Bath, Avon, England Univ Copenhagen, Computat & RNA Biol, Copenhagen, Denmark Fisheries & Oceans Canada, Bedford Inst Oceanog, Dartmouth, NS, Canada Goethe Univ, CEF MC, BMLS, Phys Biol, Frankfurt, Germany Albert Einstein Coll Med, Anat & Struct Biol, New York, NY USA Queensland Govt, Dept Environm & Sci, Brisbane, Qld, Australia Uppsala Univ, Vasc Surg Sect, Dept Surg Sci, Uppsala, Sweden Childrens Canc Hosp, Res, Cairo, Egypt Leibniz Inst Nat Prod Res & Infect Biol, Bio Pilot Plant, Jena, Germany Duy Tan Univ, Inst Res & Dev, Da Nang, Vietnam Univ Helsinki, Helsinki Inst Life Sci HiLIFE, Helsinki, Finland Univ Queensland, Australian Inst Bioengn & Nanotechnol, Brisbane, Qld, Australia George Inst Global Hlth, Sydney, NSW, Australia Griffith Univ, Griffith Inst Drug Discovery, Brisbane, Qld, Australia Dezhou Univ, Coll Phys & Elect Informat, Shandong Prov Key Lab Biophys, Dezhou, Peoples R China Henan Agr Univ, Coll Life Sci, Zhengzhou, Henan, Peoples R China Univ Tokyo, Publ Hlth, Tokyo, Japan Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Guangdong, Peoples R China Univ Illinois, Dept Med, Chicago, IL USA Beijing Inst Microbiol & Epidemiol, State Key Lab Pathogen & Biosecur, Beijing, Peoples R China Minist Hlth, Key Lab Neonatal Dis, Shanghai, Peoples R China Covenant Univ, Dept Phys, Ota, Nigeria Prince Sattam Bin Abdulaziz Univ, Dept Phys Therapy & Hlth Rehabil, Al Kharj, Saudi Arabia Lund Univ, Cognit Sci, Malmo, Sweden Natl Open Univ Nigeria, Dept Publ & Environm Hlth, Abuja, Nigeria Peking Univ, Sch Publ Hlth, Dept Lab Sci & Technol, Beijing, Peoples R China Univ Sydney, Sch Publ Hlth, Menzies Ctr Hlth Policy, Sydney, NSW, Australia Univ Auckland, Dept Elect & Comp Engn, Auckland, New Zealand Beijing Univ Chinese Med, Res Ctr TCM Informat Engn, Beijing, Peoples R China Osped Niguarda Ca Granda, Cardiac Surg, Milan, Italy Univ Vet Med, Clin Horses, Hannover, Germany Harbin Med Univ, Lab Med Genet, Harbin, Heilongjiang, Peoples R China Univ Saskatchewan, Dept Psychol, Saskatoon, SK, Canada Univ Coimbra, Ctr Studies Geog & Spatial Planning CEGOT, Coimbra, Portugal Univ Groningen, Univ Med Ctr Groningen, Epidemiol, Groningen, Netherlands South Cent High Specialty Hosp, Dept Neurol & Neurosurg, Pemex, Mexico Shandong Agr Univ, Coll Informat Sci & Engn, Tai An, Shandong, Peoples R China Curtin Univ, Natl Drug Res Inst, Perth, WA, Australia Wageningen Bioveterinary Res, Bacteriol & Epidemiol, Lelystad, Netherlands Guangdong Second Prov Gen Hosp, Dept Rheumatol & Immunol, Guangzhou, Guangdong, Peoples R China Erasmus MC, Biomed Rngineering, Rotterdam, Netherlands Hiroshima Univ, Grad Sch Biomed & Hlth Sci, Hiroshima, Japan Univ Iceland, Sch Hlth Sci, Reykjavik, Iceland Ohio State Univ, Mat Sci & Engn, Columbus, OH 43210 USA Kathmandu Univ, Sch Med Sci, Dept Physiotherapy, Dhulikhel, Nepal Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia Fraunhofer MEVIS, Image Guided Therapies, Bremen, Germany Natl Univ Hlth Syst, Haematol Oncol, Singapore, Singapore Sun Yat Sen Univ, Canc Ctr, Breast Oncol, Guangzhou, Guangdong, Peoples R China Med Coll Wisconsin, Pharmacol & Toxicol, Wauwatosa, WI USA Queensland Univ Technol, Sci & Engn Fac, Sch Chem Phys & Mech Engn, Brisbane, Qld, Australia Univ Turin, Dept Mol Biotechnol & Hlth Sci, Turin, Italy Univ Tehran Med Sci, Sch Rehabil, Physiotherapy Dept, Tehran, Iran Univ Helsinki, Dept Forest Sci, Helsinki, Finland Univ Messina, Human Pathol, Messina, Italy AO Papardo Hosp Messina, Messina, Italy Univ Ibadan, Coll Med, Inst Child Hlth, Ibadan, Nigeria King Faisal Univ, Coll Med, Fac Ophthalmol, Al Hasa, Saudi Arabia Univ Stirling, Inst Social Mkt, Stirling, Scotland Saveh Univ Med Sci, Social Determinants Hlth Res Ctr, Saveh, Iran Gakujutsu Shien Co Ltd, Tokyo, Japan Chinese Acad Sci, Inst Geochem, Guiyang, Guizhou, Peoples R China Univ Plymouth, Med Sch, Plymouth, Devon, England CHU Toulouse, Immunol, Toulouse, France Azorean Biodivers Grp, Ctr Ecol Evolut & Environm Changes, Azores, Portugal Univ Acores, Azores, Portugal RIKEN, Ctr Integrat Med Sci, Yokohama, Kanagawa, Japan Peking Univ, Sch Publ Hlth, Dept Global Hlth, Beijing, Peoples R China Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol, Linkou Med Ctr, Taoyuan, Taiwan Chang Gung Univ, Coll Med, Taoyuan, Taiwan Univ Malawi, Coll Med, Biomed Sci Dept, Blantyre, Malawi Univ Malawi, Coll Med, Pharm Dept, Blantyre, Malawi Bioself Commun, Biocurat, Marseille, France Peking Univ, Hosp 3, Dept Neurol, Beijing, Peoples R China Ahmadu Bello Univ, Fac Basic Clin Sci, Coll Hlth Sci, Dept Pathol, Zaria, Nigeria Dalhousie Univ, Dept Anesthesia Pain Management & Perioperat Med, Halifax, NS, Canada VisMederi Srl, Siena, Italy UCL, Canc Res UK, London, England UCL, UCL Canc Trials Ctr, London, England Univ Ottawa, Family Med, Ottawa, ON, Canada China Agr Univ, Coll Engn, Beijing, Peoples R China Leiden Univ, Leiden Acad Ctr Drug Res, Div Drug Discovery & Safety, Leiden, Netherlands Sun Yat Sen Univ, Affiliated Hosp 1, Dept Intervent Radiol, Guangzhou, Guangdong, Peoples R China Amer Univ Beirut, Med Ctr, Infect Dis, Beirut, Lebanon Sheffield Hallam Univ, Dept Social Work Social Care & Community Studies, Sheffield, S Yorkshire, England Mechnikov Res Inst Vaccines & Sera, Viral Hepatitis, Moscow, Russia Univ Ottawa, Pediat, Ottawa, ON, Canada Vreden Russian Res Inst Traumatol & Orthopaed, Dept Wound Infect Treatment & Prevent, St Petersburg, Russia Hangzhou Ctr Dis Control & Prevent, Dept TB Control & Prevent, Hangzhou, Zhejiang, Peoples R China Kaohsiung Med Univ, Dept Biotechnol, Kaohsiung, Taiwan Zoetis, Diagnost, Kalamazoo, MI USA Aintree Univ Hosp NHS Fdn Trust, Head & Neck Oncol Res, Liverpool, Merseyside, England Wrightington Hosp, Trauma & Orthopaed, Manchester, Lancs, England Loyola Univ, Med Ctr, Dept Psychiat, 2160 S 1st Ave, Maywood, IL 60153 USA Atkins Vet Serv, Microbiol, Calgary, AB, Canada Univ Porto, FADEUP, CIAFEL, Porto, Portugal Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore, Singapore Kangwon Natl Univ, Coll Biotechnol & Biosci, Dept Food Sci & Biotechnol, Chunchon, South Korea Kakatiya Med Coll, Internal Med, Warangal, Telangana, India Univ Antioquia, Vet Med Sch, CIBAV Res Grp, Medellin, Colombia IISER, Dept Phys, Soft & Act Matter Grp, Tirupati 517507, Andhra Pradesh, India Univ Rosario, Sch Med & Hlth, Ctr Studies Phys Activ Measurements, Bogota, Colombia Univ Hosp Essen, Cardiol & Vasc Med, Essen, Germany Univ Hosp Basel, Endocrinol, Basel, Switzerland Univ Tubingen, Inst Med Genet & Appl Genom, Tubingen, Germany Univ Hosp Munster, Div Gen Internal Med Nephrol & Rheumatolog, Dept Med D, Munster, Germany Univ Kentucky, Dept Nephrol, Lexington, KY USA Univ Freiburg, Dept Anaesthesiol & Crit Care, Med Ctr, Freiburg, Germany Univ Calif Irvine, Dept Med, Orange, CA 92668 USA Univ Hosp Leuven, Dept Urol, Leuven, Belgium Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China Univ Florida, Orthopaed & Rehabil, Gainesville, FL USA Chongqing Med Univ, Affiliated Hosp 1, Chongqing Key Lab Mol Oncol & Epigenet, Chongqing, Peoples R China Tsinghua Univ, Dept Chem Engn, Beijing, Peoples R China Yonsei Univ, Coll Med, Dept Pharmacol, Seoul, South Korea Childrens Hosp Kings Daughters, Eastern Virginia Med Sch, Dept Pediat, Norfolk, VA USA China Three Gorges Univ, Coll Sci, Dept Math, Yichang, Peoples R China Xiangtan Univ, Coll Informat Engn, Xiangtan, Hunan, Peoples R China Univ Hlth Network, Mood Disorders & Psychopharmacol, Toronto, ON, Canada Sao Paulo State Univ UNESP, Dept Anim Sci, Sao Paulo, Brazil Sao Paulo State Univ, Vet Clin, Sao Paulo, Brazil
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22. Tear Proteomics in Children and Adolescents with Type 1 Diabetes: A Promising Approach to Biomarker Identification of Diabetes Pathogenesis and Complications.
