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  • Salminen, Antti; Jambor, Ivan; Merisaari, Harri; Ettala, Otto; Virtanen, Johanna; Koskinen, Ilmari; Veskimae, Erik; Sairanen, Jukka; Taimen, Pekka; Kemppainen, Jukka; Minn, Heikki; Boström, Peter J (BioMed Central, 2018)
    Abstract Background To evaluate the accuracy of 11C-acetate Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) in bladder cancer (BC) staging and monitoring response to neoadjuvant chemotherapy (NAC). Methods Eighteen patients were prospectively enrolled. Fifteen treatment naive patients underwent 11C-acetate PET/MRI before transurethral resection of bladder tumor (TUR-BT) for primary tumor evaluation. Five patients with muscle invasive BC were imaged after NAC and prior to radical cystectomy (RC) with extended pelvic lymph node dissection (ePLND) for NAC treatment response evaluation. Two patients were part of both cohorts. 11C-acetate PET/MRI findings were correlated with histopathology. Accuracy for lymph node detection was evaluated on patient and the ePLND template (10 regions) levels. Results The sensitivity, specificity and accuracy of 11C-acetate PET/MRI for the detection of muscle invasive BC was 1.00, 0.69 and 0.73 while the area under the receiver operating characteristic curve (95% confidence interval) was 0.85 (0.55–1.0), respectively. All five NAC patients underwent chemotherapy as planned and 11C-acetate PET/MRI correctly staged three patients, overstaged one and understaged one patient compared with RC and ePLND findings. A total of 175 lymph node were removed, median of 35 (range, 27–43) per patient in five patients who had RC and ePLND while 12 (7%) harboured metastases. Sensitivity, specificity, accuracy and AUC for N-staging were 0.20, 0.96, 0.80 and 0.58 on the ePLND template (10 regions) level. Conclusions 11C-acetate PET/MRI is feasible for staging of BC although sensitivity for the detection of nodal metastases is low. Monitoring response to NAC shows promise and warrants evaluation in larger studies. Trial registration ClinicalTrials.gov Identifier: NCT01918592 , registered August 8 2013
  • Ager, Casey; Reilley, Matthew; Nicholas, Courtney; Bartkowiak, Todd; Jaiswal, Ashvin; Curran, Michael; Albershardt, Tina C; Bajaj, Anshika; Archer, Jacob F; Reeves, Rebecca S; Ngo, Lisa Y; Berglund, Peter; ter Meulen, Jan; Denis, Caroline; Ghadially, Hormas; Arnoux, Thomas; Chanuc, Fabien; Fuseri, Nicolas; Wilkinson, Robert W; Wagtmann, Nicolai; Morel, Yannis; Andre, Pascale; Atkins, Michael B; Carlino, Matteo S; Ribas, Antoni; Thompson, John A; Choueiri, Toni K; Hodi, F. S; Hwu, Wen-Jen; McDermott, David F; Atkinson, Victoria; Cebon, Jonathan S; Fitzharris, Bernie; Jameson, Michael B; McNeil, Catriona; Hill, Andrew G; Mangin, Eric; Ahamadi, Malidi; van Vugt, Marianne; van Zutphen, Mariëlle; Ibrahim, Nageatte; Long, Georgina V; Gartrell, Robyn; Blake, Zoe; Simoes, Ines; Fu, Yichun; Saito, Takuro; Qian, Yingzhi; Lu, Yan; Saenger, Yvonne M; Budhu, Sadna; De Henau, Olivier; Zappasodi, Roberta; Schlunegger, Kyle; Freimark, Bruce; Hutchins, Jeff; Barker, Christopher A; Wolchok, Jedd D; Merghoub, Taha; Burova, Elena; Allbritton, Omaira; Hong, Peter; Dai, Jie; Pei, Jerry; Liu, Matt; Kantrowitz, Joel; Lai, Venus; Poueymirou, William; MacDonald, Douglas; Ioffe, Ella; Mohrs, Markus; Olson, William; Thurston, Gavin; Capasso, Cristian; Frascaro, Federica; Carpi, Sara; Tähtinen, Siri; Feola, Sara; Fusciello, Manlio; Peltonen, Karita; Martins, Beatriz; Sjöberg, Madeleine; Pesonen, Sari; Ranki, Tuuli; Kyruk, Lukasz; Ylösmäki, Erkko; Cerullo, Vincenzo; Cerignoli, Fabio; Xi, Biao; Guenther, Garret; Yu, Naichen; Muir, Lincoln; Zhao, Leyna; Abassi, Yama; Cervera-Carrascón, Víctor; Siurala, Mikko; Santos, João; Havunen, Riikka; Parviainen, Suvi; Hemminki, Akseli; Dalgleish, Angus; Mudan, Satvinder; DeBenedette, Mark; Plachco, Ana; Gamble, Alicia; Grogan, Elizabeth W; Krisko, John; Tcherepanova, Irina; Nicolette, Charles; Dhupkar, Pooja; Yu, Ling; Kleinerman, Eugenie S; Gordon, Nancy; Grenga, Italia; Lepone, Lauren; Gameiro, Sofia; Knudson, Karin M; Fantini, Massimo; Tsang, Kwong; Hodge, James; Donahue, Renee; Schlom, Jeffrey; Evans, Elizabeth; Bussler, Holm; Mallow, Crystal; Reilly, Christine; Torno, Sebold; Scrivens, Maria; Foster, Cathie; Howell, Alan; Balch, Leslie; Knapp, Alyssa; Leonard, John E; Paris, Mark; Fisher, Terry; Hu-Lieskovan, Siwen; Ribas, Antoni; Smith, Ernest; Zauderer, Maurice; Fogler, William; Franklin, Marilyn; Thayer, Matt; Saims, Dan; Magnani, John L; Gong, Jian; Gray, Michael; Hutchins, Jeff; Freimark, Bruce; Fromm, George; de Silva, Suresh; Giffin, Louise; Xu, Xin; Rose, Jason; Schreiber, Taylor H; Fantini, Massimo; Gameiro, Sofia R; Knudson, Karin M; Clavijo, Paul E; Allen, Clint T; Donahue, Renee; Lepone, Lauren; Grenga, Italia; Hodge, James W; Tsang, Kwong Y; Schlom, Jeffrey; Gray, Michael; Gong, Jian; Hutchins, Jeff; Freimark, Bruce; Grogan, Jane; Manieri, Nicholas; Chiang, Eugene; Caplazi, Patrick; Yadav, Mahesh; Hagner, Patrick; Chiu, Hsiling; Waldman, Michelle; Klippel, Anke; Thakurta, Anjan; Pourdehnad, Michael; Gandhi, Anita; Henrich, Ian; Quick, Laura; Young, Rob; Chou, Margaret; Hotson, Andrew; Willingham, Stephen; Ho, Po; Choy, Carmen; Laport, Ginna; McCaffery, Ian; Miller, Richard; Tipton, Kimberly A; Wong, Kenneth R; Singson, Victoria; Wong, Chihunt; Chan, Chanty; Huang, Yuanhiu; Liu, Shouchun; Richardson, Jennifer H; Kavanaugh, W. M; West, James; Irving, Bryan A; Tipton, Kimberly A; Wong, Kenneth R; Singson, Victoria; Wong, Chihunt; Chan, Chanty; Huang, Yuanhiu; Liu, Shouchun; Richardson, Jennifer H; Kavanaugh, W. M; West, James; Irving, Bryan A; Jaini, Ritika; Loya, Matthew; Eng, Charis; Johnson, Melissa L; Adjei, Alex A; Opyrchal, Mateusz; Ramalingam, Suresh; Janne, Pasi A; Dominguez, George; Gabrilovich, Dmitry; de Leon, Laura; Hasapidis, Jeannette; Diede, Scott J; Ordentlich, Peter; Cruickshank, Scott; Meyers, Michael L; Hellmann, Matthew D; Kalinski, Pawel; Zureikat, Amer; Edwards, Robert; Muthuswamy, Ravi; Obermajer, Nataša; Urban, Julie; Butterfield, Lisa H; Gooding, William; Zeh, Herbert; Bartlett, David; Zubkova, Olga; Agapova, Larissa; Kapralova, Marina; Krasovskaia, Liudmila; Ovsepyan, Armen; Lykov, Maxim; Eremeev, Artem; Bokovanov, Vladimir; Grigoryeva, Olga; Karpov, Andrey; Ruchko, Sergey; Nicolette, Charles; Shuster, Alexandr; Khalil, Danny N; Campesato, Luis F; Li, Yanyun; Merghoub, Taha; Wolchok, Jedd D; Lazorchak, Adam S; Patterson, Troy D; Ding, Yueyun; Sasikumar, Pottayil; Sudarshan, Naremaddepalli; Gowda, Nagaraj; Ramachandra, Raghuveer; Samiulla, Dodheri; Giri, Sanjeev; Eswarappa, Rajesh; Ramachandra, Murali; Tuck, David; Wyant, Timothy; Leshem, Jasmin; Liu, Xiu-fen; Bera, Tapan; Terabe, Masaki; Bossenmaier, Birgit; Niederfellner, Gerhard; Reiter, Yoram; Pastan, Ira; Xia, Leiming; Xia, Yang; Hu, Yangyang; Wang, Yi; Bao, Yangyi; Dai, Fu; Huang, Shiang; Hurt, Elaine; Hollingsworth, Robert