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On February 23, 2018, PubMed Central Canada (PMC Canada) will be taken offline permanently. No author manuscripts will be deleted, and the approximately 2,900 manuscripts authored by Canadian Institutes of Health Research (CIHR)-funded researchers currently in the archive will be copied to the National Research Council’s (NRC) Digital Repository over the coming months. These manuscripts along with all other content will also remain publicly searchable on PubMed Central (US) and Europe PubMed Central, meaning such manuscripts will continue to be compliant with the Tri-Agency Open Access Policy on Publications.

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author:("Amri, hakim")
1.  Study of Clinical Survival and Gene Expression in a Sample of Pancreatic Ductal Adenocarcinoma by Parsimony Phylogenetic Analysis 
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the rapidly growing forms of pancreatic cancer with a poor prognosis and less than 5% 5-year survival rate. In this study, we characterized the genetic signatures and signaling pathways related to survival from PDAC, using a parsimony phylogenetic algorithm. We applied the parsimony phylogenetic algorithm to analyze the publicly available whole-genome in silico array analysis of a gene expression data set in 25 early-stage human PDAC specimens. We explain here that the parsimony phylogenetics is an evolutionary analytical method that offers important promise to uncover clonal (driver) and nonclonal (passenger) aberrations in complex diseases. In our analysis, parsimony and statistical analyses did not identify significant correlations between survival times and gene expression values. Thus, the survival rankings did not appear to be significantly different between patients for any specific gene (p > 0.05). Also, we did not find correlation between gene expression data and tumor stage in the present data set. While the present analysis was unable to identify in this relatively small sample of patients a molecular signature associated with pancreatic cancer prognosis, we suggest that future research and analyses with the parsimony phylogenetic algorithm in larger patient samples are worthwhile, given the devastating nature of pancreatic cancer and its early diagnosis, and the need for novel data analytic approaches. The future research practices might want to place greater emphasis on phylogenetics as one of the analytical paradigms, as our findings presented here are on the cusp of this shift, especially in the current era of Big Data and innovation policies advocating for greater data sharing and reanalysis.
doi:10.1089/omi.2016.0059
PMCID: PMC4968342  PMID: 27428255
2.  World Congress Integrative Medicine & Health 2017: Part one 
Brinkhaus, Benno | Falkenberg, Torkel | Haramati, Aviad | Willich, Stefan N. | Briggs, Josephine P. | Willcox, Merlin | Linde, Klaus | Theorell, Töres | Wong, Lisa M. | Dusek, Jeffrey | Wu, Darong | Eisenberg, David | Haramati, Aviad | Berger, Bettina | Kemper, Kathi | Stock-Schröer, Beate | Sützl-Klein, Hedda | Ferreri, Rosaria | Kaplan, Gary | Matthes, Harald | Rotter, Gabriele | Schiff, Elad | Arnon, Zahi | Hahn, Eckhard | Luberto, Christina M. | Martin, David | Schwarz, Silke | Tauschel, Diethard | Flower, Andrew | Gramminger, Harsha | Gupta, Hedwig H. | Gupta, S. N. | Kerckhoff, Annette | Kessler, Christian S. | Michalsen, Andreas | Kessler, Christian S. | Kim, Eun S. | Jang, Eun H. | Kim, Rana | Jan, Sae B. | Mittwede, Martin | Mohme, Wiebke | Ben-Arye, Eran | Bonucci, Massimo | Saad, Bashar | Breitkreuz, Thomas | Rossi, Elio | Kebudi, Rejin | Daher, Michel | Razaq, Samaher | Gafer, Nahla | Nimri, Omar | Hablas, Mohamed | Kienle, Gunver Sophia | Samuels, Noah | Silbermann, Michael | Bandelin, Lena | Lang, Anna-Lena | Wartner, Eva | Holtermann, Christoph | Binstock, Maxwell | Riebau, Robert | Mujkanovic, Edin | Cramer, Holger | Lauche, Romy | Michalsen, Andres | Ward, Lesley | Cramer, Holger | Irnich, Dominik | Stör, Wolfram | Burnstock, Geoffrey | Schaible, Hans-Georg | Ots, Thomas | Langhorst, Jost | Lauche, Romy | Sundberg, Tobias | Falkenberg, Torkel | Amarell, Catherina | Amarell, Catherina | Anheyer, Melanie | Eckert, Marion | Eckert, Marion | Ogal, Mercedes | Eckert, Marion | Amarell, Catherina | Schönauer, Annette | Reisenberger, Birgit | Brand, Bernhard | Anheyer, Dennis | Dobos, Gustav | Kroez, Matthias | Martin, David | Matthes, Harald | Ammendola, Aldo | Mao, Jun J. | Witt, Claudia | Yang, Yufei | Dobos, Gustav | Oritz, Miriam | Horneber, Markus | Voiß, Petra | Reisenberger, Birgit | von Rosenstiel, Alexandra | Eckert, Marion | Ogal, Mercedes | Amarell, Catharina | Anheyer, Melanie | Schad, Friedemann | Schläppi, Marc | Kröz, Matthias | Büssing, Arndt | Bar-Sela, Gil | Matthes, Harald | Schiff, Elad | Ben-Arye, Eran | Arnon, Zahi | Avshalomov, David | Attias, Samuel | Schönauer, Annette | Haramati, Aviad | Witt, Claudia | Brinkhaus, Benno | Cotton, Sian | Jong, Miek | Jong, Mats | Scheffer, Christian | Haramati, Aviad | Tauschel, Diethard | Edelhäuser, Friedrich | AlBedah, Abdullah | Lee, Myeong Soo | Khalil, Mohamed | Ogawa, Keiko | Motoo, Yoshiharu | Arimitsu, Junsuke | Ogawa, Masao | Shimizu, Genki | Stange, Rainer | Kraft, Karin | Kuchta, Kenny | Watanabe, Kenji | Bonin, D | Büssing, Arndt | Gruber, Harald | Koch, Sabine | Gruber, Harald | Pohlmann, Urs | Caldwell, Christine | Krantz, Barbara | Kortum, Ria | Martin, Lily | Wieland, Lisa S. | Kligler, Ben | Gould-Fogerite, Susan | Zhang, Yuqing | Wieland, Lisa S. | Riva, John J. | Lumpkin, Michael | Ratner, Emily | Ping, Liu | Jian, Pei | Hamme, Gesa-Meyer | Mao, Xiaosong | Chouping, Han | Schröder, Sven | Hummelsberger, Josef | Wullinger, Michael | Brodzky, Marc | Zalpour, Christoff | Langley, Julia | Weber, Wendy | Mudd, Lanay M. | Wayne, Peter | Witt, Clauda | Weidenhammer, Wolfgang | Fønnebø, Vinjar | Boon, Heather | Steel, Amie | Bugarcic, Andrea | Rangitakatu, Melisa | Steel, Amie | Adams, Jon | Sibbritt, David | Wardle, Jon | Leach, Matthew | Schloss, Janet | Dieze, Helene | Boon, Heather | Ijaz, Nadine | Willcox, Merlin | Heinrich, Michael | Lewith, George | Flower, Andrew | Graz, Bertrand | Adam, Daniela | Grabenhenrich, Linus | Ortiz, Miriam | Binting, Sylvia | Reinhold, Thomas | Brinkhaus, Benno | Andermo, Susanne | Sundberg, Tobias | Falkenberg, Torkel | Nordberg, Johanna Hök | Arman, Maria | Bhasin, Manoj | Fan, Xueyi | Libermann, Towia | Fricchione, Gregory | Denninger, John | Benson, Herbert | Berger, Bettina | Stange, Rainer | Michalsen, Andreas | Martin, David D. | Boers, Inge | Vlieger, Arine | Jong, Miek | Brinkhaus, Benno | Teut, Michael | Ullmann, Alexander | Ortiz, Miriam | Rotter, Gabriele | Binting, Sylvia | Lotz, Fabian | Roll, Stephanie | Canella, Claudia | Mikolasek, Michael | Rostock, Matthias | Beyer, Jörg | Guckenberger, Matthias | Jenewein, Josef | Linka, Esther | Six, Claudia | Stoll, Sarah | Stupp, Roger | Witt, Claudia M. | Chuang, Elisabeth | Kligler, Ben | McKee, Melissa D. | Cramer, Holger | Lauche, Romy | Klose, Petra | Lange, Silke | Langhorst, Jost | Dobos, Gustav | Chung, Vincent C. H. | Wong, Hoi L. C. | Wu, Xin Y. | Wen, Grace Y. G. | Ho, Robin S. T. | Ching, Jessica Y. L. | Wu, Justin C. Y. | Coakley, Amanda | Flanagan, Jane | Annese, Christine | Empoliti, Joanne | Gao, Zishan | Liu, Xugang | Yu, Shuguang | Yan, Xianzhong | Liang, Fanrong | Hohmann, Christoph D. | Steckhan, Nico | Ostermann, Thomas | Paetow, Arion | Hoff, Evelyn | Michalsen, Andreas | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Hu, Xiao-Yang | Wu, Ruo-Han | Logue, Martin | Blonde, Clara | Lai, Lily Y. | Stuart, Beth | Flower, Andrew | Fei, Yu-Tong | Moore, Michael | Liu, Jian-Ping | Lewith, George | Jeitler, Michael | Zillgen, Hannah | Högl, Manuel | Steckhan, Nico | Stöckigt, Barbara | Seifert, Georg | Michalsen, Andreas | Kessler, Christian | Khadivzadeh, Talat | Bashtian, Maryam Hassanzadeh | Aval, Shapour Badiee | Esmaily, Habibollah | Kim, Jihye | Kim, Keun H. | Klocke, Carina | Joos, Stefanie | Koshak, Abdulrahman | Wie, Li | Koshak, Emad | Wali, Siraj | Alamoudi, Omer | Demerdash, Abdulrahman | Qutub, Majdy | Pushparaj, Peter | Heinrich, Michael | Kruse, Sigrid | Fischer, Isabell | Tremel, Nadine | Rosenecker, Joseph | Leung, Brenda | Takeda, Wendy | Liang, Ning | Feng, Xue | Liu, Jian-ping | Cao, Hui-juan | Luberto, Christina M. | Shinday, Nina | Philpotts, Lisa | Park, Elyse | Fricchione, Gregory L. | Yeh, Gloria | Munk, Niki | Zakeresfahani, Arash | Foote, Trevor R. | Ralston, Rick | Boulanger, Karen | Özbe, Dominik | Gräßel, Elmar | Luttenberger, Katharina | Pendergrass, Anna | Pach, Daniel | Bellmann-Strobl, Judit | Chang, Yinhui | Pasura, Laura | Liu, Bin | Jäger, Sven F. | Loerch, Ronny | Jin, Li | Brinkhaus, Benno | Ortiz, Miriam | Reinhold, Thomas | Roll, Stephanie | Binting, Sylvia | Icke, Katja | Shi, Xuemin | Paul, Friedemann | Witt, Claudia M. | Rütz, Michaela | Lynen, Andreas | Schömitz, Meike | Vahle, Maik | Salomon, Nir | Lang, Alon | Lahat, Adi | Kopylov, Uri | Ben-Horin, Shomron | Har-Noi, Ofir | Avidan, Benjamin | Elyakim, Rami | Gamus, Dorit | NG, Siew | Chang, Jessica | Wu, Justin | Kaimiklotis, John | Schumann, Dania | Buttó, Ludovica | Langhorst, Jost | Dobos, Gustav | Haller, Dirk | Cramer, Holger | Smith, Caroline | de Lacey, Sheryl | Chapman, Michael | Ratcliffe, Julie | Johnson, Neil | Lyttleton, Jane | Boothroyd, Clare | Fahey, Paul | Tjaden, Bram | van Vliet, Marja | van Wietmarschen, Herman | Jong, Miek | Tröger, Wilfried | Vuolanto, Pia | Aarva, Paulina | Sorsa, Minna | Helin, Kaija | Wenzel, Claudia | Zoderer, Iris | Pammer, Patricia | Simon, Patrick | Tucek, Gerhard | Wode, Kathrin | Henriksson, Roger | Sharp, Lena | Stoltenberg, Anna | Nordberg, Johanna Hök | Xiao-ying, Yang | Wang, Li-qiong | Li, Jin-gen | Liang, Ning | Wang, Ying | Liu, Jian-ping | Balneaves, Lynda | Capler, Rielle | Bocci, Chiara | Guffi, Marta | Paolini, Marina | Meaglia, Ilaria | Porcu, Patrizia | Ivaldi, Giovanni B. | Dragan, Simona | Bucuras, Petru | Pah, Ana M. | Badalica-Petrescu, Marius | Buleu, Florina | Hogea-Stoichescu, Gheorghe | Christodorescu, Ruxandra | Kao, Lan | Cho, Yumin | Klafke, Nadja | Mahler, Cornelia | von Hagens, Cornelia | Uhlmann, Lorenz | Bentner, Martina | Schneeweiss, Andreas | Mueller, Andreas | Szecsenyi, Joachim | Joos, Stefanie | Neri, Isabella | Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Rossi, Elio | Baccetti, Sonia | Firenzuoli, Fabio | Monechi, Maria V. | Di Stefano, Mariella | Amunni, Gianni | Wong, Wendy | Chen, Bingzhong | Wu, Justin | Amri, Hakima | Haramati, Aviad | Kotlyanskaya, Lucy | Anderson, Belinda | Evans, Roni | Kligler, Ben | Marantz, Paul | Bradley, Ryan | Booth-LaForce, Cathryn | Zwickey, Heather | Kligler, Benjamin | Brooks, Audrey | Kreitzer, Mary J. | Lebensohn, Patricia | Goldblatt, Elisabeth | Esmel-Esmel, Neus | Jiménez-Herrera, Maria | Ijaz, Nadine | Boon, Heather | Jocham, Alexandra | Stock-Schröer, Beate | Berberat, Pascal O. | Schneider, Antonius | Linde, Klaus | Masetti, Morgana | Murakozy, Henriette | Van Vliet, Marja | Jong, Mats | Jong, Miek | Agdal, Rita | Atarzadeh, Fatemeh | Jaladat, Amir