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Angelopoulou E, Kitani RA, Stroggilos R, Lygirou V, Vasilakis IA, Letsou K, Vlahou A, Zoidakis J, Samiotaki M, Kanaka-Gantenbein C, and Nicolaides NC
- Subjects
- Humans, Child, Adolescent, Male, Female, Cross-Sectional Studies, Tandem Mass Spectrometry, Proteome analysis, Proteome metabolism, Chromatography, Liquid, Case-Control Studies, Eye Proteins metabolism, Diabetes Mellitus, Type 1 metabolism, Biomarkers metabolism, Tears metabolism, Proteomics methods
- Abstract
The aim of the current study was to investigate the tear proteome in children and adolescents with type 1 diabetes (T1D) compared to healthy controls, and to identify differences in the tear proteome of children with T1D depending on different characteristics of the disease. Fifty-six children with T1D at least one year after diagnosis, aged 6-17 years old, and fifty-six healthy age- and sex-matched controls were enrolled in this cross-sectional study. The proteomic analysis was based on liquid chromatography tandem mass spectrometry (LC-MS/MS) enabling the identification and quantification of the protein content via Data-Independent Acquisition by Neural Networks (DIA-NN). Data are available via ProteomeXchange with the identifier PXD052994. In total, 3302 proteins were identified from tear samples. Two hundred thirty-nine tear proteins were differentially expressed in children with T1D compared to healthy controls. Most of them were involved in the immune response, tissue homeostasis and inflammation. The presence of diabetic ketoacidosis at diagnosis and the level of glycemic control of children with T1D influenced the tear proteome. Tear proteomics analysis revealed a different proteome pattern in children with T1D compared to healthy controls offering insights on deregulated biological processes underlying the pathogenesis of T1D. Differences within the T1D group could unravel biomarkers for early detection of long-term complications of T1D.
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- 2024
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23. Investigation of the human-gut-kidney axis by fecal proteomics, highlights molecular mechanisms affected in CKD.
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Lohia S, Valkenburg S, Stroggilos R, Lygirou V, Makridakis M, Zoidakis J, Verbeke F, Glorieux G, and Vlahou A
- Abstract
Objective: The interplay of gut microbiota with the kidney system in chronic kidney disease (CKD), is characterized by increased concentrations of uric acid in the gut, which in turn, may increase bacterial uricase activity and may lead to the generation of uremic toxins. Nevertheless, knowledge on these underlying bidirectional molecular mechanisms is still limited., Methods: In this exploratory study, proteomic analysis was performed on fecal samples, targeting to investigate this largely unexplored biological material as a source of information reflecting the gut-kidney axis. Specifically, fecal suspension samples from patients with CKD1 ( n = 12) and CKD4 ( n = 17) were analysed by LC-MS/MS, using both the Human and Bacterial UniProt RefSeq reviewed databases., Results: This fecal proteomic analysis collectively identified 701 human and 1011 bacterial proteins of high confidence. Differential expression analysis (CKD4/CKD1) revealed significant changes in human proteins ( n = 8, including proteins such as galectin-3-binding protein and prolactin-inducible protein), that were found to be associated with inflammation and CKD. The differential protein expression of pancreatic alpha-amylase further suggested plausible reduced saccharolytic fermentation in CKD4/CKD1. Significant changes in bacterial proteins ( n = 9, such as glyceraldehyde-3-phosphate dehydrogenase and enolase), participating in various carbohydrate and metabolic pathways important for the synthesis of butyrate, in turn suggested differential butyrate synthesis in CKD4/CKD1. Further, targeted quantification of fecal pancreatic alpha-amylase and butyrate in the same fecal suspension samples, supported these hypotheses., Conclusion: Collectively, this exploratory fecal proteomic analysis highlighted changes in human and bacterial proteins reflecting inflammation and reduced saccharolytic fermentation in CKD4/CKD1, plausibly affecting the butyrate synthesis pathways in advanced stage kidney disease. Integrative multi-omics validation is planned., Competing Interests: The authors report that there are no competing interests to declare. Some components of the study design figure (Fig. 1) were exported from biorender.com., (© 2024 The Authors. Published by Elsevier Ltd.)
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- 2024
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24. Ferroptosis-protective membrane domains in quiescence.
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Megarioti AH, Esch BM, Athanasopoulos A, Koulouris D, Makridakis M, Lygirou V, Samiotaki M, Zoidakis J, Sophianopoulou V, André B, Fröhlich F, and Gournas C
- Subjects
- Saccharomyces cerevisiae, Lipid Peroxidation, Antioxidants, Fatty Acids, Unsaturated, Ferroptosis
- Abstract
Quiescence is a common cellular state, required for stem cell maintenance and microorganismal survival under stress conditions or starvation. However, the mechanisms promoting quiescence maintenance remain poorly known. Plasma membrane components segregate into distinct microdomains, yet the role of this compartmentalization in quiescence remains unexplored. Here, we show that flavodoxin-like proteins (FLPs), ubiquinone reductases of the yeast eisosome membrane compartment, protect quiescent cells from lipid peroxidation and ferroptosis. Eisosomes and FLPs expand specifically in respiratory-active quiescent cells, and mutants lacking either show accelerated aging and defective quiescence maintenance and accumulate peroxidized phospholipids with monounsaturated or polyunsaturated fatty acids (PUFAs). FLPs are essential for the extramitochondrial regeneration of the lipophilic antioxidant ubiquinol. FLPs, alongside the Gpx1/2/3 glutathione peroxidases, prevent iron-driven, PUFA-dependent ferroptotic cell death. Our work describes ferroptosis-protective mechanisms in yeast and introduces plasma membrane compartmentalization as an important factor in the long-term survival of quiescent cells., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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25. Data-Independent Acquisition Mass Spectrometry Analysis of FFPE Rectal Cancer Samples Offers In-Depth Proteomics Characterization of the Response to Neoadjuvant Chemoradiotherapy.