E; Lum, Lawrence G; Chang, Alfred E; Wicha, Max S; Li, Qiao; Mace, Thomas; Makhijani, Neil; Talbert, Erin; Young, Gregory; Guttridge, Denis; Conwell, Darwin; Lesinski, Gregory B; Gonzales, Rodney J M; Huffman, Austin P; Wang, Ximi K; Reshef, Ran; MacKinnon, Andy; Chen, Jason; Gross, Matt; Marguier, Gisele; Shwonek, Peter; Sotirovska, Natalija; Steggerda, Susanne; Parlati, Francesco; Makkouk, Amani; Bennett, Mark K; Chen, Jason; Emberley, Ethan; Gross, Matt; Huang, Tony; Li, Weiqun; MacKinnon, Andy; Marguier, Gisele; Neou, Silinda; Pan, Alison; Zhang, Jing; Zhang, Winter; Parlati, Francesco; Marshall, Netonia; Marron, Thomas U; Agudo, Judith; Brown, Brian; Brody, Joshua; McQuinn, Christopher; Mace, Thomas; Farren, Matthew; Komar, Hannah; Shakya, Reena; Young, Gregory; Ludwug, Thomas; Lesinski, Gregory B; Morillon, Y. M; Hammond, Scott A; Schlom, Jeffrey; Greiner, John W; Nath, Pulak R; Schwartz, Anthony L; Maric, Dragan; Roberts, David D; Obermajer, Nataša; Bartlett, David; Kalinski, Pawel; Naing, Aung; Papadopoulos, Kyriakos P; Autio, Karen A; Wong, Deborah J; Patel, Manish; Falchook, Gerald; Pant, Shubham; Ott, Patrick A; Whiteside, Melinda; Patnaik, Amita; Mumm, John; Janku, Filip; Chan, Ivan; Bauer, Todd; Colen, Rivka; VanVlasselaer, Peter; Brown, Gail L; Tannir, Nizar M; Oft, Martin; Infante, Jeffrey; Lipson, Evan; Gopal, Ajay; Neelapu, Sattva S; Armand, Philippe; Spurgeon, Stephen; Leonard, John P; Hodi, F. S; Sanborn, Rachel E; Melero, Ignacio; Gajewski, Thomas F; Maurer, Matthew; Perna, Serena; Gutierrez, Andres A; Clynes, Raphael; Mitra, Priyam; Suryawanshi, Satyendra; Gladstone, Douglas; Callahan, Margaret K; Crooks, James; Brown, Sheila; Gauthier, Audrey; de Boisferon, Marc H; MacDonald, Andrew; Brunet, Laura R; Rothwell, William T; Bell, Peter; Wilson, James M; Sato-Kaneko, Fumi; Yao, Shiyin; Zhang, Shannon S; Carson, Dennis A; Guiducci, Cristina; Coffman, Robert L; Kitaura, Kazutaka; Matsutani, Takaji; Suzuki, Ryuji; Hayashi, Tomoko; Cohen, Ezra E W; Schaer, David; Li, Yanxia; Dobkin, Julie; Amatulli, Michael; Hall, Gerald; Doman, Thompson; Manro, Jason; Dorsey, Frank C; Sams, Lillian; Holmgaard, Rikke; Persaud, Krishnadatt; Ludwig, Dale; Surguladze, David; Kauh, John S; Novosiadly, Ruslan; Kalos, Michael; Driscoll, Kyla; Pandha, Hardev; Ralph, Christy; Harrington, Kevin; Curti, Brendan; Sanborn, Rachel E; Akerley, Wallace; Gupta, Sumati; Melcher, Alan; Mansfield, David; Kaufman, David R; Schmidt, Emmett; Grose, Mark; Davies, Bronwyn; Karpathy, Roberta; Shafren, Darren; Shamalov, Katerina; Cohen, Cyrille; Sharma, Naveen; Allison, James; Shekarian, Tala; Valsesia-Wittmann, Sandrine; Caux, Christophe; Marabelle, Aurelien; Slomovitz, Brian M; Moore, Kathleen M; Youssoufian, Hagop; Posner, Marshall; Tewary, Poonam; Brooks, Alan D; Xu, Ya-Ming; Wijeratne, Kithsiri; Gunatilaka, Leslie A A; Sayers, Thomas J; Vasilakos, John P; Alston, Tesha; Dovedi, Simon; Elvecrog, James; Grigsby, Iwen; Herbst, Ronald; Johnson, Karen; Moeckly, Craig; Mullins, Stefanie; Siebenaler, Kristen; SternJohn, Julius; Tilahun, Ashenafi; Tomai, Mark A; Vogel, Katharina; Wilkinson, Robert W; Vietsch, Eveline E; Wellstein, Anton; Wythes, Martin; Crosignani, Stefano; Tumang, Joseph; Alekar, Shilpa; Bingham, Patrick; Cauwenberghs, Sandra; Chaplin, Jenny; Dalvie, Deepak; Denies, Sofie; De Maeseneire, Coraline; Feng, JunLi; Frederix, Kim; Greasley, Samantha; Guo, Jie; Hardwick, James; Kaiser, Stephen; Jessen, Katti; Kindt, Erick; Letellier, Marie-Claire; Li, Wenlin; Maegley, Karen; Marillier, Reece; Miller, Nichol; Murray, Brion; Pirson, Romain; Preillon, Julie; Rabolli, Virginie; Ray, Chad; Ryan, Kevin; Scales, Stephanie; Srirangam, Jay; Solowiej, Jim; Stewart, Al; Streiner, Nicole; Torti, Vince; Tsaparikos, Konstantinos; Zheng, Xianxian; Driessens, Gregory; Gomes, Bruno; Kraus, Manfred; Xu, Chunxiao; Zhang, Yanping; Kradjian, Giorgio; Qin, Guozhong; Qi, Jin; Xu, Xiaomei; Marelli, Bo; Yu, Huakui; Guzman, Wilson; Tighe, Rober; Salazar, Rachel; Lo, Kin-Ming; English, Jessie; Radvanyi, Laszlo; Lan, Yan; Zappasodi, Roberta; Budhu, Sadna; Hellmann, Matthew D; Postow, Michael; Senbabaoglu, Yasin; Gasmi, Billel; Zhong, Hong; Li, Yanyun; Liu, Cailian; Hirschhorhn-Cymerman, Daniel; Wolchok, Jedd D; Merghoub, Taha; Zha, Yuanyuan; Malnassy, Gregory; Fulton, Noreen; Park, Jae-Hyun; Stock, Wendy; Nakamura, Yusuke; Gajewski, Thomas F; Liu, Hongtao; Ju, Xiaoming; Kosoff, Rachelle; Ramos, Kimberly; Coder, Brandon; Petit, Robert; Princiotta, Michael; Perry, Kyle; Zou, Jun; Arina, Ainhoa; Fernandez, Christian; Zheng, Wenxin; Beckett, Michael A; Mauceri, Helena J; Fu, Yang-Xin; Weichselbaum, Ralph R; DeBenedette, Mark; Lewis, Whitney; Gamble, Alicia; Nicolette, Charles; Han, Yanyan; Wu, Yeting; Yang, Chou; Huang, Jing; Wu, Dongyun; Li, Jin; Liang, Xiaoling; Zhou, Xiangjun; Hou, Jinlin; Hassan, Raffit; Jahan, Thierry; Antonia, Scott J; Kindler, Hedy L; Alley, Evan W; Honarmand, Somayeh; Liu, Weiqun; Leong, Meredith L; Whiting, Chan C; Nair, Nitya; Enstrom, Amanda; Lemmens, Edward E; Tsujikawa, Takahiro; Kumar, Sushil; Coussens, Lisa M; Murphy, Aimee L; Brockstedt, Dirk G; Koch, Sven D; Sebastian, Martin; Weiss, Christian; Früh, Martin; Pless, Miklos; Cathomas, Richard; Hilbe, Wolfgang; Pall, Georg; Wehler, Thomas; Alt, Jürgen; Bischoff, Helge; Geissler, Michael; Griesinger, Frank; Kollmeier, Jens; Papachristofilou, Alexandros; Doener, Fatma; Fotin-Mleczek, Mariola; Hipp, Madeleine; Hong, Henoch S; Kallen, Karl-Josef; Klinkhardt, Ute; Stosnach, Claudia; Scheel, Birgit; Schroeder, Andreas; Seibel, Tobias; Gnad-Vogt, Ulrike; Zippelius, Alfred; Park, Ha-Ram; Ahn, Yong-Oon; Kim, Tae M; Kim, Soyeon; Kim, Seulki; Lee, Yu S; Keam, Bhumsuk; Kim, Dong-Wan; Heo, Dae S; Pilon-Thomas, Shari; Weber, Amy; Morse, Jennifer; Kodumudi, Krithika; Liu, Hao; Mullinax, John; Sarnaik, Amod A; Pike, Luke; Bang, Andrew; Ott, Patrick A; Balboni, Tracy; Taylor, Allison; Spektor, Alexander; Wilhite, Tyler; Krishnan, Monica; Cagney, Daniel; Alexander, Brian; Aizer, Ayal; Buchbinder, Elizabeth; Awad, Mark; Ghandi, Leena; Hodi, F. S; Schoenfeld, Jonathan; Schwartz, Anthony L; Nath, Pulak R; Lessey-Morillon, Elizabeth; Ridnour, Lisa; Roberts, David D; Segal, Neil H; Sharma, Manish; Le, Dung T; Ott, Patrick A; Ferris, Robert L; Zelenetz, Andrew D; Neelapu, Sattva S; Levy, Ronald; Lossos, Izidore S; Jacobson, Caron; Ramchandren, Radhakrishnan; Godwin, John; Colevas, A. D; Meier, Roland; Krishnan, Suba; Gu, Xuemin; Neely, Jaclyn; Suryawanshi, Satyendra; Timmerman, John; Vanpouille-Box, Claire I; Formenti, Silvia C; Demaria, Sandra; Wennerberg, Erik; Mediero, Aranzazu; Cronstein, Bruce N; Formenti, Silvia