7,462 results on '"Duke-NUS Medical School, Singapore"'
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2. Singapore SARS-CoV-2 Human Challenge Study (Sing-CoV)
- Author
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A*Star, Duke-NUS Medical School (Singapore), and Barnaby Young, Head of Singapore Infectious Disease Clinical Research Network
- Published
- 2024
3. Rapid T-cell Analysis Test in Patients With Chronic HBV and HBV/HDV Disease (BDTc)
- Author
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Duke-NUS Medical School (Singapore)
- Published
- 2024
4. Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment (DAPA-Shuttle1)
- Author
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Duke-NUS Medical School (Singapore)
- Published
- 2023
5. The Association of Maternal Night-Eating Pattern With Glucose Tolerance During Pregnancy
- Author
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National University of Singapore, National University Hospital, Singapore, and Duke-NUS Medical School (Singapore)
- Published
- 2022
6. Contributions of mean and shape of blood pressure distribution to worldwide trends and variations in raised blood pressure: A pooled analysis of 1018 population-based measurement studies with 88.6 million participants
- Author
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Ezzati, M. and Zhou, B. and Bentham, J. and Di Cesare, M. and Bixby, H. and Danaei, G. and Hajifathalian, K. and Taddei, C. and Carrillo-Larco, R.M. and Djalalinia, S. and Khatibzadeh, S. and Lugero, C. and Peykari, N. and Zhang, W.Z. and Bennett, J. and Bilano, V. and Stevens, G.A. and Cowan, M.J. and Riley, L.M. and Chen, Z. and Hambleton, I.R. and Jackson, R.T. and Kengne, A.P. and Khang, Y.-H. and Laxmaiah, A. and Liu, J. and Malekzadeh, R. and Neuhauser, H.K. and Sorić, M. and Starc, G. and Sundström, J. and Woodward, M. and Abarca-Gómez, L. and Abdeen, Z.A. and Abu-Rmeileh, N.M. and Acosta-Cazares, B. and Adams, R.J. and Aekplakorn, W. and Afsana, K. and Aguilar-Salinas, C.A. and Agyemang, C. and Ahmad, N.A. and Ahmadvand, A. and Ahrens, W. and Ajlouni, K. and Akhtaeva, N. and Al-Raddadi, R. and Ali, M.M. and Ali, O. and Alkerwi, A. and Aly, E. and Amarapurkar, D.N. and Amouyel, P. and Amuzu, A. and Andersen, L.B. and Anderssen, S.A. and Ängquist, L.H. and Anjana, R.M. and Ansong, D. and Aounallah-Skhiri, H. and Araújo, J. and Ariansen, I. and Aris, T. and Arlappa, N. and Arveiler, D. and Aryal, K.K. and Aspelund, T. and Assah, F.K. and Assunção, M.C.F. and Avdicová, M. and Azevedo, A. and Azizi, F. and Babu, B.V. and Bahijri, S. and Balakrishna, N. and Bamoshmoosh, M. and Banach, M. and Bandosz, P. and Banegas, J.R. and Barbagallo, C.M. and Barceló, A. and Barkat, A. and Barros, A.J.D. and Barros, M.V. and Bata, I. and Batieha, A.M. and Batyrbek, A. and Baur, L.A. and Beaglehole, R. and Romdhane, H.B. and Benet, M. and Benson, L.S. and Bernabe-Ortiz, A. and Bernotiene, G. and Bettiol, H. and Bhagyalaxmi, A. and Bharadwaj, S. and Bhargava, S.K. and Bi, Y. and Bikbov, M. and Bista, B. and Bjerregaard, P. and Bjertness, E. and Bjertness, M.B. and Björkelund, C. and Blokstra, A. and Bo, S. and Bobak, M. and Boeing, H. and Boggia, J.G. and Boissonnet, C.P. and Bongard, V. and Borchini, R. and Bovet, P. and Braeckman, L. and Brajkovich, I. and Branca, F. and Breckenkamp, J. and Brenner, H. and Brewster, L.M. and Bruno, G. and Bueno-de-Mesquita, H.B. and Bugge, A. and Burns, C. and Bursztyn, M. and de León, A.C. and Cacciottolo, J. and Cai, H. and Cameron, C. and Can, G. and Cândido, A.P.C. and Capuano, V. and Cardoso, V.C. and Carlsson, A.C. and Carvalho, M.J. and Casanueva, F.F. and Casas, J.-P. and Caserta, C.A. and Chamukuttan, S. and Chan, A.W. and Chan, Q. and Chaturvedi, H.K. and Chaturvedi, N. and Chen, C.-J. and Chen, F. and Chen, H. and Chen, S. and Cheng, C.-Y. and Dekkaki, I.C. and Chetrit, A. and Chiolero, A. and Chiou, S.-T. and Chirita-Emandi, A. and Chirlaque, M.-D. and Cho, B. and Cho, Y. and Christofaro, D.G. and Chudek, J. and Cifkova, R. and Cinteza, E. and Claessens, F. and Clays, E. and Concin, H. and Cooper, C. and Cooper, R. and Coppinger, T.C. and Costanzo, S. and Cottel, D. and Cowell, C. and Craig, C.L. and Crujeiras, A.B. and Cruz, J.J. and D'Arrigo, G. and d'Orsi, E. and Dallongeville, J. and Damasceno, A. and Dankner, R. and Dantoft, T.M. and Dauchet, L. and Davletov, K. and De Backer, G. and De Bacquer, D. and de Gaetano, G. and De Henauw, S. and de Oliveira, P.D. and De Smedt, D. and Deepa, M. and Dehghan, A. and Delisle, H. and Deschamps, V. and Dhana, K. and Di Castelnuovo, A.F. and Dias-da-Costa, J.S. and Diaz, A. and Dickerson, T.T. and Do, H.T.P. and Dobson, A.J. and Donfrancesco, C. and Donoso, S.P. and Döring, A. and Dorobantu, M. and Doua, K. and Drygas, W. and Dulskiene, V. and Džakula, A. and Dzerve, V. and Dziankowska-Zaborszczyk, E. and Eggertsen, R. and Ekelund, U. and El Ati, J. and Elliott, P. and Elosua, R. and Erasmus, R.T. and Erem, C. and Eriksen, L. and Eriksson, J.G. and Escobedo-de la Peña, J. and Evans, A. and Faeh, D. and Fall, C.H. and Farzadfar, F. and Felix-Redondo, F.J. and Ferguson, T.S. and Fernandes, R.A. and Fernández-Bergés, D. and Ferrante, D. and Ferrari, M. and Ferreccio, C. and Ferrieres, J. and Finn, J.D. and Fischer, K. and Föger, B. and Foo, L.H. and Forslund, A.-S. and Forsner, M. and Fouad, H.M. and Francis, D.K. and Franco, M.C. and Franco, O.H. and Frontera, G. and Fuchs, F.D. and Fuchs, S.C. and Fujita, Y. and Furusawa, T. and Gaciong, Z. and Galvano, F. and Garcia-de-la-Hera, M. and Gareta, D. and Garnett, S.P. and Gaspoz, J.-M. and Gasull, M. and Gates, L. and Geleijnse, J.M. and Ghasemian, A. and Ghimire, A. and Giampaoli, S. and Gianfagna, F. and Gill, T.K. and Giovannelli, J. and Goldsmith, R.A. and Gonçalves, H. and Gonzalez-Gross, M. and González-Rivas, J.P. and Gorbea, M.B. and Gottrand, F. and Graff-Iversen, S. and Grafnetter, D. and Grajda, A. and Grammatikopoulou, M.G. and Gregor, R.D. and Grodzicki, T. and Grøntved, A. and Grosso, G. and Gruden, G. and Grujic, V. and Gu, D. and Guan, O.P. and Gudmundsson, E.F. and Gudnason, V. and Guerrero, R. and Guessous, I. and Guimaraes, A.L. and Gulliford, M.C. and Gunnlaugsdottir, J. and Gunter, M. and Gupta, P.C. and Gupta, R. and Gureje, O. and Gurzkowska, B. and Gutierrez, L. and Gutzwiller, F. and Hadaegh, F. and Halkjær, J. and Hardy, R. and Kumar, R.H. and Hata, J. and Hayes, A.J. and He, J. and He, Y. and Hendriks, M.E. and Henriques, A. and Cadena, L.H. and Herrala, S. and Heshmat, R. and Hihtaniemi, I.T. and Ho, S.Y. and Ho, S.C. and Hobbs, M. and Hofman, A. and Dinc, G.H. and Horimoto, A.R. and Hormiga, C.M. and Horta, B.L. and Houti, L. and Howitt, C. and Htay, T.T. and Htet, A.S. and Htike, M.M.T. and Hu, Y. and Huerta, J.M. and Huisman, M. and Husseini, A.S. and Huybrechts, I. and Hwalla, N. and Iacoviello, L. and Iannone, A.G. and Ibrahim, M.M. and Wong, N.I. and Ikeda, N. and Ikram, M.A. and Irazola, V.E. and Islam, M. and al-Safi Ismail, A. and Ivkovic, V. and Iwasaki, M. and Jacobs, J.M. and Jaddou, H. and Jafar, T. and Jamrozik, K. and Janszky, I. and Jasienska, G. and Jelaković, A. and Jelaković, B. and Jennings, G. and Jeong, S.-L. and Jiang, C.Q. and Joffres, M. and Johansson, M. and Jokelainen, J.J. and Jonas, J.B. and Jørgensen, T. and Joshi, P. and Jóźwiak, J. and Juolevi, A. and Jurak, G. and Jureša, V. and Kaaks, R. and Kafatos, A. and Kajantie, E.O. and Kalter-Leibovici, O. and Kamaruddin, N.A. and Karki, K.B. and Kasaeian, A. and Katz, J. and Kauhanen, J. and Kaur, P. and Kavousi, M. and Kazakbaeva, G. and Keil, U. and Boker, L.K. and Keinänen-Kiukaanniemi, S. and Kelishadi, R. and Kemper, H.C.G. and Kengne, A.P. and Kerimkulova, A. and Kersting, M. and Key, T. and Khader, Y.S. and Khalili, D. and Khateeb, M. and Khaw, K.-T. and Kiechl-Kohlendorfer, U. and Kiechl, S. and Killewo, J. and Kim, J. and Kim, Y.-Y. and Klumbiene, J. and Knoflach, M. and Kolle, E. and Kolsteren, P. and Korrovits, P. and Koskinen, S. and Kouda, K. and Kowlessur, S. and Koziel, S. and Kriemler, S. and Kristensen, P.L. and Krokstad, S. and Kromhout, D. and Kruger, H.S. and Kubinova, R. and Kuciene, R. and Kuh, D. and Kujala, U.M. and Kulaga, Z. and Kumar, R.K. and Kurjata, P. and Kusuma, Y.S. and Kuulasmaa, K. and Kyobutungi, C. and Laatikainen, T. and Lachat, C. and Lam, T.H. and Landrove, O. and Lanska, V. and Lappas, G. and Larijani, B. and Laugsand, L.E. and Bao, K.L.N. and Le, T.D. and Leclercq, C. and Lee, J. and Lee, J. and Lehtimäki, T. and León-Muñoz, L.M. and Levitt, N.S. and Li, Y. and Lilly, C.L. and Lim, W.-Y. and Lima-Costa, M.F. and Lin, H.-H. and Lin, X. and Lind, L. and Linneberg, A. and Lissner, L. and Litwin, M. and Lorbeer, R. and Lotufo, P.A. and Lozano, J.E. and Luksiene, D. and Lundqvist, A. and Lunet, N. and Lytsy, P. and Ma, G. and Ma, J. and Machado-Coelho, G.L.L. and Machi, S. and Maggi, S. and Magliano, D.J. and Magriplis, E. and Majer, M. and Makdisse, M. and Malhotra, R. and Rao, K.M. and Malyutina, S. and Manios, Y. and Mann, J.I. and Manzato, E. and Margozzini, P. and Marques-Vidal, P. and Marques, L.P. and Marrugat, J. and Martorell, R. and Mathiesen, E.B. and Matijasevich, A. and Matsha, T.E. and Mbanya, J.N. and Posso, A.J.M.D. and McFarlane, S.R. and McGarvey, S.T. and McLachlan, S. and McLean, R.M. and McLean, S.B. and McNulty, B.A. and Mediene-Benchekor, S. and Medzioniene, J. and Meirhaeghe, A. and Meisinger, C. and Menezes, A.B. and Menon, G.R. and Meshram, I.I. and Metspalu, A. and Meyer, H.E. and Mi, J. and Mikkel, K. and Miller, J.C. and Minderico, C.S. and Miquel, J.F. and Miranda, J.J. and Mirrakhimov, E. and Mišigoj-Durakovic, M. and Modesti, P.A. and Mohamed, M.K. and Mohammad, K. and Mohammadifard, N. and Mohan, V. and Mohanna, S. and Yusoff, M.F.M.D. and Møllehave, L.T. and Møller, N.C. and Molnár, D. and Momenan, A. and Mondo, C.K. and Monyeki, K.D.K. and Moon, J.S. and Moreira, L.B. and Morejon, A. and Moreno, L.A. and Morgan, K. and Moschonis, G. and Mossakowska, M. and Mostafa, A. and Mota, J. and Motlagh, M.E. and Motta, J. and Msyamboza, K.P. and ThetMu, T. and Muiesan, M.L. and Müller-Nurasyid, M. and Murphy, N. and Mursu, J. and Musil, V. and Nabipour, I. and Nagel, G. and Naidu, B.M. and Nakamura, H. and Námešná, J. and Nang, E.K. and Nangia, V.B. and Narake, S. and Nauck, M. and Navarrete-Muñoz, E.M. and Ndiaye, N.C. and Neal, W.A. and Nenko, I. and Neovius, M. and Nervi, F. and Nguyen, C.T. and Nguyen, N.D. and Nguyen, Q.N. and Nguyen, Q.V. and Nieto-Martínez, R.E. and Niiranen, T.J. and Ning, G. and Ninomiya, T. and Nishtar, S. and Noale, M. and Noboa, O.A. and Noorbala, A.A. and Norat, T. and Noto, D. and Al Nsour, M. and O'Reilly, D. and Oda, E. and Oehlers, G. and Oh, K. and Ohara, K. and Olinto, M.T.A. and Oliveira, I.O. and Omar, M.A. and Onat, A. and Ong, S.K. and Ono, L.M. and Ordunez, P. and Ornelas, R. and Osmond, C. and Ostojic, S.M. and Ostovar, A. and Otero, J.A. and Overvad, K. and Owusu-Dabo, E. and Paccaud, F.M. and Padez, C. and Pahomova, E. and Pajak, A. and Palli, D. and Palmieri, L. and Pan, W.-H. and Panda-Jonas, S. and Panza, F. and Papandreou, D. and Park, S.-W. and Parnell, W.R. and Parsaeian, M. and Patel, N.D. and Pecin, I. and Pednekar, M.S. and Peer, N. and Peeters, P.H. and Peixoto, S.V. and Peltonen, M. and Pereira, A.C. and Peters, A. and Petersmann, A. and Petkeviciene, J. and Pham, S.T. and Pigeot, I. and Pikhart, H. and Pilav, A. and Pilotto, L. and Pitakaka, F. and Piwonska, A. and Plans-Rubió, P. and Polašek, O. and Porta, M. and Portegies, M.L.P. and Pourshams, A. and Poustchi, H. and Pradeepa, R. and Prashant, M. and Price, J.F. and Puder, J.J. and Puiu, M. and Punab, M. and Qasrawi, R.F. and Qorbani, M. and Bao, T.Q. and Radic, I. and Radisauskas, R. and Rahman, M. and Raitakari, O. and Raj, M. and Rao, S.R. and Ramachandran, A. and Ramos, E. and Rampal, L. and Rampal, S. and Rangel Reina, D.A. and Redon, J. and Reganit, P.M. and Ribeiro, R. and Riboli, E. and Rigo, F. and Rinke de Wit, T.F. and Ritti-Dias, R.M. and Robinson, S.M. and Robitaille, C. and Rodríguez-Artalejo, F. and Rodriguez-Perez, M.C. and Rodríguez-Villamizar, L.A. and Rojas-Martinez, R. and Romaguera, D. and Ronkainen, K. and Rosengren, A. and Roy, J.G.R. and Rubinstein, A. and Ruiz-Betancourt, B.S. and Rutkowski, M. and Sabanayagam, C. and Sachdev, H.S. and Saidi, O. and Sakarya, S. and Salanave, B. and Martinez, E.S. and Salmerón, D. and Salomaa, V. and Salonen, J.T. and Salvetti, M. and Sánchez-Abanto, J. and Sans, S. and Santos, D.A. and Santos, I.S. and Santos, R.N. and Santos, R. and Saramies, J.L. and Sardinha, L.B. and Sarganas, G. and Sarrafzadegan, N. and Saum, K.-U. and Savva, S. and Scazufca, M. and Schargrodsky, H. and Schipf, S. and Schmidt, C.O. and Schöttker, B. and Schultsz, C. and Schutte, A.E. and Sein, A.A. and Sen, A. and Senbanjo, I.O. and Sepanlou, S.G. and Sharma, S.K. and Shaw, J.E. and Shibuya, K. and Shin, D.W. and Shin, Y. and Si-Ramlee, K. and Siantar, R. and Sibai, A.M. and Silva, D.A.S. and Simon, M. and Simons, J. and Simons, L.A. and Sjöström, M. and Skovbjerg, S. and Slowikowska-Hilczer, J. and Slusarczyk, P. and Smeeth, L. and Smith, M.C. and Snijder, M.B. and So, H.-K. and Sobngwi, E. and Söderberg, S. and Solfrizzi, V. and Sonestedt, E. and Song, Y. and Sørensen, T.I.A. and Soric, M. and Jérome, C.S. and Soumare, A. and Staessen, J.A. and Stathopoulou, M.G. and Stavreski, B. and Steene-Johannessen, J. and Stehle, P. and Stein, A.D. and Stergiou, G.S. and Stessman, J. and Stieber, J. and Stöckl, D. and Stocks, T. and Stokwiszewski, J. and Stronks, K. and Strufaldi, M.W. and Sun, C.-A. and Sung, Y.-T. and Suriyawongpaisal, P. and Sy, R.G. and Tai, E.S. and Tammesoo, M.-L. and Tamosiunas, A. and Tan, E.J. and Tang, X. and Tanser, F. and Tao, Y. and Tarawneh, M.R. and Tarqui-Mamani, C.B. and Tautu, O.-F. and Taylor, A. and Theobald, H. and Theodoridis, X. and Thijs, L. and Thuesen, B.H. and Tjonneland, A. and Tolonen, H.K. and Tolstrup, J.S. and Topbas, M. and Topór-Madry, R. and Tormo, M.J. and Torrent, M. and Traissac, P. and Trichopoulos, D. and Trichopoulou, A. and Trinh, O.T.H. and Trivedi, A. and Tshepo, L. and Tulloch-Reid, M.K. and Tullu, F. and Tuomainen, T.