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Stanojevic A, Samiotaki M, Lygirou V, Marinkovic M, Nikolic V, Stojanovic-Rundic S, Jankovic R, Vlahou A, Panayotou G, Fijneman RJA, Castellví-Bel S, Zoidakis J, and Cavic M
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- Humans, Proteome metabolism, Proteomics, Treatment Outcome, Chemoradiotherapy methods, Biomarkers, RNA-Binding Proteins, Nuclear Proteins metabolism, Neoadjuvant Therapy methods, Rectal Neoplasms genetics
- Abstract
Locally advanced rectal cancer (LARC) presents a challenge in identifying molecular markers linked to the response to neoadjuvant chemoradiotherapy (nCRT). This study aimed to utilize a sensitive proteomic method, data-independent mass spectrometry (DIA-MS), to extensively analyze the LARC proteome, seeking individuals with favorable initial responses suitable for a watch-and-wait approach. This research addresses the unmet need to understand the response to treatment, potentially guiding personalized strategies for LARC patients. Post-treatment assessment included MRI scans and proctoscopy. This research involved 97 LARC patients treated with intense chemoradiotherapy, comprising radiation and chemotherapy. Out of 97 LARC included in this study, we selected 20 samples with the most different responses to nCRT for proteome profiling (responders vs. non-responders). This proteomic approach shows extensive proteome coverage in LARC samples. The analysis identified a significant number of proteins compared to a prior study. A total of 915 proteins exhibited differential expression between the two groups, with certain signaling pathways associated with response mechanisms, while top candidates had good predictive potential. Proteins encoded by genes SMPDL3A , PCTP , LGMN , SYNJ2 , NHLRC3 , GLB1, and RAB43 showed high predictive potential of unfavorable treatment outcome, while RPA2 , SARNP , PCBP2 , SF3B2 , HNRNPF , RBBP4 , MAGOHB , DUT , ERG28 , and BUB3 were good predictive biomarkers of favorable treatment outcome. The identified proteins and related biological processes provide promising insights that could enhance the management and care of LARC patients.
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- 2023
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26. Pilot proteomic study of locally advanced rectal cancer before and after neoadjuvant chemoradiotherapy indicates high metabolic activity in non-responders' tumor tissue.
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Babic T, Lygirou V, Rosic J, Miladinov M, Rom AD, Baira E, Stroggilos R, Pappa E, Zoidakis J, Krivokapic Z, and Nikolic A
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- Humans, Proteomics methods, Chromatography, Liquid, Tandem Mass Spectrometry, Biomarkers, Treatment Outcome, Neoadjuvant Therapy, Rectal Neoplasms therapy, Rectal Neoplasms metabolism, Rectal Neoplasms pathology
- Abstract
Purpose: In the search for candidate predictive biomarkers to evaluate response to neoadjuvant chemoradiotherapy (nCRT) in rectal cancer, only a few studies report proteomic profiles of tumor tissue before and after nCRT. The aim of our study was to determine differentially expressed proteins between responders and non-responders before and after the therapy in order to identify candidate molecules for prediction and follow-up of response to nCRT., Experimental Design: The study has included tissue sections of rectal tumor and non-tumor mucosa from five responders and five non-responders taken before and after nCRT from patients with locally advanced rectal cancer. Extracted proteins were analyzed by LC-MS/MS analysis followed by a set of bioinformatics analyses., Result: Proteomics analysis provided a mean of approximately 1050 protein identifications per sample. A comparison of proteomic profiles between responders and non-responders has identified 18 differentially expressed proteins. Pathway analysis demonstrated high metabolic activity in non-responders' tumors before nCRT, indicating the presence of intrinsic chemoradioresistance in these subjects. Two proteins associated with poor prognosis in colorectal cancer, ADAM10 and CAD, were identified as candidate predictive biomarkers as they were present in non-responders only., Conclusions and Clinical Relevance: Shortlisted proteins from our study should be further validated as candidate biomarkers for response to routinely applied nCRT protocols., (© 2022 Wiley-VCH GmbH.)
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- 2023
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27. Proteomic Analysis of Prostate Cancer FFPE Samples Reveals Markers of Disease Progression and Aggressiveness.
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Lygirou V, Fasoulakis K, Stroggilos R, Makridakis M, Latosinska A, Frantzi M, Katafigiotis I, Alamanis C, Stravodimos KG, Constantinides CA, Vlahou A, and Zoidakis J
- Abstract
Prostate cancer (PCa) is the second most common cancer in men. Diagnosis and risk assessment are widely based on serum Prostate Specific Antigen (PSA) and biopsy, which might not represent the exact degree of PCa risk. Towards the discovery of biomarkers for better patient stratification, we performed proteomic analysis of Formalin Fixed Paraffin Embedded (FFPE) prostate tissue specimens using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Comparative analysis of 86 PCa samples among grade groups 1-5 identified 301 significantly altered proteins. Additional analysis based on biochemical recurrence (BCR; BCR+ n = 14, BCR- n = 51) revealed 197 significantly altered proteins that indicate disease persistence. Filtering the overlapping proteins of these analyses, seven proteins ( NPM1 , UQCRH , HSPA9 , MRPL3 , VCAN , SERBP1 , HSPE1 ) had increased expression in advanced grades and in BCR+/BCR- and may play a critical role in PCa aggressiveness. Notably, all seven proteins were significantly associated with progression in Prostate Cancer Transcriptome Atles (PCTA) and NPM1NPM1 , UQCRH , and VCAN were further validated in The Cancer Genome Atlas (TCGA), where they were upregulated in BCR+/BCR-. UQCRH levels were also associated with poorer 5-year survival. Our study provides valuable insights into the key regulators of PCa progression and aggressiveness. The seven selected proteins could be used for the development of risk assessment tools.
- Published
- 2022
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28. Plasma Proteomics in Healthy Subjects with Differences in Tissue Glucocorticoid Sensitivity Identifies A Novel Proteomic Signature.
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Nicolaides NC, Makridakis M, Stroggilos R, Lygirou V, Koniari E, Papageorgiou I, Sertedaki A, Zoidakis J, and Charmandari E
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Significant inter-individual variation in terms of susceptibility to several stress-related disorders, such as myocardial infarction and Alzheimer's disease, and therapeutic response has been observed among healthy subjects. The molecular features responsible for this phenomenon have not been fully elucidated. Proteomics, in association with bioinformatics analysis, offer a comprehensive description of molecular phenotypes with clear links to human disease pathophysiology. The aim of this study was to conduct a comparative plasma proteomics analysis of glucocorticoid resistant and glucocorticoid sensitive healthy subjects and provide clues of the underlying physiological differences. For this purpose, 101 healthy volunteers were given a very low dose (0.25 mg) of dexamethasone at midnight, and were stratified into the 10% most glucocorticoid sensitive (S) ( n = 11) and 10% most glucocorticoid resistant (R) ( n = 11) according to the 08:00 h serum cortisol concentrations determined the following morning. One month following the very-low dose dexamethasone suppression test, DNA and plasma samples were collected from the 22 selected individuals. Sequencing analysis did not reveal any genetic defects in the human glucocorticoid receptor ( NR3C1 ) gene. To investigate the proteomic profile of plasma samples, we used Liquid Chromatography-Mass Spectrometry (LC-MS/MS) and found 110 up-regulated and 66 down-regulated proteins in the S compared to the R group. The majority of the up-regulated proteins in the S group were implicated in platelet activation. To predict response to cortisol prior to administration, a random forest classifier was developed by using the proteomics data in order to distinguish S from R individuals. Apolipoprotein A4 (APOA4) and gelsolin (GSN) were the most important variables in the classification, and warrant further investigation. Our results indicate that a proteomics signature may differentiate the S from the R healthy subjects, and may be useful in clinical practice. In addition, it may provide clues of the underlying molecular mechanisms of the chronic stress-related diseases, including myocardial infarction and Alzheimer's disease.
- Published
- 2022
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29. Urine peptidome analysis in cardiorenal syndrome reflects molecular processes.
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Petra E, He T, Lygirou V, Latosinska A, Mischak H, Vlahou A, and Jankowski J
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- Aged, Case-Control Studies, Female, Humans, Male, Prognosis, Cardio-Renal Syndrome pathology, Cardio-Renal Syndrome urine, Endopeptidases metabolism, Peptide Fragments urine, Urinalysis methods
- Abstract
The cardiorenal syndrome (CRS) is defined as the confluence of heart-kidney dysfunction. This study investigates the molecular differences at the level of the urinary peptidome between CRS patients and controls and their association to disease pathophysiology. The urinary peptidome of CRS patients (n = 353) was matched for age and sex with controls (n = 356) at a 1:1 ratio. Changes in the CRS peptidome versus controls were identified after applying the Mann-Whitney test, followed by correction for multiple testing. Proteasix tool was applied to investigate predicted proteases involved in CRS-associated peptide generation. Overall, 559 differentially excreted urinary peptides were associated with CRS patients. Of these, 193 peptides were specifically found in CRS when comparing with heart failure and chronic kidney disease urinary peptide profiles. Proteasix predicted 18 proteases involved in > 1% of proteolytic cleavage events including multiple forms of MMPs, proprotein convertases, cathepsins and kallikrein 4. Forty-four percent of the cleavage events were produced by 3 proteases including MMP13, MMP9 and MMP2. Pathway enrichment analysis supported that ECM-related pathways, fibrosis and inflammation were represented. Collectively, our study describes the changes in urinary peptides of CRS patients and potential proteases involved in their generation, laying the basis for further validation., (© 2021. The Author(s).)