M. | Hoseini, Leila | Amini, Fatemeh | Bai, Chen | Liu, Tiegang | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Daneshfard, Babak | Nimrouzi, Majid | Tafazoli, Vahid | Alorizi, Seyed M. Emami | Saghebi, Seyed A. | Fattahi, Mohammad R. | Salehi, Alireza | Rezaeizadeh, Hossein | Zarshenas, Mohammad M. | Nimrouzi, Majid | Fox, Kealoha | Hughes, John | Kostanjsek, Nenad | Espinosa, Stéphane | Lewith, George | Fisher, Peter | Latif, Abdul | Lefeber, Donald | Paske, William | Öztürk, Ali Ö. | Öztürk, Gizemnur | Boers, Inge | Tissing, Wim | Naafs, Marianne | Busch, Martine | Jong, Miek | Daneshfard, Babak | Sanaye, Mohammad R. | Dräger, Kilian | Fisher, Peter | Kreitzer, Mary J. | Evans, Roni | Leininger, Brent | Shafto, Kate | Breen, Jenny | Sanaye, Mohammad R. | Daneshfard, Babak | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | White, Shelley | Wiesener, Solveig | Salamonsen, Anita | Stub, Trine | Fønnebø, Vinjar | Abanades, Sergio | Blanco, Mar | Masllorens, Laia | Sala, Roser | Al-Ahnoumy, Shafekah | Han, Dongwoon | He, Luzhu | Kim, Ha Yun | In Choi, Da | Alræk, Terje | Stub, Trine | Kristoffersen, Agnete | von Sceidt, Christel | Michalsen, Andreas | Bruset, Stig | Musial, Frauke | Anheyer, Dennis | Cramer, Holger | Lauche, Romy | Saha, Felix J. | Dobos, Gustav | Anheyer, Dennis | Haller, Heidemarie | Lauche, Romy | Dobos, Gustav | Cramer, Holger | Azizi, Hoda | Khadem, Nayereh | Hassanzadeh, Malihe | Estiri, Nazanin | Azizi, Hamideh | Tavassoli, Fatemeh | Lotfalizadeh, Marzieh | Zabihi, Reza | Esmaily, Habibollah | Azizi, Hoda | Shabestari, Mahmoud Mohammadzadeh | Paeizi, Reza | Azari, Masoumeh Alvandi | Bahrami-Taghanaki, Hamidreza | Zabihi, Reza | Azizi, Hamideh | Esmaily, Habibollah | Baars, Erik | De Bruin, Anja | Ponstein, Anne | Baccetti, Sonia | Di Stefano, Mariella | Rossi, Elio | Firenzuoli, Fabio | Segantini, Sergio | Monechi, Maria Valeria | Voller, Fabio | Barth, Jürgen | Kern, Alexandra | Lüthi, Sebastian | Witt, Claudia | Barth, Jürgen | Zieger, Anja | Otto, Fabius | Witt, Claudia | Beccia, Ariel | Dunlap, Corina | Courneene, Brendan | Bedregal, Paula | Passi, Alvaro | Rodríguez, Alfredo | Chang, Mayling | Gutiérrez, Soledad | Beissner, Florian | Beissner, Florian | Preibisch, Christine | Schweizer-Arau, Annemarie | Popovici, Roxana | Meissner, Karin | Beljanski, Sylvie | Belland, Laura | Rivera-Reyes, Laura | Hwang, Ula | Berger, Bettina | Sethe, Dominik | Hilgard, Dörte | Heusser, Peter | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Al-Abbadey, Miznah | Bradbury, Katherine | Carnes, Dawn | Dimitrov, Borislav | Fawkes, Carol | Foster, Jo | MacPherson, Hugh | Roberts, Lisa | Yardley, Lucy | Lewith, George | Bishop, Felicity | Holmes, Michelle | Lewith, George | Yardley, Lucy | Little, Paul | Cooper, Cyrus | Bogani, Patrizia | Maggini, Valentina | Gallo, Eugenia | Miceli, Elisangela | Biffi, Sauro | Mengoni, Alessio | Fani, Renato | Firenzuoli, Fabio | Brands-Guendling, Nadine | Guendling, Peter W. | Bronfort, Gert | Evans, Roni | Haas, Mitch | Leininger, Brent | Schulz, Craig | Bu, Xiangwei | Wang, J. | Fang, T. | Shen, Z. | He, Y. | Zhang, X. | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Büssing, Arndt | Baumann, Klaus | Frick, Eckhard | Jacobs, Christoph | Büssing, Arndt | Grünther, Ralph-Achim | Lötzke, Désirée | Büssing, Arndt | Jung, Sonny | Lötzke, Désirée | Recchia, Daniela R. | Robens, Sibylle | Ostermann, Thomas | Berger, Bettina | Stankewitz, Josephin | Kröz, Matthias | Jeitler, Mika | Kessler, Christian | Michalsen, Andreas | Cheon, Chunhoo | Jang, Bo H. | Ko, Seong G. | Huang, Ching W. | Sasaki, Yui | Ko, Youme | Cheshire, Anna | Ridge, Damien | Hughes, John | Peters, David | Panagioti, Maria | Simon, Chantal | Lewith, George | Cho, Hyun J. | Han, Dongwoon | Choi, Soo J. | Jung, Young S. | Im, Hyea B | Cooley, Kieran | Tummon-Simmons, Laura | Cotton, Sian | Luberto, Christina M. | Wasson, Rachel | Kraemer, Kristen | Sears, Richard | Hueber, Carly | Derk, Gwendolyn | Lill, JR | An, Ruopeng | Steinberg, Lois | Rodriguez, Lourdes Diaz | la Fuente, Francisca García-de | De la Vega, Miguel | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Cantarero-Villanueva, Irene | Rodriguez, Lourdes Diaz | García-De la Fuente, Francisca | Jiménez-Guerrero, Fanny | Vargas-Román, Keyla | Fernández-Ruiz, Jonatan | Galiano-Castillo, Noelia | Diaz-Saez, Gualberto | Torres-Jimenez, José I. | Garcia-Gomez, Olga | Hortal-Muñoz, Luis | Diaz-Diez, Camino | Dicen, Demijon | Diezel, Helene | Adams, Jon | Steel, Amie | Wardle, Jon | Diezel, Helene | Steel, Amie | Frawley, Jane | Wardle, Jon | Broom, Alex | Adams, Jon | Dong, Fei | Yu, He | Liu, Tiegang | Ma, Xueyan | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Gu, Xiaohong | Dong, Fei | Yu, He | Wu, Liqun | Liu, Tiegang | Ma, Xueyan | Ma, Jiaju | Yan, Liyi | Wan, Yuxiang | Zheng, Zian | Zhen, Jianhua | Gu, Xiaohong | Dubois, Julie | Rodondi, Pierre-Yves | Edelhäuser, Friedrich | Schwartze, Sophia | Trapp, Barbara | Cysarz, Dirk
doi:10.1186/s12906-017-1782-4
PMCID: PMC5498855
3.  World Congress Integrative Medicine & Health 2017: part three 