C; Demaria, Sandra; Gustafson, Michael P; DiCostanzo, AriCeli; Wheatley, Courtney; Kim, Chul-Ho; Bornschlegl, Svetlana; Gastineau, Dennis A; Johnson, Bruce D; Dietz, Allan B; MacDonald, Cameron; Bucsek, Mark; Qiao, Guanxi; Hylander, Bonnie; Repasky, Elizabeth; Turbitt, William J; Xu, Yitong; Mastro, Andrea; Rogers, Connie J; Withers, Sita; Wang, Ziming; Khuat, Lam T; Dunai, Cordelia; Blazar, Bruce R; Longo, Dan; Rebhun, Robert; Grossenbacher, Steven K; Monjazeb, Arta; Murphy, William J; Rowlinson, Scott; Agnello, Giulia; Alters, Susan; Lowe, David; Scharping, Nicole; Menk, Ashley V; Whetstone, Ryan; Zeng, Xue; Delgoffe, Greg M; Santos, Patricia M; Menk, Ashley V; Shi, Jian; Delgoffe, Greg M; Butterfield, Lisa H; Whetstone, Ryan; Menk, Ashley V; Scharping, Nicole; Delgoffe, Greg; Nagasaka, Misako; Sukari, Ammar; Byrne-Steele, Miranda; Pan, Wenjing; Hou, Xiaohong; Brown, Brittany; Eisenhower, Mary; Han, Jian; Collins, Natalie; Manguso, Robert; Pope, Hans; Shrestha, Yashaswi; Boehm, Jesse; Haining, W. N; Cron, Kyle R; Sivan, Ayelet; Aquino-Michaels, Keston; Gajewski, Thomas F; Orecchioni, Marco; Bedognetti, Davide; Hendrickx, Wouter; Fuoco, Claudia; Spada, Filomena; Sgarrella, Francesco; Cesareni, Gianni; Marincola, Francesco; Kostarelos, Kostas; Bianco, Alberto; Delogu, Lucia; Hendrickx, Wouter; Roelands, Jessica; Boughorbel, Sabri; Decock, Julie; Presnell, Scott; Wang, Ena; Marincola, Franco M; Kuppen, Peter; Ceccarelli, Michele; Rinchai, Darawan; Chaussabel, Damien; Miller, Lance; Bedognetti, Davide; Nguyen, Andrew; Sanborn, J. Z; Vaske, Charles; Rabizadeh, Shahrooz; Niazi, Kayvan; Benz, Steven; Patel, Shashank; Restifo, Nicholas; White, James; Angiuoli, Sam; Sausen, Mark; Jones, Sian; Sevdali, Maria; Simmons, John; Velculescu, Victor; Diaz, Luis; Zhang, Theresa; Sims, Jennifer S; Barton, Sunjay M; Gartrell, Robyn; Kadenhe-Chiweshe, Angela; Dela Cruz, Filemon; Turk, Andrew T; Lu, Yan; Mazzeo, Christopher F; Kung, Andrew L; Bruce, Jeffrey N; Saenger, Yvonne M; Yamashiro, Darrell J; Connolly, Eileen P; Baird, Jason; Crittenden, Marka; Friedman, David; Xiao, Hong; Leidner, Rom; Bell, Bryan; Young, Kristina; Gough, Michael; Bian, Zhen; Kidder, Koby; Liu, Yuan; Curran, Emily; Chen, Xiufen; Corrales, Leticia P; Kline, Justin; Dunai, Cordelia; Aguilar, Ethan G; Khuat, Lam T; Murphy, William J; Guerriero, Jennifer; Sotayo, Alaba; Ponichtera, Holly; Pourzia, Alexandra; Schad, Sara; Carrasco, Ruben; Lazo, Suzan; Bronson, Roderick; Letai, Anthony; Kornbluth, Richard S; Gupta, Sachin; Termini, James; Guirado, Elizabeth; Stone, Geoffrey W; Meyer, Christina; Helming, Laura; Tumang, Joseph; Wilson, Nicholas; Hofmeister, Robert; Radvanyi, Laszlo; Neubert, Natalie J; Tillé, Laure; Barras, David; Soneson, Charlotte; Baumgaertner, Petra; Rimoldi, Donata; Gfeller, David; Delorenzi, Mauro; Fuertes Marraco, Silvia A; Speiser, Daniel E; Abraham, Tara S; Xiang, Bo; Magee, Michael S; Waldman, Scott A; Snook, Adam E; Blogowski, Wojciech; Zuba-Surma, Ewa; Budkowska, Marta; Salata, Daria; Dolegowska, Barbara; Starzynska, Teresa; Chan, Leo; Somanchi, Srinivas; McCulley, Kelsey; Lee, Dean; Buettner, Nico; Shi, Feng; Myers, Paisley T; Curbishley, Stuart; Penny, Sarah A; Steadman, Lora; Millar, David; Speers, Ellen; Ruth, Nicola; Wong, Gabriel; Thimme, Robert; Adams, David; Cobbold, Mark; Thomas, Remy; Hendrickx, Wouter; Al-Muftah, Mariam; Decock, Julie; Wong, Michael K; Morse, Michael; McDermott, David F; Clark, Joseph I; Kaufman, Howard L; Daniels, Gregory A; Hua, Hong; Rao, Tharak; Dutcher, Janice P; Kang, Kai; Saunthararajah, Yogen; Velcheti, Vamsidhar; Kumar, Vikas; Anwar, Firoz; Verma, Amita; Chheda, Zinal; Kohanbash, Gary; Sidney, John; Okada, Kaori; Shrivastav, Shruti; Carrera, Diego A; Liu, Shuming; Jahan, Naznin; Mueller, Sabine; Pollack, Ian F; Carcaboso, Angel M; Sette, Alessandro; Hou, Yafei; Okada, Hideho; Field, Jessica J; Zeng, Weiping; Shih, Vincent F; Law, Che-Leung; Senter, Peter D; Gardai, Shyra J; Okeley, Nicole M; Penny, Sarah A; Abelin, Jennifer G; Saeed, Abu Z; Malaker, Stacy A; Myers, Paisley T; Shabanowitz, Jeffrey; Ward, Stephen T; Hunt, Donald F; Cobbold, Mark; Profusek, Pam; Wood, Laura; Shepard, Dale; Grivas, Petros; Kapp, Kerstin; Volz, Barbara; Oswald, Detlef; Wittig, Burghardt; Schmidt, Manuel; Sefrin, Julian P; Hillringhaus, Lars; Lifke, Valeria; Lifke, Alexander; Skaletskaya, Anna; Ponte, Jose; Chittenden, Thomas; Setiady, Yulius; Valsesia-Wittmann, Sandrine; Sivado, Eva; Thomas, Vincent; El Alaoui, Meddy; Papot, Sébastien; Dumontet, Charles; Dyson, Mike; McCafferty, John; El Alaoui, Said; Verma, Amita; Kumar, Vikas; Bommareddy, Praveen K; Kaufman, Howard L; Zloza, Andrew; Kohlhapp, Frederick; Silk, Ann W; Jhawar, Sachin; Paneque, Tomas; Bommareddy, Praveen K; Kohlhapp, Frederick; Newman, Jenna; Beltran, Pedro; Zloza, Andrew; Kaufman, Howard L; Cao, Felicia; Hong, Bang-Xing; Rodriguez-Cruz, Tania; Song, Xiao-Tong; Gottschalk, Stephen; Calderon, Hugo; Illingworth, Sam; Brown, Alice; Fisher, Kerry; Seymour, Len; Champion, Brian; Eriksson, Emma; Wenthe, Jessica; Hellström, Ann-Charlotte; Paul-Wetterberg, Gabriella; Loskog, Angelica; Eriksson, Emma; Milenova, Ioanna; Wenthe, Jessica; Ståhle, Magnus; Jarblad-Leja, Justyna; Ullenhag, Gustav; Dimberg, Anna; Moreno, Rafael; Alemany, Ramon; Loskog, Angelica; Eriksson, Emma; Milenova, Ioanna; Moreno, Rafael; Alemany, Ramon; Loskog, Angelica; Jhawar, Sachin; Goyal, Sharad; Bommareddy, Praveen K; Paneque, Tomas; Kaufman, Howard L; Zloza, Andrew; Kaufman, Howard L; Silk, Ann; Mehnert, Janice; Gabrail, Nashat; Bryan, Jennifer; Medina, Daniel; Bommareddy, Praveen K; Shafren, Darren; Grose, Mark; Zloza, Andrew; Mitchell, Leah; Yagiz, Kader; Lopez, Fernando; Mendoza, Daniel; Munday, Anthony; Gruber, Harry; Jolly, Douglas; Fuhrmann, Steven; Radoja, Sasa; Tan, Wei; Pourchet, Aldo; Frey, Alan; Mohr, Ian; Mulvey, Matthew; Ranki, Tuuli; Pesonen, Sari; Capasso, Cristian; Ylösmäki, Erkko; Cerullo, Vincenzo; Andtbacka, Robert H I; Ross, Merrick; Agarwala, Sanjiv; Grossmann, Kenneth; Taylor, Matthew; Vetto, John; Neves, Rogerio; Daud, Adil; Khong, Hung; Meek, Stephanie M; Ungerleider, Richard; Welden, Scott; Tanaka, Maki; Williams, Matthew; Andtbacka, Robert H I; Curti, Brendan; Hallmeyer, Sigrun; Fox, Bernard; Feng, Zipei; Paustian, Christopher; Bifulco, Carlo; Grose, Mark; Shafren, Darren; Zafar, Sadia; Parviainen, Suvi; Siurala, Mikko; Hemminki, Otto; Havunen, Riikka; Tähtinen, Siri; Bramante, Simona; Vassilev, Lotta; Wang, Hongjie; Lieber, Andre; Hemmi, Silvio; de Gruijl, Tanja; Kanerva, Anna; Hemminki, Akseli; Ansari, Tameem; Sundararaman, Srividya; Roen, Diana; Lehmann, Paul; Bloom, Anja C; Bender, Lewis H; Walters, Ian B; Terabe, Masaki; Berzofsky, Jay A; Chapelin, Fanny; Okada, Hideho; Ahrens, Eric