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- 2021
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30. A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients' Omics Signatures.
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Mokou M, Lygirou V, Angelioudaki I, Paschalidis N, Stroggilos R, Frantzi M, Latosinska A, Bamias A, Hoffmann MJ, Mischak H, and Vlahou A
- Abstract
Multi-omics signatures of patients with bladder cancer (BC) can guide the identification of known de-risked therapeutic compounds through drug repurposing, an approach not extensively explored yet. In this study, we target drug repurposing in the context of BC, driven by tissue omics signatures. To identify compounds that can reverse aggressive high-risk Non-Muscle Invasive BC (NMIBC) to less aggressive low-risk molecular subtypes, the next generation Connectivity Map (CMap) was employed using as input previously published proteomics and transcriptomics respective signatures. Among the identified compounds, the ATP-competitive inhibitor of mTOR, WYE-354, showed a consistently very high score for reversing the aggressive BC molecular signatures. WYE-354 impact was assessed in a panel of eight multi-origin BC cell lines and included impaired colony growth and proliferation rate without any impact on apoptosis. Overall, with this study we introduce a promising pipeline for the repurposing of drugs for BC treatment, based on patients' omics signatures.
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- 2020
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31. Proteomics Analysis of Formalin Fixed Paraffin Embedded Tissues in the Investigation of Prostate Cancer.
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Mantsiou A, Makridakis M, Fasoulakis K, Katafigiotis I, Constantinides CA, Zoidakis J, Roubelakis MG, Vlahou A, and Lygirou V
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- Animals, Chromatography, Liquid, Formaldehyde, Humans, Male, Mice, Paraffin Embedding, Reproducibility of Results, Tandem Mass Spectrometry, Tissue Fixation, Prostatic Neoplasms, Proteomics
- Abstract
Prostate cancer (PCa) is one of the leading causes of death in men worldwide. The molecular features, associated with the onset and progression of the disease, are under vigorous investigation. Formalin-fixed paraffin-embedded (FFPE) tissues are valuable resources for large-scale studies; however, their application in proteomics is limited due to protein cross-linking. In this study, the adjustment of a protocol for the proteomic analysis of FFPE tissues was performed which was followed by a pilot application on FFPE PCa clinical samples to investigate whether the optimized protocol can provide biologically relevant data for the investigation of PCa. For the optimization, FFPE mouse tissues were processed using seven protein extraction protocols including combinations of homogenization methods (beads, sonication, boiling) and buffers (SDS based and urea-thiourea based). The proteome extraction efficacy was then evaluated based on protein identifications and reproducibility using SDS electrophoresis and high resolution LC-MS/MS analysis. Comparison between the FFPE and matched fresh frozen (FF) tissues, using an optimized protocol involving protein extraction with an SDS-based buffer following beads homogenization and boiling, showed a substantial overlap in protein identifications with a strong correlation in relative abundances ( r
s = 0.819, p < 0.001). Next, FFPE tissues (3 sections, 15 μm each per sample) from 10 patients with PCa corresponding to tumor (GS = 6 or GS ≥ 8) and adjacent benign regions were processed with the optimized protocol. Extracted proteins were analyzed by GeLC-MS/MS followed by statistical and bioinformatics analysis. Proteins significantly deregulated between PCa GS ≥ 8 and PCa GS = 6 represented extracellular matrix organization, gluconeogenesis, and phosphorylation pathways. Proteins deregulated between cancerous and adjacent benign tissues, reflected increased translation, peptide synthesis, and protein metabolism in the former, which is consistent with the literature. In conclusion, the results support the relevance of the proteomic findings in the context of PCa and the reliability of the optimized protocol for proteomics analysis of FFPE material.- Published
- 2020
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32. Multiplexed MRM-based protein quantification of putative prognostic biomarkers for chronic kidney disease progression in plasma.
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Makridakis M, Kontostathi G, Petra E, Stroggilos R, Lygirou V, Filip S, Duranton F, Mischak H, Argiles A, Zoidakis J, and Vlahou A
- Subjects
- Adult, Aged, Aged, 80 and over, Biomarkers blood, Cohort Studies, Disease Progression, Female, Follow-Up Studies, Glomerular Filtration Rate, Hemoglobin Subunits, Humans, Longitudinal Studies, Male, Middle Aged, Prognosis, Alpha-Globulins, Complement C1 Inhibitor Protein, Mass Spectrometry methods, Muramidase blood, Renal Insufficiency, Chronic diagnosis, beta 2-Microglobulin blood
- Abstract
Current diagnostic measures for Chronic Kidney Disease (CKD) include detection of reduced estimated glomerular filtration rate (eGFR) and albuminuria, which have suboptimal accuracies in predicting disease progression. The disease complexity and heterogeneity underscore the need for multiplex quantification of different markers. The goal of this study was to determine the association of six previously reported CKD-associated plasma proteins [B2M (Beta-2-microglobulin), SERPINF1 (Pigment epithelium-derived factor), AMBP (Protein AMBP), LYZ (Lysozyme C), HBB (Hemoglobin subunit beta) and IGHA1 (Immunoglobulin heavy constant alpha 1)], as measured in a multiplex format, with kidney function, and outcome. Antibody-free, multiple reaction monitoring mass spectrometry (MRM) assays were developed, characterized for their analytical performance, and used for the analysis of 72 plasma samples from a patient cohort with longitudinal follow-up. The MRM significantly correlated (Rho = 0.5-0.9) with results from respective ELISA. Five proteins [AMBP, B2M, LYZ, HBB and SERPINF1] were significantly associated with eGFR, with the three former also associated with unfavorable outcome. The combination of these markers provided stronger associations with outcome (p < 0.0001) compared to individual markers. Collectively, our study describes a multiplex assay for absolute quantification and verification analysis of previously described putative CKD prognostic markers, laying the groundwork for further use in prospective validation studies.
- Published
- 2020
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33. Proteome-based classification of Nonmuscle Invasive Bladder Cancer.
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Stroggilos R, Mokou M, Latosinska A, Makridakis M, Lygirou V, Mavrogeorgis E, Drekolias D, Frantzi M, Mullen W, Fragkoulis C, Stasinopoulos K, Papadopoulos G, Stathouros G, Lazaris AC, Makrythanasis P, Ntoumas K, Mischak H, Zoidakis J, and Vlahou A
- Subjects
- Aged, Biomarkers, Tumor metabolism, Chromatography, Liquid methods, Disease Progression, Female, Humans, Inflammation metabolism, Inflammation pathology, Kaplan-Meier Estimate, Male, Phenotype, Prognosis, Proteomics methods, RNA, Messenger metabolism, Tandem Mass Spectrometry methods, Urinary Bladder Neoplasms pathology, Proteome metabolism, Urinary Bladder Neoplasms metabolism
- Abstract
DNA/RNA-based classification of bladder cancer (BC) supports the existence of multiple molecular subtypes, while investigations at the protein level are scarce. Here, we aimed to investigate if Nonmuscle Invasive Bladder Cancer (NMIBC) can be stratified to biologically meaningful groups based on the proteome. Tissue specimens from 117 patients at primary diagnosis (98 with NMIBC and 19 with MIBC), were processed for high-resolution proteomics analysis by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteomics output was subjected to unsupervised consensus clustering, principal component analysis (PCA) and investigation of subtype-specific features, pathways, and gene sets. NMIBC patients were optimally stratified to three NMIBC proteomic subtypes (NPS), differing in size, clinicopathologic and molecular backgrounds: NPS1 (mostly high stage/grade/risk samples) was the smallest in size (17/98) and overexpressed proteins reflective of an immune/inflammatory phenotype, involved in cell proliferation, unfolded protein response and DNA damage response, whereas NPS2 (mixed stage/grade/risk composition) presented with an infiltrated/mesenchymal profile. NPS3 was rich in luminal/differentiation markers, in line with its pathological composition (mostly low stage/grade/risk samples). PCA revealed a close proximity of NPS1 and conversely, remoteness of NPS3 to the proteome of MIBC. Proteins distinguishing these two extreme subtypes were also found to consistently differ at the mRNA levels between high and low-risk subtypes of the UROMOL and LUND cohorts. Collectively, our study identifies three proteomic NMIBC subtypes and following a cross-omics validation in two independent cohorts, shortlists molecular features meriting further investigation for their biomarker or potentially therapeutic value., (© 2019 UICC.)