Ortiz, Miriam | Schnabel, Katharina | Teut, Michael | Rotter, Gabriele | Binting, Sylvia | Cree, Margit | Lotz, Fabian | Suhr, Ralf | Brinkhaus, Benno | Parvizi, Mohammad M. | Handjani, Farhad | Zarshenas, Mohammad M. | Moein, Mahmood R. | Nimrouzi, Majid | Hatam, Gholamreza | Hasanzadeh, Jafar | Hamidizadeh, Nasrin | Parvizi, Mohammad M. | Heydari, Mojtaba | Namazi, Mohammad R. | Parvizi, Zahra | Pasalar, Mehdi | Mosaffa-Jahromi, Maryam | Bagheri-Lankarani, Kamran | Afsharypuor, Suleiman | Tamaddon, Ali M. | Ostovar, Mohadeseh | Peloni, Giuseppe | Bolliger, Ingo | Faria, Rui M. Da Cunha | Quadri, Pierluigi | Sanzeni, Wilma | Zemp, Damiano | Risvoll, Hilde | Giverhaug, Trude | Halvorsen, Kjell H. | Waaseth, Marit | Musial, Frauke | Rossi, Elio | Baccetti, Sonia | Picchi, Marco | Conti, Tommaso | Firenzuoli, Fabio | Guido, Carmelo | Bosco, Filippo | Guido, Carmelo | Rossi, Elio | Panozzo, Marialessandra | Picchi, Marco | Cervino, Chiara | Nurra, Linda | Rossi, Elio | Picchi, Marco | Firenzuoli, Fabio | Traversi, Antonella | Vuono, Katia | Sabatini, Federica | Bellandi, Tommaso | Rutert, Britta | Eggert, Angelika | Seifert, Georg | Stritter, Wiebke | Holmberg, Christine | Längler, Alfred | Salamonsen, Anita | Wiesener, Solveig | Schad, Friedemann | Steele, Megan | Kröz, Matthias | Matthes, Harald | Herbstreit, Cornelia | Thronicke, Anja | Schlingensiepen, Irene | von Schoen-Angerer, Tido | Schneider, Romy | Waeber, Livia | Vagedes, Jan | Kaczala, Gregor | Pharisa, Cosette | Wildhaber, Johannes | Huber, Benedikt | Sidorov, Pavel | Sovershaeva, Evgeniya | Simões-Wüst, Ana P. | Nietlispach, Anna | Mennet, Mónica | Schnelle, Martin | von Mandach, Ursula | Wang, Xia | Woo, Hye L. | Lee, Jin M. | Wu, Yuhao | Cho, Yumin | Yun, Younghee | Kim, Hyunho | Jung, Wonmo | Jang, Bo-Hyung | Ziea, Eric | Hui, Henny | Li, Mia | Tsui, Dora | Lam, Christine | Hsieh, Joyce | Chan, Edith | Balneaves, Lynda | Burnside, Sandra | Doyle, Ethel | Dorazio, Shelley | Chan, Pak K. | Bhagra, Anjali | Chen, Po-Hsu | Chung, Vincent C. H. | Wu, Justin C. Y. | Lin, Zhi X. | Wong, Wendy | Wu, Xin Y. | Ho, Robin S. T. | Wong, Charlene H. L. | Chan, Lily | Ziea, Eric T. C. | Elder, William | Cardarelli, Roberto | Kaspar, Cornelia | Kempenich, Robert | Kopferschmitt, Jacques | Marinko, Zulj | Damir, Sebo | Vcev, Aleksandar | Monezi, Ricardo | Ruggerini, Eny Márcia | Fuchigami, Ivna M. | Mazini, Ana C. Moreno | Monezi, Ricardo | Oliveira, Maria Waldenez | Papuga, Petar | Schloss, Janet | Steel, Amie | Jacobsen, Márcia da Silva | Monezi, Ricardo | Jacobsen, Miranda Rodrigo | Mangini, Maria T. | Trapani, Gianfranco | Di Giampietro, Tiziana | Zanino, Luisella | Ciullo, Luigi | Lanaro, Diego | Cerritelli, Francesco | Macrì, Francesco | Tsai, Andre | Lin, Chin | Wu, Tu-Hsing | D’Alessandro, Eduardo | Watts, Sam | Zhang, Ying | Wu, Xufang | Li, Xun | Fei, Yutong | Liu, Jianping | Zhao, Nanqi | Jia, Liyan | Yan, Xiaoyi | Zhen, Fei | Liu, Zhaolan | Liu, Jianping | Ahn, Jinhyang | Yun, Younghee | AlEidi, Sulaiman | Mohamed, Ashry Gad | Al-Beda, Abdullah M. | Abutalib, Raid A. | Khalil, Mohemmed K. M. | Amri, Hakima | Badekila, Sathyanarayana | Behmanesh, Elham | Mozaffarpour, Seyyedali | Behmanesh, Elham | Mozaffarpour, Seyyedali | Behmanesh, Elham | Shirooye, Pantea | Meybodi, Razie N. | Mokaberinejad, Roshanak | Tansaz, Mojgan | Mozaffarpour, Seyyedali | Chung, Vincent C. H. | Wu, Xin Y. | Wu, Justin C. Y. | Daneshfard, Babak | Hosseinkhani, Ayda | Tafazoli, Vahid | Jaladat, Amir M. | Jaladat, Amir M. | Sadeghi, Hasan | Jia, Liyan | Zhao, Nanqi | Yan, Xiaoyi | Zhou, Li | Zhao, Meng | Li, Weiwei | Liu, Jianping | Liu, Zhaolan | Jia, Liyan | Zhao, Nanqi | Yan, Xiaoyi | Zhou, Li | Zhao, Meng | Li, Weiwei | Liu, Jianping | Liu, Zhaolan | Larsen, Anette L. | Salamonsen, Anita | Kristoffersen, Agnete E. | Hamran, Torunn | Evjen, Bjørg | Stub, Trine | Li, Meiling | Cai, Jianxiong | Lu, Taoying | Yin, Lingjia | Wu, Darong | Wang, Lixin | Liew, Siaw M. | Liu, Tiegang | Bai, Chen | Zheng, Zian | Wan, Yuxiang | Xu, Jingnan | Wang, Xuan | Yu, He | Gu, Xiaohong | Liu, Zhaolan | Yan, Xiaoyi | Jia, Liyan | Zhao, Nanqi | Yang, Guoyan | Liu, Jianping | Mozaffarpour, Seyyedali | Behmanesh, Elham | Nimrouzi, Majid | Tafazoli, Vahid | Daneshfard, Babak | Ostrowski, Deja | Fox, Kealoha | Pasalar, Mehdi | Tabatabei, Fatemeh | Amini, Fatemeh | Sathasivampillai, Saravanan | Rajamanoharan, Pholtan | Munday, Michael | Heinrich, Michael | Scherrer, Yvonne M. | Heinrich, Michael | Szuter, Carolyn | Amini, Fatemeh | Tabatabaei, Fatemeh | Tavakoli, Ali | Tavakoli, Fatemeh | Pasalar, Mehdi | rostami, Mahsa | Torri, Maria C. | Szuter, Carolyn | Walach, Harald | Warner, Faith | Majumdar, Anne | Serasingh, Palitha | Yan, Xiaoyi | Jia, Liyan | Zhao, Nanqi | Liu, Zhaolan | Liu, Jianping | Zhao, Nanqi | Zhen, Fei | Jia, Liyan | Yan, Xiaoyi | Liu, Zhaolan | Liu, Jianping | Abbing, Annemarie | Ponstein, Anne | Baars, Erik | Croke, Sarah | Hanser, Suzanne | Heckel, Viola | Krüerke, Daniel | Simões-Wüst, Ana P. | Weiss, Sebastian | Metzner, Susanne | Lee, Jang W. | Hyun, Min K. | Masetti, Morgana | Oepen, Renate | Gruber, Harald | Heusser, Peter | Pelz, Holger | Perlitz, Volker | Ponstein, Anne | Abbing, Annemarie | Baars, Erik | Robinson, Nicola | Ronan, Patricia | Mian, Awais | Madge, Su | Lorenc, Ava | Agent, Penny | Carr, Siobhan | Ronan, Patricia | Robinson, Nicola | Carr, Siobhan | Mian, Awais | Lorenc, Ava | Agent, Penny | Madge, Su | Winnubst, Monica E. | Monezi, Ricardo | Abolghasemi, Jafar | Heydari, Mojtaba | Baccetti, Sonia | Rossi, Elio | Fedi, Paolo | Di Stefano, Mariella | Belvedere, Katia | Baccetti, Sonia | Rossi, Elio | Firenzuoli, Fabio | Di Stefano, Mariella | Belvedere, Katia | Beaven, Katherine | Rose, Anita | Florschutz, Gerhard | Phil, Nicola Brough | Parsons, Helen | Stewart-Brown, Sarah | Burke, Katherine | Busch, Martine | Heyning, Fenna | Smit, Jan | Jeekel, Hans | de Goeij, Hans | Guido, Paulo Caceres | Barraza, Norma | Balbarrey, Ziomara | Ribas, Alejandra | Jimenez, Beatriz | Iachino, Claudia | Quattrone, Fabiana | Gaioli, Marisa | Dell’Orso, Marta | Villanueva, Silvia | Rocha, Carmen | Macchi, Adriana | Cai, Jianxiong | Chen, Lina | Wu, Darong | Wang, Sicheng | Choi, Eunji | Go, Namgyeong | Lee, Yongho | Dahal, Gokarna | Frauenknecht, Xaver | Gerhardt, Heike | Galanti, Mónica | Cerda, Carmen J. | Galanti, Mónica | Galanti, Mónica | Heckersdorf, Daniela Navarrete | Jorquera, Héctor | Saldivia, María L. Alcázar | Jakubonienė, Daiva | McEwen, Bradley | Melo, Francislete | Fontana, Fernanda Mulinari | Valle, Ana C. Viana | Neres, Maria T. Borges | Mohagheghzadeh, Abolali | Zohalinezhad, Mohammad E. | Njaradi, Olja | Dunjic, Momir | Njaradi, Olja | Dunjic, Momir | Ostrowski, Deja | Fox, Kealoha | Pokladnikova, Jitka | Selke-Krulichova, Iva | Seo, Jinsoon | Jang, Hyunchul | Simões-Wüst, Ana P. | Moltó-Puigmartí, Carolina | van Dongen, Martien | Dagnelie, Pieter | Thijs, Carel | Tihanyi, Eva | Hegyi, Gabriella | Zhang, Ying | Li, Xun | Fei, Yutong | Liu, Jianping | Zhang, Ying | Liu, Jianping | Tong, Xiaolin
doi:10.1186/s12906-017-1784-2
PMCID: PMC5499100
4.  Computational Tools for Parsimony Phylogenetic Analysis of Omics Data 
Abstract
High-throughput assays from genomics, proteomics, metabolomics, and next generation sequencing produce massive omics datasets that are challenging to analyze in biological or clinical contexts. Thus far, there is no publicly available program for converting quantitative omics data into input formats to be used in off-the-shelf robust phylogenetic programs. To the best of our knowledge, this is the first report on creation of two Windows-based programs, OmicsTract and SynpExtractor, to address this gap. We note, as a way of introduction and development of these programs, that one particularly useful bioinformatics inferential modeling is the phylogenetic cladogram. Cladograms are multidimensional tools that show the relatedness between subgroups of healthy and diseased individuals and the latter's shared aberrations; they also reveal some characteristics of a disease that would not otherwise be apparent by other analytical methods. The OmicsTract and SynpExtractor were written for the respective tasks of (1) accommodating advanced phylogenetic parsimony analysis (through standard programs of MIX [from PHYLIP] and TNT), and (2) extracting shared aberrations at the cladogram nodes. OmicsTract converts comma-delimited data tables through assigning each data point into a binary value (“0” for normal states and “1” for abnormal states) then outputs the converted data tables into the proper input file formats for MIX or with embedded commands for TNT. SynapExtractor uses outfiles from MIX and TNT to extract the shared aberrations of each node of the cladogram, matching them with identifying labels from the dataset and exporting them into a comma-delimited file. Labels may be gene identifiers in gene-expression datasets or m/z values in mass spectrometry datasets. By automating these steps, OmicsTract and SynpExtractor offer a veritable opportunity for rapid and standardized phylogenetic analyses of omics data; their model can also be extended to next generation sequencing (NGS) data. We make OmicsTract and SynpExtractor publicly and freely available for non-commercial use in order to strengthen and build capacity for the phylogenetic paradigm of omics analysis.
doi:10.1089/omi.2015.0018
PMCID: PMC4529085  PMID: 26230532
5.  China's Other Medical Systems: Recognizing Uyghur, Tibetan, and Mongolian Traditional Medicines 
Background:
Traditional Chinese medicine, as it is understood and adopted by those with a growing interest in complementary and alternative practices to biomedicine, is often used as an umbrella term for traditional medical practices from regions within and bordering the People's Republic of China. However, there are multiple distinct medical traditions in China, including that of the Uyghurs, Tibetans, and Mongolians.
Objective:
It is important to recognize the commonalities and differences of these unique systems of medicine practiced by the 3 different cultures among China's borders.
Methods:
Through an in-depth analysis of the individual beliefs and theories that form the foundation of each system, we trace the origins of the concepts that were synthesized into the Uyghur, Tibetan, and Mongolian medical systems. Furthermore, we compare diagnostic techniques and contrast treatment modalities among the 3 systems.
Discussion:
We discuss humoral theory, constitution theory, elemental theory, organ theory, and yin and yang theory. We find that imbalance is the common cause of disease or illness, but the conditions and external factors that explain such imbalances differ among the Uyghur, Tibetan, and Mongolian systems. Through these comparisons, we seek to highlight the unique beliefs, practices, and treatments utilized by these cultures.
Conclusion:
The features and attributes, while not exclusive to each population, are nonetheless uniquely synthesized by each system and thus demonstrate the distinct nature of Uyghur, Tibetan, and Mongolian medical systems.
doi:10.7453/gahmj.2015.116
PMCID: PMC4756788  PMID: 26937317
Uyghur medicine; Tibetan medicine; Mongolian medicine; traditional Chinese medicine; humoral medicine
6.  A LARGE-SAMPLE SURVEY OF FIRST- AND SECOND-YEAR MEDICAL STUDENT ATTITUDES TOWARD COMPLEMENTARY AND ALTERNATIVE MEDICINE IN THE CURRICULUM AND IN PRACTICE 
Purpose
To assess attitudes toward complementary and alternative medicine (CAM) and its place in the medical school curriculum and medical practice among preclinical students at Georgetown University School of Medicine (GUSOM), Washington, DC.