-P. and Tuomilehto, J. and Turley, M.L. and Tynelius, P. and Tzourio, C. and Ueda, P. and Ugel, E.E. and Ulmer, H. and Uusitalo, H.M.T. and Valdivia, G. and Valvi, D. and van der Schouw, Y.T. and Van Herck, K. and Van Minh, H. and van Rossem, L. and Van Schoor, N.M. and van Valkengoed, I.G.M. and Vanderschueren, D. and Vanuzzo, D. and Vatten, L. and Vega, T. and Velasquez-Melendez, G. and Veronesi, G. and Verschuren, W.M.M. and Verstraeten, R. and Victora, C.G. and Viet, L. and Viikari-Juntura, E. and Vineis, P. and Vioque, J. and Virtanen, J.K. and Visvikis-Siest, S. and Viswanathan, B. and Vlasoff, T. and Vollenweider, P. and Voutilainen, S. and Wade, A.N. and Wagner, A. and Walton, J. and Wan Bebakar, W.M. and Wan Mohamud, W.N. and Wanderley, R.S., Jr. and Wang, M.-D. and Wang, Q. and Wang, Y.X. and Wang, Y.-W. and Wannamethee, S.G. and Wareham, N. and Wedderkopp, N. and Weerasekera, D. and Whincup, P.H. and Widhalm, K. and Widyahening, I.S. and Wiecek, A. and Wijga, A.H. and Wilks, R.J. and Willeit, J. and Willeit, P. and Williams, E.A. and Wilsgaard, T. and Wojtyniak, B. and Wong-McClure, R.A. and Wong, J.Y.Y. and Wong, T.Y. and Woo, J. and Wu, A.G. and Wu, F.C. and Wu, S. and Xu, H. and Yan, W. and Yang, X. and Ye, X. and Yiallouros, P.K. and Yoshihara, A. and Younger-Coleman, N.O. and Yusoff, A.F. and Zainuddin, A.A. and Zambon, S. and Zampelas, A. and Zdrojewski, T. and Zeng, Y. and Zhao, D. and Zhao, W. and Zheng, W. and Zheng, Y. and Zhu, D. and Zhussupov, B. and Zimmermann, E. and Cisneros, J.Z. and NCD Risk Factor Collaboration (NCD-RisC), Imperial College London, London, W2 1PG, United Kingdom, Imperial College London, United Kingdom, University of Kent, United Kingdom, Middlesex University, United Kingdom, Harvard TH Chan School of Public Health, United States, Cleveland Clinic, United States, Universidad Peruana Cayetano Heredia, Peru, Tehran University of Medical Sciences, Iran, Ministry of Health and Medical Education, Iran, Brandeis University, United States, Mulago Hospital, Uganda, Uganda Heart Institute, Uganda, World Health Organization, Switzerland, University of Oxford, United Kingdom, The University of the West Indies, Barbados, University of Auckland, New Zealand, South African Medical Research Council, South Africa, Seoul National University, South Korea, National Institute of Nutrition, India, Capital Medical University Beijing An Zhen Hospital, China, Robert Koch Institute, Germany, German Center for Cardiovascular Research, Germany, University of Zagreb, Croatia, University of Ljubljana, Slovenia, Uppsala University, Sweden, University of New South Wales, Australia, Caja Costarricense de Seguro Social, Costa Rica, Al-Quds University, Palestine, Birzeit University, Palestine, Instituto Mexicano del Seguro Social, Mexico, The University of Adelaide, Australia, Mahidol University, Thailand, BRAC, Bangladesh, Instituto Nacional de Ciencias Médicas y Nutricion, Mexico, University of Amsterdam, Netherlands, Ministry of Health Malaysia, Malaysia, Non- Communicable Diseases Research Center, Iran, Leibniz Institute for Prevention Research and Epidemiology - BIPS, Germany, National Center for Diabetes and Endocrinology, Jordan, Kazakh National Medical University, Kazakhstan, King Abdulaziz University, Saudi Arabia, Universiti Malaysia Sabah, Malaysia, Luxembourg Institute of Health, Luxembourg, World Health Organization Regional Office for the Eastern Mediterranean, Egypt, Bombay Hospital and Medical Research Centre, India, Lille University and Hospital, France, London School of Hygiene and Tropical Medicine, United Kingdom, Western Norway University of Applied Sciences, Norway, Norwegian School of Sport Sciences, Norway, Bispebjerg and Frederiksberg Hospitals, Denmark, Madras Diabetes Research Foundation, India, Komfo Anokye Teaching Hospital, Ghana, National Institute of Public Health, Tunisia, Universidade do Porto, Portugal, Norwegian Institute of Public Health, Norway, Strasbourg University and Hospital, France, Nepal Health Research Council, Nepal, University of Iceland, Iceland, University of Yaoundé 1, Cameroon, Federal University of Pelotas, Brazil, Regional Authority of Public Health, Banska Bystrica, Slovakia, University of Porto Medical School, Portugal, Shahid Beheshti University of Medical Sciences, Iran, Indian Council of Medical Research, India, University of Science and Technology, Yemen, Medical University of Lodz, Poland, Medical University of Gdansk, Poland, Universidad Autónoma de Madrid, Spain, University of Palermo, Italy, Pan American Health Organization, United States, Université Mohammed V de Rabat, Morocco, University of Pernambuco, Brazil, Dalhousie University, Canada, Jordan University of Science and Technology, Jordan, University of Sydney, Australia, University Tunis El Manar, Tunisia, CAFAM University Foundation, Colombia, University of Utah School of Medicine, United States, Lithuanian University of Health Sciences, Lithuania, University of São Paulo, Brazil, BJ Medical College, India, Chirayu Medical College, India, SL Jain Hospital, India, Shanghai Jiao-Tong University School of Medicine, China, Ufa Eye Research Institute, Russian Federation, University of Southern Denmark, Denmark, University of Greenland, Greenland, University of Oslo, Norway, University of Gothenburg, Sweden, National Institute for Public Health and the Environment, Netherlands, University of Turin, Italy, University College London, United Kingdom, German Institute of Human Nutrition, Germany, Universidad de la República, Uruguay, CEMIC, Argentina, Toulouse University School of Medicine, France, University Hospital of Varese, Italy, Ministry of Health, Seychelles, University of Lausanne, Switzerland, Ghent University, Belgium, Universidad Central de Venezuela, Venezuela, Bielefeld University, Germany, German Cancer Research Center, Germany, Cork Institute of Technology, Ireland, Hadassah-Hebrew University Medical Center, Israel, Universidad de La Laguna, Spain, University of Malta, Malta, Vanderbilt University, United States, Canadian Fitness and Lifestyle Research Institute, Canada, Istanbul University, Turkey, Universidade Federal de Juiz de Fora, Brazil, Cardiologia di Mercato S. Severino, Italy, Karolinska Institutet, Sweden, University of Porto, Portugal, Santiago de Compostela University, Spain, Associazione Calabrese di Epatologia, Italy, India Diabetes Research Foundation, India, Duke-NUS Medical School, Singapore, National Institute of Medical Statistics, India, Academia Sinica, Taiwan, Capital Institute of Pediatrics, China, Duke University, United States, Kailuan General Hospital, China, The Gertner Institute for Epidemiology and Health Policy Research, Israel, University of Bern, Switzerland, Ministry of Health and Welfare, Taiwan, Victor Babes University of Medicine and Pharmacy Timisoara, Romania, Murcia Regional Health Council, Spain, Seoul National University College of Medicine, South Korea, Korea Centers for Disease Control and Prevention, South Korea, Universidade Estadual Paulista, Brazil, Medical University of Silesia, Poland, Charles University in Prague, Czech Republic, Carol Davila University of Medicine and Pharmacy, Romania, Katholieke Universiteit Leuven, Belgium, Agency for Preventive and Social Medicine, Austria, University of Southampton, United Kingdom, IRCCS Istituto Neurologico Mediterraneo Neuromed, Italy, Institut Pasteur de Lille, France, CIBEROBN, Spain, National Council of Research, Italy, Universidade Federal de Santa Catarina, Brazil, Eduardo Mondlane University, Mozambique, Bispebjerg and Frederiksberg Hospital, Denmark, Lille University Hospital, France, Erasmus Medical Center Rotterdam, Netherlands, University of Montreal, Canada, French Public Health Agency, France, Universidade do Vale do Rio dos Sinos, Brazil, National Council of Scientific and Technical Research, Argentina, National Institute of Nutrition, Viet Nam, University of Queensland, Australia, Istituto Superiore di Sanità, Italy, Universidad de Cuenca, Ecuador, Helmholtz Zentrum München, Germany, Ministère de la Santé et de la Lutte Contre le Sida, Cote d'Ivoire, The Cardinal Wyszynski Institute of Cardiology, Poland, University of Latvia, Latvia, National Institute of Nutrition and Food Technology, Tunisia, Institut Hospital del Mar d'Investigacions Mèdiques, Spain, University of Stellenbosch, South Africa, Karadeniz Technical University, Turkey, National Institute for Health and Welfare, Finland, Queen's University of Belfast, United Kingdom, University of Zurich, Switzerland, Centro de Salud Villanueva Norte, Spain, The University of the West Indies, Jamaica, Hospital Don Benito-Villanueva de la Serena, Spain, Ministry of Health, Argentina, Council for Agricultural Research and Economics, Italy, Pontificia Universidad Católica de Chile, Chile, University of Manchester, United Kingdom, University of Tartu, Estonia, Universiti Sains Malaysia, Malaysia, Umeå University, Sweden, Dalarna University, Sweden, Federal University of São Paulo, Brazil, Hospital Universitario Son Espases, Spain, Hospital de Clinicas de Porto Alegre, Brazil, Universidade Federal do Rio Grande do Sul, Brazil, Kindai University, Japan, Kyoto University, Japan, Medical University of Warsaw, Poland, University of Catania, Italy, CIBER en Epidemiología y Salud Pública, Spain, University of KwaZulu-Natal, South Africa, Geneva University Hospitals, Switzerland, Australian Bureau of Statistics, Australia, Wageningen University, Netherlands, B P Koirala Institute of Health Sciences, Nepal, University of Insubria, Italy, Ministry of Health, Israel, The Andes Clinic of Cardio-Metabolic Studies, Venezuela, National Institute of Hygiene, Epidemiology and Microbiology, Cuba, Université de Lille 2, France, Institute for Clinical and Experimental Medicine, Czech Republic, Children'sMemorial Health Institute, Poland, Alexander Technological Educational Institute, Greece, Jagiellonian University Medical College, Poland, Azienda Ospedaliera Universitaria Policlinico Vittorio Emanuele, Italy, University of Novi Sad, Serbia, National Center of Cardiovascular Diseases, China, Singapore Eye Research Institute, Singapore, Icelandic Heart Association, Iceland, Universidad Icesi, Colombia, King's College London, United Kingdom, International Agency for Research on Cancer, France, Healis-Sekhsaria Institute for Public Health, India, Eternal Heart Care Centre and Research Institute, India, University of Ibadan, Nigeria, Children's Memorial Health Institute, Poland, Institute for Clinical Effectiveness and Health Policy, Argentina, Danish Cancer Society Research Centre, Denmark, Kyushu University, Japan, Tulane University, United States, Chinese Center for Disease Control and Prevention, China, Academic Medical Center of University of Amsterdam, Netherlands, National Institute of Public Health, Mexico, Oulu University Hospital, Finland, Chronic Diseases Research Center, Iran, University of Hong Kong, Hong Kong, The Chinese University of Hong Kong, Hong Kong, University of Western Australia, Australia, Celal Bayar University, Turkey, Heart Institute, Brazil, Fundación Oftalmológica de Santander, Colombia, University of Oran 1, Algeria, Independent Public Health Specialist, Myanmar, Ministry of Health, Myanmar, Peking University, China, VU University Medical Center and VU University, Netherlands, American University of Beirut, Lebanon, Cairo University, Egypt, National Institute of Health and Nutrition, Japan, Aga Khan University, Pakistan, UHC Zagreb, Croatia, Niigata University, Japan, Hadassah University Medical Center, Israel, Duke- NUS Medical School, Singapore, Norwegian University of Science and Technology, Norway, University of Zagreb School of Medicine, Croatia, Heart Foundation, Australia, National Health Insurance Service, South Korea, Guangzhou 12th Hospital, China, Simon Fraser University, Canada, Ruprecht-Karls- University of Heidelberg, Germany, Research Centre for Prevention and Health, Denmark, World Health Organization Country Office, India, Czestochowa University of Technology, Poland, University of Crete, Greece, Universiti Kebangsaan Malaysia, Malaysia, Johns Hopkins Bloomberg School of Public Health, United States, University of Eastern Finland, Finland, National Institute of Epidemiology, India, University of Münster, Germany, Israel Center for Disease Control, Israel, Research Institute for Primordial Prevention of Noncommunicable Disease, Iran, VU University Medical Center, Netherlands, Kyrgyz State Medical Academy, Kyrgyzstan, Research Institute of Child Nutrition, Germany, University of Cambridge, United Kingdom, Medical University of Innsbruck, Austria, Muhimbili University of Health and Allied Sciences, Tanzania, National Cancer Center, South Korea, Institute of Tropical Medicine, Belgium, Tartu University Clinics, Estonia, Ministry of Health and Quality of Life, Mauritius, Polish Academy of Sciences Anthropology Unit in Wroclaw, Poland, University of Zürich, Switzerland, University of Groningen, Netherlands, North-West University, South Africa, National Institute of Public Health, Czech Republic, University of Jyväskylä, Finland, Amrita Institute of Medical Sciences, India, All India Institute of Medical Sciences, India, African Population and Health Research Center, Kenya, Ministerio de Salud Pública, Cuba, Sahlgrenska Academy, Sweden, Endocrinology and Metabolism Research Center, Iran, Food and Agriculture Organization of the United Nations, Italy, National University of Singapore, Singapore, Tampere University Hospital, Finland, University of Cape Town, South Africa, West Virginia University, United States, Oswaldo Cruz Foundation Rene Rachou Research Institute, Brazil, National Taiwan University, Taiwan, University of Chinese Academy of Sciences, China, University Medicine Greifswald, Germany, Consejería de Sanidad Junta de Castilla y León, Spain, University of Uppsala, Sweden, Universidade Federal de Ouro Preto, Brazil, The Jikei University School of Medicine, Japan, National Research Council, Italy, Baker Heart and Diabetes Institute, Australia, Agricultural University of Athens, Greece, Hospital Israelita Albert Einstein, Brazil, Shiraz University of Medical Sciences, Iran, Institute of Internal and Preventive Medicine, Russian Federation, Harokopio University, Greece, University of Otago, New Zealand, University of Padova, Italy, Lausanne University Hospital, Switzerland, CIBERCV, Spain, Emory University, United States, UiT The Arctic University of Norway, Norway, Cape Peninsula University of Technology, South Africa, Gorgas Memorial Institute of Health Studies, Panama, Brown University, United States, University of Edinburgh, United Kingdom, Statistics Canada, Canada, University College Dublin, Ireland, Institut National de la Santé et de la Recherche Médicale, France, Lusófona University, Portugal, Universita' degli Studi di Firenze, Italy, Ain Shams University, Egypt, Hypertension Research Center, Iran, University