- Published
- 2020
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34. High resolution analysis of the intracellular proteome of cervical cancer cell lines unveils novel regulators of cervical carcinogenesis.
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Pappa KI, Lygirou V, Kontostathi G, Makridakis M, Vougas K, Sfakianakis A, Daskalakis G, Zoidakis J, and Anagnou NP
- Abstract
Cervical cancer remains the fourth most common and most lethal type of cancer in women, despite the applied regular screening and prevention strategies, while the available treatment schemes still pose a threat to fertility. Substantial understanding of the underlying mechanisms and development of novel diagnostic, prognostic and therapeutic approaches are critical steps for improving cervical cancer management. Towards this goal, a comparative proteomic analysis was conducted between three cervical cancer cell lines (HeLa: HPV18+, SiHa: HPV16+, C33A: HPV‑) and normal cervical keratinocytes (HCK1T). The total cell extract of each cell line was analyzed by liquid chromatography coupled to tandem mass spectrometry (LC‑MS/MS). Differential expression analysis revealed 919, 826 and 1,370 deregulated proteins in the comparisons of HeLa, SiHa and C33A with HCK1T cell lines, respectively. Pathway enrichment analysis of the differentially expressed proteins highlighted common cancer characteristics such as high metabolic demands and increased cell turnover, confirming the validity of the proteomic results. Extensive literature mining of the consistently differentially expressed proteins that resulted from the three comparisons was performed leading to a shortlist of 21 proteins that are potentially involved in cervical malignancy. The criteria for this shortlisting were the association of the proteins with various types of cancer, while there is no study as yet associating their expression to cervical cancer. Moreover, the expression trend of two of the shortlisted proteins was validated using western blot analysis. The proteomic datasets generated in this study can be utilized to enrich the current knowledge on cervical cancer pathology and unveil key molecular mechanisms of carcinogenesis. In conclusion, the shortlist of consistently deregulated proteins between cervical cancer cell lines and normal cervical keratinocytes can be used for validation in clinical samples and in functional investigation experiments that could ultimately lead to the discovery of novel disease biomarkers and drug targets.
- Published
- 2019
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35. Implications of the mitochondrial interactome of mammalian thioredoxin 2 for normal cellular function and disease.
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Chasapis CT, Makridakis M, Damdimopoulos AE, Zoidakis J, Lygirou V, Mavroidis M, Vlahou A, Miranda-Vizuete A, Spyrou G, and Vlamis-Gardikas A
- Subjects
- Animals, Humans, Male, Mice, Mice, Inbred C57BL, Mitochondrial Proteins metabolism, Oxidation-Reduction, Protein Binding, Protein Interaction Maps, Rats, Reactive Oxygen Species metabolism, Saccharomyces cerevisiae genetics, Mitochondria metabolism, Parkinson Disease metabolism, Protein Isoforms metabolism, RNA, Mitochondrial genetics, Thioredoxins metabolism
- Abstract
Multiple thioredoxin isoforms exist in all living cells. To explore the possible functions of mammalian mitochondrial thioredoxin 2 (Trx2), an interactome of mouse Trx2 was initially created using (i) a monothiol mouse Trx2 species for capturing protein partners from different organs and (ii) yeast two hybrid screens on human liver and rat brain cDNA libraries. The resulting interactome consisted of 195 proteins (Trx2 included) plus the mitochondrial 16S RNA. 48 of these proteins were classified as mitochondrial (MitoCarta2.0 human inventory). In a second step, the mouse interactome was combined with the current four-membered mitochondrial sub-network of human Trx2 (BioGRID) to give a 53-membered human Trx2 mitochondrial interactome (52 interactor proteins plus the mitochondrial 16S RNA). Although thioredoxins are thiol-employing disulfide oxidoreductases, approximately half of the detected interactions were not due to covalent disulfide bonds. This finding reinstates the extended role of thioredoxins as moderators of protein function by specific non-covalent, protein-protein interactions. Analysis of the mitochondrial interactome suggested that human Trx2 was involved potentially in mitochondrial integrity, formation of iron sulfur clusters, detoxification of aldehydes, mitoribosome assembly and protein synthesis, protein folding, ADP ribosylation, amino acid and lipid metabolism, glycolysis, the TCA cycle and the electron transport chain. The oxidoreductase functions of Trx2 were verified by its detected interactions with mitochondrial peroxiredoxins and methionine sulfoxide reductase. Parkinson's disease, triosephosphate isomerase deficiency, combined oxidative phosphorylation deficiency, and lactate dehydrogenase b deficiency are some of the diseases where the proposed mitochondrial network of Trx2 may be implicated., (Copyright © 2019 Elsevier Inc. All rights reserved.)
- Published
- 2019
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36. Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment.
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Schanstra JP, Luong TT, Makridakis M, Van Linthout S, Lygirou V, Latosinska A, Alesutan I, Boehme B, Schelski N, Von Lewinski D, Mullen W, Nicklin S, Delles C, Feuillet G, Denis C, Lang F, Pieske B, Bascands JL, Mischak H, Saulnier-Blache JS, Voelkl J, Vlahou A, and Klein J
- Subjects
- Adult, Animals, Apolipoproteins E genetics, Arachidonic Acids, Atherosclerosis, Cardiovascular Diseases, Disease Models, Animal, Female, Humans, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Myocytes, Smooth Muscle metabolism, Up-Regulation, Antigens, Human Platelet metabolism, Cytosol metabolism, Systems Biology, Vascular Calcification metabolism, Vascular Calcification therapy
- Abstract
Although cardiovascular disease (CVD) is the leading cause of morbimortality worldwide, promising new drug candidates are lacking. We compared the arterial high-resolution proteome of patients with advanced versus early-stage CVD to predict, from a library of small bioactive molecules, drug candidates able to reverse this disease signature. Of the approximately 4000 identified proteins, 100 proteins were upregulated and 52 were downregulated in advanced-stage CVD. Arachidonyl trifluoromethyl ketone (AACOCF3), a cytosolic phospholipase A2 (cPLA2) inhibitor was predicted as the top drug able to reverse the advanced-stage CVD signature. Vascular cPLA2 expression was increased in patients with advanced-stage CVD. Treatment with AACOCF3 significantly reduced vascular calcification in a cholecalciferol-overload mouse model and inhibited osteoinductive signaling in vivo and in vitro in human aortic smooth muscle cells. In conclusion, using a systems biology approach, we have identified a potentially new compound that prevented typical vascular calcification in CVD in vivo. Apart from the clear effect of this approach in CVD, such strategy should also be able to generate novel drug candidates in other complex diseases.
- Published
- 2019
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37. Diagnostic and Prognostic Performance of Secreted Protein Acidic and Rich in Cysteine (SPARC) Assay for Detecting Primary and Recurrent Urinary Bladder Cancer.
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Critselis E, Rava M, Marquez M, Lygirou V, Chatzicharalambous D, Liapi P, Lichtinghagen R, Brand K, Cecchini L, Vlahou A, Malats N, and Zoidakis J
- Subjects
- Aged, Biomarkers, Tumor metabolism, Disease Progression, Female, Humans, Male, Middle Aged, Prognosis, Recurrence, Osteonectin metabolism, Proteomics, Urinary Bladder Neoplasms diagnosis, Urinary Bladder Neoplasms metabolism
- Abstract
Purpose: To evaluate the diagnostic and prognostic performance of Secreted Protein Acidic and Rich in Cysteine (SPARC) in detecting urinary bladder cancer (UBC)., Methods: The Integrated Study on Bladder Cancer (n = 571; mean age:69.4 ± 12.2 years) evaluates cross-sectionally SPARC diagnostic performance in primary (n = 264) and recurrent (n = 307) UBC. SPARC prognostic performance is evaluated in a nested cohort (n = 250) prospectively followed for 80 months to detect tumor relapse, recurrence and/or progression. Baseline urine samples are analyzed blindly using a commercially available SPARC ELISA assay, characterized for its analytical performance according to clinical test regulatory requirements (R&D Manufactures Inc.)., Results: While higher mean SPARC levels are detected in primary (p = 0.008) and recurrent (p < 0.0001) UBC, the assay has limited diagnostic performance (AUC:0.593; 95% CI:0.524-0.663). SPARC positive patients undergoing disease monitoring are more likely to develop tumor relapse (age and gender Adj. HR:1.52; 95% CI:1.04-2.22) and progression (Adj. HR:1.83; 95% CI:1.02-3.27). However, prognostic performance is affected by hematuria., Conclusions: SPARC diagnostic performance for detecting UBC appears insufficient for clinical implementation. In patients undergoing disease monitoring, SPARC is a promising prognostic marker for tumor relapse and/or progression, but is affected by hematuria., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2019
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38. Membrane proteomics of cervical cancer cell lines reveal insights on the process of cervical carcinogenesis.