Method
Two-hundred sixty-six first-year (n=111) and second-year (n=155) medical students rated their attitudes toward CAM and 15 CAM modalities in terms of personal use, inclusion in the curriculum, and use/utility in clinical practice.
Results
Nearly all (91%) students agreed that “CAM includes ideas and methods from which Western medicine could benefit”; more than 85% agreed that “knowledge about CAM is important to me as a student/future practicing health professional”; and more than 75% felt that CAM should be included in the curriculum. Among all students, the most frequently indicated level of desired training was “sufficient to advise patients about use,” for 11 of the 15 modalities. The greatest level of training was wanted for acupuncture, chiropractic, herbal medicine, and nutritional supplements. The descriptions of CAM in future clinical practice that occurred most frequently were endorsement, referral, or provision of acupuncture, biofeedback, chiropractic, herbal medicine, massage, nutritional supplements, prayer, and meditation.
Conclusions
Interest in and enthusiasm about CAM modalities was high in this sample; personal experience was much less prevalent. Students were in favor of CAM training in the curriculum to the extent that they could provide advice to patients; the largest proportions of the sample planned to endorse, refer patients for, or provide 8 of the 15 modalities surveyed in their future practice.
PMCID: PMC4371739  PMID: 17283739
7.  Promoting self-awareness and reflection through an experiential Mind-Body Skills course for first year medical students 
Medical teacher  2007;29(8):778-784.
Background
This research examines student evaluations of their experience and attitudes in an 11 week mind-body skills course for first year medical students.
Aims
The aim is to understand the impact of this course on students’ self-awareness, self-reflection, and self-care as part of their medical education experience.
Methods
This study uses a qualitative content analysis approach to data analysis. The data are 492 verbatim responses from 82 students to six open-ended questions about the students’ experiences and attitudes after a mind-body skills course. These questions queried students’ attitudes about mind-body medicine, complementary medicine, and their future as physicians using these approaches.
Results
The data revealed five central themes in students’ responses: connections, self discovery, stress relief, learning, and medical education.
Conclusions
Mind-body skills groups represent an experiential approach to teaching mind-body techniques that can enable students to achieve self-awareness and self-reflection in order to engage in self-care and to gain exposure to mind-body medicine while in medical school.
doi:10.1080/01421590701509647
PMCID: PMC4372185  PMID: 17852720
8.  The EPI Bioassay identifies natural compounds with estrogenic activity that are potent inhibitors of androgenic pathways in human prostate stromal and epithelial cells 
The reactive stromal phenotype is an important factor for prostate cancer progression and may be a new target for treatment and prevention. A new high efficiency preclinical protocol, the EPI bioassay, reflects the interaction of endocrine, paracrine and immune, (EPI) factors on induced androgen metabolism in human prostate reactive stroma. The bioassay is based on co-culturing human primary prostate stromal cells and LAPC-4 prostatic adenocarcinoma cells in a downscaled format of 96-well-plates for testing multiple doses of multiple target compounds. Metabolism of dehydroepiandrosterone (DHEA) with or without TGFβ1–induced stimulation (D+T) of the reactive stroma phenotype was assessed by increased testosterone in the media and PSA production of the epithelial prostate cancer cells. By using the non-metabolizable androgen R1881, effects from direct androgen action were distinguished from stromal androgen production from DHEA. Stromal cell androgenic bioactivity was confirmed using conditioned media from D+T-treated stromal cell monocultures in an androgen-inducible AR screening assay. We further showed that both agonists to estrogen receptor (ER), DPN (ERβ) and PPT (ERα), as well as estrogenic natural compounds including soy isoflavones attenuated D+T-induced PSA production. Studies with the pure ER agonists showed that activating either ERα or ERβ could inhibit both D+T-mediated and R1881-mediated PSA production with the D+T effect being more pronounced. In conclusion, natural compounds with estrogenic activity and pure ER agonists are very potent inhibitors of stromal conversion of DHEA to androgenic metabolites. More studies are needed to characterize the mechanisms involved in estrogenic modulation of the endocrine-immune-paracrine balance of the prostate microenvironment.
doi:10.1016/j.jsbmb.2011.12.003
PMCID: PMC3311472  PMID: 22207083
9.  Analyzing Heterogeneous Complexity in Complementary and Alternative Medicine Research: A Systems Biology Solution via Parsimony Phylogenetics 
Summary
Systems biology offers cutting-edge tools for the study of complementary and alternative medicine (CAM). The advent of ‘omics’ techniques and the resulting avalanche of scientific data have introduced an unprecedented level of complexity and heterogeneous data to biomedical research, leading to the development of novel research approaches. Statistical averaging has its limitations and is unsuitable for the analysis of heterogeneity, as it masks diversity by homogenizing otherwise heterogeneous populations. Unfortunately, most researchers are unaware of alternative methods of analysis capable of accounting for individual variability. This paper describes a systems biology solution to data complexity through the application of parsimony phylogenetic analysis. Maximum parsimony (MP) provides a data-based modeling paradigm that will permit a priori stratification of the study cohort(s), better assessment of early diagnosis, prognosis, and treatment efficacy within each stratum, and a method that could be used to explore, identify and describe complex human patterning.
doi:10.1159/000335190
PMCID: PMC3292783  PMID: 22327551
Heterogeneity; Parsimony; Phylogenetics; Synapomorphies; Systems biology; Clinical trial design; Complementary and alternative medicine
10.  Biomarkers in the Age of Omics: Time for a Systems Biology Approach 
Abstract
Limitations to biomarker discovery are not only technical or bioinformatic but conceptual as well. In our attempt to offer a solution, we are highlighting three issues that we think are limiting progress in biomarkers discovery. First, the confusion stemming from the imposition of a pathology-type immunohistochemical marker (IHCM) concept on omics data without fully understanding the characteristics and limitations of IHCMs as applied in clinical pathology. Second, the lack of serious consideration for the scope of disease heterogeneity. Third, the refusal of the biomedical community to borrow from other biological disciplines their well established methods for dealing with heterogeneity. Therefore, real progress in biomarker discovery will be attained when we recognize that an omics biomarker cannot be assigned and validated without a priori data modeling and subtyping of the disease itself to reveal the extent of its heterogeneity, and its omics' clonal aberrations (drivers) underlying its subtypes and pathways' diversity. To further support our viewpoints, we are contributing a novel a systems biology method such as parsimony phylogenetic approach for disease modeling prior to biomarker circumscription. As an analytical approach that has been successfully used for a half of a century in other biological disciplines, parsimony phylogenetics simultaneously achieves several objectives: it provides disease modeling in a hierarchical phylogenetic classification, identifies biomarkers as the shared derived expressions or mutations—synapomorphies, constructs the omics profiles of specimens based on the most parsimonious arrangement of their heterogeneous data, and permits network profiling of affected signaling pathways as the biosignature of disease classes.
