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PubMed Central Canada to be taken offline in February 2018

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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1.  Evaluation of the Predictive Validity of Thermography in Identifying Extravasation With Intravenous Chemotherapy Infusions 
Journal of Infusion Nursing  2017;40(6):367-374.
Early detection of extravasation is important, but conventional methods of detection lack objectivity and reliability. This study evaluated the predictive validity of thermography for identifying extravasation during intravenous antineoplastic therapy. Of 257 patients who received chemotherapy through peripheral veins, extravasation was identified in 26. Thermography was performed every 15 to 30 minutes during the infusions. Sensitivity, specificity, positive predictive value, and negative predictive value using thermography were 84.6%, 94.8%, 64.7%, and 98.2%, respectively. This study showed that thermography offers an accurate prediction of extravasation.
doi:10.1097/NAN.0000000000000250
PMCID: PMC5680995  PMID: 29112585
antineoplastic agents; extravasation; thermography
2.  In vivo imaging xenograft models for the evaluation of anti‐brain tumor efficacy of targeted drugs 
Cancer Medicine  2017;6(12):2972-2983.
Abstract
Molecular‐targeted drugs are generally effective against tumors containing driver oncogenes, such as EGFR,ALK, and NTRK1. However, patients harboring these oncogenes frequently experience a progression of brain metastases during treatment. Here, we present an in vivo imaging model for brain tumors using human cancer cell lines, including the EGFR‐L858R/T790M‐positive H1975 lung adenocarcinoma cells, the NUGC4 hepatocyte growth factor (HGF)‐dependent gastric cancer cells, and the KM12SM colorectal cancer cells containing the TPM3‐NTRK1 gene fusion. We investigated the efficacy of targeted drugs by comparison with their effect in extracranial models. In vitro, H1975 cells were sensitive to the third‐generation epidermal growth factor receptor inhibitor osimertinib. Moreover, HGF stimulated the proliferation of NUGC4 cells, that was inhibited by crizotinib, which has anti‐MET activity. KM12SM cells were sensitive to the tropomyosin‐related kinase‐A inhibitors crizotinib and entrectinib. In in vivo H1975 cell models, osimertinib inhibited the progression of both brain and subcutaneous tumors. Furthermore, in in vivo NUGC4 cell models, crizotinib remarkably delayed the progression of brain tumors, and that of peritoneal carcinomatosis. Interestingly, in in vivo KM12SM cell models, treatment with crizotinib delayed the progression of liver metastases, but not that of brain tumors. Conversely, treatment with entrectinib discernibly delayed the progression of both tumor types. Thus, the effect of targeted drugs against brain tumors can differ from the one reported in extracranial tumors. Moreover, the same multikinase inhibitory drug can display different efficacies in brain tumor models containing different drivers. Therefore, our in vivo imaging model for brain tumors may prove useful for preclinical drug screening against brain metastases.
doi:10.1002/cam4.1255
PMCID: PMC5727243  PMID: 29125233
Brain tumor; entrectinib; NTRK1; osimertinib; TRK‐A
3.  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
4.  World Congress Integrative Medicine & Health 2017: part two 
Ee, Carolyn | Thuraisingam, Sharmala | Pirotta, Marie | French, Simon | Xue, Charlie | Teede, Helena | Kristoffersen, Agnete E. | Sirois, Fuschia | Stub, Trine | Engler, Jennifer | Joos, Stefanie | Güthlin, Corina | Felenda, Jennifer | Beckmann, Christiane | Stintzing, Florian | Evans, Roni | Bronfort, Gert | Keefe, Daniel | Taberko, Anna | Hanson, Linda | Haley, Alex | Ma, Haiwei | Jolton, Joseph | Yarosh, Lana | Keefe, Francis | Nam, Jung | Evans, Roni | Ojala, Liwanag | Kreitzer, Mary J. | Hanson, Linda | Fink, Careen | Kraft, Karin | Flower, Andrew | Lewith, George | Harman, Kim | Stuart, Beth | Bishop, Felicity L. | Frawley, Jane | Füleki, Lilla | Kiss, Eva | Vancsik, Tamas | Krenacs, Tibor | Funabashi, Martha | Pohlman, Katherine A. | Mior, Silvano | Thiel, Haymo | Hill, Michael D. | Cassidy, David J. | Westaway, Michael | Yager, Jerome | Hurwitz, Eric | Kawchuk, Gregory N. | O’Beirne, Maeve | Vohra, Sunita | Gaboury, Isabelle | Morin, Chantal | Gaertner, Katharina | Torchetti, Loredana | Frei-Erb, Martin | Kundi, Michael | Frass, Michael | Gallo, Eugenia | Maggini, Valentina | Comite, Mattia | Sofi, Francesco | Baccetti, Sonia | Vannacci, Alfredo | Di Stefano, Mariella | Monechi, Maria V. | Gori, Luigi | Rossi, Elio | Firenzuoli, Fabio | Mediati, Rocco D. | Ballerini, Giovanna | Gardiner, Paula | Lestoquoy, Anna S. | Negash, Lily | Stillman, Sarah | Shah, Prachi | Liebschutz, Jane | Adelstein, Pamela | Farrell-Riley, Christine | Brackup, Ivy | Penti, Brian | Saper, Robert | Sampedro, Isabel Giralt | Carvajal, Gilda | Gleiss, Andreas | Gross, Marie M. | Brendlin, Dorothea | Röttger, Jonas | Stritter, Wiebke | Seifert, Georg | Grzanna, Noelle | Stange, Rainer | Guendling, Peter W. | Gu, Wen | Lu, Yan | Wang, Jie | Zhang, Chengcheng | Bai, Hua | He, Yuxi | Zhang, Xiaoxu | Zhang, Zhengju | Wang, Dali | Meng, Fengxian | Hagel, Alexander | Albrecht, Heinz | Vollbracht, Claudia | Dauth, Wolfgang | Hagel, Wolfgang | Vitali, Francesco | Ganzleben, Ingo | Schultis, Hans | Konturek, Peter | Stein, Jürgen | Neurath, Markus | Raithel, Martin | Hagel, Alexander | Vollbracht, Claudia | Raithel, Martin | Konturek, Peter | Krick, Bianka | Haller, Heidemarie | Klose, Petra | Dobos, Gustav | Kümmel, Sherko | Cramer, Holger | Haller, Heidemarie | Saha, Felix J. | Kowoll, Anna | Ebner, Barbara | Berger, Bettina | Dobos, Gustav | Choi, Kyung-Eun | He, Lisha | Wang, Han | He, X. | Gu, C. | Zhang, Y. | Zhao, Linhua | Tong, Xiaolin | He, Lisha | Wang, Han | He, Xinhui | Gu, Chengjuan | Zhang, Ying | Zhao, Linhua | Tong, Xiaolin | He, Lisha | Wang, Han | He, Xinhui | Gu, Chengjuan | Zhang, Ying | Zhao, Linhua | Tong, Xiaolin | Ho, Robin S. T. | Chung, Vincent C. H. | Wu, Xinyin | Wong, Charlene H. L. | Wu, Justin C. Y. | Wong, Samuel Y. S. | Lau, Alexander Y. L. | Sit, Regina W. S. | Wong, Wendy | Holmes, Michelle | Bishop, Felicity | Calman, Lynn | Holmes, Michelle | Bishop, Felicity | Lewith, George | Newell, Dave | Field, Jonathan | Htut, Win L. | Han, Dongwoon | Choi, Da I. | Choi, Soo J. | Kim, Ha Y. | Hwang, Jung H. | Huang, Ching W. | Jang, Bo H. | Chen, Fang P. | Ko, Seong G. | Huang, Wenjing | Jin, De | Lian, Fengmei | Jang, Soobin | Kim, Kyeong H. | Lee, Eun K. | Sun, Seung H. | Go, Ho Y. | Ko, Youme | Park, Sunju | Jang, Bo H. | Shin, Yong C. | Ko, Seong G. | Janik, Hubert | Greiffenhagen, Natalie | Bolte, Jürgen | Kraft, Karin | Jaworski, Mariusz | Adamus, Miroslawa | Dobrzynska, Aleksandra | Jeitler, Michael | Jaspers, Jessica | von Scheidt, Christel | Koch, Barbara | Michalsen, Andreas | Steckhan, Nico | Kessler, Christian | Jin, De | Huang, Wen-jing | Pang, Bing | Lian, Feng-Mei | Jong, Miek | Baars, Erik | Glockmann, Anja | Hamre, Harald | Kainuma, Mosaburo | Murakami, Aya | Kubota, Toshio | Kobayashi, Daisuke | Sumoto, Yasuhiro | Furusyo, Norihiro | Ando, Shin-Ichi | Shimazoe, Takao | Kelber, Olaf | Verjee, S. | Gorgus, Eva | Schrenk, Dieter | Kemper, Kathi | Hill, Ellie | Kemper, Kathi | Rao, Nisha | Gascon, Gregg | Mahan, John | Kienle, Gunver | Dietrich, Jörg | Schmoor, Claudia | Huber, Roman | Kim, Weon H. | Han, Dongwoon | Ahmed, Mansoor | He, Luzhu | Hwang, Jung Hye | Kiss, Eva | Vancsik, Tamas | Meggyeshazi, Nora | Kovago, Csaba | Krenacs, Tibor | Klaus, Anne K. | Zerm, Roland | Pranga, Danilo | Ostermann, Thomas | Reif, Marcus | von Laue, Hans Broder | Brinkhaus, Benno | Kröz, Matthias | Klaus, Anne K. | Zerm, Roland | Pranga, Danilo | Recchia, Daniela Rodrigues | Ostermann, Thomas | Reif, Marcus | von Laue, Hans B. | Brinkhaus, Benno | Kröz, Matthias | Klein-Laansma, Christien T. | Jong, Mats | von Hagens, Cornelia | Jansen, Jean P. | van Wietmarschen, Herman | Jong, Miek C. | Ko, Youme | Sun, Seung-Ho | Go, Ho-Yeon | Jeon, Chan-Yong | Song, Yun-Kyung | Ko, Seong-Gyu | Koch, Anna K. | Rabsilber, Sybille | Lauche, Romy | Kümmel, Sherko | Dobos, Gustav | Langhorst, Jost | Cramer, Holger | Koch, Anna K. | Trifunovic-Koenig, Milena | Klose, Petra | Cramer, Holger | Dobos, Gustav | Langhorst, Jost | Koster, Evi | Baars, Erik | Delnoij, Diana | Kroll, Lena | Weiss, Kathrin | Kubo, Ai | Hendlish, Sarah | Altschuler, Andrea | Connolly, Nancy | Avins, Andy | Lauche, Romy | Recchia, Daniela Rodrigues | Cramer, Holger | Wardle, Jon | Lee, David | Sibbritt, David | Adams, Jon | Ostermann, Thomas | Lauche, Romy | Sibbritt, David | Park, Crystal | Mishra, Gita | Adams, Jon | Cramer, Holger | Lechner, Johann | Lee, Inseon | Chae, Younbyoung | Lee, Jisu | Cho, Seung H. | Choi, Yujin | Lee, Jee Y. | Ryu, Han S. | Yoon, Sung S. | Oh, Hye K. | Hyun, Lyun K. | Kim, Jin O. | Yoon, Seong W. | Lee, Ju-Yeon | Shin, Sang-Hoon | Jang, Min | Müller, Indra | Park, So-Hyun Janson | Lestoquoy, Anna S. | Laird, Lance | Negash, Lily | Mitchell, Suzanne | Gardiner, Paula | Li, Xiaofei | Wang, Yunhui | Zhen, Jianhua | Yu, He | Liu, Tiegang | Gu, Xiaohong | Liu, Hui | Ma, Weiguo | Zhang, Chengcheng | Shang, Xuezheng | Bai, Yu | Meng, Fengxian | Liu, Wei | Rooney, Collin | Smith, Amos | Lopes, Shirlene | Demarzo, Marcelo | do Patrocínio Nunes, Maria | Lorenz, Peter | Gründemann, Carsten | Heinrich, Miriam | Garcia-Käufer, Manuel | Grunewald, Franziska | Messerschmidt, Silke | Herrick, Anja | Gruber, Kim | Beckmann, Christiane | Knödler, Matthias | Huber, Roman | Steinborn, Carmen | Stintzing, Florian | Lu, Taoying | Wang, Lixin | Wu, Darong | Luberto, Christina M | Hall, Daniel L. | Chad-Friedman, Emma | Lechner, Suzanne | Park, Elyse R. | Luberto, Christina M. | Park, Elyse | Goodman, Janice | Luer, Sonja | Heri, Matthias | von Ammon, Klaus | Frei-Erb, Martin | Ma, Weiguo | Meng, Fengxian | Maggini, Valentina | Gallo, Eugenia | Landini, Ida | Lapucci, Andrea | Nobili, Stefania | Mini, Enrico | Firenzuoli, Fabio | McDermott, Clare | Lewith, George | Richards, Selwyn | Cox, Diane | Frossell, Sarah | Leydon, Geraldine | Eyles, Caroline | Raphael, Hilly | Rogers, Rachael | Selby, Michelle | Adler, Charlotte | Allam, Jo | Meng, Fengxian | Gu, Wen | Zhang, Chengcheng | Bai, Hua | Zhang, Zhengju | Wang, Dali | Bu, Xiangwei | Zhang, Honghong | Zhang, Jianpeng | Liu, Hui | Mikolasek, Michael | Berg, Jonas | Witt, Claudia | Barth, Jürgen | Miskulin, Ivan | Lalic, Zdenka | Miskulin, Maja | Dumic, Albina | Sebo, Damir | Vcev, Aleksandar | Mohammed, Nasr A. A. | Han, Dongwoon | Ahmed, Mansoor | Choi, Soo Jeung | Im, Hyea Bin | Hwang, Jung Hye | Mukherjee, Anwesha | Kandhare, Amit | Bodhankar, Subhash | Mukherjee, Anwesha | Kandhare, Amit | Thakurdesai, Prasad | Bodhankar, Subhash | Munk, Niki | Evans, Erica | Froman, Amanda | Kline, Matthew | Bair, Matthew J. | Musial, Frauke | Kristoffersen, Agnete E. | Alræk, Terje | Hamre, Harald J. | Stub, Trine | Björkman, Lars | Fønnebø, Vinjar M. | Pang, Bing | Lian, Feng-mei | Ni, Qing | Tong, Xiao-lin | Li, Xin-long | Liu, Wen-ke | Feng, Shuo | Zhao, Xi-yan | Zheng, Yu-jiao | Zhao, Xue-min | Lin, Yi-qun | Pang, Bing | Lian, Feng-mei | Tong, Xiao-lin | Zhao, Tian-yu | Zhao, Xi-Yan | Phd, Hui Che | Zhang, Chen | Pang, Bing | Liu, Feng | Tong, Xiao-lin | Zhao, Lin-hua | Zhao, Xue-min | Ye, Ru | Gu, Cheng-juan | Pang, Bing | Ni, Qing | Tong, Xiao-lin | Lian, Feng-mei | Zhao, Xi-yan | Jin, De | Zhao, Xue-min | Zheng, Yu-jiao | Lin, Yi-qun | Peng, Wenbo | Lauche, Romy | Sibbritt, David | Adams, Jon | Peng, Wenbo | Wardle, Jon | Cramer, Holger | Mishra, Gita | Lauche, Romy | Pohlman, Katherine A. | Mior, Silvano | Funabashi, Martha | De Carvalho, Diana | El-Bayoumi, Mohamed | Haig, Bob | Kelly, Kimbalin | Wade, Darrell J. | O’Beirne, Maeve | Vohra, Sunita | Portalupi, Emanuela | Gobo, Giampietro | Bellavita, Luigi | Guglielmetti, Chiara | Raak, Christa | Teuber, Myriam | Molsberger, Friedrich | von Rath, Ulrich | Reichelt, Ulrike | Schwanebeck, Uta | Zeil, Sabine | Vogelberg, Christian | Veintimilla, Dolores Rodríguez | Vollbracht, Claudia | Mery, Guerrero Tapia | Villavicencio, Marisol Maldonado | Moran, Sandra Herrera | Sachse, Christian | Gündlin, Peter W | Stange, Rainer | Sahebkarkhorasani, Monirsadat | Azizi, Hoda | Schumann, Dania | Lauche, Romy | Sundberg, Tobias | Leach, Matthew J. | Cramer, Holger | Seca, Susana | Greten, Henry | Selliah, Sugir | Shakya, Anu | Han, Dongwoon | Kim, Ha Yun | Choi, Da I. | Im, Hyea B. | Choi, Soo J. | Sherbakova, Anna | Ulrich-Merzenich, Gudrun | Kelber, Olaf | Abdel-Aziz, Heba | Sibinga, Erica | Webb, Lindsey | Ellen, Jonathan | Skrautvol, Kari | Nåden, Dagfinn | Song, Rhayun | Grabowska, Weronika | Osypiuk, Kamila | Diaz, Gloria V. | Bonato, Paolo | Park, Moonkyoung | Hausdorff, Jeffrey | Fox, Michael | Sudarsky, Lewis R. | Tarsy, Daniel | Novakowski, James | Macklin, Eric A. | Wayne, Peter M. | Song, Rhayun | Hwang, Inok | Ahn, Sukhee | Lee, Myung-Ah | Wayne, Peter M. | Sohn, Min K. | Sorokin, Oleg | Steckhan, Nico | Heydeck, Dagmar | Borchert, Astrid | Hohmann, Christoph-Daniel | Kühn, Harmut | Michalsen, Andreas | Kessler, Christian | Steckhan, Nico | Hohmann, Christoph-Daniel | Cramer, Holger | Michalsen, Andreas | Dobos, Gustav | von Scheidt, Christel | Kirschbaum, Clemens | Stalder, Tobias | Stöckigt, Barbara | Teut, Michael | Suhr, Ralf | Sulmann, Daniela | Brinkhaus, Benno | Streeter, Chris | Gerbarg, Patrica | Silveri, Marisa | Brown, Richard | Jensen, John | Stritter, Wiebke | Rutert, Britta | Eggert, Angelika | Längler, Alfred | Seifert, Georg | Holmberg, Christine | Sun, Jin | Deng, Xin | Li, Wen-Yuan | Wen, Bin | Robinson, Nicola | Liu, Jian-Ping | Sung, Hyun K. | Yang, Narae | Go, Ho Y. | Shin, Seon M. | Jung, Hee | Kim, Young J. | Jung, Woo S. | Park, Tae Y. | Suzuki, Kiyoshi | Ito, Toshinori | Uchida, Seiya | Kamohara, Seika | Ono, Naoya | Takamura, Mitsuyuki | Yokochi, Ayumu | Maruyama, Kazuo | Tapia, Patricio | Thabaut, Katarzyna | Brinkhaus, Benno | Stöckigt, Barbara | Thronicke, Anja | Kröz, Matthias | Steele, Megan | Matthes, Harald | Herbstreit, Cornelia | Schad, Friedemann | Tian, Jiaxing | Lian, Fengmei | Yang, Libo | Tong, Xiaolin | Tian, Tian | Zhang, Hewei | Tian, Xia | Wang, CongCong | Chai, Qian Yun | Zhang, Lijuan | Xia, Ruyu | Huang, Na | Fei, Yutong | Liu, Jianpin | Trent, Natalie | Miraglia, Mindy | Dusek, Jeffrey | Pasalis, Edi | Khalsa, Sat B. | Trifunovic-König, Milena | Klose, Petra | Cramer, Holger | Lauche, Romy | Koch, Anna | Dobos, Gustav | Langhorst, Jost | Uebelacker, Lisa | Tremont, Geoffrey | Gillette, Lee | Epstein-Lubow, Gary | Strong, David | Abrantes, Ana | Tyrka, Audrey | Tran, Tanya | Gaudiano, Brandon | Miller, Ivan | Ullmann, Gerhild | Ullmann, Gerhild | Li, Yuhua | Vaidya, Sujata | Marathe, Vinod | Vale, Ana C. | Motta, Jacquelyne | Donadão, Fabíola | Valente, Angela C. | Valente, Luana C. Carvalho | Ghelman, Ricardo | Vesovic, Dusan | Jevdic, Dragan | Jevdic, Aleksandar | Jevdic, Katarina | Djacic, Mihael | Letic, Dragica | Bozic, Drago | Markovic, Marija | Dunjic, Slobodan | Vesovic, Dusan | Jevdic, Dragan | Jevdic, Aleksandar | Jevdic, Katarina | Djacic, Mihael | Letic, Dragica | Bozic, Drago | Markovic, Marija | Ruscuklic, Gordana | Baksa, Dezire | Dunjic, Slobodan | Vesovic, Dusan | Jevdic, Dragan | Jevdic, Aleksandar | Jevdic, Katarina | Djacic, Mihael | Letic, Dragica | Bozic, Drago | Markovic, Marija | Ruscuklic, Gordana | Baksa, Dezire | Dunjic, Slobodan | Vesovic, Dusan | Jevdic, Dragan | Jevdic, Aleksandar | Jevdic, Katarina | Djacic, Mihael | Letic, Dragica | Bozic, Drago | Markovic, Marija | Ruscuklic, Gordana | Baksa, Dezire | Dunjic, Slobodan | Vesovic, Dusan | Jevdic, Dragan | Jevdic, Aleksandar | Jevdic, Katarina | Djacic, Mihael | Letic, Dragica | Bozic, Drago | Markovic, Marija | Vrca, Kenan | Dunjic, Slobodan | Vincent, Ann | Wahner-Roedler, Dietlind | Whipple, Mary | Vogelius, Maria M. | Vollbracht, Claudia | Friesecke, Iris | Gündling, Peter W. | Wahner-Roedler, Dietlind | Mahapatra, Saswati | Hynes, Rebecca | Van Rooy, Kimberly | Looker, Sherry | Ghosh, Aditya | Bauer, Brent | Cutshall, Susanne | Walach, Harald | Flores, Ana Borges | Walach, Harald | Ofner, Michael | Kastner, Andreas | Schwarzl, Gerhard | Schwameder, Hermann | Alexander, Nathalie | Strutzenberger, Gerda | Wang, Jie | Lu, Yan | Gu, Wen | Zhang, Chengcheng | Bu, Xianwei | Zhang, Honghong | Zhang, Jianping | He, Yuxi | Zhang, Xiaoxu | Meng, Fengxian | Wang, Shang | Yu, He | Shi, Jinfeng | Hao, Yu | Liu, Tiegang | Wu, Jun | Qiu, Zeji | Gu, Xiaohong | Wang, Yuh-Hai | Lou, Chi-Jung | Watts, Sam | Wayne, Peter | Osypiuk, Kamila | Vergara-Diaz, Gloria | Bonato, Paolo | Gow, Brian | Hausdorff, Jeffrey | Miranda, Jose | Sudarsky, Lewis | Tarsy, Daniel | Fox, Michael | Macklin, Eric | Wode, Kathrin | Bergqvist, Jenny | Bernhardsson, Britt-Marie | Nordberg, Johanna Hök | Kienle, Gunver | Sharp, Lena | Henriksson, Roger | Woo, Yeonju | Hyun, Min K. | Wu, Hao | Wang, Tian-Fang | Zhao, Yan | Wei, Yu | Tian, Lei | He, Lei | Wang, Xue | Wu, Ruohan | Feng, Shuo | Han, Mei | Caldwell, Patrina H. Y. | Liu, Shigang | Zhang, Jing | Liu, Jianping | Xia, Ruyu | Chai, Qianyun | Fei, Yutong | Guo, Zhongning | Wang, Congcong | Liu, Zhijun | Li, Xun | Zhang, Ying | Liu, Jianping | Yang, I. J. | Lincha, V. Ruberio | Ahn, S. H. | Lee, D. U. | Shin, H. M. | Yang, Lu | Sibbritt, David | Peng, Wenbo | Adams, Jon | Yang, N. | Sung, H. | Shin, S. M. | Go, H. Y. | Jung, H. | Kim, Y. | Park, T. Y. | Yap, Angela | Kwan, Yu H. | Tan, Chuen S. | Ibrahim, Syed | Ang, Seng B. | Yayi, Alfred | Han, Dongwoon | Im, Hyea Bin | Hwang, Jung Hye | Choi, Soo Jeung | Yoo, Jeong E. | Yoo, Ho R. | Jang, Sae B. | Lee, Hye L. | Youssef, Ala’a | Ezzat, Shahira | Motaal, Amira Abdel | El-Askary, Hesham | Yu, Xiaotong | Cui, Yashan | Zhang, Ying | Lian, Fengmei | Yun, Younghee | Ko, Youme | Ahn, Jin-Hyang | Jang, Bo-Hyung | Kim, Kyu-Seok | Ko, Seong-Gyu | Choi, Inhwa | Zerm, Roland | Glinz, Augustina | Pranga, Danilo | Berger, Bettina | ten Brink, Fadime | Reif, Marcus | Büssing, Arnd | Gutenbrunner, Christoph | Kröz, Matthias | Zerm, Roland | Helbrecht, Bert | Pranga, Danilo | Brinkhaus, Benno | Michalsen, Andreas | Kröz, Matthias | Zhang, Honghong | Fang, Tiesheng | Wang, Jie | Zhang, Chengcheng | He, Yuxi | Zhang, Xiaoxu | Zhang, Zhengju | Wang, Dali | Meng, Fengxion | Zhang, Jianping | Zhang, Chengcheng | Bai, Hua | Shen, Zhiming | Ma, Weiguo | Liu, Hui | Bai, Yu | Shang, Xuezheng | Meng, Fengxian | Zhang, Ruixin | Wu, Fan | Li, Ming | Xuan, Xinyun | Shen, Xueyong | Ren, Ke | Berman, Brian | Zhen, Jianhua | Li, Xiaofei | Gu, Xiaohong | Yu, He | Zheng, Zian | Wan, Yuxiang | Wang, Yunhui | Ma, Xueyan | Dong, Fei | Liu, Tiegang | Zhen, Jianhua | Li, Xiaofei | Gu, Xiaohong | Yu, He | Zheng, Zian | Wan, Yuxiang | Wang, Yunhui | Ma, Xueyan | Dong, Fei | Liu, Tiegang | Zick, Suzie | Harris, Richard | Bae, Go E. | Kwon, Jung N. | Lee, Hye Y. | Nam, Jong K. | Lee, Sang D. | Lee, Dong H. | Han, Ji Y. | Yun, Young J. | Lee, Ji H. | Park, Hye L. | Park, Seong H. | Bocci, Chiara | Ivaldi, Giovanni B. | Vietti, Ilaria | Meaglia, Ilaria | Guffi, Marta | Ruggiero, Rubina | Gualea, Marita | Longa, Emanuela | Bonucci, Massimo | Croke, Sarah | Rodriguez, Lourdes Diaz | Caracuel-Martínez, Juan C. | Fajardo-Rodríguez, Manuel F. | Ariza-García, Angélica | la Fuente, Francisca García-De | Arroyo-Morales, Manuel | Estrems, Maria S. | Gómez, Vicente G. | Estrems, Maria S. | Sabater, Mónica Valero | Ferreri, Rosaria | Bernardini, Simonetta | Pulcri, Roberto | Cracolici, Franco | Rinaldi, Massimo | Porciani, Claudio | Firenzuoli, Fabio | Baccetti, Sonia | Di Stefano, Mariella | Monechi, Maria V. | Gallo, Eugenia | Maggini, Valentina | Gori, Luigi | Rossi, Elio | Fisher, Peter | Hughes, John | Mendoza, Ariadna | MacPherson, Hugh | Witt, Claudia | Filshie, Jacqueline | Lewith, George | Di Francesco, Antonia | Bernardini, Alberto | Messe, Monica | Primitivo, Vincenzo | Iasella, Piera A. | Ghelman, Ricardo | Taminato, Monica | Alcantara, Jaqueline Do Carmo | De Oliveira, Katia R. | Rodrigues, Debora C. De Azevedo | Mumme, Juliana R. Campana | Sunakozawa, Olga K. Matsumoto | Filho, Vicente Odone | Seifert, Georg | Goldenberg, Joshua | Day, Andrew | Sasagawa, Masa | Ward, Lesley | Cooley, Kieran | Gunnarsdottir, Thora | Hjaltadottir, Ingibjorg | Hajimonfarednejad, Mahdie
doi:10.1186/s12906-017-1783-3
PMCID: PMC5498867
6.  Use of Kampo Diagnosis in Randomized Controlled Trials of Kampo Products in Japan: A Systematic Review 
PLoS ONE  2014;9(8):e104422.