- Author
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Pappa KI, Christou P, Xholi A, Mermelekas G, Kontostathi G, Lygirou V, Makridakis M, Zoidakis J, and Anagnou NP
- Subjects
- Cell Line, Tumor, Chromatography, Liquid, Female, HeLa Cells, Humans, Membrane Proteins isolation & purification, Protein Interaction Maps, Reproducibility of Results, Software, Tandem Mass Spectrometry, Uterine Cervical Neoplasms metabolism, Membrane Proteins analysis, Membrane Proteins metabolism, Proteomics methods, Uterine Cervical Neoplasms pathology
- Abstract
The available therapeutic approaches for cervical cancer can seriously affect the fertility potential of patient; thus, there is a pressing requirement for less toxic and targeted therapies. The membrane proteome is a potential source of therapeutic targets; however, despite the significance of membrane proteins in cancer, proteomic analysis has been a challenging task due to their unique biochemical properties. The aim of the present study was to develop an efficient membrane protein enrichment protocol, and to the best of our knowledge, to compare for the first time the expression pattern of membrane proteins of one normal cell line, HCK1T, and three cervical cancer cell lines, C33A, a human papilloma virus (HPV)-negative cell line, and two HPV-positive cell lines, SiHa (HPV16+) and HeLa (HPV18+). The study aimed to identify the proteins that are involved in cervical carcinogenesis and may constitute novel drug targets. Membrane protein isolation, liquid chromatography coupled with tandem mass spectrometry proteomics and bioinformatics analysis were performed in the membrane fraction of the informative cervical cell lines following a novel enrichment protocol. The percentages of membrane and transmembrane proteins in the enrichment protocol were higher compared with those of the corresponding data derived from total cell extract analysis. Differentially expressed proteins were detected by the comparison of the cervical cancer cell lines with the normal cell line. These proteins constitute molecular features of cancer pathology and participate in biological pathways relevant to malignancy, including 'HIPPO signaling', 'PI3K/Akt signaling', 'cell cycle: G2/M DNA damage checkpoint regulation' and 'EIF2 signaling'. These unique membrane protein identifications offer insights on a previously inaccessible region of the cervical cancer proteome, and may represent putative diagnostic and prognostic markers, and eventually therapeutic targets.
- Published
- 2018
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- View/download PDF
39. Plasma proteomic analysis reveals altered protein abundances in cardiovascular disease.
- Author
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Lygirou V, Latosinska A, Makridakis M, Mullen W, Delles C, Schanstra JP, Zoidakis J, Pieske B, Mischak H, and Vlahou A
- Subjects
- Adult, Aged, Databases, Protein, Female, Humans, Male, Reproducibility of Results, Cardiovascular Diseases blood, Proteome metabolism, Proteomics
- Abstract
Background: Cardiovascular disease (CVD) describes the pathological conditions of the heart and blood vessels. Despite the large number of studies on CVD and its etiology, its key modulators remain largely unknown. To this end, we performed a comprehensive proteomic analysis of blood plasma, with the scope to identify disease-associated changes after placing them in the context of existing knowledge, and generate a well characterized dataset for further use in CVD multi-omics integrative analysis., Methods: LC-MS/MS was employed to analyze plasma from 32 subjects (19 cases of various CVD phenotypes and 13 controls) in two steps: discovery (13 cases and 8 controls) and test (6 cases and 5 controls) set analysis. Following label-free quantification, the detected proteins were correlated to existing plasma proteomics datasets (plasma proteome database; PPD) and functionally annotated (Cytoscape, Ingenuity Pathway Analysis). Differential expression was defined based on identification confidence (≥ 2 peptides per protein), statistical significance (Mann-Whitney p value ≤ 0.05) and a minimum of twofold change., Results: Peptides detected in at least 50% of samples per group were considered, resulting in a total of 3796 identified proteins (838 proteins based on ≥ 2 peptides). Pathway annotation confirmed the functional relevance of the findings (representation of complement cascade, fibrin clot formation, platelet degranulation, etc.). Correlation of the relative abundance of the proteins identified in the discovery set with their reported concentrations in the PPD was significant, confirming the validity of the quantification method. The discovery set analysis revealed 100 differentially expressed proteins between cases and controls, 39 of which were verified (≥ twofold change) in the test set. These included proteins already studied in the context of CVD (such as apolipoprotein B, alpha-2-macroglobulin), as well as novel findings (such as low density lipoprotein receptor related protein 2 [LRP2], protein SZT2) for which a mechanism of action is suggested., Conclusions: This proteomic study provides a comprehensive dataset to be used for integrative and functional studies in the field. The observed protein changes reflect known CVD-related processes (e.g. lipid uptake, inflammation) but also novel hypotheses for further investigation including a potential pleiotropic role of LPR2 but also links of SZT2 to CVD.
- Published
- 2018
- Full Text
- View/download PDF
40. Novel structural approaches concerning HPV proteins: Insight into targeted therapies for cervical cancer (Review).
- Author
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Pappa KI, Kontostathi G, Lygirou V, Zoidakis J, and Anagnou NP
- Subjects
- Epithelium pathology, Epithelium virology, Female, Host-Pathogen Interactions genetics, Human papillomavirus 16 genetics, Human papillomavirus 16 pathogenicity, Human papillomavirus 18 genetics, Human papillomavirus 18 pathogenicity, Humans, Keratinocytes chemistry, Keratinocytes virology, Precancerous Conditions genetics, Precancerous Conditions pathology, Precancerous Conditions virology, Structure-Activity Relationship, Uterine Cervical Neoplasms pathology, Uterine Cervical Neoplasms virology, Viral Proteins genetics, Human papillomavirus 16 chemistry, Human papillomavirus 18 chemistry, Uterine Cervical Neoplasms genetics, Viral Proteins chemistry
- Abstract
Cervical cancer incidence is tightly linked to HPV infection, and particularly virus types 16 and 18 cause the majority of cases presenting with pre-cancerous stages of cervical intraepithelial neoplasia (CIN). Structural and functional information concerning HPV proteins can offer novel insight into the mechanism(s) of cancer progression in the cervical epithelium. Recently, novel structural determinants of the interactions of viral proteins with their targets in keratinocytes have been elucidated. These exciting findings open the way for the development of targeted anti-oncogenic therapies, and may eventually allow the introduction of novel approaches for a rational cervical cancer treatment.
- Published
- 2018
- Full Text
- View/download PDF
41. High Resolution Proteomic Analysis of the Cervical Cancer Cell Lines Secretome Documents Deregulation of Multiple Proteases.
- Author
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Pappa KI, Kontostathi G, Makridakis M, Lygirou V, Zoidakis J, Daskalakis G, and Anagnou NP
- Subjects
- Cell Line, Tumor, Female, Humans, Chromatography, Liquid methods, Mass Spectrometry methods, Matrix Metalloproteinases genetics, Peptide Hydrolases genetics, Proteomics methods, Uterine Cervical Neoplasms genetics
- Abstract
Background: Oncogenic infection by HPV, eventually leads to cervical carcinogenesis, associated by deregulation of specific pathways and protein expression at the intracellular and secretome level. Thus, secretome analysis can elucidate the biological mechanisms contributing to cervical cancer. In the present study we systematically analyzed its constitution in four cervical cell lines employing a highly sensitive proteomic technology coupled with bioinformatics analysis., Materials and Methods: LC/MS-MS proteomics and bioinformatics analysis were performed in the secretome of four informative cervical cell lines SiHa (HPV16
+ ), HeLa (HPV18+ ), C33A (HPV- ) and HCK1T (normal)., Results: The proteomic pattern of each cancer cell line compared to HCK1T was identified and a detailed bioinformatics analysis disclosed inhibition of matrix metalloproteases in cancer cell lines. This prediction was further confirmed via zymography for MMP-2 and MMP-9, western blot analysis for ADAM10 and by MRM for TIMP1. The differential expression of important secreted proteins such as CATD, FUCA1 and SOD2 was also confirmed by western blot analysis. MRM-targeted proteomics analysis confirmed the differential expression of CATD, CATB, SOD2, QPCT and NEU1., Conclusion: High resolution proteomics analysis of cervical cancer secretome revealed significantly deregulated biological processes and proteins implicated in cervical carcinogenesis., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)- Published
- 2017
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- View/download PDF
42. Proteomic Analysis of Normal and Cancer Cervical Cell Lines Reveals Deregulation of Cytoskeleton-associated Proteins.