of Pécs, Hungary, Seoul National University Children's Hospital, South Korea, University Medical Science, Cuba, Universidad de Zaragoza, Spain, RCSI Dublin, Ireland, La Trobe University, Australia, International Institute of Molecular and Cell Biology, Poland, Ahvaz Jundishapur University of Medical Sciences, Iran, Gorgas Memorial Institute of Public Health, Panama, World Health Organization Country Office, Malawi, Department of Public Health, Myanmar, University of Brescia, Italy, Bushehr University of Medical Sciences, Iran, Ulm University, Germany, Kobe University, Japan, Suraj Eye Institute, India, University Medicine of Greifswald, Germany, INSERM, France, National Institute of Hygiene and Epidemiology, Viet Nam, The University of Pharmacy and Medicine of Ho Chi Minh City, Viet Nam, Hanoi Medical University, Viet Nam, National Hospital of Endocrinology, Viet Nam, Miami Veterans Affairs Healthcare System, United States, University of Turku Tyks, Finland, Heartfile, Pakistan, Eastern Mediterranean Public Health Network, Jordan, Tachikawa General Hospital, Japan, Academic Hospital of Paramaribo, Suriname, Ministry of Health, Brunei Darussalam, University of Madeira, Portugal, MRC Lifecourse Epidemiology Unit, United Kingdom, Aarhus University, Denmark, Kwame Nkrumah University of Science and Technology, Ghana, Institute for Social and Preventive Medicine, Switzerland, University of Coimbra, Portugal, Cancer Prevention and Research Institute, Italy, Ruprecht-Karls-University of Heidelberg, Germany, IRCCS Casa Sollievo della Sofferenza, Italy, Zayed University, United Arab Emirates, Catholic University of Daegu, South Korea, Jivandeep Hospital, India, University Hospital Centre Zagreb, Croatia, University Medical Center Utrecht, Netherlands, Vietnam National Heart Institute, Viet Nam, University of Sarajevo, Bosnia and Herzegovina, Cardiovascular Prevention Centre Udine, Italy, Ministry of Health and Medical Services, Solomon Islands, Public Health Agency of Catalonia, Spain, University of Split, Croatia, Digestive Oncology Research Center, Iran, Digestive Disease Research Institute, Iran, Alborz University of Medical Sciences, Iran, Ministry of Health, Viet Nam, University of Turku, Finland, Universiti Putra Malaysia, Malaysia, University of Malaya, Malaysia, University of Valencia, Spain, University of the Philippines, Philippines, Minas Gerais State Secretariat for Health, Brazil, Health Center San Agustín, Spain, PharmAccess Foundation, Netherlands, Universidade Nove de Julho, Brazil, Public Health Agency of Canada, Canada, Canarian Health Service, Spain, Universidad Industrial de Santander, Colombia, Instituto Nacional de Salud Pública, Mexico, Sitaram Bhartia Institute of Science and Research, India, Marmara University, Turkey, CIBER de Epidemiología y Salud Pública, Spain, University of Helsinki, Finland, National Institute of Health, Peru, Catalan Department of Health, Spain, Universidade de Lisboa, Portugal, University of Sao Paulo Clinics Hospital, Brazil, South Karelia Social and Health Care District, Finland, Isfahan Cardiovascular Research Center, Iran, Research and Education Institute of Child Health, Cyprus, Hospital Italiano de Buenos Aires, Argentina, Lagos State University College of Medicine, Nigeria, The University of Tokyo, Japan, Samsung Medical Center, South Korea, Federal University of Santa Catarina, Brazil, St Vincent's Hospital, Australia, Academic Medical Center Amsterdam, Netherlands, University of Bari, Italy, Lund University, Sweden, University of Copenhagen, Denmark, Institut Régional de Santé Publique, Benin, University of Bordeaux, France, University of Leuven, Belgium, Bonn University, Germany, Sotiria Hospital, Greece, National Institute of Public Health- National Institute of Hygiene, Poland, Fu Jen Catholic University, Taiwan, Ministry of Health, Jordan, Health Service of Murcia, Spain, IB-SALUT Area de Salut de Menorca, Spain, Institut de Recherche pour le Développement, France, Hellenic Health Foundation, Greece, GovernmentMedical College, India, Sefako Makgatho Health Science University, South Africa, Addis Ababa University, Ethiopia, Dasman Diabetes Institute, Kuwait, Ministry of Health, New Zealand, Universidad Centro-Occidental Lisandro Alvarado, Venezuela, University of Tampere Tays Eye Center, Finland, Utrecht University, Netherlands, Hanoi University of Public Health, Viet Nam, Amsterdam Public Health Research Institute, Netherlands, Universidade Federal de Minas Gerais, Brazil, Finnish Institute of Occupational Health, Finland, Universidad Miguel Hernandez, Spain, North Karelian Center for Public Health, Finland, University of the Witwatersrand, South Africa, University of Strasbourg, France, Institute for Medical Research, Malaysia, Xinjiang Medical University, China, Capital Medical University, China, St George's, University of London, United Kingdom, Medical University of Vienna, Austria, Universitas Indonesia, Indonesia, National Institute of Public Health-National Institute of Hygiene, Poland, Institute of Food and Nutrition Development of Ministry of Agriculture, China, Children's Hospital of Fudan University, China, University of Cyprus, Cyprus, Universiti Teknologi MARA, Malaysia, Inner Mongolia Medical University, China, Universidad Politécnica de Madrid, Spain, State University of Montes Claros, Brazil, and University of Limpopo, South Africa
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sense organs - Abstract
Background: Change in the prevalence of raised blood pressure could be due to both shifts in the entire distribution of blood pressure (representing the combined effects of public health interventions and secular trends) and changes in its high-blood-pressure tail (representing successful clinical interventions to control blood pressure in the hypertensive population). Our aim was to quantify the contributions of these two phenomena to the worldwide trends in the prevalence of raised blood pressure. Methods: We pooled 1018 population-based studies with blood pressure measurements on 88.6 million participants from 1985 to 2016. We first calculated mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP) and prevalence of raised blood pressure by sex and 10-year age group from 20-29 years to 70-79 years in each study, taking into account complex survey design and survey sample weights, where relevant. We used a linear mixed effect model to quantify the association between (probittransformed) prevalence of raised blood pressure and age-group- and sex-specific mean blood pressure. We calculated the contributions of change in mean SBP and DBP, and of change in the prevalence-mean association, to the change in prevalence of raised blood pressure. Results: In 2005-16, at the same level of population mean SBP and DBP, men and women in South Asia and in Central Asia, the Middle East and North Africa would have the highest prevalence of raised blood pressure, and men and women in the highincome Asia Pacific and high-income Western regions would have the lowest. In most region-sex-age groups where the prevalence of raised blood pressure declined, one half or more of the decline was due to the decline in mean blood pressure. Where prevalence of raised blood pressure has increased, the change was entirely driven by increasing mean blood pressure, offset partly by the change in the prevalence-mean association. Conclusions: Change in mean blood pressure is the main driver of the worldwide change in the prevalence of raised blood pressure, but change in the high-blood-pressure tail of the distribution has also contributed to the change in prevalence, especially in older age groups. © The Author(s) 2018.
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- 2018
7. Natural killer cell memory precedes HLH in monozygotic twins discordant for chronic active Epstein-Barr virus disease
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Chrissie K. Lim, Youjia Zhong, Richard Hopkins, Wei-Xiang Sin, Bijin Veonice Au, Sriram Narayanan, Chiung-Hui Huang, Colin YC Lee, Ming Liang Oon, Avisha Chowdhury, Benjamin Wong, Frances Yeap, Mariflor Villegas, Julien Pompon, Patricia PL Ng, Siok-Bian Ng, Thuan Chong T Quah, Poh-Lin Tan, Keh-Chuang Chin, John E Connolly, National University Hospital [Singapore] (NUH), University Health Network, Duke-NUS Medical School [Singapore], Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), National University of Singapore (NUS), Baylor University, and Parker Institute for Cancer Immunotherapy [San Francisco, CA] (PICI)
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MESH: Killer Cells, Natural ,MESH: Humans ,MESH: Epstein-Barr Virus Infections ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Immunology ,MESH: Herpesvirus 4, Human ,[SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology ,Cell Biology ,Hematology ,MESH: Twins, Monozygotic ,[SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology ,Biochemistry - Abstract
International audience; Severe mosquito bite allergy (SMBA) is a manifestation of chronic active Epstein-Barr virus (CAEBV) infection defined by necrotic ulceration of the stings. CAEBV with SMBA has a high mortality rate as most patients eventually develop fulminant and refractory hemophagocytic lymphohistiocytosis (HLH). However, how self-resolving SMBA escalates to systemic lethal HLH remains unclear. Through comprehensive immune profiling of a SMBA patient with CAEBV and her healthy monozygotic twin, we found that both twins were seropositive for EBV but showed high discordance in their circulating natural killer (NK) cells. The patient's EBV-infected NK cells displayed memory-like properties, including low CD16, high CD226 and induction of enhanced IFNγ production by IL-2 or IL-12. Her leukocytes also produced high levels of IL-2 and IL-12 when stimulated with salivary gland extract (SGE) specifically from A. albopictus mosquitoes, connected again with hyperproduction of IFNγ by her NK cells. Strikingly, pharmacological inhibition of STAT3 suppressed the NK memory-associated cytokine axis of IFNγ, IL-2 and IL-12 that is generated by A. albopictus SGE stimulation. Altogether, this study shows that NK memory is promoted during CAEBV with SMBA by repeated cytokine restimulation leading up to lethal HLH, and proposes STAT3 as a therapeutic target to halt its progression.
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- 2023
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8. Right-left ventricular shape variations in tetralogy of Fallot: associations with pulmonary regurgitation
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Andrew D. McCulloch, Sachin Govil, Tarique Hussain, J. Omens, Radomir Chabiniok, Kuberan Pushparajah, James C. Perry, Alistair A. Young, Sanjeet Hegde, Charlene Mauger, Christopher J. Occleshaw, Liang Zhong, Kathleen Gilbert, Avan Suinesiaputra, University of Auckland [Auckland], Auckland Bioengineering Institute, University of California [San Diego] (UC San Diego), University of California (UC), King‘s College London, Czech Technical University in Prague (CTU), Mathematical and Mechanical Modeling with Data Interaction in Simulations for Medicine (M3DISIM), Laboratoire de mécanique des solides (LMS), École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), University of Texas Southwestern Medical Center [Dallas], Guy's and St Thomas' Hospital [London], Rady Children's Hospital San Diego, Department of Cardiology, Auckland District Health Board, Auckland, King's College London School of Medicine at Guy's, King's College and St Thomas' Hospitals, University of Leeds, Duke-NUS Medical School [Singapore], National Heart Centre Singapore (NHCS), University of California San Diego, La Jolla, CA, École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, and University of California San Diego, La Jolla
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Adult ,Multivariate statistics ,medicine.medical_specialty ,Adolescent ,030204 cardiovascular system & hematology ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Predictive Value of Tests ,Bayesian multivariate linear regression ,Internal medicine ,Pulmonary Valve Replacement ,Pulmonary regurgitation ,Medicine ,Humans ,Diseases of the circulatory (Cardiovascular) system ,Radiology, Nuclear Medicine and imaging ,Wall motion ,cardiovascular diseases ,Child ,Ventricular function ,Tetralogy of Fallot ,Angiology ,Retrospective Studies ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Myocardial deformation ,Research ,Magnetic resonance imaging ,Atlases ,medicine.disease ,Pulmonary Valve Insufficiency ,Cross-Sectional Studies ,RC666-701 ,Cardiology ,Ventricular Function, Right ,[SDV.IB]Life Sciences [q-bio]/Bioengineering ,Cardiovascular magnetic resonance ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background Relationships between right ventricular (RV) and left ventricular (LV) shape and function may be useful in determining optimal timing for pulmonary valve replacement in patients with repaired tetralogy of Fallot (rTOF). However, these are multivariate and difficult to quantify. We aimed to quantify variations in biventricular shape associated with pulmonary regurgitant volume (PRV) in rTOF using a biventricular atlas. Methods In this cross-sectional retrospective study, a biventricular shape model was customized to cardiovascular magnetic resonance (CMR) images from 88 rTOF patients (median age 16, inter-quartile range 11.8–24.3 years). Morphometric scores quantifying biventricular shape at end-diastole and end-systole were computed using principal component analysis. Multivariate linear regression was used to quantify biventricular shape associations with PRV, corrected for age, sex, height, and weight. Regional associations were confirmed by univariate correlations with distances and angles computed from the models, as well as global systolic strains computed from changes in arc length from end-diastole to end-systole. Results PRV was significantly associated with 5 biventricular morphometric scores, independent of covariates, and accounted for 12.3% of total shape variation (p Conclusion A biventricular atlas of rTOF patients quantified multivariate relationships between left–right ventricular morphometry and wall motion with pulmonary regurgitation. Regional RV dilation, LV reduction, LV septal-lateral flattening and increased RV strain were all associated with increased pulmonary regurgitant volume. Morphometric scores provide simple metrics linking mechanisms for structural and functional alteration with important clinical indices.