doi:10.1089/omi.2010.0023
PMCID: PMC3060038  PMID: 21319991
11.  Endometriosis Gene Expression Heterogeneity and Biosignature: A Phylogenetic Analysis 
Endometriosis is a multifactorial disease with poorly understood etiology, and reflecting an evolutionary nature where genetic alterations accumulate throughout pathogenesis. Our objective was to characterize the heterogeneous pathological process using parsimony phylogenetics. Gene expression microarray data of ovarian endometriosis obtained from NCBI database were polarized and coded into derived (abnormal) and ancestral (normal) states. Such alterations are referred to as synapomorphies in a phylogenetic sense (or biomarkers). Subsequent gene linkage was modeled by Genomatix BiblioSphere Pathway software. A list of clonally shared derived (abnormal) expressions revealed the pattern of heterogeneity among specimens. In addition, it has identified disruptions within the major regulatory pathways including those involved in cell proliferation, steroidogenesis, angiogenesis, cytoskeletal organization and integrity, and tumorigenesis, as well as cell adhesion and migration. Furthermore, the analysis supported the potential central involvement of ESR2 in the initiation of endometriosis. The pathogenesis mapping showed that eutopic and ectopic lesions have different molecular biosignatures.
doi:10.1155/2011/719059
PMCID: PMC3238413  PMID: 22203846
12.  Stress Biomarkers in Medical Students Participating in a Mind Body Medicine Skills Program 
Georgetown University School of Medicine offers an elective Mind-Body Medicine Skills (MBMS) course to medical students to promote self-care and self-awareness. Participating medical students reported better management of academic stress and well-being than non-participants. In this study, we sought to assess the stress-reducing effects of MBMS by measuring physiological changes in first-year medical students. Saliva samples were collected before (January, time 1 (T1)-pre-intervention) and upon completion of the course (May, time 2 (T2p)-post-intervention), as well as from non-participating medical students (May, time 2 (T2c)-control). The T2p and T2c collections coincided with the period of final examinations. Cortisol, dehydroepiandrosterone-sulfate (DHEA-S), testosterone and secretory immunoglobulin A (sIgA) were measured. The mean morning salivary cortisol at T2p was 97% of the mean at baseline T1 which was significantly lower than for T2c (2.4) (95% confidence interval (CI) 0.57–1.60, P =  .001); DHEA-S showed similar pattern as cortisol where the T2p levels were significantly lower than T2c (P <  .001) in both morning and evening collections. Testosterone ratio at T2p (0.85) was also lower than T2c (1.6) (95% CI 0.53–1.3, P =  .01). sIgA levels were not statistically different. On direct comparison, the T2c and T2p means were significantly different for all cortisol, DHEA-S and testosterone values. Participants maintained their hormonal balance within the normal range throughout the academic semester while the control group showed significantly increased levels, probably exacerbated by the end of the semester exam stress. To our knowledge, this is the first study to assess the physiologic benefits of a MBMS program in medical students.
doi:10.1093/ecam/neq039
PMCID: PMC3137844  PMID: 21799696
13.  Biomarkers in the Age of Omics: Time for a Systems Biology Approach 
Limitations to biomarker discovery are not only technical or bioinformatic but conceptual as well. In our attempt to offer a solution, we are highlighting three issues that we think are limiting progress in biomarkers discovery. First, the confusion stemming from the imposition of a pathology-type immunohistochemical marker (IHCM) concept on omics data without fully understanding the characteristics and limitations of IHCMs as applied in clinical pathology. Second, the lack of serious consideration for the scope of disease heterogeneity. Third, the refusal of the biomedical community to borrow from other biological disciplines their well established methods for dealing with heterogeneity. Therefore, real progress in biomarker discovery will be attained when we recognize that an omics biomarker cannot be assigned and validated without a priori data modeling and subtyping of the disease itself to reveal the extent of its heterogeneity, and its omics’ clonal aberrations (drivers) underlying its subtypes and pathways’ diversity. To further support our viewpoints, we are contributing a novel a systems biology method such as parsimony phylogenetic approach for disease modeling prior to biomarker circumscription. As an analytical approach that has been successfully used for a half of a century in other biological disciplines, parsimony phylogenetics simultaneously achieves several objectives: it provides disease modeling in a hierarchical phylogenetic classification, identifies biomarkers as the shared derived expressions or mutations—synapomorphies, constructs the omics profiles of specimens based on the most parsimonious arrangement of their heterogeneous data, and permits network profiling of affected signaling pathways as the biosignature of disease classes.
doi:10.1089/omi.2010.0023
PMCID: PMC3060038  PMID: 21319991
14.  Using Basic Science to Develop an Innovative Program in Complementary and Alternative Medicine 
The growing interest in Complementary and Alternative Medicine (CAM) and the increasing incorporation of its modalities in the United States' healthcare system have exposed a number of problems in the field. These include a shortage of qualified CAM providers, scarcity of evidence-based research, lack of trained scientists in the field, and the ubiquitous marketing of frequently uncontrolled CAM products. Thus, the development of a comprehensive and scientifically sound educational infrastructure has become a crucial initial step in redirecting these adverse trends.
With support from the NIH-sponsored curricular CAM initiative, faculty from the department of physiology and biophysics at Georgetown University developed a M.S. program in CAM in 2003. This unique, first of its kind, science-based graduate program offers a master's degree (MS) in physiology with an emphasis on CAM. The CAM-MS degree in physiology is designed to enable students to critically assess various CAM modalities, apply scientific rigor, and carry out evidence-based CAM research. The curriculum includes core science courses and CAM-related classes. Additionally, in order to emphasize the application of academic knowledge and further strengthen problem-solving skills, the students complete an eight-week summer practicum in a professional CAM-related environment.
Here, we report on our innovative and interdisciplinary CAM graduate program where creative teaching is implemented by basic scientists and enhanced by the application of their disciplines in tandem with the clinical expertise of CAM practitioners in the community. Thus, the faculty in the Department of Physiology & Biophysics is developing emerging cross disciplinary areas of study and interest in order to prepare new generations of future physicians, health professionals, educators, and researchers capable of objectively assessing the safety and efficacy of various CAM modalities, and introducing scientific rigor to much needed research into the various aspects of CAM therapies.
PMCID: PMC3019605  PMID: 21243105
Graduate education; Basic science; Complementary and Alternative Medicine
15.  Understanding behavioral and physiological phenotypes of stress and anxiety in zebrafish 
Behavioural brain research  2009;205(1):38-44.