- Author
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Pappa KI, Lygirou V, Kontostathi G, Zoidakis J, Makridakis M, Vougas K, Daskalakis G, Polyzos A, and Anagnou NP
- Subjects
- Cell Line, Tumor, Electrophoresis, Gel, Two-Dimensional, Female, Humans, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Uterine Cervical Neoplasms pathology, Cytoskeletal Proteins metabolism, Proteomics, Uterine Cervical Neoplasms metabolism
- Abstract
Background: Both HPV-positive and -negative cervical cancers are primarily associated with features of cell cycle and cytoskeletal disruption; however, the actual biological processes affected remain elusive. To this end, we systematically characterized the intracellular proteomic profiles of four distinct and informative cervical cell lines., Materials and Methods: Cell extracts from a normal cervical (HCK1T) and three cervical cancer cell lines, one HPV-negative (C33A), and two HPV-positive, SiHa (HPV16+) and HeLa (HPV18+), were analyzed by 2-dimensional electrophoresis and differentially expressed proteins were identified by MALDI-TOF mass spectrometry, while differential expression was confirmed by western blot analysis., Results: In total, 113 proteins were found differentially expressed between the normal and the cervical cancer lines. Bioinformatics analysis revealed the actin cytoskeleton signaling pathway to be significantly affected, while up-regulation of cofilin-1, an actin depolymerizing factor, was documented and further validated by western blotting. Furthermore, two-way comparisons among the four cell lines, revealed a set of 18 informative differentially expressed proteins., Conclusion: These novel identified proteins provide the impetus for further functional studies to dissect the mechanisms operating in the two distinct pathways of cervical carcinogenesis., (Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
- Published
- 2017
- Full Text
- View/download PDF
43. Proteomics analysis of bladder cancer invasion: Targeting EIF3D for therapeutic intervention.
- Author
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Latosinska A, Mokou M, Makridakis M, Mullen W, Zoidakis J, Lygirou V, Frantzi M, Katafigiotis I, Stravodimos K, Hupe MC, Dobrzynski M, Kolch W, Merseburger AS, Mischak H, Roubelakis MG, and Vlahou A
- Abstract
Patients with advanced bladder cancer have poor outcomes, indicating a need for more efficient therapeutic approaches. This study characterizes proteomic changes underlying bladder cancer invasion aiming for the better understanding of disease pathophysiology and identification of drug targets. High resolution liquid chromatography coupled to tandem mass spectrometry analysis of tissue specimens from patients with non-muscle invasive (NMIBC, stage pTa) and muscle invasive bladder cancer (MIBC, stages pT2+) was conducted. Comparative analysis identified 144 differentially expressed proteins between analyzed groups. These included proteins previously associated with bladder cancer and also additional novel such as PGRMC1, FUCA1, BROX and PSMD12, which were further confirmed by immunohistochemistry. Pathway and interactome analysis predicted strong activation in muscle invasive bladder cancer of pathways associated with protein synthesis e.g. eIF2 and mTOR signaling. Knock-down of eukaryotic translation initiation factor 3 subunit D (EIF3D) (overexpressed in muscle invasive disease) in metastatic T24M bladder cancer cells inhibited cell proliferation, migration, and colony formation in vitro and decreased tumor growth in xenograft models. By contrast, knocking down GTP-binding protein Rheb (which is upstream of EIF3D) recapitulated the effects of EIF3D knockdown in vitro , but not in vivo . Collectively, this study represents a comprehensive analysis of NMIBC and MIBC providing a resource for future studies. The results highlight EIF3D as a potential therapeutic target., Competing Interests: CONFLICTS OF INTEREST Harald Mischak is the founder and co-owner of Mosaiques Diagnostics. Dr. Maria Frantzi is employed by Mosaiques Diagnostics. Dr. Agnieszka Latosinska is also currently employed by Mosaiques Diagnostics.
- Published
- 2017
- Full Text
- View/download PDF
44. Proteomics in cardiovascular disease: recent progress and clinical implication and implementation.
- Author
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Mokou M, Lygirou V, Vlahou A, and Mischak H
- Subjects
- Aging, Arteries metabolism, Arteries pathology, Biomarkers metabolism, Cardiovascular Diseases pathology, Diet, Extracellular Matrix metabolism, Female, Humans, Male, Myocardium metabolism, Plaque, Atherosclerotic metabolism, Plaque, Atherosclerotic pathology, Protein Modification, Translational, Renal Dialysis, Biomarkers analysis, Cardiovascular Diseases metabolism, Proteomics methods
- Abstract
Introduction: Although multiple efforts have been initiated to shed light into the molecular mechanisms underlying cardiovascular disease, it still remains one of the major causes of death worldwide. Proteomic approaches are unequivocally powerful tools that may provide deeper understanding into the molecular mechanisms associated with cardiovascular disease and improve its management. Areas covered: Cardiovascular proteomics is an emerging field and significant progress has been made during the past few years with the aim of defining novel candidate biomarkers and obtaining insight into molecular pathophysiology. To summarize the recent progress in the field, a literature search was conducted in PubMed and Web of Science. As a result, 704 studies from PubMed and 320 studies from Web of Science were retrieved. Findings from original research articles using proteomics technologies for the discovery of biomarkers for cardiovascular disease in human are summarized in this review. Expert commentary: Proteins associated with cardiovascular disease represent pathways in inflammation, wound healing and coagulation, proteolysis and extracellular matrix organization, handling of cholesterol and LDL. Future research in the field should target to increase proteome coverage as well as integrate proteomics with other omics data to facilitate both drug development as well as clinical implementation of findings.
- Published
- 2017
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45. Cervical Cancer Cell Line Secretome Highlights the Roles of Transforming Growth Factor-Beta-Induced Protein ig-h3, Peroxiredoxin-2, and NRF2 on Cervical Carcinogenesis.
- Author
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Kontostathi G, Zoidakis J, Makridakis M, Lygirou V, Mermelekas G, Papadopoulos T, Vougas K, Vlamis-Gardikas A, Drakakis P, Loutradis D, Vlahou A, Anagnou NP, and Pappa KI
- Subjects
- Algorithms, Carcinogenesis, Cell Line, Tumor, Computational Biology, Electrophoresis, Gel, Two-Dimensional, Female, HeLa Cells, Human papillomavirus 16, Humans, Papillomavirus Infections complications, Peptides chemistry, Proteomics, Signal Transduction, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Tandem Mass Spectrometry, Extracellular Matrix Proteins metabolism, Gene Expression Regulation, Neoplastic, NF-E2-Related Factor 2 metabolism, Peroxiredoxins metabolism, Transforming Growth Factor beta metabolism, Uterine Cervical Neoplasms metabolism
- Abstract
Cancer cells acquire unique secretome compositions that contribute to tumor development and metastasis. The aim of our study was to elucidate the biological processes involved in cervical cancer, by performing a proteomic analysis of the secretome from the following informative cervical cell lines: SiHa (HPV16+), HeLa (HPV18+), C33A (HPV-), and HCK1T (normal). Proteins were analyzed by 2D gel electrophoresis coupled to MALDI-TOF-MS. Enrichment of secreted proteins with characteristic profiles for each cell line was followed by the identification of differentially expressed proteins. Particularly, transforming growth factor-beta-induced protein ig-h3 (Beta ig-h3) and peroxiredoxin-2 (PRDX2) overexpression in the secretome of cancer cell lines was detected and confirmed by Western blot. Bioinformatics analysis identified the transcription factor NRF2 as a regulator of differentially expressed proteins in the cervical cancer secretome. NRF2 levels were measured by both Western blot and Multiple Reaction Monitoring (MRM) in the total cell extract of the four cell lines. NRF2 was upregulated in SiHa and C33A compared to HCK1T. In conclusion, the secreted proteins identified in cervical cancer cell lines indicate that aberrant NRF2-mediated oxidative stress response (OSR) is a prominent feature of cervical carcinogenesis., Competing Interests: The authors declare that there is no conflict of interests regarding the publication of this paper.
- Published
- 2017
- Full Text
- View/download PDF
46. Silencing of Profilin-1 suppresses cell adhesion and tumor growth via predicted alterations in integrin and Ca2+ signaling in T24M-based bladder cancer models.