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- 2021
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9. Genomic epidemiology of SARS-CoV-2 in Cambodia, January 2020 to February 2021
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Yvonne C F Su, Jordan Z J Ma, Tey Putita Ou, Leakhena Pum, Sidonn Krang, Philomena Raftery, Michael H Kinzer, Jennifer Bohl, Vanra Ieng, Vannda Kab, Sarika Patel, Borann Sar, Wong Foong Ying, Jayanthi Jayakumar, Viseth Srey Horm, Narjis Boukli, Sokhoun Yann, Cecile Troupin, Vireak Heang, Jose A Garcia-Rivera, Yi Sengdoeurn, Seng Heng, Sreyngim Lay, Sophana Chea, Chau Darapheak, Chin Savuth, Asheena Khalakdina, Sowath Ly, Laurence Baril, Jessica E Manning, Etienne Simone-Loriere, Veasna Duong, Philippe Dussart, Ly Sovann, Gavin J D Smith, Erik A Karlsson, Duke-NUS Medical School [Singapore], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Université de Montpellier (UM), Ministry of Health [Phnom Penh], World Health Organization [Phnom Penh] (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centers for Disease Control and Prevention [Phnom Penh], Embassy of the United States of America, National Institute of Allergy and Infectious Diseases [Phnom Penh, Cambodia] (NIAID), National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), US Naval Medical Research Unit n°2, National Institute of Public Health [Phnom Penh, Cambodge], Département de Virologie - Department of Virology, Institut Pasteur [Paris] (IP), Duke University [Durham], The work at Institut Pasteur du Cambodge is supported by the WHO, the European Union, The Pasteur International Center for Research on Emerging Infectious Diseases National Institutes of Health, Department of Health and Human Services funded project No. 1U01AI151758-01, Wellcome Trust grant 222574/Z/21/Z, the British Embassy in Cambodia, and French Development Agency-funded ECOnomic development, ECOsystem MOdifications, and emerging infectious diseases Risk Evaluation (ECOMORE) 2 COVID-19 top up project No. CZZ 2146 01A. E.A.K. was funded, in part, by federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services Contract No. 75N93021C00015. The study was supported by the Duke-NUS Signature Research Programme funded by the Ministry of Health, Singapore, and by contracts HHSN272201400006C and 75N93021C00016 from the National Institute of Allergy and Infectious Disease, National Institutes of Health, Department of Health and Human Services, USA. This work was funded in part by the Division of Intramural Research at National Institute of Allergy and Infectious Diseases at the National Institutes of Health and Bill and Melinda Gates Foundation Grant OPP1211806. E.S.L. acknowledges funding from the INCEPTION programme (Investissements d’Avenir), grant number ANR-16-CONV-0005., and ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016)
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pandemic ,[SDV]Life Sciences [q-bio] ,Virology ,coronavirus ,COVID-19 ,genetic diversity ,phylogeny ,Microbiology - Abstract
The first case of coronavirus disease 2019 (COVID-19) in Cambodia was confirmed on 27 January 2020 in a traveller from Wuhan. Cambodia subsequently implemented strict travel restrictions, and although intermittent cases were reported during the first year of the COVID-19 pandemic, no apparent widespread community transmission was detected. Investigating the routes of severe acute respiratory coronavirus 2 (SARS-CoV-2) introduction into the country was critical for evaluating the implementation of public health interventions and assessing the effectiveness of social control measures. Genomic sequencing technologies have enabled rapid detection and monitoring of emerging variants of SARS-CoV-2. Here, we detected 478 confirmed COVID-19 cases in Cambodia between 27 January 2020 and 14 February 2021, 81.3 per cent in imported cases. Among them, fifty-four SARS-CoV-2 genomes were sequenced and analysed along with representative global lineages. Despite the low number of confirmed cases, we found a high diversity of Cambodian viruses that belonged to at least seventeen distinct PANGO lineages. Phylogenetic inference of SARS-CoV-2 revealed that the genetic diversity of Cambodian viruses resulted from multiple independent introductions from diverse regions, predominantly, Eastern Asia, Europe, and Southeast Asia. Most cases were quickly isolated, limiting community spread, although there was an A.23.1 variant cluster in Phnom Penh in November 2020 that resulted in a small-scale local transmission. The overall low incidence of COVID-19 infections suggests that Cambodia’s early containment strategies, including travel restrictions, aggressive testing and strict quarantine measures, were effective in preventing large community outbreaks of COVID-19.
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- 2022
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10. Treatment of nonarteritic anterior ischemic optic neuropathy with an endothelin antagonist: ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy)—a multicentre randomised controlled trial protocol
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Christophe, Chiquet, Catherine, Vignal, Philippe, Gohier, Emmanuel, Heron, Gilles, Thuret, Marie Bénédicte, Rougier, Audrey, Lehmann, Laurent, Flet, Jean-Louis, Quesada, Mathieu, Roustit, Dan, Milea, Jean-Louis, Pepin, SALAS, Danielle, Hypoxie et PhysioPathologie (HP2), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), CHU Grenoble, Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Saint-Etienne, Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Centre hospitalier universitaire de Nantes (CHU Nantes), Duke-NUS Medical School [Singapore], and Singapore Eye Research Institute [Singapore] (SERI)
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Randomised controlled trial ,Retinal Ganglion Cells ,Endothelin Receptor Antagonists ,Receptors, Endothelin ,[SDV]Life Sciences [q-bio] ,Medicine (miscellaneous) ,Bosentan ,Middle Aged ,Visual field ,Endothelin ,[SDV] Life Sciences [q-bio] ,Nonarteritic anterior ischaemic optic neuropathy (NAAION) ,Clinical Trials, Phase III as Topic ,Humans ,Multicenter Studies as Topic ,Optic Neuropathy, Ischemic ,Pharmacology (medical) ,Prospective Studies ,Tomography, Optical Coherence ,Randomized Controlled Trials as Topic - Abstract
Background Nonarteritic anterior ischemic optic neuropathy (NAAION) is a major cause of blindness in individuals over 50 years of age, with no available effective treatment. The oral dual endothelin receptor antagonist, bosentan, increases retinal optic nerve head blood flow in healthy humans and glaucoma patients. The objective of this trial is to assess the efficacy of bosentan administered at the acute stage in improving outcomes in NAAION patients. Methods ENDOTHELION (ENDOTHELin antagonist receptor in Ischemic Optic Neuropathy) is a phase III, interventional, prospective, multicentre, placebo-controlled randomised double-blind clinical trial. The primary outcome is change in the visual field mean deviation (MD) at 3 months (Humphrey 30-2 SITA standard programme). Secondary outcomes include MD and visual acuity changes up to 24 months, changes in peripapillary retinal nerve fibre and macular ganglion cell layer thickness in the affected eye, as measured by optical coherence tomography, rate of NAAION bilateralisation at 2 years, and quality-of-life. Patients over 50 years of age presenting with typical NAAION of recent onset (less than 21 days) are randomly assigned to either 125 mg oral bosentan or placebo, twice a day, during 8 weeks. Besides visits during the treatment phase, patients attend follow-up visits at 2, 3, 6, 12 and 24 months. The inclusion of patients began in August 2015 at five French University hospital ophthalmology departments and two specialised ophthalmology centres. It is planned to include 86 patients in this trial. To date we have included 72 patients and 49 have completed the full follow-up process. Discussion An endothelin receptor antagonist is a potential approach to improving the anatomical and functional prognosis of patients with NAAION. This multicentre double-blind randomised controlled trial is an opportunity to assess (1) the effect of bosentan on the structure and function of the optic nerve in NAAION, at 3 months, (2) the effect of bosentan on the bilateralisation rate at 24 months and (3) the tolerance profile of bosentan in this population. Trial registration ClinicalTrials.gov NCT02377271. Registered on March 3, 2015.
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- 2022
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11. Lessons from the pandemic: Responding to emerging zoonotic viral diseases-a Keystone Symposia report
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Jennifer Cable, Anthony Fauci, William E. Dowling, Stephan Günther, Dennis A. Bente, Pragya Dhruv Yadav, Lawrence C. Madoff, Lin‐Fa Wang, Rahul K. Arora, Maria Van Kerkhove, May C. Chu, Thomas Jaenisch, Jonathan H. Epstein, Simon David William Frost, Daniel G. Bausch, Lisa E. Hensley, Éric Bergeron, Ioannis Sitaras, Michael D. Gunn, Thomas W. Geisbert, César Muñoz‐Fontela, Florian Krammer, Emmie de Wit, Pontus Nordenfelt, Erica Ollmann Saphire, Sarah C. Gilbert, Kizzmekia S. Corbett, Luis M. Branco, Sylvain Baize, Neeltje van Doremalen, Marco A. Krieger, Sue Ann Costa Clemens, Renske Hesselink, Dan Hartman, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Coalition for Epidemic Preparedness Innovations [Oslo] (CEPI), Bernhard Nocht Institute for Tropical Medicine - Bernhard-Nocht-Institut für Tropenmedizin [Hamburg, Germany] (BNITM), University of Texas Medical Branch at Galveston, California Institute of Technology (CALTECH), National Institute of Virology - National Influenza Center [Pune, India] (NIV), University of Massachusetts System (UMASS), Duke-NUS Medical School [Singapore], University of Calgary, University of Oxford, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Colorado Anschutz [Aurora], EcoHealth Alliance [New York], Microsoft Research [Redmond], Microsoft Corporation [Redmond, Wash.], Foundation for Innovative New Diagnostics (FIND), PREVAIL, Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Johns Hopkins Bloomberg School of Public Health [Baltimore], Johns Hopkins University (JHU), Duke University [Durham], University of Manitoba [Winnipeg], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Lund University [Lund], La Jolla Institute for Immunology [La Jolla, CA, États-Unis], Harvard T.H. Chan School of Public Health, Zalgen Labs, Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Fiocruz Paraná - Instituto Carlos Chagas / Carlos Chagas Institute [Curitiba, Brésil] (ICC), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Università degli Studi di Siena = University of Siena (UNISI), Bill & Melinda Gates Foundation [Seattle], R.K.A. and M.V.K. presented work funded by the WHO Solidarity Response Fund and the German Federal Ministry of Health COVID-19 Research and Development. R.K.A. would also like to thank the following additional funders of SeroTracker's SARS-CoV-2 evidence synthesis efforts: the Public Health Agency of Canada through Canada's COVID-19 Immunity Task Force, the Robert Koch Institute, and the Canadian Medical Association Joule Innovation Fund. M.V.K. is employed by the WHO, and the authors alone are responsible for the views expressed in this publication and they do not necessarily represent the decisions, policies, or views of WHO. E.d.W. and N.v.D. are supported by the Intramural Research Program of NIAID, NIH.
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Ebola virus ,History and Philosophy of Science ,General Neuroscience ,[SDV]Life Sciences [q-bio] ,COVID-19 ,Nipah virus ,vaccines ,zoonotic diseases ,infectious diseases ,Lassa virus ,General Biochemistry, Genetics and Molecular Biology - Abstract
International audience; The COVID-19 pandemic caught the world largely unprepared, including scientific and policy communities. On April 10-13, 2022, researchers across academia, industry, government, and nonprofit organizations met at the Keystone symposium "Lessons from the Pandemic: Responding to Emerging Zoonotic Viral Diseases" to discuss the successes and challenges of the COVID-19 pandemic and what lessons can be applied moving forward. Speakers focused on experiences not only from the COVID-19 pandemic but also from outbreaks of other pathogens, including the Ebola virus, Lassa virus, and Nipah virus. A general consensus was that investments made during the COVID-19 pandemic in infrastructure, collaborations, laboratory and manufacturing capacity, diagnostics, clinical trial networks, and regulatory enhancements-notably, in low-to-middle income countries-must be maintained and strengthened to enable quick, concerted responses to future threats, especially to zoonotic pathogens.
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- 2022
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12. Sodium–glucose co‐transporter 2 inhibition in patients hospitalized for acute decompensated heart failure: rationale for and design of the <scp>EMPULSE</scp> trial
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Afshin Salsali, João Pedro Ferreira, Mitchell A. Psotka, Martina Brueckmann, Mikhail Kosiborod, Jan Biegus, Adriaan A. Voors, Claudia Grauer, Christiane E. Angermann, John R. Teerlink, Jon Blatchford, Sean P. Collins, Piotr Ponikowski, Michael E. Nassif, Jasper Tromp, Cardiovascular Centre (CVC), University Medical Center Groningen [Groningen] (UMCG), Duke-NUS Medical School [Singapore], National Heart Centre Singapore (NHCS), University of Wrocław [Poland] (UWr), Boehringer Ingelheim Pharma GmbH & Co. KG, Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers), University Hospital of Würzburg, Boehringer Ingelheim International GmbH, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Saint Luke's Mid America Heart Institute, University of New South Wales [Sydney] (UNSW), Inova Heart and Vascular Institute, Falls Church, Medizinische Fakultät Mannheim, University of California [San Francisco] (UCSF), University of California, Veterans Affairs Medical Center, San Francisco, California, and The EMPULSE trial is funded by the Boehringer Ingelheim & Eli Lilly and Company Diabetes Alliance.
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Sodium-glucose co-transporter 2 inhibitors ,Trial design ,medicine.medical_specialty ,Asia ,Acute decompensated heart failure ,Heart failure ,030204 cardiovascular system & hematology ,Placebo ,Sodium–glucose co‐transporter 2 inhibitors ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Sodium-Glucose Transporter 2 ,glucose co‐ ,Diabetes mellitus ,Internal medicine ,Empagliflozin ,medicine ,Humans ,In patient ,Sodium– ,Study Design ,Ejection fraction ,business.industry ,Sodium ,Stroke Volume ,medicine.disease ,3. Good health ,Europe ,Glucose ,Kansas City Cardiomyopathy Questionnaire ,North America ,Cardiology and Cardiovascular Medicine ,business ,transporter 2 inhibitors - Abstract
International audience; Aims: Treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors improves outcomes in patients with chronic heart failure (HF) with reduced ejection fraction. There is limited experience with the in-hospital initiation of SGLT2 inhibitors in patients with acute HF (AHF) with or without diabetes. EMPULSE is designed to assess the clinical benefit and safety of the SGLT2 inhibitor empagliflozin compared with placebo in patients hospitalized with AHF.Methods: EMPULSE is a randomized, double-blind, parallel-group, placebo-controlled multinational trial comparing the in-hospital initiation of empagliflozin (10 mg once daily) with placebo. Approximately 500 patients admitted for AHF with dyspnoea, signs of fluid overload, and elevated natriuretic peptides will be randomized 1:1 stratified to HF status (de-novo and decompensated chronic HF) to either empagliflozin or placebo at approximately 165 sites across North America, Europe and Asia. Patients will be enrolled regardless of ejection fraction and diabetes status and will be randomized during hospitalization and after stabilization (between 24 h and 5 days after admission), with treatment continued up to 90 days after initiation. The primary outcome is clinical benefit at 90 days, consisting of a composite of all-cause death, HF events, and ≥5 point change from baseline in Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ-TSS), assessed using a 'win-ratio' approach. Secondary outcomes include assessments of safety, change in KCCQ-TSS from baseline to 90 days and change in natriuretic peptides from baseline to 30 days.Conclusion: The EMPULSE trial will evaluate the clinical benefit and safety of empagliflozin in patients hospitalized for AHF.