Background
The Committee for Evidence-based Medicine (EBM) of the Japan Society for Oriental Medicine started compiling Evidence Reports of Kampo Treatment (EKAT) in 2007. EKAT is a compilation of structured abstracts of randomized controlled trials (RCTs), along with comments by a third party reviewer. As of 31 December, 2012, there were 378 RCTs of Kampo medicines in Japan. The primary research question of this study is “How frequently is Kampo diagnosis used in RCTs of Kampo medicines?” The secondary research question is “When is Kampo diagnosis used in RCTs?”
Materials and Methods
The structured abstract (SA) of each RCT article was reviewed to examine how Kampo diagnosis was used in RCTs, especially how Kampo diagnosis was used in the randomization process.
Results
Kampo diagnosis was used before randomization in 27 RCTs (7.1%), after randomization in 31 RCTs (8.2%), and not used in 320 RCTs (84.7%). Before randomization, Kampo diagnosis was used as a criterion for inclusion in 10 RCTs, criterion for exclusion in 9 RCTs, and criteria for both inclusion and exclusion in 2 RCTs. Kampo formulas were determined according to Kampo diagnosis in 7 RCTs. After randomization, subgroup analyses according to Kampo diagnosis were done in 27 RCTs, and grade of disease severity at Kampo diagnosis was used for analysis as an endpoint in 4 RCTs.
Conclusions
Kampo diagnosis was used before randomization only in approximately 15% of RCTs, and the number of RCT articles using Kampo diagnosis after randomization was almost the same as that before randomization. Further studies to determine the good RCTs conforming to CONSORT requirements and good systematic reviews conforming to PRISMA requirements are needed to clarify the significance of Kampo diagnosis.
doi:10.1371/journal.pone.0104422
PMCID: PMC4132104  PMID: 25119187
7.  Role of Kampo Medicine in Integrative Cancer Therapy 
Clinical trials to date demonstrate that standard cancer treatments are currently the most efficient treatments for large numbers of cancer patients. Cancer treatments will increasingly require approaches that allow patients to live with cancer, by increasing their natural healing power and tumor immunity, as well as attenuating the progression of their cancers, instead of only attacking the cancer cells directly. Complementary and alternative medicine, including Kampo medicine, compensates for the drawbacks of western medicine by increasing patients' self-defense mechanisms. In Japan, clinicians who have studied both western medicine and Kampo treat cancer patients by fusing the two medical systems into a unitary one. The goal of the system is to assist the functional maintenance and recovery of the living body complex with the physical, mental, social, and spiritual balance, rather than addressing direct antitumor effects. In this review, we describe the usefulness of Kampo medicine, especially juzentaihoto, and outline the reports on evidence, in addition to the report on an attitudinal survey about the use of Kampo medicine in cancer treatment in Japan.
doi:10.1155/2013/570848
PMCID: PMC3723058  PMID: 23997796
8.  Significance of Kampo, Traditional Japanese Medicine, in Supportive Care of Cancer Patients 
The current standard treatment for cancer is a multidisciplinary therapy whereby various types of treatment are properly combined. Chemotherapy with multiple anticancer drugs is now common, and traditional, complementary, and alternative therapies are adopted as supportive measures. Medical care in Japan is distinguished by the ability for patients to access both Western and Kampo medical cares at the same time. There is a high degree of trust in the safety of Kampo therapies because they are practiced by medical doctors who are educated with fundamental diagnosis of Western medicine. Highly reliable clinical studies are being published, demonstrating that palliative or supportive care for cancer patients using Kampo preparations alleviates adverse effects of chemotherapy or radiotherapy. This paper reports the circumstances around cancer care in Japan where traditional therapeutic Kampo formulas are used for patients undergoing cancer treatment with cutting-edge chemotherapy, specifically to alleviate adverse effects of anticancer drugs.
doi:10.1155/2013/746486
PMCID: PMC3703882  PMID: 23861712
9.  Significance of Kampo, Japanese Traditional Medicine, in the Treatment of Obesity: Basic and Clinical Evidence 
The cause of obesity includes genetic and environmental factors, including cytokines derived from adipocytes (adipo-cytokines). Although drug therapy is available for obesity, it is highly risky. Our main focus in this review is on the traditional form of Japanese medicine, Kampo, in the treated of obesity. Two Kampo formulas, that is, bofutsushosan (防風通聖散) and boiogito (防己黄耆湯), are covered by the national health insurance in Japan for the treatment of obesity. Various issues related to their action mechanisms remain unsolved. Considering these, we described the results of basic experiments and presented clinical evidence and case reports on osteoarthritis as examples of clinical application of their two Kampo medicine. Traditional medicine is used not only for treatment but also for prevention. In clinical practice, it is of great importance to prove the efficacy of combinations of traditional medicine and Western medicine and the utility of traditional medicine in the attenuation of adverse effects of Western medicine.
doi:10.1155/2013/943075
PMCID: PMC3639634  PMID: 23662155
10.  Aberrant Glycogen Synthase Kinase 3β Is Involved in Pancreatic Cancer Cell Invasion and Resistance to Therapy 
PLoS ONE  2013;8(2):e55289.
Background and Purpose
The major obstacles to treatment of pancreatic cancer are the highly invasive capacity and resistance to chemo- and radiotherapy. Glycogen synthase kinase 3β (GSK3β) regulates multiple cellular pathways and is implicated in various diseases including cancer. Here we investigate a pathological role for GSK3β in the invasive and treatment resistant phenotype of pancreatic cancer.