- Author
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Frantzi M, Klimou Z, Makridakis M, Zoidakis J, Latosinska A, Borràs DM, Janssen B, Giannopoulou I, Lygirou V, Lazaris AC, Anagnou NP, Mischak H, Roubelakis MG, and Vlahou A
- Subjects
- Actins metabolism, Animals, Cell Adhesion, Cell Line, Tumor, Cell Movement, Cell Proliferation, Disease Progression, Down-Regulation, Endothelin-1 metabolism, Flow Cytometry, Humans, Immunohistochemistry, Male, Mice, Mice, Inbred NOD, Mice, SCID, Muscle Neoplasms secondary, Profilins genetics, Protein Multimerization, RNA Interference, RNA, Small Interfering metabolism, Urinary Bladder pathology, Wnt Signaling Pathway, Xenograft Model Antitumor Assays, Calcium metabolism, Integrin alpha5beta1 metabolism, Muscle Neoplasms pathology, Profilins metabolism, Urinary Bladder Neoplasms pathology
- Abstract
Bladder cancer (BC) is the second most common malignancy of the genitourinary system, characterized by the highest recurrence rate of all cancers. Treatment options are limited; thus a thorough understanding of the underlying molecular mechanisms is needed to guide the discovery of novel therapeutic targets. Profilins are actin binding proteins with attributed pleiotropic functions to cytoskeletal remodeling, cell adhesion, motility, even transcriptional regulation, not fully characterized yet. Earlier studies from our laboratory revealed that decreased tissue levels of Profilin-1 (PFN1) are correlated with BC progression to muscle invasive disease. Herein, we describe a comprehensive analysis of PFN1 silencing via shRNA, in vitro (by employing T24M cells) and in vivo [(with T24M xenografts in non-obese diabetic severe combined immunodeficient mice (NOD/SCID) mice]. A combination of phenotypic and molecular assays, including migration, proliferation, adhesion assays, flow cytometry and total mRNA sequencing, as well as immunohistochemistry for investigation of selected findings in human specimens were applied. A decrease in BC cell adhesion and tumor growth in vivo following PFN downregulation are observed, likely associated with the concomitant downregulation of Fibronectin receptor, Endothelin-1, and Actin polymerization. A decrease in the levels of multiple key members of the non-canonical Wnt/Ca2+ signaling pathway is also detected following PFN1 suppression, providing the groundwork for future studies, addressing the specific role of PFN1 in Ca2+ signaling, particularly in the muscle invasive disease.
- Published
- 2016
- Full Text
- View/download PDF
47. Analytical Performance of ELISA Assays in Urine: One More Bottleneck towards Biomarker Validation and Clinical Implementation.
- Author
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Chatziharalambous D, Lygirou V, Latosinska A, Stravodimos K, Vlahou A, Jankowski V, and Zoidakis J
- Subjects
- Humans, Reproducibility of Results, Biomarkers, Tumor urine, Enzyme-Linked Immunosorbent Assay, Urinary Bladder Neoplasms urine
- Abstract
ELISA is the main approach for the sensitive quantification of protein biomarkers in body fluids and is currently employed in clinical laboratories for the measurement of clinical markers. As such, it also constitutes the main methodological approach for biomarker validation and further qualification. For the latter, specific assay performance requirements have to be met, as described in respective guidelines of regulatory agencies. Even though many clinical ELISA assays in serum are regularly used, ELISA clinical applications in urine are significantly less. The scope of our study was to evaluate ELISA assay analytical performance in urine for a series of potential biomarkers for bladder cancer, as a first step towards their large scale clinical validation. Seven biomarkers (Secreted protein acidic and rich in cysteine, Survivin, Slit homolog 2 protein, NRC-Interacting Factor 1, Histone 2B, Proteinase-3 and Profilin-1) previously described in the literature as having differential expression in bladder cancer were included in the study. A total of 11 commercially available ELISA tests for these markers were tested by standard curve analysis, assay reproducibility, linearity and spiking experiments. The results show disappointing performance with coefficients of variation>20% for the vast majority of the tests performed. Only 3 assays (for Secreted protein acidic and rich in cysteine, Survivin and Slit homolog 2 protein) passed the accuracy thresholds and were found suitable for further application in marker quantification. These results collectively reflect the difficulties in developing urine-based ELISA assays of sufficient analytical performance for clinical application, presumably attributed to the urine matrix itself and/or presence of markers in various isoforms.
- Published
- 2016
- Full Text
- View/download PDF
48. Effect of Heme Oxygenase-1 Deficiency on Glomerular Proteomics.
- Author
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Detsika MG, Lygirou V, Frantzis V, Zoidakis J, Atsaves V, Poulaki E, Gakiopoulou H, Vlahou A, and Lianos EA
- Subjects
- Anemia, Hemolytic pathology, Animals, Growth Disorders pathology, Heme Oxygenase-1 metabolism, Iron Metabolism Disorders pathology, Kidney Glomerulus pathology, Male, Proteome, Rats, Sprague-Dawley, Anemia, Hemolytic metabolism, Growth Disorders metabolism, Heme Oxygenase-1 deficiency, Iron Metabolism Disorders metabolism, Kidney Glomerulus metabolism
- Abstract
Background: The cytoprotective effect of heme oxygenase (HO)-1 in various forms of renal glomerular injury is established. However, little is known on the role of HO-1 in preserving glomerular structural/functional integrity in the absence of injury. The present study addressed this question in HO-1-deficient rats., Methods: HO-1-deficient rats were generated using zinc finger nuclease-mediated HO-1 gene (Hmox1) disruption and studied. Glomeruli were isolated from HO-1-deficient (Hmox1-/-) rats and their wild type (WT) littermates for proteomic analysis., Results: Glomerular lesions were characterized and differentially expressed proteins important for preserving integrity of the glomerular filtration barrier were identified. HO-1-deficient (Hmox1-/-) rats developed albuminuria with decreased glomerular filtration rate. In albuminuric rats, there were lesions resembling focal and segmental glomerulosclerosis (FSGS). Western blot analysis of the integral slit diaphragm proteins, nephrin and podocin revealed a significant decrease in nephrin, with no change in podocin. Proteomic analysis of glomerular protein lysates from Hmox1-/- and WT rats revealed differential expression of proteins previously linked with FSGS pathogenesis. Specifically, α-actinin-4, actin related protein 3, cytokeratins and novel candidates including transgelin-2 and lamins. Bioinformatic analysis predicted the upregulation of pathways implicated in platelet aggregation and fibrin clot formation., Conclusion: HO-1 is a putative regulator of proteins important in preserving glomerular structural stability and integrity, and in minimizing the activity of proinflammatory pathways., (© 2016 S. Karger AG, Basel.)
- Published
- 2016
- Full Text
- View/download PDF
49. Biological sample collection for clinical proteomics: existing SOPs.
- Author
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Lygirou V, Makridakis M, and Vlahou A
- Subjects
- Body Fluids metabolism, Humans, Proteomics, Specimen Handling methods
- Abstract
Proteomic study of clinical samples aims at the better understanding of physiological and pathological conditions, as well as the discovery of diagnostic and prognostic markers for the latter. Quantitative and/or qualitative variations of body fluid proteome may reflect health- or disease-associated events connected to the adjacent or distant body regions of the fluid production/secretion/excretion and/or systemic reactions to the presence of disease. Sample collection and preparation is a critical step in order to obtain useful and valid information in clinical proteomics analysis. In this chapter, we present the current protocols and guidelines for human body fluid collection and storage, prior to proteomic analysis. A variety of body fluids that are currently being used in proteomic analysis and have potential interest in clinical practice are presented including blood plasma and serum, urine, cerebrospinal fluid, cerumen, nasal secretions, saliva, tears, breast milk, bronchoalveolar fluid, nipple aspirate fluid, amniotic fluid, bile, cervico-vaginal fluid, and seminal plasma. With no doubt these body fluids differ in the extent of their application in clinical proteomics investigations, hence in some cases the presented SOPs are established following more extensive testing (e.g., plasma, serum, urine, CSF) than others (nasal secretions, saliva, tears, breast milk, bronchoalveolar fluid, nipple aspirate fluid, amniotic fluid, bile, cervico-vaginal fluid, and seminal plasma). However, even in these latter cases, the presented protocols were reported by at least two independent groups according to the literature. We hope they can thus serve as a reliable guide for sample collection based on our current knowledge in the field and excellent starting points for proteomics investigators. It should also be pointed that variations to these protocols exist and their further refinement in the future is foreseen following the evolution of the proteomics technologies.
- Published
- 2015
- Full Text
- View/download PDF
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