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- 2021
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13. The identification, assessment and management of difficult-to-treat depression: An international consensus statement
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Allan H. Young, Gin S Malhi, RH McAllister-Williams, Eduard Vieta, Philip Gorwood, Afzal Javed, Peter Falkai, Andrew Papadopoulos, A. J. Rush, Celso Arango, Jair C. Soares, Malcolm Hopwood, Pierre Blier, Koen Demyttenaere, Siegfried Kasper, Martinez Rico, Clara, Newcastle University [Newcastle], Newcastle Upon Tyne Hospitals NHS Foundation Trust, Instituto de Investigación Sanitaria Gregorio Marañón [Madrid, Spain] ( IiSGM), Centro de Investigación Biomédica en Red Salud Mental [Madrid] (CIBER-SAM), University of Ottawa [Ottawa], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Ludwig Maximilian University [Munich] (LMU), Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of Melbourne, University of Warwick [Coventry], Medizinische Universität Wien = Medical University of Vienna, The University of Sydney, Royal North Shore Hospital (RNSH), The University of Texas Health Science Center at Houston (UTHealth), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB), King‘s College London, South London and Maudsley NHS Foundation Trust, Somerset Partnership NHS Foundation Trust, Duke University [Durham], Texas Tech University Health Sciences Center, Texas Tech University [Lubbock] (TTU), Duke-NUS Medical School [Singapore], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)
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VAGUS NERVE-STIMULATION ,TRANSCRANIAL MAGNETIC STIMULATION ,medicine.medical_specialty ,Consensus ,2016 CLINICAL GUIDELINES ,SEROTONIN REUPTAKE INHIBITORS ,medicine.medical_treatment ,Clinical Neurology ,GENERALIZED ANXIETY DISORDER ,Difficult-to-treat depression ,Depressive Disorder, Treatment-Resistant ,DOUBLE-BLIND ,03 medical and health sciences ,POSTTRAUMATIC-STRESS-DISORDER ,0302 clinical medicine ,Pharmacotherapy ,Diagnosis ,medicine ,Humans ,Symptom control ,COGNITIVE-BEHAVIORAL THERAPY ,Intensive care medicine ,Neurostimulation ,Psychiatry ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,Science & Technology ,Conceptualization ,Depression ,Clinical management ,business.industry ,Treatment options ,MAJOR DEPRESSION ,medicine.disease ,3. Good health ,030227 psychiatry ,Psychotherapy ,Psychiatry and Mental health ,Clinical Psychology ,Management implications ,Quality of Life ,TREATMENT-RESISTANT DEPRESSION ,Neurosciences & Neurology ,Treatment-resistant depression ,business ,Life Sciences & Biomedicine ,Psychosocial ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,030217 neurology & neurosurgery - Abstract
BACKGROUND: Many depressed patients are not able to achieve or sustain symptom remission despite serial treatment trials - often termed "treatment resistant depression". A broader, perhaps more empathic concept of "difficult-to-treat depression" (DTD) was considered. METHODS: A consensus group discussed the definition, clinical recognition, assessment and management implications of the DTD heuristic. RESULTS: The group proposed that DTD be defined as "depression that continues to cause significant burden despite usual treatment efforts". All depression management should include a thorough initial assessment. When DTD is recognized, a regular reassessment that employs a multi-dimensional framework to identify addressable barriers to successful treatment (including patient-, illness- and treatment-related factors) is advised, along with specific recommendations for addressing these factors. The emphasis of treatment, in the first instance, shifts from a goal of remission to optimal symptom control, daily psychosocial functional and quality of life, based on a patient-centred approach with shared decision-making to enhance the timely consideration of all treatment options (including pharmacotherapy, psychotherapy, neurostimulation, etc.) to optimize outcomes when sustained remission is elusive. LIMITATIONS: The recommended definition and management of DTD is based largely on expert consensus. While DTD would seem to have clinical utility, its specificity and objectivity may be insufficient to define clinical populations for regulatory trial purposes, though DTD could define populations for service provision or phase 4 trials. CONCLUSIONS: DTD provides a clinically useful conceptualization that implies a search for and remediation of specific patient-, illness- and treatment obstacles to optimizing outcomes of relevance to patients. ispartof: Journal of Affective Disorders vol:267 pages:264-282 ispartof: location:Netherlands status: published
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- 2020
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14. Maternal Glycemic Dysregulation During Pregnancy and Neonatal Blood DNA Methylation: Meta-analyses of Epigenome-Wide Association Studies
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Elmar W. Tobi, Diana L. Juvinao-Quintero, Justiina Ronkainen, Raffael Ott, Rossella Alfano, Mickaël Canouil, Madelon L. Geurtsen, Amna Khamis, Leanne K. Küpers, Ives Y. Lim, Patrice Perron, Giancarlo Pesce, Johanna Tuhkanen, Anne P. Starling, Toby Andrew, Elisabeth Binder, Robert Caiazzo, Jerry K.Y. Chan, Romy Gaillard, Peter D. Gluckman, Elina Keikkala, Neerja Karnani, Sanna Mustaniemi, Tim S. Nawrot, François Pattou, Michelle Plusquin, Violeta Raverdy, Kok Hian Tan, Evangelia Tzala, Katri Raikkonen, Christiane Winkler, Anette-G. Ziegler, Isabella Annesi-Maesano, Luigi Bouchard, Yap Seng Chong, Dana Dabelea, Janine F. Felix, Barbara Heude, Vincent W.V. Jaddoe, Jari Lahti, Brigitte Reimann, Marja Vääräsmäki, Amélie Bonnefond, Philippe Froguel, Sandra Hummel, Eero Kajantie, Marjo-Riita Jarvelin, Regine P.M. Steegers-Theunissen, Caitlin G. Howe, Marie-France Hivert, Sylvain Sebert, Erasmus University Medical Center [Rotterdam] (Erasmus MC), Harvard Pilgrim Health Care Institute, University of Oulu, Helmholtz Zentrum München = German Research Center for Environmental Health, Klinikums rechts der Isar, Hasselt University (UHasselt), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), The Generation R Study Group, Imperial College London, Bioinformatics Institute (A*STAR), Singapore Institute for Clinical Sciences [Singapour] (SICS), Agency for science, technology and research [Singapore] (A*STAR), Université de Sherbrooke (UdeS), Centre Hospitalier Universitaire de Sherbrooke, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Epidemiology of Allergic and Respiratory Diseases Department [iPlesp] (EPAR), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), TKK Helsinki University of Technology (TKK), Colorado School of Public Health [Aurora, CO, USA] (CSPH), University of Colorado Anschutz [Aurora], Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Emory University School of Medicine, Emory University [Atlanta, GA], Recherche translationnelle sur le diabète - U 1190 (RTD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), KK Women's and Children's Hospital [Singapore], Duke-NUS Medical School [Singapore], Liggins Institute, University of Auckland [Auckland], Finnish Institute for Health and Welfare [Helsinki, Finland] (FIHW), Oulu University Hospital [Oulu], Bioinformatics Institute [Singapore], Yong Loo Lin School of Medicine [Singapore], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université du Québec à Chicoutimi (UQAC), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Norwegian University of Life Sciences (NMBU), Brunel University London [Uxbridge], Geisel School of Medicine at Dartmouth, Harvard Medical School [Boston] (HMS), Massachusetts General Hospital [Boston], Salvy-Córdoba, Nathalie, Obstetrics & Gynecology, Pediatrics, Binder, Elisabeth, Küpers, Leanne K., Geurtsen, Madelon L., Raikkonen, Katri, Tuhkanen, Johanna, Felix, Janine F., ALFANO, Rossella, Winkler, Christiane, Ott, Raffael, Dabelea, Dana, Khamis, Amna, Bouchard, Luigi, Bonnefond, Amélie, Canouil, Mickaël, Karnani, Neerja, Hummel, Sandra, Tobi, Elmar W, Sebert, Sylvain, Jarvelin, Marjo-Riita, Keikkala, Elina, Heude, Barbara, Pesce, Giancarlo, Steegers-Theunissen, Regine P.M., Lim, Ives Y., REIMANN, Brigitte, Caiazzo, Robert, Hian Tan, Kok, Chan, Jerry K.Y., Ronkainen, Justiina, Ziegler, Anette-G., NAWROT, Tim, Froguel, Philippe, Gluckman, Peter D., Raverdy, Violeta, Starling, Anne P., Howe, Caitlin G., Lahti, Jari, Mustaniemi, Sanna, Hivert, Marie-France, Seng Chong, Yap, Jaddoe, Vincent W.V., Perron, Patrice, Pattou, François, Annesi-Maesano, Isabella, Juvinao-Quintero, Diana L., Gaillard, Romy, Vääräsmäki, Marja, Plusquin, Michelle, Andrew, Toby, Kajantie, Eero, and Tzala, Evangelia
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Endocrinology, Diabetes and Metabolism ,MESH: Epigenome ,[SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,Epigenesis, Genetic ,Endocrinology & Metabolism ,Epigenome ,MESH: DNA Methylation ,MESH: Pregnancy ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,SDG 3 - Good Health and Well-being ,HYPERGLYCEMIA ,Pregnancy ,Internal Medicine ,Humans ,MESH: Fetal Blood ,MESH: Epigenesis, Genetic ,Advanced and Specialized Nursing ,MESH: Diabetes, Gestational ,[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,Science & Technology ,MESH: Humans ,MESH: Infant, Newborn ,Infant, Newborn ,DNA Methylation ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,Fetal Blood ,Diabetes, Gestational ,[SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,Diabetes Mellitus, Type 2 ,Female ,Life Sciences & Biomedicine ,MESH: Female ,MESH: Diabetes Mellitus, Type 2 - Abstract
OBJECTIVE Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring; a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized that changes in offspring DNA methylation (DNAm) underline these associations. RESEARCH DESIGN AND METHODS To address this hypothesis, we conducted fixed-effect meta-analyses of epigenome-wide association study (EWAS) results from eight birth cohorts investigating relationships between cord blood DNAm and fetal exposure to maternal glucose (Nmax= 3,503), insulin (Nmax= 2,062), and the area under the curve of glucose (AUCgluc) following oral glucose tolerance tests (OGTT, Nmax= 1,505). We performed look-up analyses for identified CpG dinucleotides (CpGs) in independent observational cohorts to examine associations between DNAm and cardiometabolic traits as well as tissue-specific gene expression. RESULTS Greater maternal AUCgluc was associated with lower cord blood DNAm at neighboring CpGs cg26974062 (β= -0.013 [SE=2.1x10-3], PFDR= 5.1x10-3) and cg02988288 (β= -0.013 [SE=2.3x10-3], PFDR =0.031) in TXNIP. These associations were attenuated in women with GDM. Lower blood DNAm at these two CpGs near TXNIP was associated with multiple metabolic traits later in life, including type 2 diabetes. TXNIP DNAm in liver biopsies was associated with hepatic expression of TXNIP. We observed little evidence of associations between either maternal glucose or insulin and cord blood DNAm. CONCLUSION Maternal hyperglycemia, as reflected by AUCgluc, was associated with lower cord blood DNAm at TXNIP. Associations between DNAm at these CpGs and metabolic traits in subsequent look-up analyses suggest that these may be candidate loci to investigate in future causal and mediation analyses.
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- 2022
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15. Y-box binding protein 1 interacts with dengue virus nucleocapsid and mediates viral assembly
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Mayra Diosa-Toro, Debbie R. Kennedy, Vanessa Chuo, Vsevolod L. Popov, Julien Pompon, Mariano A. Garcia-Blanco, Duke-NUS Medical School [Singapore], The University of Texas Medical Branch (UTMB), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), and Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)
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viruses ,Virion ,virus assembly ,RNA-Binding Proteins ,Dengue Virus ,Virus Replication ,dengue ,Microbiology ,YBX1 ,Virology ,Humans ,RNA, Viral ,RNA ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Y-Box-Binding Protein 1 ,Nucleocapsid ,Protein Binding - Abstract
Infection with dengue virus (DENV) induces vast rearrangements of the endoplasmic reticulum, which allows the compartmentalization of viral RNA replication and particle assembly. Both processes occur in concert with viral and cellular proteins. Prior studies from our group suggest that the host RNA-binding protein (RBP) Y-box binding protein 1 (YBX1) is required for a late step in the DENV replication cycle. Here we report that YBX1 interacts with the viral nucleocapsid, distributes to DENV assembly sites and is required for efficient assembly of intracellular infectious virions and their secretion. Genetic ablation of YBX1 decreased the spatial proximity between capsid and envelope, increased the susceptibility of envelope to proteinase-K mediated degradation, resulted in the formation of rough empty-looking particles, and decreased the secretion of viral particles. We propose a model wherein YBX1 enables the interaction between the viral nucleocapsid with the structural protein E, which is required for proper assembly of intracellular virus particles and their secretion.ImportanceThe global incidence of dengue virus (DENV) infections has steadily increased over the past decades representing an enormous challenge for public health. During infection, DENV viral RNA interacts with numerous host RNA binding proteins (RBPs) that aid viral replication and thus constitute potential molecular targets to curb infection. We recently reported that Y-box-binding protein 1 (YBX1) interacts with DENV RNA and is required at a late step of the replication cycle. Here we describe the molecular mechanism by which YBX1 mediates DENV infection. We show that YBX1 interacts with the viral nucleocapsid, distributes to DENV assembly sites and is required for efficient assembly of intracellular infectious virions. These results provide important insights into DENV assembly, revealing novel functions of host RBPs during viral infection and opening new avenues for antiviral intervention.
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- 2022
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16. Characterization of dengue virus 3’UTR RNA binding proteins in mosquitoes reveals that AeStaufen reduces subgenomic flaviviral RNA in saliva
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Yeh, Shih-Chia, Diosa-Toro, Mayra, Tan, Wei-Lian, Rachenne, Florian, Hain, Arthur, Yeo, Celestia Pei Xuan, Bribes, Inès, Xiang, Benjamin Wong Wei, Sathiamoorthy Kannan, Gayathiri, Manuel, Menchie Casayuran, Missé, Dorothée, Mok, Yu Keung, Pompon, Julien, Duke-NUS Medical School [Singapore], Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), National University of Singapore (NUS), and ANR-20-CE15-0006,VirSalivaEnhancer,Amplificateur de transmission d'origine flavivirale dans la salive de moustique(2020)
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[SDV.BA.ZI]Life Sciences [q-bio]/Animal biology/Invertebrate Zoology ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology - Abstract
International audience; Dengue viruses (DENV) are expanding global pathogens that are transmitted through the bite of mosquitoes, mostly Aedes aegypti . As RNA viruses, DENV rely on RNA-binding proteins (RBPs) to complete their life cycle. Alternatively, RBPs can act as restriction factors that prevent DENV multiplication. While the importance of RBPs is well-supported in humans, there is a dearth of information about their influence on DENV transmission by mosquitoes. Such knowledge could be harnessed to design novel, effective interventions against DENV. Here, we successfully adapted RNA-affinity chromatography coupled with mass spectrometry–a technique initially developed in mammalian cells–to identify RBPs in Ae . aegypti cells. We identified fourteen RBPs interacting with DENV serotype 2 3’UTR, which is involved in the viral multiplication and produces subgenomic flaviviral RNA (sfRNA). We validated the RNA affinity results for two RBPs by confirming that AePur binds the 3’UTR, whereas AeStaufen interacts with both 3’UTR and sfRNA. Using in vivo functional evaluation, we determined that RBPs like AeRan, AeExoRNase, and AeRNase have pro-viral functions, whereas AeGTPase, AeAtu, and AePur have anti-viral functions in mosquitoes. Furthermore, we showed that human and mosquito Pur homologs have a shared affinity to DENV2 RNA, although the anti-viral effect is specific to the mosquito protein. Importantly, we revealed that AeStaufen mediates a reduction of gRNA and sfRNA copies in several mosquito tissues, including the salivary glands and that AeStaufen-mediated sfRNA reduction diminishes the concentration of transmission-enhancing sfRNA in saliva, thereby revealing AeStaufen’s role in DENV transmission. By characterizing the first RBPs that associate with DENV2 3’UTR in mosquitoes, our study unravels new pro- and anti-viral targets for the design of novel therapeutic interventions as well as provides foundation for studying the role of RBPs in virus-vector interactions.