T; DeFalco, Jeff; Harbell, Michael; Manning-Bog, Amy; Scholz, Alexander; Zhang, Danhui; Baia, Gilson; Tan, Yann C; Sokolove, Jeremy; Kim, Dongkyoon; Williamson, Kevin; Chen, Xiaomu; Colrain, Jillian; Santo, Gregg E; Nguyen, Ngan; Volkmuth, Wayne; Greenberg, Norman; Robinson, William; Emerling, Daniel; Drake, Charles G; Petrylak, Daniel P; Antonarakis, Emmanuel S; Kibel, Adam S; Chang, Nancy N; Vu, Tuyen; Campogan, Dwayne; Haynes, Heather; Trager, James B; Sheikh, Nadeem A; Quinn, David I; Kirk, Peter; Addepalli, Murali; Chang, Thomas; Zhang, Ping; Konakova, Marina; Hagihara, Katsunobu; Pai, Steven; VanderVeen, Laurie; Obalapur, Palakshi; Kuo, Peiwen; Quach, Phi; Fong, Lawrence; Charych, Deborah H; Zalevsky, Jonathan; Langowski, John L; Addepalli, Murali; Kirksey, Yolanda; Nutakki, Ravi; Kolarkar, Shalini; Pena, Rhoneil; Hoch, Ute; Zalevsky, Jonathan; Doberstein, Stephen K; Charych, Deborah H; Cha, John; Mallon, Zach; Perez, Myra; McDaniel, Amanda; Anand, Snjezana; Uecker, Darrin; Nuccitelli, Richard; McDaniel, Amanda; Anand, Snjezana; Cha, John; Uecker, Darrin; Nuccitelli, Richard; Obermajer, Nataša; Urban, Julie; Wieckowski, Eva; Muthuswamy, Ravikumar; Ravindranathan, Roshni; Bartlett, David; Kalinski, Pawel; Renrick, Ariana N; Thounaojam, Menaka; Thomas, Portia; Pellom, Samuel; Shanker, Anil; Pellom, Samuel; Thounaojam, Menaka; Dudimah, Duafalia; Brooks, Alan; Sayers, Thomas J; Shanker, Anil; Su, Yu-Lin; Adamus, Tomasz; Zhang, Qifang; Nechaev, Sergey; Kortylewski, Marcin; Wei, Spencer; Allison, James; Anderson, Clark; Tang, Chad; Schoenhals, Jonathan; Tsouko, Efrosini; Heymach, John; de Groot, Patricia; Chang, Joe; Hess, Kenneth R; Diab, Adi; Sharma, Padmanee; Allison, James; Naing, Aung; Hong, David; Welsh, James; Albershardt, Tina C; Parsons, Andrea J; Leleux, Jardin; Reeves, Rebecca S; ter Meulen, Jan; Berglund, Peter; Ascarateil, Stephane; Koziol, Marie E; Penny, Sarah A; Malaker, Stacy A; Steadman, Lora; Myers, Paisley T; Bai, Dina; Shabanowitz, Jeffrey; Hunt, Donald F; Cobbold, Mark; Dai, Peihong; Wang, Weiyi; Yang, Ning; Shuman, Stewart; Merghoub, Taha; Wolchok, Jedd D; Deng, Liang; Dillon, Patrick; Petroni, Gina; Brenin, David; Bullock, Kim; Olson, Walter; Smolkin, Mark E; Smith, Kelly; Nail, Carmel; Slingluff, Craig L; Sharma, Meenu; Fa’ak, Faisal; Janssen, Louise; Khong, Hiep; Xiao, Zhilan; Hailemichael, Yared; Singh, Manisha; Vianden, Christina; Diab, Adi; Zalevsky, Jonathan; Hoch, Ute; Overwijk, Willem W; Facciabene, Andrea; Stefano, Pierini; Chongyung, Fang; Rafail, Stavros; Hailemichael, Yared; Nielsen, Michael; Fa’ak, Faisal; Vanderslice, Peter; Woodside, Darren G; Market, Robert V; Biediger, Ronald J; Marathi, Upendra K; Overwijk, Willem W; Hollevoet, Kevin; Geukens, Nick; Declerck, Paul; Joly, Nathalie; McIntosh, Laura; Paramithiotis, Eustache; Rizell, Magnus; Sternby, Malin; Andersson, Bengt; Karlsson-Parra, Alex; Kuai, Rui; Ochyl, Lukasz; Schwendeman, Anna; Moon, James; Deng, Weiwen; Hudson, Thomas E; Lemmens, Edward E; Hanson, Bill; Rae, Chris S; Burrill, Joel; Skoble, Justin; Katibah, George; Murphy, Aimee L; deVries, Michele; Brockstedt, Dirk G; Leong, Meredith L; Lauer, Peter; Dubensky, Thomas W; Whiting, Chan C; Chen, Xin; Hu, Yangyang; Xia, Yang; Zhou, Li; Bao, Yangyi; Huang, Shiang; Ren, Xiubao; Hurt, Elaine; Hollingsworth, Robert E; Chang, Alfred E; Wicha, Max S; Li, Qiao; Aggarwal, Charu; Mangrolia, Drishty; Cohen, Roger; Weinstein, Gregory; Morrow, Matthew; Bauml, Joshua; Kraynyak, Kim; Boyer, Jean; Yan, Jian; Lee, Jessica; Humeau, Laurent; Oyola, Sandra; Duff, Susan; Weiner, David; Yang, Zane; Bagarazzi, Mark; McNeel, Douglas G; Eickhoff, Jens; Jeraj, Robert; Staab, Mary J; Straus, Jane; Rekoske, Brian; Liu, Glenn; Melssen, Marit; Petroni, Gina; Grosh, William; Varhegyi, Nikole; Bullock, Kim; Smolkin, Mark E; Smith, Kelly; Galeassi, Nadejda; Deacon, Donna H; Gaughan, Elizabeth; Slingluff, Craig L; Ghisoli, Maurizio; Barve, Minal; Mennel, Robert; Wallraven, Gladice; Manning, Luisa; Senzer, Neil; Nemunaitis, John; Ogasawara, Masahiro; Ota, Shuichi; Peace, Kaitlin M; Hale, Diane F; Vreeland, Timothy J; Jackson, Doreen O; Berry, John S; Trappey, Alfred F; Herbert, Garth S; Clifton, Guy T; Hardin, Mark O; Toms, Anne; Qiao, Na; Litton, Jennifer; Peoples, George E; Mittendorf, Elizabeth A; Ghamsari, Lila; Flano, Emilio; Jacques, Judy; Liu, Biao; Havel, Jonathan; Makarov, Vladimir; Merghoub, Taha; Wolchok, Jedd D; Hellmann, Matthew D; Chan, Timothy A; Flechtner, Jessica B; Stefano, Pierini; Facciabene, Andrea; Facciponte, John; Ugel, Stefano; De Sanctis, Francesco; Coukos, George; Paris, Sébastien; Pottier, Agnes; Levy, Laurent; Lu, Bo; Cappuccini, Federica; Pollock, Emily; Bryant, Richard; Hamdy, Freddie; Hill, Adrian; Redchenko, Irina; Sultan, Hussein; Kumai, Takumi; Fesenkova, Valentyna; Celis, Esteban; Tsang, Kwong; Fantini, Massimo; Fernando, Ingrid; Palena, Claudia; David, Justin M; Hodge, James; Gabitzsch, Elizabeth; Jones, Frank; Gulley, James L; Schlom, Jeffrey; Herranz, Mireia U; Rafail, Stavros; Ugel, Stefano; Facciponte, John; Stefano, Pierini; Facciabene, Andrea; Wada, Hiroshi; Shimizu, Atsushi; Osada, Toshihiro; Fukaya, Satoshi; Sasaki, Eiji; Abolhalaj, Milad; Askmyr, David; Lundberg, Kristina; Albrekt, Ann-Sofie; Greiff, Lennart; Lindstedt, Malin; Flies, Dallas B; Higuchi, Tomoe; Ornatowski, Wojciech; Harris, Jaryse; Adams, Sarah F; Aguilera, Todd; Rafat, Marjan; Castellini, Laura; Shehade, Hussein; Kariolis, Mihalis; Jang, Dadi; vonEbyen, Rie; Graves, Edward; Ellies, Lesley; Rankin, Erinn; Koong, Albert; Giaccia, Amato; Ajina, Reham; Wang, Shangzi; Smith, Jill; Pierobon, Mariaelena; Jablonski, Sandra; Petricoin, Emanuel; Weiner, Louis M; Sherry, Lorcan; Waller, John; Anderson, Mark; Bigley, Alison; Bernatchez, Chantale; Haymaker, Cara; Tannir, Nizar M; Kluger, Harriet; Tetzlaff, Michael; Jackson, Natalie; Gergel, Ivan; Tagliaferri, Mary; Zalevsky, Jonathan; Hoch, Ute; Hwu, Patrick; Snzol, Mario; Hurwitz, Michael; Diab, Adi; Barberi, Theresa; Martin, Allison; Suresh, Rahul; Barakat, David; Harris-Bookman, Sarah; Drake, Charles; Friedman, Alan; Berkey, Sara; Downs-Canner, Stephanie; Delgoffe, Greg M; Edwards, Robert P; Curiel, Tyler; Odunsi, Kunle; Bartlett, David; Obermajer, Nataša; Bruno, Tullia C; Moore, Brandon; Squalls, Olivia; Ebner, Peggy; Waugh, Katherine; Mitchell, John; Franklin, Wilbur; Merrick, Daniel; McCarter, Martin; Palmer, Brent; Kern, Jeffrey; Vignali, Dario; Slansky, Jill; Chan, Anissa S H; Qiu, Xiaohong; Fraser, Kathryn; Jonas, Adria; Ottoson, Nadine; Gordon, Keith; Kangas, Takashi