The zebrafish (Danio rerio) is emerging as a promising model organism for experimental studies of stress and anxiety. Here we further validate zebrafish models of stress by analyzing how environmental and pharmacological manipulations affect their behavioral and physiological phenotypes. Experimental manipulations included exposure to alarm pheromone, chronic exposure to fluoxetine, acute exposure to caffeine, as well as acute and chronic exposure to ethanol. Acute (but not chronic) alarm pheromone and acute caffeine produced robust anxiogenic effects, including reduced exploration, increased erratic movements and freezing behavior in zebrafish tested in the novel tank diving test. In contrast, ethanol and fluoxetine had robust anxiolytic effects, including increased exploration and reduced erratic movements. The behavior of several zebrafish strains was also quantified to ascertain differences in their behavioral profiles, revealing high-anxiety (leopard, albino) and low-anxiety (wild type) strains. We also used LocoScan (CleverSys Inc.) video-tracking tool to quantify anxiety-related behaviors in zebrafish, and dissect anxiety-related phenotypes from locomotor activity. Finally, we developed a simple and effective method of measuring zebrafish physiological stress responses (based on a human salivary cortisol assay), and showed that alterations in whole-body cortisol levels in zebrafish parallel behavioral indices of anxiety. Collectively, our results confirm zebrafish as a valid, reliable, and high-throughput model of stress and affective disorders.
doi:10.1016/j.bbr.2009.06.022
PMCID: PMC2922906  PMID: 19540270
Zebrafish; Anxiety; Stress; Novel tank test; Cortisol
16.  Algorithmic Assessment of Vaccine-Induced Selective Pressure and Its Implications on Future Vaccine Candidates 
Advances in Bioinformatics  2010;2010:178069.
Posttrial assessment of a vaccine's selective pressure on infecting strains may be realized through a bioinformatic tool such as parsimony phylogenetic analysis. Following a failed gonococcal pilus vaccine trial of Neisseria gonorrhoeae, we conducted a phylogenetic analysis of pilin DNA and predicted peptide sequences from clinical isolates to assess the extent of the vaccine's effect on the type of field strains that the volunteers contracted. Amplified pilin DNA sequences from infected vaccinees, placebo recipients, and vaccine specimens were phylogenetically analyzed. Cladograms show that the vaccine peptides have diverged substantially from their paternal isolate by clustering distantly from each other. Pilin genes of the field clinical isolates were heterogeneous, and their peptides produced clades comprised of vaccinated and placebo recipients' strains indicating that the pilus vaccine did not exert any significant selective pressure on gonorrhea field strains. Furthermore, sequences of the semivariable and hypervariable regions pointed out heterotachous rates of mutation and substitution.
doi:10.1155/2010/178069
PMCID: PMC2817498  PMID: 20150957
17.  Phylogenetic Modeling of Heterogeneous Gene-Expression Microarray Data from Cancerous Specimens 
Abstract
The qualitative dimension of gene expression data and its heterogeneous nature in cancerous specimens can be accounted for by phylogenetic modeling that incorporates the directionality of altered gene expressions, complex patterns of expressions among a group of specimens, and data-based rather than specimen-based gene linkage. Our phylogenetic modeling approach is a double algorithmic technique that includes polarity assessment that brings out the qualitative value of the data, followed by maximum parsimony analysis that is most suitable for the data heterogeneity of cancer gene expression. We demonstrate that polarity assessment of expression values into derived and ancestral states, via outgroup comparison, reduces experimental noise; reveals dichotomously expressed asynchronous genes; and allows data pooling as well as comparability of intra- and interplatforms. Parsimony phylogenetic analysis of the polarized values produces a multidimensional classification of specimens into clades that reveal shared derived gene expressions (the synapomorphies); provides better assessment of ontogenic pathways and phyletic relatedness of specimens; efficiently utilizes dichotomously expressed genes; produces highly predictive class recognition; illustrates gene linkage and multiple developmental pathways; provides higher concordance between gene lists; and projects the direction of change among specimens. Further implication of this phylogenetic approach is that it may transform microarray into diagnostic, prognostic, and predictive tool.
doi:10.1089/omi.2008.0010
PMCID: PMC2583934  PMID: 18699725
18.  Phylogenetic Modeling of Heterogeneous Gene-Expression Microarray Data from Cancerous Specimens 
The qualitative dimension of gene expression data and its heterogeneous nature in cancerous specimens can be accounted for by phylogenetic modeling that incorporates the directionality of altered gene expressions, complex patterns of expressions among a group of specimens, and data-based rather than specimen-based gene linkage. Our phylogenetic modeling approach is a double algorithmic technique that includes polarity assessment that brings out the qualitative value of the data, followed by maximum parsimony analysis that is most suitable for the data heterogeneity of cancer gene expression. We demonstrate that polarity assessment of expression values into derived and ancestral states, via outgroup comparison, reduces experimental noise; reveals dichotomously expressed asynchronous genes; and allows data pooling as well as comparability of intra- and interplatforms. Parsimony phylogenetic analysis of the polarized values produces a multidimensional classification of specimens into clades that reveal shared derived gene expressions (the synapomorphies); provides better assessment of ontogenic pathways and phyletic relatedness of specimens; efficiently utilizes dichotomously expressed genes; produces highly predictive class recognition; illustrates gene linkage and multiple developmental pathways; provides higher concordance between gene lists; and projects the direction of change among specimens. Further implication of this phylogenetic approach is that it may transform microarray into diagnostic, prognostic, and predictive tool.
doi:10.1089/omi.2008.0010
PMCID: PMC2583934  PMID: 18699725
19.  Evolutionary medicine: A meaningful connection between omics, disease, and treatment 
The evolutionary nature of diseases requires that their omics be analyzed by evolution-compatible analytical tools such as parsimony phylogenetics in order to reveal common mutations and pathways’ modifications. Since the heterogeneity of the omics data renders some analytical tools such as phenetic clustering and Bayesian likelihood inefficient, a parsimony phylogenetic paradigm seems to connect between the omics and medicine. It offers a seamless, dynamic, predictive, and multidimensional analytical approach that reveals biological classes, and disease ontogenies; its analysis can be translated into practice for early detection, diagnosis, biomarker identification, prognosis, and assessment of treatment. Parsimony phylogenetics identifies classes of specimens, the clades, by their shared derived expressions, the synapomorphies, which are also the potential biomarkers for the classes that they delimit. Synapomorphies are determined through polarity assessment (ancestral vs. derived) of m/z or gene-expression values and parsimony analysis; this process also permits intra and interplatform comparability and produces higher concordance between platforms. Furthermore, major trends in the data are also interpreted from the graphical representation of the data as a tree diagram termed cladogram; it depicts directionality of change, identifies the transitional patterns from healthy to diseased, and can be developed into a predictive tool for early detection.
doi:10.1002/prca.200780047
PMCID: PMC2367146  PMID: 18458745
Biomarkers; Cancer; Early detection; Evolution; Omics; Parsimony; Phylogenetics
20.  Phyloproteomics: What Phylogenetic Analysis Reveals about Serum Proteomics 
Journal of proteome research  2006;5(9):2236-2240.
Phyloproteomics is a novel analytical tool that solves the issue of comparability between proteomic analyses, utilizes a total spectrum-parsing algorithm, and produces biologically meaningful classification of specimens. Phyloproteomics employs two algorithms: a new parsing algorithm (UNIPAL) and a phylogenetic algorithm (MIX). By outgroup comparison, the parsing algorithm identifies novel or vanished MS peaks and peaks signifying up or down regulated proteins and scores them as derived or ancestral. The phylogenetic algorithm uses the latter scores to produce a biologically meaningful classification of the specimens.
doi:10.1021/pr0504485
PMCID: PMC2270414  PMID: 16944935
Cancer; dichotomous development; mass spectrometry; phylogenetics; phyloproteomics; proteomics; serum; transitional clades

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