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- 2022
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17. The anti-immune dengue subgenomic flaviviral RNA is present in vesicles in mosquito saliva and is associated with increased infectivity
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Yeh, Shih-Chia, Strilets, Tania, Tan, Wei-Lian, Castillo, David, Medkour, Hacene, Rey-Cadilhac, Félix, Serrato-Pomar, Idalba, Rachenne, Florian, Chowdhury, Avisha, Chuo, Vanessa, Azar, Sasha, Singh, Moirangthem Kiran, Hamel, Rodolphe, Missé, Dorothée, Kini, R, Kenney, Linda, Vasilakis, Nikos, Marti-Renom, Marc a, Nir, Guy, Pompon, Julien, Garcia-Blanco, Mariano, Duke-NUS Medical School [Singapore], The University of Texas Medical Branch (UTMB), Centro Nacional de Analisis Genomico [Barcelona] (CNAG), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), National University of Singapore (NUS), Department of Computer and Information Science [Pennsylvania] (CIS), University of Pennsylvania, Barcelona Institute of Science and Technology (BIST), Universitat Pompeu Fabra [Barcelona] (UPF), ICREA Infection Biology Laboratory (Department of Experimental and Health Sciences), University of Texas Medical Branch at Galveston, Support for this research came from a fellowship from the McLauglin Family Foundation to TS, scholarships from the Fondation pour la Recherche Médicale (FRM project SPF202110013925) to HM, from the Institut Méditerranéen Hospitalier (IHU, Marseille) to IMSP and from the graduate school French Ministry of Higher Education and Research to FRC and FR, UTMB start-up funds and Cancer Prevention & Research Institute of Texas grant RP200650 to LJK and MKS, the Ministerio de Ciencia e Innovación (PID2020-115696RB-I00) to MAM-R, Cancer Prevention & Research Institute of Texas grant ID RR210018 to GN, Ministry of Education (Singapore) Tier3 grant (MOE2015-T3-1-003) to RMK and JP, a National Medical Research Council (Singapore) ZRRF grant (ZRRF/007/2017) to JP, a French Agence Nationale de la Recherche grant (ANR-20-CE15-0006) to JP, and the Duke-NUS Signature Research Programme funded by the Agency for Science Technology and Research (A*Star Singapore) and NIH/NIAID P01 AI150585 to MAGB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., and ANR-20-CE15-0006,VirSalivaEnhancer,Amplificateur de transmission d'origine flavivirale dans la salive de moustique(2020)
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3' UTR ,Immunology ,MESH: Dengue ,Transfection ,Mosquitoes ,Microbiology ,Dengue virus ,Guide RNA ,Ribonucleases ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN] ,Virology ,Genetics ,MESH: Flavivirus ,MESH: Animals ,MESH: Saliva ,Saliva ,Molecular Biology ,MESH: Humans ,MESH: Subgenomic RNA ,MESH: Virus Replication ,MESH: Aedes ,MESH: 3' Untranslated Regions ,RNA extraction ,MESH: RNA, Viral ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Parasitology ,MESH: Culicidae - Abstract
Mosquito transmission of dengue viruses to humans starts with infection of skin resident cells at the biting site. There is great interest in identifying transmission-enhancing factors in mosquito saliva in order to counteract them. Here we report the discovery of high levels of the anti-immune subgenomic flaviviral RNA (sfRNA) in dengue virus 2-infected mosquito saliva. We established that sfRNA is present in saliva using three different methods: northern blot, RT-qPCR and RNA sequencing. We next show that salivary sfRNA is protected in detergent-sensitive compartments, likely extracellular vesicles. In support of this hypothesis, we visualized viral RNAs in vesicles in mosquito saliva and noted a marked enrichment of signal from 3'UTR sequences, which is consistent with the presence of sfRNA. Furthermore, we show that incubation with mosquito saliva containing higher sfRNA levels results in higher virus infectivity in a human hepatoma cell line and human primary dermal fibroblasts. Transfection of 3'UTR RNA prior to DENV2 infection inhibited type I and III interferon induction and signaling, and enhanced viral replication. Therefore, we posit that sfRNA present in salivary extracellular vesicles is delivered to cells at the biting site to inhibit innate immunity and enhance dengue virus transmission. Support for this research came from a fellowship from the McLauglin Family Foundation to TS, scholarships from the Fondation pour la Recherche Médicale (FRM project SPF202110013925) to HM, from the Institut Méditerranéen Hospitalier (IHU, Marseille) to IMSP and from the graduate school French Ministry of Higher Education and Research to FRC and FR, UTMB start-up funds and Cancer Prevention & Research Institute of Texas grant RP200650 to LJK and MKS, the Ministerio de Ciencia e Innovación (PID2020-115696RB-I00) to MAM-R, Cancer Prevention & Research Institute of Texas grant ID RR210018 to GN, Ministry of Education (Singapore) Tier3 grant (MOE2015-T3-1-003) to RMK and JP, a National Medical Research Council (Singapore) ZRRF grant (ZRRF/007/2017) to JP, a French Agence Nationale de la Recherche grant (ANR-20-CE15-0006) to JP, and the Duke-NUS Signature Research Programme funded by the Agency for Science Technology and Research (A*Star Singapore) and NIH/NIAID P01 AI150585 to MAGB. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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- 2023
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18. Social Deficits or Interactional Differences? Interrogating Perspectives on Social Functioning in Autism
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Xiangting Bernice Lin, Choon Guan Lim, Tih-Shih Lee, School of Social Sciences, Duke-NUS Medical School, Singapore, and Institute of Mental Health, Singapore
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Psychiatry and Mental health ,Autism Spectrum Disorder ,Psychology [Social sciences] ,Social Functioning - Abstract
Social dysfunction is a key characteristic of autism. Determining and treating autism-related social deficits have been challenging. The medical model views interpersonal difficulties in autism as a localized set of deficits to be managed, whereas the neurodiversity movement calls for the accommodation of differences by the larger community. One common assumption underlying these perspectives is a misalignment in social behaviors between autistic individuals and neurotypicals. This paper reviews and interrogates current perspectives on social functioning in autism to uncover the intricacies of such a notion. Even though extant literature has alluded to a misalignment in social behaviors between autistic and neurotypical individuals, it is uncertain where this disparity lies. Implications for future research and practice are discussed.
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- 2021
19. 24-hour movement behaviour profiles and their transition in children aged 5.5 and 8 years – findings from a prospective cohort study
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Falk Müller-Riemenschneider, Claire Goh, Keith M. Godfrey, Yap Seng Chong, Natarajan Padmapriya, Johan G. Eriksson, Shiao-Yng Chan, Lynette Pei-Chi Shek, Bozhi Chen, Jonathan Y. Bernard, Fabian Yap, Yung Seng Lee, Kok Hian Tan, National University of Singapore (NUS), Saw Swee Hock School of Public Health [Singapore, Singapore], Singapore Institute for Clinical Sciences [Singapour] (SICS), Agency for science, technology and research [Singapore] (A*STAR), Khoo Teck Puat – National University Children’s Medical Institute (NUHkids) [Singapore] (KTP-NUCMI), National University Health System [Singapore] (NUHS), KK Women's and Children's Hospital [Singapore], Duke-NUS Medical School [Singapore], Nanyang Technological University [Singapour], University of Southampton, University Hospital Southampton NHS Foundation Trust, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Berlin Institute of Health (BIH), Bernard, Jonathan, Clinicum, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, HUS Helsinki and Uusimaa Hospital District, Lee Kong Chian School of Medicine (LKCMedicine), KK Women’s and Children’s Hospital, and Duke-National University of Singapore
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CHILDHOOD ,Ethnic group ,Medicine (miscellaneous) ,Cohort Studies ,PANDAS ,Accelerometry ,LONGITUDINAL ASSOCIATIONS ,EPIDEMIOLOGY ,Prospective Studies ,Movement Behaviour ,Prospective cohort study ,Nutritional diseases. Deficiency diseases ,Children ,Singapore ,Nutrition and Dietetics ,1184 Genetics, developmental biology, physiology ,TIME ,Cohort ,SLEEP DURATION ,Rabbits ,3143 Nutrition ,Public aspects of medicine ,RA1-1270 ,Inactivity ,medicine.medical_specialty ,RC620-627 ,Physical activity ,Physical Therapy, Sports Therapy and Rehabilitation ,Clinical nutrition ,DIET ,medicine ,Animals ,Humans ,Medicine [Science] ,OVERWEIGHT ,Health consequences ,business.industry ,Public health ,Research ,Movement behaviour ,Sedentary behaviour ,medicine.disease ,PHYSICAL-ACTIVITY ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,3121 General medicine, internal medicine and other clinical medicine ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Sedentary Behavior ,business ,Sleep ,Demography - Abstract
Background Time spent in movement behaviours, including physical activity (PA), sedentary behaviour (SB) and sleep, across the 24-h day may have distinct health consequences. We aimed to describe 24-h movement behaviour (24 h-MB) profiles in children and how profile membership changed from age 5.5 to 8 years. Methods Children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort were asked to wear an accelerometer (ActiGraph-GT3X+) on their wrist for seven consecutive days at ages 5.5 and 8 years to measure 24 h-MB patterns. Time spent in night sleep, inactivity (proxy for SB), light PA, moderate PA (MPA), and vigorous PA (VPA) per day were calculated using the R-package GGIR 2.0. Using latent profile analyses (n = 442) we identified 24 h-MB profiles, which were given animal names to convey key characteristics. Latent transition analyses were used to describe the profile membership transition from ages 5.5 to 8 years. Associations with sex and ethnicity were examined. Results We identified four profiles, “Rabbits” (very high-MPA/VPA, low-inactivity and average-night-sleep), “Chimpanzees” (high-MPA, low-inactivity and average-night-sleep), “Pandas” (low-PA, high-inactivity and high-night-sleep) and “Owls” (low-PA, high-inactivity and low-night-sleep), among children at both time points. At ages 5.5 and 8 years, the majority of children were classified into profiles of “Chimpanzees” (51 and 39%, respectively) and “Pandas” (24 and 37%). Half of the sample (49%), particularly “Rabbits”, remained in the same profile at ages 5.5 and 8 years: among children who changed profile the predominant transitions occurred from “Chimpanzees” (27%) and “Owls” (56%) profiles to “Pandas”. Sex, but not ethnicity, was associated with profile membership: compared to girls, boys were more likely to be in the “Rabbits” profile (adjusted OR [95% CI]: 3.6 [1.4, 9.7] and 4.5 [1.8, 10.9] at ages 5.5 and 8 years, respectively) and less likely to be in the “Pandas” profile (0.5 [0.3, 0.9] and 0.4 [0.2, 0.6]) at both ages. Conclusions With increasing age about half the children stayed in the same of four 24 h-MB profiles, while the predominant transition for the remaining children was towards lower PA, higher inactivity and longer sleep duration. These findings can aid development and implementation of public health strategies to promote better health. Study registration This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.
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- 2021
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20. Lipid Interactions Between Flaviviruses and Mosquito Vectors
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Vial, Thomas, Marti, Guillaume, Missé, Dorothée, Pompon, Julien, Duke-NUS Medical School [Singapore], Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), MetaToul Agromix, MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Laboratoire de Recherche en Sciences Végétales (LRSV), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), and ANR-20-CE15-0006,VirSalivaEnhancer,Amplificateur de transmission d'origine flavivirale dans la salive de moustique(2020)
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flavivirus ,Physiology ,[SDV]Life Sciences [q-bio] ,Physiology (medical) ,viruses ,parasitic diseases ,transmission ,virus diseases ,lipids (amino acids, peptides, and proteins) ,mosquito ,Review ,metabolomics ,phospholipids - Abstract
International audience; Mosquito-borne flaviviruses, such as dengue (DENV), Zika (ZIKV), yellow fever (YFV), West Nile (WNV), and Japanese encephalitis (JEV) viruses, threaten a large part of the human populations. In absence of therapeutics and effective vaccines against each flaviviruses, targeting viral metabolic requirements in mosquitoes may hold the key to new intervention strategies. Development of metabolomics in the last decade opened a new field of research: mosquito metabolomics. It is now clear that flaviviruses rely on mosquito lipids, especially phospholipids, for their cellular cycle and propagation. Here, we review the biosyntheses of, biochemical properties of and flaviviral interactions with mosquito phospholipids. Phospholipids are structural lipids with a polar headgroup and apolar acyl chains, enabling the formation of lipid bilayer that form plasma- and endomembranes. Phospholipids are mostly synthesized through the de novo pathway and remodeling cycle. Variations in headgroup and acyl chains influence phospholipid physicochemical properties and consequently the membrane behavior. Flaviviruses interact with cellular membranes at every step of their cellular cycle. Recent evidence demonstrates that flaviviruses reconfigure the phospholipidome in mosquitoes by regulating phospholipid syntheses to increase virus multiplication. Identifying the phospholipids involved and understanding how flaviviruses regulate these in mosquitoes is required to design new interventions.
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- 2021
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21. Repositioning TH cell polarization from single cytokines to complex help
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Thomas Korn, Francisco J. Quintana, Matteo Iannacone, Florent Ginhoux, Anne Dejean, Burkhard Becher, Selma Tuzlak, Ari Waisman, Universität Zürich [Zürich] = University of Zurich (UZH), Institut Toulousain des Maladies Infectieuses et Inflammatoires (Infinity), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IRCCS San Raffaele Scientific Institute [Milan, Italie], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), University Medical Center of the Johannes Gutenberg-University Mainz, Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Duke-NUS Medical School [Singapore], Shangaï Jiao Tong University [Shangaï], Technische Universität München = Technical University of Munich (TUM), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), ARSEP foundation (ARSEP R19191BB, FRM (R20097BB), Italian Ministry of Health grants RF-2018-12365801 and COVID-2020-12371617, Lombardy Foundation for Biomedical Research grant 2015-0010, ANR-16-CE15-0007,FOxOTiC,Rôle du facteur de transcription Foxo3 dans les lymphocytes T CD4(2016), European Project: 957502,ERC, Tuzlak, S., Dejean, A. S., Iannacone, M., Quintana, F. J., Waisman, A., Ginhoux, F., Korn, T., Becher, B., Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Pistre, Karine, Rôle du facteur de transcription Foxo3 dans les lymphocytes T CD4 - - FOxOTiC2016 - ANR-16-CE15-0007 - AAPG2016 - VALID, and Proof of Concept grant - ERC - 957502 - INCOMING
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[SDV.IMM] Life Sciences [q-bio]/Immunology ,[SDV]Life Sciences [q-bio] ,Immunology ,Cell ,Cell Plasticity ,MESH: Cell Plasticity / immunology ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,Epithelium ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,MESH: Eosinophils / immunology ,MESH: Phagocytes / immunology ,Cell polarity ,medicine ,Immunology and Allergy ,Animals ,Humans ,MESH: Animals ,MESH: Cytokines / immunology ,Lymphocytes ,Transcription factor ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,MESH: Immunity, Innate / immunology ,030304 developmental biology ,0303 health sciences ,B-Lymphocytes ,Phagocytes ,MESH: Epithelium / immunology ,MESH: Humans ,Innate lymphoid cell ,T-Lymphocytes, Helper-Inducer ,Phenotype ,Immunity, Innate ,Cell biology ,MESH: B-Lymphocytes / immunology ,[SDV] Life Sciences [q-bio] ,Eosinophils ,MESH: Lymphocytes / immunology ,medicine.anatomical_structure ,Cytokines ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,MESH: T-Lymphocytes, Helper-Inducer / immunology ,030215 immunology - Abstract
International audience; When helper T (TH) cell polarization was initially described three decades ago, the TH cell universe grew dramatically. New subsets were described based on their expression of few specific cytokines. Beyond TH1 and TH2 cells, this led to the coining of various TH17 and regulatory (Treg) cell subsets as well as TH22, TH25, follicular helper (TFH), TH3, TH5 and TH9 cells. High-dimensional single-cell analysis revealed that a categorization of TH cells into a single-cytokine-based nomenclature fails to capture the complexity and diversity of TH cells. Similar to the simple nomenclature used to describe innate lymphoid cells (ILCs), we propose that TH cell polarization should be categorized in terms of the help they provide to phagocytes (type 1), to B cells, eosinophils and mast cells (type 2) and to non-immune tissue cells, including the stroma and epithelium (type 3). Studying TH cells based on their helper function and the cells they help, rather than phenotypic features such as individual analyzed cytokines or transcription factors, better captures TH cell plasticity and conversion as well as the breadth of immune responses in vivo.