O; Leonardo, Steven; Ertelt, Kathleen; Walsh, Richard; Uhlik, Mark; Graff, Jeremy; Bose, Nandita; Gupta, Ravi; Mandloi, Nitin; Paul, Kiran; Patil, Ashwini; Sathian, Rekha; Mohan, Aparna; Manoharan, Malini; Chaudhuri, Amitabha; Chen, Yu; Lin, Jing; Ye, Yun-bin; Xu, Chun-wei; Chen, Gang; Guo, Zeng-qing; Komarov, Andrey; Chenchik, Alex; Makhanov, Michael; Frangou, Costa; Zheng, Yi; Coltharp, Carla; Unfricht, Darryn; Dilworth, Ryan; Fridman, Leticia; Liu, Linying; Rajopadhye, Milind; Miller, Peter; Concha-Benavente, Fernando; Bauman, Julie; Trivedi, Sumita; Srivastava, Raghvendra; Ohr, James; Heron, Dwight; Duvvuri, Uma; Kim, Seungwon; Gooding, William; Ferris, Robert L; Torrey, Heather; Mera, Toshi; Okubo, Yoshiaki; Vanamee, Eva; Foster, Rosemary; Faustman, Denise; Gartrell, Robyn; Stack, Edward; Lu, Yan; Izaki, Daisuke; Beck, Kristen; Jia, Dan T; Armenta, Paul; White-Stern, Ashley; Fu, Yichun; Blake, Zoe; Marks, Douglas; Kaufman, Howard L; Taback, Bret; Horst, Basil; Saenger, Yvonne M; Glickman, Laura H; Kanne, David B; Gauthier, Kelsey S; Desbien, Anthony L; Francica, Brian; Katibah, George; Corrales, Leticia P; Leong, Justin L; Sung, Leonard; Metchette, Ken; Kasibhatla, Shailaja; Pferdekamper, Anne M; Zheng, Lianxing; Cho, Charles; Feng, Yan; McKenna, Jeffery M; Tallarico, John; Bender, Steven; Ndubaku, Chudi; McWhirter, Sarah M; Drake, Charles G; Gajewski, Thomas F; Dubensky, Thomas W; Gugel, Elena G; Bell, Charles J M; Munk, Adiel; Muniz, Luciana; Bhardwaj, Nina; Zhao, Fei; Evans, Kathy; Xiao, Christine; Holtzhausen, Alisha; Hanks, Brent A; Scholler, Nathalie; Yin, Catherine; Van der Meijs, Pien; Prantner, Andrew M; Krejsa, Cecile M; Smith, Leia; Johnson, Brian; Branstetter, Daniel; Stein, Paul L; Jaen, Juan C; Tan, Joanne B; Chen, Ada; Chen, Yu; Park, Timothy; Powers, Jay P; Sexton, Holly; Xu, Guifen; Young, Steve W; Schindler, Ulrike; Deng, Wentao; Klinke, David J; Komar, Hannah M; Mace, Thomas; Serpa, Gregory; Elnaggar, Omar; Conwell, Darwin; Hart, Philip; Schmidt, Carl; Dillhoff, Mary; Jin, Ming; Ostrowski, Michael C; Lesinski, Gregory B; Koti, Madhuri; Au, Katrina; Peterson, Nichole; Truesdell, Peter; Reid-Schachter, Gillian; Graham, Charles; Craig, Andrew; Francis, Julie-Ann; Kotlan, Beatrix; Balatoni, Timea; Farkas, Emil; Toth, Laszlo; Ujhelyi, Mihaly; Savolt, Akos; Doleschall, Zoltan; Horvath, Szabolcs; Eles, Klara; Olasz, Judit; Csuka, Orsolya; Kasler, Miklos; Liszkay, Gabriella; Barnea, Eytan; Kumar, Sushil; Tsujikawa, Takahiro; Blakely, Collin; Flynn, Patrick; Goodman, Reid; Bueno, Raphael; Sugarbaker, David; Jablons, David; Broaddus, V. C; West, Brian; Coussens, Lisa M; Kunk, Paul R; Obeid, Joseph M; Winters, Kevin; Pramoonjago, Patcharin; Smolkin, Mark E; Stelow, Edward B; Bauer, Todd W; Slingluff, Craig L; Rahma, Osama E; Lamble, Adam; Kosaka, Yoko; Huang, Fei; Saser, Kate A; Adams, Homer; Tognon, Christina E; Laderas, Ted; McWeeney, Shannon; Loriaux, Marc; Tyner, Jeffery W; Druker, Brian J; Lind, Evan F; Liu, Zhuqing; Lu, Shanhong; Kane, Lawrence P; Ferris, Robert L; Liu, Zhuqing; Shayan, Gulidanna; Lu, Shanhong; Ferris, Robert L; Femel, Julia; Tsujikawa, Takahiro; Lane, Ryan; Booth, Jamie; Lund, Amanda W; Melssen, Marit; Rodriguez, Anthony; Slingluff, Craig L; Engelhard, Victor H; Metelli, Alessandra; Wu, Bill X; Fugle, Caroline W; Saleh, Rachidi; Sun, Shaoli; Wu, Jennifer; Liu, Bei; Li, Zihai; Morris, Zachary S; Guy, Emily I; Heinze, Clinton; Kler, Jasdeep; Gressett, Monica M; Werner, Lauryn R; Gillies, Stephen D; Korman, Alan J; Loibner, Hans; Hank, Jacquelyn A; Rakhmilevich, Alexander L; Harari, Paul M; Sondel, Paul M; Newman, Jenna; Zloza, Andrew; Huelsmann, Erica; Broucek, Joseph; Kaufman, Howard L; Brech, Dorothee; Straub, Tobias; Irmler, Martin; Beckers, Johannes; Buettner, Florian; Schaeffeler, Elke; Schwab, Matthias; Noessner, Elfriede; Anand, Snjezana; McDaniel, Amanda; Cha, John; Uecker, Darrin; Nuccitelli, Richard; Ordentlich, Peter; Wolfreys, Alison; Da Costa, Andre; Silva, John; Crosby, Andrea; Staelens, Ludovicus; Craggs, Graham; Cauvin, Annick; Mason, Sean; Paterson, Alison M; Lake, Andrew C; Armet, Caroline M; O’Connor, Rachel W; Hill, Jonathan A; Normant, Emmanuel; Adam, Ammar; Biniszkiewicz, Detlev M; Chappel, Scott C; Palombella, Vito J; Holland, Pamela M; Powers, Jay P; Becker, Annette; Chen, Ada; Leleti, Manmohan R; Newcomb, Eric; Sexton, Holly; Schindler, Ulrike; Tan, Joanne B L; Young, Steve W; Jaen, Juan C; Rapisuwon, Suthee; Radfar, Arash; Gardner, Kellie; Gibney, Geoffrey; Atkins, Michael; Rennier, Keith R; Crowder, Robert; Wang, Ping; Pachynski, Russell K; Carrero, Rosa M S; Rivas, Sarai; Beceren-Braun, Figen; Anthony, Scott; Schluns, Kimberly S; Sawant, Deepali; Chikina, Maria; Yano, Hiroshi; Workman, Creg; Vignali, Dario; Salerno, Elise; Bedognetti, Davide; Mauldin, Ileana; Deacon, Donna; Shea, Sofia; Pinczewski, Joel; Obeid, Joseph M; Coukos, George; Wang, Ena; Gajewski, Thomas; Marincola, Franco M; Slingluff, Craig L; Spranger, Stefani; Horton, Brendan; Gajewski, Thomas F; Suzuki, Akiko; Leland, Pamela; Joshi, Bharat H; Puri, Raj K; Sweis, Randy F; Bao, Riyue; Luke, Jason; Gajewski, Thomas F; Theodoraki, Marie-Nicole; Mogundo, Frances-Mary; Edwards, Robert P; Kalinski, Pawel; Won, Haejung; Moreira, Dayson; Gao, Chan; Zhao, Xingli; Duttagupta, Priyanka; Jones, Jeremy; D’Apuzzo, Massimo; Pal, Sumanta; Kortylewski, Marcin (BioMed Central, 2016)
  • Öman, Olli; Mäkelä, Teemu; Salli, Eero; Savolainen, Sauli; Kangasniemi, Marko (Springer International Publishing, 2019)
    Abstract Background The aim of this study was to investigate the feasibility of ischemic stroke detection from computed tomography angiography source images (CTA-SI) using three-dimensional convolutional neural networks. Methods CTA-SI of 60 patients with a suspected acute ischemic stroke of the middle cerebral artery were randomly selected for this study; 30 patients were used in the neural network training, and the subsequent testing was performed using the remaining 30 patients. The training and testing were based on manually segmented lesions. Cerebral hemispheric comparison CTA and non-contrast computed tomography (NCCT) were studied as additional input features. Results All ischemic lesions in the testing data were correctly lateralized, and a high correspondence to manual segmentations was achieved. Patients with a diagnosed stroke had clinically relevant regions labeled infarcted with a 0.93 sensitivity and 0.82 specificity. The highest achieved voxel-wise area under receiver operating characteristic curve was 0.93, and the highest Dice similarity coefficient was 0.61. When cerebral hemispheric comparison was used as an input feature, the algorithm performance improved. Only a slight effect was seen when NCCT was included. Conclusion The results support the hypothesis that an acute ischemic stroke lesion can be detected with 3D convolutional neural network-based software from CTA-SI. Utilizing information from the contralateral hemisphere appears to be beneficial for reducing false positive findings.