Methods
Pancreatic cancer cells were examined for GSK3β expression, phosphorylation and activity using Western blotting and in vitro kinase assay. The effects of GSK3β inhibition on cancer cell survival, proliferation, invasive ability and susceptibility to gemcitabine and radiation were examined following treatment with a pharmacological inhibitor or by RNA interference. Effects of GSK3β inhibition on cancer cell xenografts were also examined.
Results
Pancreatic cancer cells showed higher expression and activity of GSK3β than non-neoplastic cells, which were associated with changes in its differential phosphorylation. Inhibition of GSK3β significantly reduced the proliferation and survival of cancer cells, sensitized them to gemcitabine and ionizing radiation, and attenuated their migration and invasion. These effects were associated with decreases in cyclin D1 expression and Rb phosphorylation. Inhibition of GSK3β also altered the subcellular localization of Rac1 and F-actin and the cellular microarchitecture, including lamellipodia. Coincident with these changes were the reduced secretion of matrix metalloproteinase-2 (MMP-2) and decreased phosphorylation of focal adhesion kinase (FAK). The effects of GSK3β inhibition on tumor invasion, susceptibility to gemcitabine, MMP-2 expression and FAK phosphorylation were observed in tumor xenografts.
Conclusion
The targeting of GSK3β represents an effective strategy to overcome the dual challenges of invasiveness and treatment resistance in pancreatic cancer.
doi:10.1371/journal.pone.0055289
PMCID: PMC3568118  PMID: 23408967
11.  Aberrant glycogen synthase kinase 3β in the development of pancreatic cancer 
Development and progression of pancreatic cancer involves general metabolic disorder, local chronic inflammation, and multistep activation of distinct oncogenic molecular pathways. These pathologic processes result in a highly invasive and metastatic tumor phenotype that is a major obstacle to curative surgical intervention, infusional gemcitabine-based chemotherapy, and radiation therapy. Many clinical trials with chemical compounds and therapeutic antibodies targeting growth factors, angiogenic factors, and matrix metalloproteinases have failed to demonstrate definitive therapeutic benefits to refractory pancreatic cancer patients. Glycogen synthase kinase 3β (GSK3β), a serine/threonine protein kinase, has emerged as a therapeutic target in common chronic and progressive diseases, including cancer. Here we review accumulating evidence for a pathologic role of GSK3β in promoting tumor cell survival, proliferation, invasion, and resistance to chemotherapy and radiation in pancreatic cancer. We also discuss the putative involvement of GSK3β in mediating metabolic disorder, local inflammation, and molecular alteration leading to pancreatic cancer development. Taken together, we highlight potential therapeutic as well as preventive effects of GSK3β inhibition in pancreatic cancer.
doi:10.4103/1477-3163.100866
PMCID: PMC3516047  PMID: 23230392
Carcinogenesis; GSK3β; pancreatic cancer; tumor progression
12.  Characterization of proteins secreted by pancreatic cancer cells with anticancer drug treatment in vitro 
Oncology Reports  2012;28(6):1968-1976.
Pancreatic cancer is one of the most lethal cancers, with an incidence equaling mortality. It is a heterogeneous group of neoplasms in which pancreatic ductal adenocarcinoma is most common. Pancreatic cancer cannot be cured even if detected early. When treatment is initiated, a suitable method of administration of anticancer drugs must be chosen. Anticancer drugs kill tumor cells. However, side effects including initiation are problematic in anticancer drug therapy. Improved methods for the diagnosis of side effects of pancreatic cancer by using sensitive and specific tumor markers are highly desirable. Therefore, efficient strategies for biomarker discovery are urgently needed. Here, we present an approach based on direct experimental access to proteins released by PANC-1 human pancreatic cancer cells in vitro. A two-dimensional (2-D) map and catalog of this subproteome, herein termed the secretome, were established comprising more than 1,000 proteins observed by ‘2-D difference in-gel electrophoresis analysis using cyanine dye’. We investigated 22 spots that were 1.20-fold upregulated and 31 spots that were 0.66-fold downregulated by gemcitabine chloride treatment. Proteins in these spots were identified by nano-high-performance liquid chromatography electrospray ionization time of flight mass spectrometry/mass spectrometry. Most secretome constituents were nominally cellular proteins. By mass spectrometry screening, 14-3-3 protein sigma (14-3-3 σ), protein S100-A8, protein S100-A9, galectin-7, lactotransferrin (lactoferrin, LF) precursor, serotransferrin (transferrin) precursor, and vitamin D binding protein precursor were identified. Western blotting confirmed the presence of 14-3-3 σ and LF. We found that upregulation of 14-3-3 σ was associated with apoptosis, and downregulation of LF was found to suppress tumorigenesis.
doi:10.3892/or.2012.2020
PMCID: PMC3583485  PMID: 22961650
Panc-1; gemcitabin; secretome; 14-3-3 protein sigma; lactoferrin
13.  Meaning of tumor protein 53-induced nuclear protein 1 in the molecular mechanism of gemcitabine sensitivity 
Molecular and Clinical Oncology  2012;1(1):100-104.
Stress proteins of the pancreas, such as tumor protein 53-induced nuclear protein 1 (TP53INP1), are important factors in the invasion and metastasis of pancreatic cancer. TP53INP1 is a pro-apoptotic factor and is transcriptionally regulated in p53-dependent and -independent manners. A previous study proved that gemcitabine induces TP53INP1 expression in pancreatic cancer cells and the pancreatic cancer cell line (PANC-1). The present study aimed to clarify the association between TP53INP1 and gemcitabine sensitivity. The expression of TP53INP1 and its related factors, such as cell growth and cell cycle status in TP53INP1-knockout mouse embryonic fibroblasts [TP53INP1−/−-mouse embryonic fibroblasts (MEFs)] to those in wild-type counterparts (TP53INP1+/+-MEFs) were compared. Flow cytometric analysis demonstrated no difference of the checkpoint function in TP53INP1−/−-MEFs and TP53INP1+/+-MEFs when exposed to 10 ng/ml of gemcitabine. No significant difference was found in the level of p53 expression in the cell types, although the base level and gemcitabine-induced expression of p21 were significantly decreased in TP53INP1−/−-MEFs, compared to those in wild-type counterparts. Results showed that gemcitabine induced the p21 expression in TP53INP1+/+-MEFs, although not in TP53INP1−/−-MEFs. However, their respective cell-cycle checkpoints were not different. Therefore, TP53INP1 was found to be associated with drug sensitivity through control of the cell cycle.
doi:10.3892/mco.2012.8
PMCID: PMC3956314  PMID: 24649130
gemcitabine; tumor protein 53-induced nuclear protein 1; p21; p53; cell cycle
14.  Prediction of docetaxel monotherapy-induced neutropenia based on the monocyte percentage 
Oncology Letters  2012;3(4):860-864.