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- 2021
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22. The longitudinal association between early-life screen viewing and abdominal adiposity—findings from a multiethnic birth cohort study
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Yung Seng Lee, Suresh Anand Sadananthan, Carla Costa Lança, Seang-Mei Saw, Falk Müller-Riemenschneider, Shirong Cai, Fabian Yap, Mya-Thway Tint, Lynette Pei-Chi Shek, Johan G. Eriksson, Michael S. Kramer, Marielle V. Fortier, Keith M. Godfrey, Yap Seng Chong, Natarajan Padmapriya, Navin Michael, Jia Ying Toh, S. Sendhil Velan, Bozhi Chen, Peter D. Gluckman, Jonathan Y. Bernard, Kok Hian Tan, Mary Foong-Fong Chong, National University of Singapore (NUS), Saw Swee Hock School of Public Health [Singapore, Singapore], Agency for science, technology and research [Singapore] (A*STAR), Singapore Institute for Clinical Sciences [Singapour] (SICS), Singapore Eye Research Institute [Singapore] (SERI), KK Women's and Children's Hospital [Singapore], Duke-National University of Singapore Graduate Medical School, Khoo Teck Puat – National University Children’s Medical Institute (NUHkids) [Singapore] (KTP-NUCMI), National University Health System [Singapore] (NUHS), University of Auckland [Auckland], Duke-NUS Medical School [Singapore], Nanyang Technological University [Singapour], University of Southampton, University Hospital Southampton NHS Foundation Trust, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Yong Loo Lin School of Medicine [Singapore], Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, McGill University = Université McGill [Montréal, Canada], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Berlin Institute of Health (BIH), and Bernard, Jonathan
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Male ,Pediatric Obesity ,medicine.medical_specialty ,Screen viewing ,Endocrinology, Diabetes and Metabolism ,Abdominal Fat ,Medicine (miscellaneous) ,Adipose tissue ,030209 endocrinology & metabolism ,Article ,Cohort Studies ,Screen Time ,03 medical and health sciences ,0302 clinical medicine ,Adverse Childhood Experiences ,Risk Factors ,Internal medicine ,Humans ,Medicine ,030212 general & internal medicine ,Correlation of Data ,Singapore ,Nutrition and Dietetics ,medicine.diagnostic_test ,business.industry ,Confounding ,Magnetic resonance imaging ,Magnetic Resonance Imaging ,Early life ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Child, Preschool ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Subcutaneous adipose tissue ,business ,Birth cohort ,Cohort study - Abstract
Importance: screen-viewing in adults has been associated with greater abdominal adiposity, with the magnitude of associations varying by sex and ethnicity, but the evidence is lacking at younger ages. We aimed to investigate sex- and ethnic-specific associations of screen-viewing time at ages 2 and 3 years with abdominal adiposity measured by magnetic resonance imaging at age 4.5 years.Methods: The Growing Up in Singapore Towards healthy Outcomes is an ongoing prospective mother-offspring cohort study. Parents/caregivers reported the time their child spent viewing television, handheld devices and computer screens at ages 2 and 3 years. Superficial and deep subcutaneous and visceral abdominal adipose tissue volumes were quantified from magnetic resonance images acquired at age 4.5 years. Associations between screen-viewing time and abdominal adipose tissue volumes were examined by multivariable linear regression adjusting for confounding factors.Results: in the overall sample (n=307), greater total screen-viewing time and handheld device times were associated with higher superficial and deep subcutaneous adipose tissue volumes, but not with visceral adipose tissue volumes. Interactions with child sex were found, with significant associations with superficial and deep subcutaneous and visceral adipose tissue volumes in boys, but not in girls. Among boys, the increases in mean (95% CI) superficial and deep subcutaneous and visceral adipose tissue volumes were 24.3 (9.9, 38.7), 17.6 (7.4, 27.8), and 7.8 (2.1, 13.6) mL per hour increase in daily total screen-viewing time, respectively. Ethnicity-specific analyses showed associations of total screen-viewing time with abdominal adiposity only in Malay children. Television viewing time was not associated with abdominal adiposity.Conclusion: greater total screen-viewing time (and in particular, handheld device viewing time) was associated with higher abdominal adiposity in boys and Malay children. Additional studies are necessary to confirm these associations and to examine screen-viewing interventions for preventing excessive abdominal adiposity and its adverse cardiometabolic consequences.
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- 2021
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23. High resolution proteomics of Aedes aegypti salivary glands infected with either dengue, Zika or chikungunya viruses identify new virus specific and broad antiviral factors
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Avisha Chowdhury, Cassandra M. Modahl, Dorothée Missé, R. Manjunatha Kini, Julien Pompon, National University of Singapore (NUS), Liverpool School of Tropical Medicine (LSTM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Yong Loo Lin School of Medicine [Singapore], Duke-NUS Medical School [Singapore], and ANR-20-CE15-0006,VirSalivaEnhancer,Amplificateur de transmission d'origine flavivirale dans la salive de moustique(2020)
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Proteomics ,Science ,viruses ,virus diseases ,Computational Biology ,Zika Virus ,Dengue Virus ,Salivary Glands ,Article ,Aedes ,Tandem Mass Spectrometry ,Host-Pathogen Interactions ,Medicine ,Animals ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Female ,Chikungunya virus ,Entomology ,Phylogeny ,Chromatography, Liquid ,Disease Resistance - Abstract
International audience; Abstract Arboviruses such as dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses infect close to half a billion people per year, and are primarily transmitted through Aedes aegypti bites. Infection-induced changes in mosquito salivary glands (SG) influence transmission by inducing antiviral immunity, which restricts virus replication in the vector, and by altering saliva composition, which influences skin infection. Here, we profiled SG proteome responses to DENV serotype 2 (DENV2), ZIKV and CHIKV infections by using high-resolution isobaric-tagged quantitative proteomics. We identified 218 proteins with putative functions in immunity, blood-feeding or related to the cellular machinery. We observed that 58, 27 and 29 proteins were regulated by DENV2, ZIKV and CHIKV infections, respectively. While the regulation patterns were mostly virus-specific, we separately depleted four uncharacterized proteins that were upregulated by all three viral infections to determine their effects on these viral infections. Our study suggests that gamma-interferon responsive lysosomal thiol-like (GILT-like) has an anti-ZIKV effect, adenosine deaminase (ADA) has an anti-CHIKV effect, salivary gland surface protein 1 (SGS1) has a pro-ZIKV effect and salivary gland broad-spectrum antiviral protein (SGBAP) has an antiviral effect against all three viruses. The comprehensive description of SG responses to three global pathogenic viruses and the identification of new restriction factors improves our understanding of the molecular mechanisms influencing transmission.
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- 2021
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24. Prolonged SARS-CoV-2 RNA virus shedding and lymphopenia are hallmarks of COVID-19 in cancer patients with poor prognosis
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Goubet, Anne-Gaëlle, Dubuisson, Agathe, Geraud, Arthur, Danlos, François-Xavier, Terrisse, Safae, Silva, Carolina Alves Costa, Drubay, Damien, Touri, Lea, Picard, Marion, Mazzenga, Marine, Silvin, Aymeric, Dunsmore, Garett, Haddad, Yacine, Pizzato, Eugenie, Ly, Pierre, Flament, Caroline, Melenotte, Cléa, Solary, Eric, Fontenay, Michaela, Garcia, Gabriel, Balleyguier, Corinne, Lassau, Nathalie, Maeurer, Markus, Grajeda-Iglesias, Claudia, Nirmalathasan, Nitharsshini, Aprahamian, Fanny, Durand, Sylvère, Kepp, Oliver, Ferrere, Gladys, Thelemaque, Cassandra, Lahmar, Imran, Fahrner, Jean-Eudes, Meziani, Lydia, Ahmed-Belkacem, Abdelhakim, Saïdani, Nadia, La Scola, Bernard, Raoult, Didier, Gentile, Stéphanie, Cortaredona, Sébastien, Ippolito, Giuseppe, Lelouvier, Benjamin, Roulet, Alain, Andre, Fabrice, Barlesi, Fabrice, Soria, Jean-Charles, Pradon, Caroline, Gallois, Emmanuelle, Pommeret, Fanny, Colomba, Emeline, Ginhoux, Florent, Kazandjian, Suzanne, Elkrief, Arielle, Routy, Bertrand, Miyara, Makoto, Gorochov, Guy, Deutsch, Eric, Albiges, Laurence, Stoclin, Annabelle, Gachot, Bertrand, Florin, Anne, Merad, Mansouria, Scotte, Florian, Assaad, Souad, Kroemer, Guido, Blay, Jean-Yves, Marabelle, Aurélien, Griscelli, Frank, Zitvogel, Laurence, Derosa, Lisa, Immunologie des tumeurs et immunothérapie (UMR 1015), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Saclay, Institut Gustave Roussy (IGR), Oncostat (U1018 (Équipe 2)), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), LaBoratoire d'Imagerie biOmédicale MultimodAle Paris-Saclay (BIOMAPS), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Champalimaud Centre for the Unknown [Lisbon], Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, IMRB - 'Transfusion et Maladies du Globule Rouge' [Créteil] (U955 Inserm - UPEC), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Centre Hospitalier Intercommunal de Cornouaille (CHIC), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Vecteurs - Infections tropicales et méditerranéennes (VITROME), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA), National Institute for Infectious Diseases 'Lazzaro Spallanzani', Vaiomer, Biomarqueurs prédictifs et nouvelles stratégies moléculaires en thérapeutique anticancéreuse (U981), Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), E-institute of Shanghai University Immunology Division, Shanghai University, Duke-NUS Medical School [Singapore], McGill University Health Center [Montreal] (MUHC), Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CR CHUM), Centre Hospitalier de l'Université de Montréal (CHUM), Université de Montréal (UdeM)-Université de Montréal (UdeM), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, UNICANCER, Université Paris Cité (UPCité), Karolinska Institutet [Stockholm], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Chinese Academy of Medical Sciences [Suzhou, Chine] (CAMS), Modèles de Cellules Souches Malignes et Thérapeutiques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, National Infrastructure INGESTEM, Université Paris Sud, A-GG was supported by Fondation pour la Recherche Médicale (FRM). LD has received support by the Philanthropia Fondation Gustave Roussy. The Gustave Roussy sponsored clinical study on COVID-19 (ONCOVID, NCT NCT04341207 has been supported by the Fondation Gustave Roussy, the Dassault family, Malakoff Humanis, Agnès b., Izipizi, Ralph Lauren and Sanofi). LZ and GK were supported by RHU Torino Lumière (ANR-16-RHUS-0008), ONCOBIOME H2020 network, the Seerave Foundation, the Ligue contre le Cancer (équipe labelisée), Agence Nationale de la Recherche (ANR)—Projets blancs, ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases, Association pour la recherche sur le cancer (ARC), Cancéropôle Ile-de-France, FRM, a donation by Elior, the European Research Council (ERC), Fondation Carrefour, High-end Foreign Expert Program in China (GDW20171100085 and GDW20181100051), Institut National du Cancer (INCa), Inserm (HTE), Institut Universitaire de France, LeDucq Foundation, the LabEx Immuno-Oncology, the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE), CARE network (directed by Prof. Mariette, Kremlin Bicêtre AP-HP), and the SIRIC Cancer Research and Personalized Medicine (CARPEM). GI was supported by Italian Ministry of Health (grants Ricerca CorrenteLinea 1, 1 'Infezioni Emergenti e Riemergenti', projects COVID-2020-12371675 and COVID‐2020‐12371817). MMy and GG were supported by ANR Flash COVID-19 program and ARS-CoV-2 Program of the Faculty of Medicine from Sorbonne University ICOViD programs (PI: GG)., ANR-16-RHUS-0008,LUMIERE,LUMIERE(2016), European Project: 825410,ONCOBIOME, École pratique des hautes études (EPHE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut de Recherche Biomédicale des Armées (IRBA), COMBE, Isabelle, LUMIERE - - LUMIERE2016 - ANR-16-RHUS-0008 - RHUS - VALID, European Union’s Horizon 2020 research and innovation programme under grant agreement. - ONCOBIOME - 825410 - INCOMING, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Oncostat team [Villejuif], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Unité BioMaps (BIOMAPS), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université de Paris (UP), Department of Radiology, Gustave Roussy Cancer Campus, Université Paris-Saclay, Villejuif, France, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPC), Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de Recherche Biomédicale des Armées (IRBA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Université Paris Cité (UPC)
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Adult ,DNA, Bacterial ,Male ,Time Factors ,Adolescent ,Article ,Cohort Studies ,Young Adult ,Prognostic markers ,Medical research ,Enterobacteriaceae ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Lymphopenia ,Nasopharynx ,Neoplasms ,Humans ,Pandemics ,Aged ,Aged, 80 and over ,SARS-CoV-2 ,COVID-19 ,Middle Aged ,Prognosis ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Virus Shedding ,Interferon Type I ,[SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,RNA, Viral ,Female ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Micrococcaceae - Abstract
International audience; Patients with cancer are at higher risk of severe coronavirus infectious disease 2019 (COVID-19), but the mechanisms underlying virus–host interactions during cancer therapies remain elusive. When comparing nasopharyngeal swabs from cancer and noncancer patients for RT-qPCR cycle thresholds measuring acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in 1063 patients (58% with cancer), we found that malignant disease favors the magnitude and duration of viral RNA shedding concomitant with prolonged serum elevations of type 1 IFN that anticorrelated with anti-RBD IgG antibodies. Cancer patients with a prolonged SARS-CoV-2 RNA detection exhibited the typical immunopathology of severe COVID-19 at the early phase of infection including circulation of immature neutrophils, depletion of nonconventional monocytes, and a general lymphopenia that, however, was accompanied by a rise in plasmablasts, activated follicular T-helper cells, and non-naive Granzyme B + FasL + , Eomes high TCF-1 high , PD-1 + CD8 + Tc1 cells. Virus-induced lymphopenia worsened cancer-associated lymphocyte loss, and low lymphocyte counts correlated with chronic SARS-CoV-2 RNA shedding, COVID-19 severity, and a higher risk of cancer-related death in the first and second surge of the pandemic. Lymphocyte loss correlated with significant changes in metabolites from the polyamine and biliary salt pathways as well as increased blood DNA from Enterobacteriaceae and Micrococcaceae gut family members in long-term viral carriers. We surmise that cancer therapies may exacerbate the paradoxical association between lymphopenia and COVID-19-related immunopathology, and that the prevention of COVID-19-induced lymphocyte loss may reduce cancer-associated death.
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- 2021
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25. LRG1 Promotes Metastatic Dissemination of Melanoma through Regulating EGFR/STAT3 Signalling
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Yuet Ping Kwan, Michelle Siying Tan, Xiaomeng Wang, Walter Wahli, Jonathan Chee Woei Lim, Graciella Rosellinny, Melissa Hui Yen Teo, Duke-NUS Medical School [Singapore], Singapore Eye Research Institute [Singapore] (SERI), Universiti Putra Malaysia, National University of Singapore (NUS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Agency for science, technology and research [Singapore] (A*STAR), This project was supported by the MOE Academic Research Fund Tier 2 (MOE2014-T2-1036) to X.W. andW.W., the Duke-NUS Start-Up Grant to X.W. and the Singapore National Medical Research Council DYNAMO NMRC/OFLCG/001/2017 and TAPP NMRC/OFLCG/004/2018 to X.W., and the Lee Kong Chian School of Medicine, Nanyang Technological University Singapore Start-up Grant to W.W., and Lee Kong Chian School of Medicine (LKCMedicine)
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0301 basic medicine ,leucine-rich α-2-glycoprotein-1 ,Cancer Research ,Angiogenesis ,[SDV]Life Sciences [q-bio] ,EGFR ,Cell ,Article ,Metastasis ,STAT3 ,03 medical and health sciences ,0302 clinical medicine ,leucine-rich alpha-2-glycoprotein-1 ,medicine ,melanoma ,metastasis ,Medicine [Science] ,Melanoma ,neoplasms ,RC254-282 ,Cell growth ,business.industry ,Leucine-Rich α-2-Glycoprotein-1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cell migration ,medicine.disease ,3. Good health ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,LRG1 ,030220 oncology & carcinogenesis ,Cancer research ,Skin cancer ,business - Abstract
Although less common, melanoma is the deadliest form of skin cancer largely due to its highly metastatic nature. Currently, there are limited treatment options for metastatic melanoma and many of them could cause serious side effects. A better understanding of the molecular mechanisms underlying the complex disease pathophysiology of metastatic melanoma may lead to the identification of novel therapeutic targets and facilitate the development of targeted therapeutics. In this study, we investigated the role of leucine-rich α-2-glycoprotein 1 (LRG1) in melanoma development and progression. We first established the association between LRG1 and melanoma in both human patient biopsies and mouse melanoma cell lines and revealed a significant induction of LRG1 expression in metastatic melanoma cells. We then showed no change in tumour cell growth, proliferation, and angiogenesis in the absence of the host Lrg1. On the other hand, there was reduced melanoma cell metastasis to the lungs in Lrg1-deficient mice. This observation was supported by the promoting effect of LRG1 in melanoma cell migration, invasion, and adhesion. Mechanistically, LRG1 mediates melanoma cell invasiveness in an EGFR/STAT3-dependent manner. Taken together, our studies provided compelling evidence that LRG1 is required for melanoma metastasis but not growth. Targeting LRG1 may offer an alternative strategy to control malignant melanoma. Ministry of Education (MOE) National Medical Research Council (NMRC) Published version This project was supported by the MOE Academic Research Fund Tier 2 (MOE2014-T2-1- 036) to X.W. and W.W., the Duke-NUS Start-Up Grant to X.W. and the Singapore National Medical Research Council DYNAMO NMRC/OFLCG/001/2017 and TAPP NMRC/OFLCG/004/2018 to X.W., and the Lee Kong Chian School of Medicine, Nanyang Technological University Singapore Start-up Grant to W.W.