  • Khattab, Ayman; Jylhä, Kaisa; Hakala, Tomi; Aalto, Mikko; Malima, Robert; Kisinza, William; Honkala, Markku; Nousiainen, Pertti; Meri, Seppo (BioMed Central, 2017)
    Abstract Background Mosquitoes are vectors for many diseases such as malaria. Insecticide-treated bed nets and indoor residual spraying of insecticides are the principal malaria vector control tools used to prevent malaria in the tropics. Other interventions aim at reducing man-vector contact. For example, house screening provides additive or synergistic effects to other implemented measures. We used commercial screen materials made of polyester, polyethylene or polypropylene to design novel mosquito screens that provide remarkable additional benefits to those commonly used in house screening. The novel design is based on a double screen setup made of a screen with 3D geometric structures parallel to a commercial mosquito screen creating a trap between the two screens. Owing to the design of the 3D screen, mosquitoes can penetrate the 3D screen from one side but cannot return through the other side, making it a unidirectional mosquito screen. Therefore, the mosquitoes are trapped inside the double screen system. The permissiveness of both sides of the 3D screens for mosquitoes to pass through was tested in a wind tunnel using the insectary strain of Anopheles stephensi. Results Among twenty-five tested 3D screen designs, three designs from the cone, prism, or cylinder design groups were the most efficient in acting as unidirectional mosquito screens. The three cone-, prism-, and cylinder-based screens allowed, on average, 92, 75 and 64% of Anopheles stephensi mosquitoes released into the wind tunnel to penetrate the permissive side and 0, 0 and 6% of mosquitoes to escape through the non-permissive side, respectively. Conclusions A cone-based 3D screen fulfilled the study objective. It allowed capturing 92% of mosquitoes within the double screen setup inside the wind tunnel and blocked 100% from escaping. Thus, the cone-based screen effectively acted as a unidirectional mosquito screen. This 3D screen-based trap design could therefore be used in house screening as a means of avoiding infective bites and reducing mosquito population size.
  • Tian, Xiaoqing; Pan, Huachen; Köngäs, Petrina; Horppila, Jukka (Springer Berlin Heidelberg, 2017)
    Abstract A 3D-model was developed to study the effects of hypolimnetic aeration on the temperature profile of a thermally stratified Lake Vesijärvi (southern Finland). Aeration was conducted by pumping epilimnetic water through the thermocline to the hypolimnion without breaking the thermal stratification. The model used time transient equation based on Navier–Stokes equation. The model was fitted to the vertical temperature distribution and environmental parameters (wind, air temperature, and solar radiation) before the onset of aeration, and the model was used to predict the vertical temperature distribution 3 and 15 days after the onset of aeration (1 August and 22 August). The difference between the modelled and observed temperature was on average 0.6 °C. The average percentage model error was 4.0% on 1 August and 3.7% on 22 August. In the epilimnion, model accuracy depended on the difference between the observed temperature and boundary conditions. In the hypolimnion, the model residual decreased with increasing depth. On 1 August, the model predicted a homogenous temperature profile in the hypolimnion, while the observed temperature decreased moderately from the thermocline to the bottom. This was because the effect of sediment was not included in the model. On 22 August, the modelled and observed temperatures near the bottom were identical demonstrating that the heat transfer by the aerator masked the effect of sediment and that exclusion of sediment heat from the model does not cause considerable error unless very short-term effects of aeration are studied. In all, the model successfully described the effects of the aerator on the lake’s temperature profile. The results confirmed the validity of the applied computational fluid dynamic in artificial aeration; based on the simulated results, the effect of aeration can be predicted.
  • Tammiste, Triin; Kask, Keiu; Padrik, Peeter; Idla, Külli; Rosenstein, Karin; Jatsenko, Tatjana; Veerus, Piret; Salumets, Andres (BioMed Central, 2019)
    Abstract Background Ovarian insufficiency is a major concern for long-term cancer survivors. Although semen freezing is well established to preserve male fertility, the possibilities to secure post-cancer female fertility are mostly limited to oocyte or embryo freezing. These methods require time-consuming ovarian stimulation with or without in vitro fertilization (IVF) that evidently delays cancer therapy. Ovarian tissue cryopreservation and subsequent thawed tissue autotransplantation are considered the most promising alternative strategy for restoring the fertility of oncology patients, which has not yet received the full clinical acceptance. Therefore, all successful cases are needed to prove its reliability and safety. Case presentation Here we report a single case in Estonia, where a 28-year-old woman with malignant breast neoplasm had ovarian cortex cryopreserved before commencing gonadotoxic chemo- and radiotherapy. Two years after cancer therapy, the patient underwent heterotopic ovarian tissue transplantation into the lateral pelvic wall. The folliculogenesis was stimulated in the transplanted tissue by exogenous follicle-stimulating hormone and oocytes were collected under ultrasound guidance for IVF and embryo transfer. The healthy boy was born after full-term gestation in 2014, first in Eastern Europe. Conclusion Despite many countries have reported the first implementation of the ovarian tissue freezing and transplantation protocols, the data is still limited on the effectiveness of heterotopic ovarian transplant techniques. Thus, all case reports of heterotopic ovarian tissue transplantation and long-term follow-ups to describe the children’s health are valuable source of clinical experience.
  • Breidenbach, Johannes; McRoberts, Ronald E.; Alberdi, Iciar; Antón-Fernández, Clara; Tomppo, Erkki (Springer Singapore, 2021)
    Abstract In 2019, 100 years had elapsed since the first National Forest Inventory (NFI) was established in Norway. Motivated by a fear of over-exploitation of timber resources, NFIs today enable informed policy making by providing data vital to decision support at international, national, regional, and local scales. This Collection of articles celebrates the 100th anniversary of NFIs with a description of past, present, and future research aiming at improving the monitoring of forest and other terrestrial ecosystems.
  • Kemp, Kirsi; Mertanen, Reija; Niemi-Murola, Leila; Lehtonen, Lasse; Castrén, Maaret (BioMed Central, 2021)
  • Turjanmaa, Elina; Jasinskaja-Lahti, Inga (Springer International Publishing, 2020)
    Abstract In general, parental knowledge is known to support adolescents’ adaptation. Less is known about the role of parental knowledge in psychological (i.e., anxiety) and socio-cultural (i.e., school achievement) adaptation of adolescents with immigrant background, and how parental knowledge and social characteristics (i.e., gender, generational status, immigrant background, and family’ socioeconomic background) of immigrant adolescents jointly influence their adaptation outcomes. This study explores the role of adolescent-reported parental knowledge in explaining adaptation outcomes among first- and second-generation immigrant boys and girls from four different immigrant groups. The study utilizes the national Finnish School Health Promotion survey data (N = 2697, 45% female, M age = 15.6 years, SD = .91) and illustrates the complex relationship between parental knowledge and adolescents’ adaptation.
  • Kotisalmi, Emma; Hakulinen, Auli; Mäkelä, Mika; Toppila-Salmi, Sanna; Kauppi, Paula (BioMed Central, 2020)
    Abstract Background Anti-IgE (omalizumab) and anti-IL5/IL5R (reslizumab, mepolizumab and benralizumab) treatments are available for severe allergic and eosinophilic asthma. In these patients, studies have shown beneficial effects in oral corticosteroid use and exacerbations. The aim of this retrospective single-center study was to evaluate the effect of biological therapy on severe asthma and to compare different therapies. Methods We collected and analysed results of anti-IL5/IL5R and anti-IgE therapies for asthma from January 2009 until October 2019 in specialized care. We compared number of exacerbations, asthma symptoms and use of per oral corticosteroids and antimicrobics because of asthma before and during biological therapy, and in a separate analysis need for per oral corticosteroids, antimicrobics or surgery due to upper respiratory tract diseases in asthmatics receiving biologicals. The analyses were done using the Chi square test, T-test or Mann-Whitney U -test, the Kruskall-Wallis test or the Wilcoxon test. Results Of 64 patients, 40 used continuous per oral corticosteroid therapy prior to biological therapy. The mean daily dose of per oral corticosteroid was reduced in those with anti-IL5/IL5R therapy (− 3.0 mg, p = 0.02). The number of annual per oral corticosteroid courses decreased in both the anti-IL5/IL5R (− 2.8 courses, p < 0.05) and anti-IgE groups (− 1.3 courses, p < 0.05). The number of annual antibiotic courses (− 0.7 courses, p = 0.04) and total number of exacerbation events (− 4.4 events/year, p < 0.05) were reduced in the anti-IL5/IL5R group. In the 55 asthma patients analysed for upper respiratory tract findings, the results suggested a reduction in need for chronic rhinosinusitis surgery during biological therapy. Conclusions Results with biological therapies in this real-life clinical setting are comparable to those reported in clinical trials. Biological therapy reduces exacerbations and per oral corticosteroid use. Trial registration NCT04158050, retrospectively registered 6.11.2019.