We retrospectively reviewed the medical records of 32 chemonaïve patients with either breast, lung or prostate cancer, who were treated with docetaxel (DOC) monotherapy, and evaluated whether the proportion of peripheral blood monocytes was capable of predicting the occurrence of neutropenia following chemotherapy. In the granulocyte-colony stimulating factor (G-CSF) non‑administration group, the monocyte percentage was inversely correlated with the decrease in neutrophils (P=0.01; corrected correlation coefficient, -0.71). The neutrophil count decreased by ≥30% in 7 of 8 patients with <5% monocytes, whereas it decreased by >30% in 1 of 6 patients with ≥5% monocytes (P=0.01). Three of 8 patients with <5% monocytes experienced grade 4 neutropenia, while in the group with ≥5% monocytes, 1 of 6 patients experienced grade 4 neutropenia. The frequency of grade 3 or 4 neutropenia was lower in patients with ≥5% monocytes than in patients with <5% monocytes, but the difference was not significant (P=0.41). Following G-CSF administration, grade 3 or 4 neutropenia had the tendency of lasting longer in patients with <5% monocytes than in those with ≥5% monocytes; however, the monocyte percentage was not correlated with the grade of neutropenia (P=0.34). The monocyte percentage following chemotherapy was inversely correlated with the decrease in neutrophils. The percentage of monocytes that are available in clinical practice may be predictive of neutropenia following chemotherapy. Our findings suggest that patients with <5% monocytes following DOC monotherapy are at risk of severe neutropenia and should be carefully monitored.
doi:10.3892/ol.2012.556
PMCID: PMC3362462  PMID: 22741007
monocyte; neutropenia; docetaxel; granulocyte-colony stimulating factor; chemotherapy
15.  Metabolic Disorder, Inflammation, and Deregulated Molecular Pathways Converging in Pancreatic Cancer Development: Implications for New Therapeutic Strategies 
Cancers  2011;3(1):446-460.
Pancreatic cancer develops and progresses through complex, cumulative biological processes involving metabolic disorder, local inflammation, and deregulated molecular pathways. The resulting tumor aggressiveness hampers surgical intervention and renders pancreatic cancer resistant to standard chemotherapy and radiation therapy. Based on these pathologic properties, several therapeutic strategies are being developed to reverse refractory pancreatic cancer. Here, we outline molecular targeting therapies, which are primarily directed against growth factor receptor-type tyrosine kinases deregulated in tumors, but have failed to improve the survival of pancreatic cancer patients. Glycogen synthase kinase-3β (GSK3β) is a member of a serine/threonine protein kinase family that plays a critical role in various cellular pathways. GSK3β has also emerged as a mediator of pathological states, including glucose intolerance, inflammation, and various cancers (e.g., pancreatic cancer). We review recent studies that demonstrate the anti-tumor effects of GSK3β inhibition alone or in combination with chemotherapy and radiation. GSK3β inhibition may exert indirect anti-tumor actions in pancreatic cancer by modulating metabolic disorder and inflammation.
doi:10.3390/cancers3010446
PMCID: PMC3756371  PMID: 24212624
pancreatic cancer; glucose intolerance; inflammation; oncogenic pathways; therapeutic target; GSK3β
16.  The combination of baicalin and baicalein enhances apoptosis via the ERK/p38 MAPK pathway in human breast cancer cells 
Acta Pharmacologica Sinica  2009;30(12):1648-1658.
Aim:
To examine whether the cell growth inhibitory effect of the combination of baicalin and baicalein is related to apoptosis. Moreover, to determine whether the expression of some apoptosis-related proteins is regulated by the ERK/p38 MAPK pathway.
Methods:
Cell viability was measured using a 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Apoptosis was detected by acridine orange (AO) staining, DNA ladder assay and flow cytometric analysis. Apoptosis-related proteins were observed using Western blot analysis.
Results:
Compared with baicalin or baicalein alone, the combination treatment of baicalin (50 μmol/L) and baicalein (25 μmol/L) had an anti-proliferative effect in a time-dependent manner. Isobologram analysis demonstrated that the combination treatment had a synergistic effect. Moreover, apoptosis in MCF-7 cells was increased by 12% and 20% with the combination treatment at 24 h and 48 h, respectively. With the combination treatment in MCF-7 cells, cleaved caspase-3 and caspase-9 were observed, and the level of bcl-2 expression was decreased approximately 20% and 40% at 24 h and 48 h, respectively. The expression of bax and p53 were increased about 25% and 15% at 48 h, respectively. Moreover, the activation of caspase-3, -9 and the regulation of bcl-2, bax and p53 were related to ERK /p38 MAPK activation.
Conclusion:
In this study, apoptosis was enhanced by the combination treatment of baicalin and baicalein, which activated caspases-3 and caspase-9, downregulated the level of bcl-2 and upregulated the level of bax or p53 via the ERK/p38 MAPK pathway.
doi:10.1038/aps.2009.166
PMCID: PMC4007493  PMID: 19960010
baicalin; baicalein; combination therapy; apoptosis; breast cancer cells
17.  A Kampo Medicine, Boi-ogi-to, Inhibits Obesity in Ovariectomized Rats 
In women facing menopause, end of menstrual activity is accompanied by lower levels of estrogen and gradual weight gain. Postmenopausal weight gain sounds an alarm for women's health and may lead to hyperlipidemia, a lipid increase and glucose intolerance. These phenomena are connected to lifestyle-related diseases such as hypertension, type II diabetes mellitus, arteriosclerosis and metabolic syndrome, making it essential to prevent weight gain in women. A Kampo medicine, Boi-ogi-to, is traditionally used to treat obese conditions, but the mechanism has not yet been investigated. In this experiment, we tested the antiobesity properties of Boi-ogi-to in ovariectomized rats by measuring changes of serum cytokine levels and adipocytokines in fat cells. After treatment with this extract for 6 weeks (20-week-old rats), we found that there was a significant weight decrease in rats treated with Boi-ogi-to as compared with that in the control group. Serum tumor necrosis factor (TNF)-α levels increased significantly in a dose-dependent manner. Gene expression of adipose tissue in uterus also dose dependently showed a significant increase of TNF-α levels, suggesting that secretion of TNF-α by fat cells might play a role in the ability of Boi-ogi-to to inhibit weight gain. While peroxisome proliferators-activated receptor-γ and adiponectin levels did not show a significant difference as compared with those in the control, levels of mRNA expression showed a tendency to increase dose dependently. Resistin did not show any significant change. These results suggest that Boi-ogi-to might be useful for the prevention of obesity that occurs in women with reduction of estrogen.
doi:10.1093/ecam/nem153
PMCID: PMC2816381  PMID: 18955282
Adipocytokines; Boi-ogi-to; obesity; ovariectomized rats
18.  Pancreatitis-associated protein: From a lectin to an anti-inflammatory cytokine 
Pancreatitis-associated protein (PAP) was discovered in the pancreatic juice of rats with acute pancreatitis. PAP is a 16 kDa secretory protein structurally related to the C-type lectins although classical lectin-related function has not been reported yet. Then, it was demonstrated that PAP expression may be activated in some tissues in a constitutive or injury- and inflammation-induced manner. More recently, it has been found that PAP acts as an anti-inflammatory factor in vitro and in vivo. PAP expression can be induced by several pro- and anti-inflammatory cytokines and by itself through a JAK/STAT3-dependent pathway. PAP is able to activate the expression of the anti-inflammatory factor SOCS3 through the JAK/STAT3-dependent pathway. The JAK/STAT3/SOCS3 pathway seems to be a common point between PAP and several cytokines. Therefore, it is reasonable to propose that PAP is a new anti-inflammatory cytokine.
doi:10.3748/wjg.v13.i2.170
PMCID: PMC4065945  PMID: 17226896
Pancreatitis-associated protein; Pancreatitis; Janus kinases; STAT3; SOCS3; Anti-inflammatory; Lectin
19.  Effect of gemcitabine on the expression of apoptosis-related genes in human pancreatic cancer cells 
AIM: To investigate the expression of genes involved in the gemcitabine-induced cytotoxicity in human pancreatic cancer cells.
METHODS: A human pancreatic cancer cell line, PANC-1, was cultured. 1 x 104 PANC-1 cells were plated in 96-well microtiter plates. After being incubated for 24 h, gemcitabine was added to the medium at concentrations ranging 2.5 -1 000 mg/L. The AlamarBlue dye method was used for cell growth analysis. DNA fragmentation was quantitatively assayed using a DNA fragmentation enzyme-linked immunosorbent assay (ELISA) kit. PAP and TP53INP1 mRNA expression was determined using the reverse transcription-polymerase chain reaction with semi-quantitative analysis. The expression of GSK-3β and phospho-GSK-3β proteins was examined with Western blot analysis.
RESULTS: The IC50 for the drug after a 48-h exposure to gemcitabine was 16 mg/L. The growth of PANC-1 cells was inhibited by gemcitabine in a concentration-dependent manner (P < 0.0001) and the cell growth was also inhibited throughout the time course (P < 0.0001). The DNA fragmentation rate in the gemcitabine-treated group at 48 h was 44.7 %, whereas it was 25.3 % in the untreated group. The PAP mRNA expression was decreased after being treated with gemcitabine, whereas the TP53INP1 mRNA was increased by the gemcitabine treatment. Western blot analysis showed that phospho- GSK-3βser9 was induced by the gemcitabine treatment.
CONCLUSION: Gemcitabine suppresses PANC-1 cell proliferation and induces apoptosis. Apoptosis is considered to be associated with the inhibition of PAP and GSK-3β, and the activation of TP53INP1 and pospho-GSK-3βser9.
doi:10.3748/wjg.v12.i10.1597
PMCID: PMC4124293  PMID: 16570353
Gemcitabine; Pancreatitis-associated protein; TP53INP1; GSK-3β; PANC-1
20.  Down-expression of tumor protein p53-induced nuclear protein 1 in human gastric cancer 
AIM: Overexpression of tumor protein p53-induced nuclear protein 1 (TP53INP1) induces G1 cell cycle arrest and increases p53-mediated apoptosis. To clarify the clinical importance of TP53INP1, we analyzed TP53INP1 and p53 expression in gastric cancer.
METHODS: TP53INP1 and p53 expression were examined using immunohistochemistry in 142 cases of gastric cancer. The apoptosis of gastric cancer cells was analyzed using the TUNEL method. The relationship between the expression of TP53INP1 and clinicopathological factors was statistically analyzed.
RESULTS: TP53INP1 was expressed in 98% (139/142 cases) of non-cancerous gastric tissues and was down-expressed in 64% (91/142 cases) of gastric cancer lesions from the same patients. TP53INP1 expression was significantly decreased (43.9%) in poorly differentiated adenocarcinoma compared with well or moderately differentiated adenocarcinoma (81.6%). Cancers invading the submucosa or deeper showed lower positively (59.1%) compared with mucosal cancers (85.2%). Decrease or loss of TP53INP1 expression was significantly correlated with lymphatic invasion (54.3% vs 82.0% without lymphatic invasion) and node-positive patients (31.3% vs 68.3% in node-negative patients). P53 was expressed in 68 (47.9%) patients of gastric cancer, whereas it was absent in normal gastric tissues. A significant association was also observed between TP53INP1 status and the level of apoptosis in tumor cells: the apoptotic index in TP53INP1-positive tissues was significantly higher than that in TP53INP1-negative portions. Finally, when survival data were analyzed, loss of TP53INP1 expression had a significant effect in predicting a poor prognosis (P = 0.0006).
CONCLUSION: TP53INP1-positive rate decreases with the progression of gastric cancer. TP53INP1 protein negativity is significantly associated with aggressive pathological phenotypes of gastric cancer. TP53INP1 is related to the apoptosis of gastric cancer cells. The decreased expression of the TP53INP1 protein may reflect the malignant grade of gastric cancer and is regarded as an adverse prognostic factor.
doi:10.3748/wjg.v12.i5.691
PMCID: PMC4066117  PMID: 16521180
Tumor protein 53-induced nuclear protein 1; p53; Gastric cancer
21.  Herbal medicine Ninjinyoeito ameliorates ribavirin-induced anemia in chronic hepatitis C: A randomized controlled trial 
AIM: Ribavirin (RBV) shows a strong antiviral effect on hepatitis C virus when used in combination with interferon. However, RBV-induced anemia is a major problem in this therapy. It would be of great clinical importance to ameliorate the anemia without reducing the RBV dose. We report here that, Ninjinyoeito (NYT), a herbal medicine can reduce the RBV-induced anemia.
METHODS: Twenty-three patients with chronic hepatitis C were treated with interferon alpha 2b plus RBV with (NYT group) or without (control group) NYT by a randomized selection. Eighteen patients completed the treatment schedule, and hemato-biochemical and virological effects were evaluated.
RESULTS: There was no significant difference in biochemical and virological responses between the two groups. However, anemia was significantly reduced in the NYT group compared with the control group. The maximal decrease of Hb in the NYT group (2.59 ± 1.10 g/dL) was significantly (P = 0.026) smaller than that in the control group (3.71 ± 0.97 g/dL). There was no significant difference in serum glutathione peroxidase activity, serum RBV concentration, and Th1/Th2 balance between the two groups. There was no specific adverse effect in NYT administration.
CONCLUSION: These results suggest that NYT could be used as a supportive remedy to reduce the RBV-induced anemia in the treatment of chronic hepatitis C.
doi:10.3748/wjg.v11.i26.4013
PMCID: PMC4502096  PMID: 15996025
Chronic hepatitis C; Ribavirin; Interferon; Herbal medicine; Anemia

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