  • Lehtovuori, Tuomo; Raina, Marko; Suominen, Lasse; Kauppila, Timo (BioMed Central, 2017)
    Abstract Objective To improve the recording of diagnoses in visits to general practitioners, an observational retrospective study based on a before-after design was performed by installing an electronic reminder in the computerized patient chart system, reinforced in feedback delivered in superior-subordinate or development discussions with the general practitioners. The monthly rate of recording diagnoses was observed before and after the intervention. The effect of this intervention on recording of diagnoses was compared with the effects of financial group bonuses on the same parameter in a neighbouring city. Results Before intervention, the level of recording diagnoses was about 45% in the primary care units. Nine months after this intervention there was not yet any statistically significant increase in recording of diagnoses but after 21 months it yielded a recording rate of 90% (P < 0.001). In three years, this percentage reached level over 95%. Group bonuses, a financial incentive serving as a control intervention, increased this parameter from 50 to 80% (P < 0.001) in nine months, and in 21 months the level of recording diagnoses was 90%. The both methods increased the level of recording diagnoses at the same level. Group bonuses acted faster but were also more expensive.
  • Junkkari, Reija; Simojoki, Heli; Heiskanen, Minna-Liisa; Pelkonen, Sinikka; Sankari, Satu; Tulamo, Riitta-Mari; Mykkänen, Anna (BioMed Central, 2017)
    Abstract Background Newly weaned horses in Finland are often moved to unheated loose housing systems in which the weanlings have free access to a paddock and a shelter. This practice is considered to be good for the development of young horses. The daily temperatures can stay below − 20 °C in Finland for several consecutive weeks during the winter season. However, the effect of unheated housing in a cold climatic environment on the respiratory health of weanlings under field conditions has not been studied before. This investigation was an observational field-study comprising 60 weanlings among 11 different voluntary participant rearing farms in Finland. Weanlings were either kept in unheated loose housing systems (n = 36) or in stables (n = 24) and were clinically examined on two separate occasions 58 days apart in cold winter conditions. Results The odds of clinical respiratory disease were lower in the older foals (loge days); OR = 0.009, P = 0.044). The plasma fibrinogen concentration was higher when the available space (m2/weanling) in the sleeping hall was smaller (P = 0.014) and it was lower when the sleeping hall was not insulated (P = 0.010). The plasma fibrinogen concentrations at the second examination were lower with a body condition score above 3 (P = 0.070). Standardbreds kept in loose housing systems had a lower body condition score than Finnhorses or Standardbreds kept in stables at both examinations (P = 0.026 and P = 0.007, respectively). Haemoglobin level was lower in weanlings in loose housing systems compared to their counterparts at the first examination (P = 0.037). Finnhorses had higher white blood cell count than Standardbreds at first (P = 0.002) and at the second examination (P = 0.001). Conclusions Keeping weanling horses in cold loose housing systems does not seem to increase the occurrence of respiratory disease, but special attention should be focused on ventilation, air quality and feeding-practices. Our field study data suggest it might be advantageous to keep Standardbred foals born late in the season in a stable over the Finnish winter.
  • Kvist, Jouni; Athanàsio, Camila G; Pfrender, Michael E; Brown, James B; Colbourne, John K; Mirbahai, Leda (BioMed Central, 2020)
    Abstract Background Daphnia species reproduce by cyclic parthenogenesis involving both sexual and asexual reproduction. The sex of the offspring is environmentally determined and mediated via endocrine signalling by the mother. Interestingly, male and female Daphnia can be genetically identical, yet display large differences in behaviour, morphology, lifespan and metabolic activity. Our goal was to integrate multiple omics datasets, including gene expression, splicing, histone modification and DNA methylation data generated from genetically identical female and male Daphnia pulex under controlled laboratory settings with the aim of achieving a better understanding of the underlying epigenetic factors that may contribute to the phenotypic differences observed between the two genders. Results In this study we demonstrate that gene expression level is positively correlated with increased DNA methylation, and histone H3 trimethylation at lysine 4 (H3K4me3) at predicted promoter regions. Conversely, elevated histone H3 trimethylation at lysine 27 (H3K27me3), distributed across the entire transcript length, is negatively correlated with gene expression level. Interestingly, male Daphnia are dominated with epigenetic modifications that globally promote elevated gene expression, while female Daphnia are dominated with epigenetic modifications that reduce gene expression globally. For examples, CpG methylation (positively correlated with gene expression level) is significantly higher in almost all differentially methylated sites in male compared to female Daphnia. Furthermore, H3K4me3 modifications are higher in male compared to female Daphnia in more than 3/4 of the differentially regulated promoters. On the other hand, H3K27me3 is higher in female compared to male Daphnia in more than 5/6 of differentially modified sites. However, both sexes demonstrate roughly equal number of genes that are up-regulated in one gender compared to the other sex. Since, gene expression analyses typically assume that most genes are expressed at equal level among samples and different conditions, and thus cannot detect global changes affecting most genes. Conclusions The epigenetic differences between male and female in Daphnia pulex are vast and dominated by changes that promote elevated gene expression in male Daphnia. Furthermore, the differences observed in both gene expression changes and epigenetic modifications between the genders relate to pathways that are physiologically relevant to the observed phenotypic differences.
  • Alekseev, Alexander; Tomppo, Erkki; McRoberts, Ronald E; von Gadow, Klaus (Springer Singapore, 2019)
    Abstract The State Forest Inventory (SFI) in the Russian Federation is a relatively new project that is little known in the English-language scientific literature. Following the stipulations of the Forest Act of 2006, the first SFI sample plots in this vast territory were established in 2007. The 34 Russian forest regions were the basic geographical units for all statistical estimates and served as a first-level stratification, while a second level was based on old inventory data and remotely sensed data. The sampling design was to consist of a simple random sample of 84,700 circular 500 m2 sample plots over forest land. Each sample plot consists of three nested concentric circular subplots with radii of 12.62, 5.64 and 2.82 m and additional subplots for assessing and describing undergrowth, regeneration and ground vegetation. In total, 117 variables were to be measured or assessed on each plot. Although field work has begun, the methodology has elicited some criticism. The simple random sampling design is less efficient than a systematic design featuring sample plot clusters and a mix of temporary and permanent plots. The second-level stratification is mostly ineffective for increasing precision. Qualitative variables, which are not always essential, are dominant, while important quantitative variables are under-represented. Because of very slow progress, in 2018 the original plan was adjusted by reducing the number of permanent sample plots from 84,700 to 68,287 so that the first SFI cycle could be completed by 2020.
  • Prokić, Ivana; Lahousse, Lies; de Vries, Maaike; Liu, Jun; Kalaoja, Marita; Vonk, Judith M; van der Plaat, Diana A; van Diemen, Cleo C; van der Spek, Ashley; Zhernakova, Alexandra; Fu, Jingyuan; Ghanbari, Mohsen; Ala-Korpela, Mika; Kettunen, Johannes; Havulinna, Aki S; Perola, Markus; Salomaa, Veikko; Lind, Lars; Ärnlöv, Johan; Stricker, Bruno H C; Brusselle, Guy G; Boezen, H. M; van Duijn, Cornelia M; Amin, Najaf (BioMed Central, 2020)
    Abstract Background Chronic obstructive pulmonary disease (COPD) is a common lung disorder characterized by persistent and progressive airflow limitation as well as systemic changes. Metabolic changes in blood may help detect COPD in an earlier stage and predict prognosis. Methods We conducted a comprehensive study of circulating metabolites, measured by proton Nuclear Magnetic Resonance Spectroscopy, in relation with COPD and lung function. The discovery sample consisted of 5557 individuals from two large population-based studies in the Netherlands, the Rotterdam Study and the Erasmus Rucphen Family study. Significant findings were replicated in 12,205 individuals from the Lifelines-DEEP study, FINRISK and the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) studies. For replicated metabolites further investigation of causality was performed, utilizing genetics in the Mendelian randomization approach. Results There were 602 cases of COPD and 4955 controls used in the discovery meta-analysis. Our logistic regression results showed that higher levels of plasma Glycoprotein acetyls (GlycA) are significantly associated with COPD (OR = 1.16, P = 5.6 × 10− 4 in the discovery and OR = 1.30, P = 1.8 × 10− 6 in the replication sample). A bi-directional two-sample Mendelian randomization analysis suggested that circulating blood GlycA is not causally related to COPD, but that COPD causally increases GlycA levels. Using the prospective data of the same sample of Rotterdam Study in Cox-regression, we show that the circulating GlycA level is a predictive biomarker of COPD incidence (HR = 1.99, 95%CI 1.52–2.60, comparing those in the highest and lowest quartile of GlycA) but is not significantly associated with mortality in COPD patients (HR = 1.07, 95%CI 0.94–1.20). Conclusions Our study shows that circulating blood GlycA is a biomarker of early COPD pathology.
  • Stahlmann, Katharina; Hebestreit, Antje; DeHenauw, Stefaan; Hunsberger, Monica; Kaprio, Jaakko; Lissner, Lauren; Molnár, Dénes; Ayala-Marín, Alelí M; Reisch, Lucia A; Russo, Paola; Tornaritis, Michael; Veidebaum, Toomas; Pohlabeln, Hermann; Bogl, Leonie H (BioMed Central, 2020)
    Abstract Background There has been an increase in children growing up in non-traditional families, such as single-parent and blended families. Children from such families have a higher prevalence of obesity and poorer health outcomes, but research on the relationship with obesogenic behaviours is limited. Objectives Therefore, the aim of this study was to investigate whether there are associations between family structures and obesogenic behaviours and related family rules in European children and adolescents. Methods The sample included 7664 children (mean age ± SD: 10.9 ± 2.9) from 4923 families who were participants of the multi-centre I.Family study (2013/2014) conducted in 8 European countries. Family structure was assessed by a detailed interview on kinship and household. Obesogenic behaviours (screen time, sleep duration, consumption of sugar-sweetened beverages (SSBs)) and family rules (rules for computer and television, bedtime routine, availability of SSBs during meals) were determined by standardized questionnaires. Multilevel mixed-effects linear and logistic regression models were used to model the associations of family structure with obesogenic behaviours and family rules. Sex, age, parental education level, number of children and adults in the household and BMI z-score were covariates in the models. Two-parent biological families were set as the reference category. Results Children from single-parent families were less likely to have family rules regarding screen time (OR: 0.62, 95% CI: 0.40–0.94, p = 0.026) with higher reported hours of screen time per week (β = 2.70 h/week, 95% CI: 1.39–4.00, p < 0.001). The frequency of weekly SSB consumption differed by family structure in a sex-specific manner: girls from single-parent (β = 3.19 frequency/week, 95% CI: 0.91–5.47, p = 0.006) and boys from blended/adoptive families (β = 3.01 frequency/week, 95% CI: 0.99–5.03, p = 0.004) consumed more SSBs. Sleep duration, bedtime routines and availability of SSBs during meals did not differ between children from these family structures. Parental education did not modify any of these associations. Conclusions Parents in non-traditional family structures appear to experience more difficulties in restricting screen time and the intake of SSBs in their children than parents in traditional two-parent family structures. Our findings therefore suggest that additional support and effective strategies for parents in non-traditional families may help to reduce obesogenic behaviours in children from such family types.
  • Berk, Benjamin A; Packer, Rowena M A; Law, Tsz H; Wessmann, Annette; Bathen-Nöthen, Andrea; Jokinen, Tarja S; Knebel, Anna; Tipold, Andrea; Pelligand, Ludovic; Volk, Holger A (BioMed Central, 2019)
    Abstract Background Epilepsy is the most common brain disease in dogs. Recently, diets have been reported to have a positive impact on seizure activity and behaviour in various species including dogs with idiopathic epilepsy (IE). Historically, classic high fat ketogenic diets (KD) and medium chain triglycerides (MCT) KD have been successfully used to manage drug-resistant epilepsy. Similarly, an MCT enriched diet has been shown to improve seizure control and behavioural comorbidities in some dogs with IE. However, it is unknown whether an MCT dietary supplement (DS) may provide similar positive effects. Methods A 6-month prospective, randomised, double-blinded, placebo-controlled, crossover, multicentre dietary trial is designed comparing a 9% metabolic energy based calculated medium-chain triglyceride (MCT) oil supplement to a conventional ‘control’ DS. Only dogs which will have an International Veterinary Epilepsy Task Force Tier II level like diagnosis of IE which satisfied the following inclusion criteria are included: age between 6 months and ≤ 12 years; weighing between 4 and ≤ 65 kg; unremarkable interictal neurological examinations; no clinically significant findings on routine laboratory diagnostics; unremarkable brain MRI scan; have had at least 3 seizures in the previous 3 months prior to enrolment; treated with at least one ASD and being classified as resistant. All dogs are fed initially for 90 ± 2 days with either the control oil or the MCT oil alongside their normal diet, followed by 97 ± 2 days with the other supplement including a 7-day washout period. Overall, the aim is to recruit thirty-six patients at five different centres and to investigate the effect of MCTs as DS on seizure activity, tolerability, behavioural comorbidities and quality of life (QoL). Discussion Dietary interventions are rarely studied in a standardised form in veterinary medicine. The background diet, the cohort of animals and ASD received is standardised in this prospective diet trial to ensure representative data about the potential effect of MCT DS. If the study data confirms former findings, this would provide further evidence for the efficacy of MCTs as a management option for canine epilepsy. This publication should offer a repository of trial conditions and variable description with forecasted statistical analysis.
  • Reinsalu, Olavi; Scheler, Ott; Mikelsaar, Ruth; Mikelsaar, Aavo-Valdur; Hallap, Triin; Jaakma, Ülle; Padrik, Peeter; Kavak, Ants; Salumets, Andres; Kurg, Ants (BioMed Central, 2019)
    Abstract Background Usage of sexed semen that allows to choose the gender of the calves, is commonly practiced in livestock industry as a profitable breeding alternative, especially in dairy farming. The flow cytometric cell sorting is the only commercially available method for bovine sperm sexing. For validation of the sexing procedure several methods have been developed including sperm fluorescence in situ hybridisation techniques. Latter usually include the use of pre-labelled nucleotides for probe synthesis which is relatively expensive approach compared to combined application of aminoallyl-dUTP and chemical binding of fluorescent dyes. Here a sex determining dual colour bovine sperm fluorescence in situ hybridisation method is presented which is considered more cost-effective technique than the previously reported approaches. Results The reliability of sex chromosome identifying probes, designed in silico, was proven on bovine metaphase plate chromosomes and through comparison with a commercially available standard method. In the dual colour FISH experiments of unsexed and sexed bovine sperm samples the hybridisation efficiency was at least 98%, whereas the determined sex ratios were not statistically different from the expected. Very few cells carried both of the sex chromosome-specific signals (less than 0.2%). Conclusions A protocol for a dual colour bovine sperm FISH method is provided which is cost-effective, simple and fast for sex determination of spermatozoa in bull semen samples.
  • Pausch, Hubert; Venhoranta, Heli; Wurmser, Christine; Hakala, Kalle; Iso-Touru, Terhi; Sironen, Anu; Vingborg, Rikke K; Lohi, Hannes; Söderquist, Lennart; Fries, Ruedi; Andersson, Magnus (BioMed Central, 2016)
    Abstract Background Artificial insemination is widely used in many cattle breeding programs. Semen samples of breeding bulls are collected and closely examined immediately after collection at artificial insemination centers. Only ejaculates without anomalous findings are retained for artificial insemination. Although morphological aberrations of the spermatozoa are a frequent reason for discarding ejaculates, the genetic determinants underlying poor semen quality are scarcely understood. Results A tail stump sperm defect was observed in three bulls of the Swedish Red cattle breed. The spermatozoa of affected bulls were immotile because of severely disorganized tails indicating disturbed spermatogenesis. We genotyped three affected bulls and 18 unaffected male half-sibs at 46,035 SNPs and performed homozygosity mapping to map the fertility disorder to an 8.42 Mb interval on bovine chromosome 13. The analysis of whole-genome re-sequencing data of an affected bull and 300 unaffected animals from eleven cattle breeds other than Swedish Red revealed a 1 bp deletion (Chr13: 24,301,425 bp, ss1815612719) in the eleventh exon of the armadillo repeat containing 3-encoding gene (ARMC3) that was compatible with the supposed recessive mode of inheritance. The deletion is expected to alter the reading frame and to induce premature translation termination (p.A451fs26). The mutated protein is shortened by 401 amino acids (46 %) and lacks domains that are likely essential for normal protein function. Conclusions We report the phenotypic and genetic characterization of a sterilizing tail stump sperm defect in the Swedish Red cattle breed. Exploiting high-density genotypes and massive re-sequencing data enabled us to identify the most likely causal mutation for the fertility disorder in bovine ARMC3. Our results provide the basis for monitoring the mutated variant in the Swedish Red cattle population and for the early identification of infertile animals.
  • Alanko, Jarno; Cunial, Fabio; Belazzougui, Djamal; Mäkinen, Veli (BioMed Central, 2017)
    Abstract Background A metagenomic sample is a set of DNA fragments, randomly extracted from multiple cells in an environment, belonging to distinct, often unknown species. Unsupervised metagenomic clustering aims at partitioning a metagenomic sample into sets that approximate taxonomic units, without using reference genomes. Since samples are large and steadily growing, space-efficient clustering algorithms are strongly needed. Results We design and implement a space-efficient algorithmic framework that solves a number of core primitives in unsupervised metagenomic clustering using just the bidirectional Burrows-Wheeler index and a union-find data structure on the set of reads. When run on a sample of total length n, with m reads of maximum length ℓ each, on an alphabet of total size σ, our algorithms take O(n(t+logσ)) time and just 2n+o(n)+O(max{ℓ σlogn,K logm}) bits of space in addition to the index and to the union-find data structure, where K is a measure of the redundancy of the sample and t is the query time of the union-find data structure. Conclusions Our experimental results show that our algorithms are practical, they can exploit multiple cores by a parallel traversal of the suffix-link tree, and they are competitive both in space and in time with the state of the art.