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- 2021
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26. Trends of the dengue serotype-4 circulation with epidemiological, phylogenetic, and entomological insights in Lao PDR between 2015 and 2019
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Phaithong Bounmany, Thonglakhone Xaybounsou, Marc Choisy, Sitsana Keosenhom, Julien Pompon, Elodie Calvez, Marc Grandadam, Thep Aksone Chindavong, Paul T. Brey, Virginie Pommelet, Phoyphaylinh Prasayasith, Somphavanh Somlor, Souksakhone Viengphouthong, Sébastien Marcombe, Olivier Telle, Institut Pasteur du Laos, Réseau International des Instituts Pasteur (RIIP), Duke-NUS Medical School [Singapore], Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Centre de sciences humaines de New Delhi (CSH), Ministère de l'Europe et des Affaires étrangères (MEAE)-Centre National de la Recherche Scientifique (CNRS), Centre for Policy Research [New Delhi] (CPR), Nuffield Department of Medicine [Oxford, UK] (Big Data Institute), University of Oxford [Oxford], Oxford University Clinical Research Unit [Ho Chi Minh City] (OUCRU), Institut de Recherche Biomédicale des Armées (IRBA), This work was funded by the Agence Française de Développement grant n° CZZ 2146 01 (Ecomore2 project) and by UNITEDengue and Global Partnership Programme, Canada (ASEAN-GPP Grant Phase 3—Laboratory Capacity Development for diagnostics of Emerging Dangerous Pathogens)., We thank Lee Ching Ng, Director, Environmental Health Institute (EHI), National Environment Agency, Chanditha Hapuarachchi, and Carmen Koo for their sequencing technical assistance. We also thank the Institut Pasteur du Laos staff for the mosquito collections and identification (Phoutmany Thammavong, Phonesavanh Luangamath, Kaithong Lakeomany, Somphat Nilaxay, and Vaekey Vungkyly)., Géographie-cités (GC (UMR_8504)), Université Paris 1 Panthéon-Sorbonne (UP1)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), University of Oxford, and Institut de Recherche Biomédicale des Armées [Brétigny-sur-Orge] (IRBA)
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Microbiology (medical) ,Serotype ,medicine.medical_specialty ,Aedes vectors ,viruses ,030231 tropical medicine ,lcsh:Medicine ,PARIS team ,phylogeny ,Arbovirus ,Article ,epidemic ,Dengue fever ,03 medical and health sciences ,0302 clinical medicine ,Lao PDR ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Epidemiology ,medicine ,Immunology and Allergy ,Socioeconomics ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,General Immunology and Microbiology ,Phylogenetic tree ,ACL ,lcsh:R ,Significant difference ,virus diseases ,Outbreak ,DENV-4 ,Integrated approach ,medicine.disease ,dengue ,3. Good health ,Infectious Diseases ,Geography - Abstract
Dengue outbreaks have regularly been recorded in Lao People&rsquo, s Democratic Republic (PDR) since the first detection of the disease in 1979. In 2012, an integrated arbovirus surveillance network was set up in Lao PDR and an entomological surveillance has been implemented since 2016 in Vientiane Capital. Here, we report a study combining epidemiological, phylogenetic, and entomological analyzes during the largest DENV-4 epidemic ever recorded in Lao PDR (2015&ndash, 2019). Strikingly, from 2015 to 2019, we reported the DENV-4 emergence and spread at the country level after two large epidemics predominated by DENV-3 and DENV-1, respectively, in 2012&ndash, 2013 and 2015. Our data revealed a significant difference in the median age of the patient infected by DENV-4 compared to the other serotypes. Phylogenetic analysis demonstrated the circulation of DENV-4 Genotype I at the country level since at least 2013. The entomological surveillance showed a predominance of Aedesaegypti compared to Aedesalbopictus and high abundance of these vectors in dry and rainy seasons between 2016 and 2019, in Vientiane Capital. Overall, these results emphasized the importance of an integrated approach to evaluate factors, which could impact the circulation and the epidemiological profile of dengue viruses, especially in endemic countries like Lao PDR.
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- 2021
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27. Maternal height, gestational diabetes mellitus and pregnancy complications
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Fabian Yap, Mya-Thway Tint, Sarah Su Tin Ho-Lim, Kok Hian Tan, Keith M. Godfrey, Wen Lun Yuan, Adaikalavan Ramasamy, Jonathan Y. Bernard, See Ling Loy, Johan G. Eriksson, Claudia Chi, Yap Seng Chong, Anne H. Y. Chu, Li Ting Ang, Lynette Pei-Chi Shek, Lin Lin Su, Arijit Biswas, Shu E Soh, Claire Goh, Yung Seng Lee, Huecin Goh, Mukkesh Kumar, Shiao-Yng Chan, Agency for science, technology and research [Singapore] (A*STAR), National University of Singapore (NUS), KK Women's and Children's Hospital [Singapore], Duke-NUS Medical School [Singapore], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Singapore Institute for Clinical Sciences [Singapour] (SICS), National University Hospital [Singapore] (NUH), Nanyang Technological University [Singapour], University of Southampton, University Hospital Southampton NHS Foundation Trust, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, and Bernard, Jonathan
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Blood Glucose ,medicine.medical_specialty ,Neonatal intensive care unit ,endocrine system diseases ,Endocrinology, Diabetes and Metabolism ,Gestational diabetes mellitus ,Article ,Fetal Macrosomia ,Endocrinology ,Insulin resistance ,Pregnancy ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Glucose tolerance test ,medicine.diagnostic_test ,Obstetrics ,business.industry ,Cesarean Section ,Infant, Newborn ,Pregnancy Outcome ,nutritional and metabolic diseases ,General Medicine ,Odds ratio ,Glucose Tolerance Test ,medicine.disease ,female genital diseases and pregnancy complications ,Gestational diabetes ,Pregnancy Complications ,Standing height ,Diabetes, Gestational ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Female ,Cohort study ,business - Abstract
International audience; Aims: To explore the glucose-overload hypothesis of artefactual gestational diabetes (GDM) diagnosis in shorter women during oral glucose tolerance testing (OGTT), by investigating associations between height and maternal glycemia; and GDM and pregnancy complications in height-groups.Methods: Women from GUSTO (n = 1100, 2009-2010) and NUH (n = 4068, 2017-2018) cohorts underwent a mid-gestation two and three time-point 75 g 2-hour OGTT, respectively. GDM-related complications (hypertensive disorders of pregnancy, preterm delivery, emergency cesarean section, neonatal intensive care unit admission, macrosomia, birthweight) were compared within shorter and taller groups, dichotomized by ethnic-specific median height.Results: Using WHO-1999 criteria, 18.8% (GUSTO) to 22.9% (NUH) of women were diagnosed with GDM-1999; and by WHO-2013 criteria, 21.9% (NUH) had GDM-2013. Each 5-cm height increment was inversely associated with GDM-1999 (adjusted odds ratio [aOR, 95% CI] = 0.81 [0.76-0.87], 2-h glycemia (adjusted β [aβ, 95% CI] = -0.171 mmol/L [-0.208, -0.135]) and 1-h glycemia (aβ = -0.160 mmol/L [-0.207, -0.112]). The inverse association between height and 2-h glycemia was most marked in "Other" ethnicities (Eurasians/Caucasians/mixed/other Asians) and Indians, followed by Chinese, then Malays. Compared with non-GDM, GDM-1999 was associated with preterm delivery (aOR = 1.76 [1.19-2.61]) and higher birthweight (aβ = 57.16 g [20.95, 93.38]) only among taller but not shorter women.Conclusions: Only taller women had an increased odds of GDM-related pregnancy complications. An artefactual GDM diagnosis due to glucose-overload among shorter women is plausible.
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- 2021
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28. Identification of Aedes aegypti salivary gland proteins interacting with human immune receptor proteins
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Edem Gavor, Yeu Khai Choong, Yonghao Liu, Julien Pompon, Eng Eong Ooi, Yu Keung Mok, Haiyan Liu, R Manjunatha Kini, J. Sivaraman, National University of Singapore (NUS), Duke-NUS Medical School [Singapore], Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), This work was support by the Ministry of Education, Singapore (R154-000-697-112 to J.S, R154-000-C07-114 to J.S, and A-8000477-00-00 to J.S).
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Toll-Like Receptor 4 ,Infectious Diseases ,Aedes ,Apyrase ,Public Health, Environmental and Occupational Health ,Animals ,Humans ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Intercellular Adhesion Molecule-3 ,Mosquito Vectors ,Allergens ,Salivary Proteins and Peptides ,Recombinant Proteins - Abstract
Mosquito saliva proteins modulate the human immune and hemostatic systems and control mosquito-borne pathogenic infections. One mechanism through which mosquito proteins may influence host immunity and hemostasis is their interactions with key human receptor proteins that may act as receptors for or coordinate attacks against invading pathogens. Here, using pull-down assays and proteomics-based mass spectrometry, we identified 11Ae.aegyptisalivary gland proteins (SGPs) (e.g., apyrase,Ae.aegyptivenom allergen-1 [AaVA-1], neutrophil stimulating protein 1 [NeSt1], and D7 proteins), that interact with one or more of five human receptor proteins (cluster of differentiation 4 [CD4], CD14, CD86, dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin [DC-SIGN], and Toll-like receptor 4 [TLR4]). We focused on CD4- and DC-SIGN-interacting proteins and confirmed that CD4 directly interacts with AaVA-1, D7, and NeST1 recombinant proteins and that AaVA-1 showed a moderate interaction with DC-SIGN using ELISA. Bacteria responsive protein 1 (AgBR1), anAe.aegyptisaliva protein reported to enhance ZIKV infection in humans but that was not identified in our pull-down assay moderately interacts with CD4 in the ELISA assay. Functionally, we showed that AaVA-1 and NeST1 proteins promoted activation of CD4+T cells. We propose the possible impact of these interactions and effects on mosquito-borne viral infections such as dengue, Zika, and chikungunya viruses. Overall, this study provides key insight into the vector-host (protein-protein) interaction network and suggests roles for these interactions in mosquito-borne viral infections.
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- 2022
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29. A call to action for new global approaches to cardiovascular disease drug solutions
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Carolyn S.P. Lam, Grant R Drummond, Calum A. MacRae, Joseph C. Wu, Gemma A. Figtree, Filippo Crea, David G. Harrison, James L. Januzzi, Barbara Casadei, Rebecca H. Ritchie, Maciej Tomaszewski, Faiez Zannad, Robert M. Califf, Frank Misselwitz, Jane E. Freedman, Bronwyn A. Kingwell, Derek J. Hausenloy, Tetsuji Miura, Keith Broadfoot, Junjie Xiao, Joseph A. Hill, Tomasz J. Guzik, Royal North Shore Hospital (RNSH), The University of Sydney, Clinical Committee, National Heart Foundation of Australia, Radcliffe Department of Medicine [Oxford], University of Oxford, Oxford NIHR Biomedical Research Centre, British Heart Foundation Centre of Research Excellence [Oxford, Royaume-Uni] (Oxford BHF-CRE), Verily Life Sciences Inc, Università cattolica del Sacro Cuore = Catholic University of the Sacred Heart [Roma] (Unicatt), La Trobe University [Melbourne], University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS), University of Glasgow, Vanderbilt University School of Medicine [Nashville], National University of Singapore (NUS), University of Texas Southwestern Medical Center, Massachusetts General Hospital [Boston], CSL Ltd, National Heart Centre Singapore (NHCS), Duke-National University of Singapore Graduate Medical School, Brigham and Women’s Hospital [Boston, MA], Harvard Medical School [Boston] (HMS), Bayer AG, Pharmaceuticals Division, Sapporo Medical University, Monash Institute of Pharmaceutical Sciences [Parkville] (MIPS), Faculty of Pharmacy and Pharmaceutical Sciences - Monash University [Parkville], Monash university-Monash university, Faculty of Biology, Medicine and Health [Manchester, UK], University of Manchester [Manchester], Stanford Cardiovascular Institute, University of Shanghai [Shanghai], Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), BOZEC, Erwan, British Heart Foundation Centre of Research Excellence, University of Cambridge, CSL Limited, and Duke-NUS Medical School [Singapore]
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Drug ,Arterial disease ,Therapeutic target ,media_common.quotation_subject ,precision medicine ,heart failure ,Heart failure ,Disease ,030204 cardiovascular system & hematology ,Cardiovascular ,drug discovery ,03 medical and health sciences ,pharmacotherapy ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Physiology (medical) ,therapeutics ,Medicine ,Humans ,030212 general & internal medicine ,organoids ,030304 developmental biology ,media_common ,0303 health sciences ,Multi-omics ,business.industry ,Drug discovery ,cardiovascular ,Precision medicine ,Atherosclerosis ,Pharmacotherapy ,drug therapy ,Call to action ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Organoids ,Incentive ,Risk analysis (engineering) ,Pharmaceutical Preparations ,Cardiovascular Diseases ,Settore MED/11 - MALATTIE DELL'APPARATO CARDIOVASCOLARE ,cardiovascular system ,atherosclerosis ,Cardiology and Cardiovascular Medicine ,business ,Product identification ,Biomarkers - Abstract
Whilst we continue to wrestle with the immense challenge of implementing equitable access to established evidence-based treatments, substantial gaps remain in our pharmacotherapy armament for common forms of cardiovascular disease including coronary and peripheral arterial disease, heart failure, hypertension, and arrhythmia. We need to continue to invest in the development of new approaches for the discovery, rigorous assessment, and implementation of new therapies. Currently, the time and cost to progress from lead compound/product identification to the clinic, and the success rate in getting there reduces the incentive for industry to invest, despite the enormous burden of disease and potential size of market. There are tremendous opportunities with improved phenotyping of patients currently batched together in syndromic ‘buckets’. Use of advanced imaging and molecular markers may allow stratification of patients in a manner more aligned to biological mechanisms that can, in turn, be targeted by specific approaches developed using high-throughput molecular technologies. Unbiased ‘omic’ approaches enhance the possibility of discovering completely new mechanisms in such groups. Furthermore, advances in drug discovery platforms, and models to study efficacy and toxicity more relevant to the human disease, are valuable. Re-imagining the relationships among discovery, translation, evaluation, and implementation will help reverse the trend away from investment in the cardiovascular space, establishing innovative platforms and approaches across the full spectrum of therapeutic development.
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- 2021
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30. Mosquito metabolomics reveal that dengue virus replication requires phospholipid reconfiguration via the remodeling cycle
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Thomas Vial, Julien Pompon, Dorothée Missé, Wei-Lian Tan, Guillaume Marti, Eric Deharo, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Duke-NUS Medical School [Singapore], Interhuman Arbovirus Transmission (MIVEGEC-iHAT), Biologie des infections virales: Emergence, DIFfusion, Impact, Contrôle, Elimination (EDIFICE), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD)
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replication ,viruses ,Cell ,Phospholipid ,mosquito ,Genome, Viral ,Mosquito Vectors ,Dengue virus ,Biology ,Virus Replication ,medicine.disease_cause ,Virus ,Cell Line ,Dengue fever ,03 medical and health sciences ,chemistry.chemical_compound ,Aedes ,medicine ,Animals ,Humans ,Endomembrane system ,Vector (molecular biology) ,Phospholipids ,phospholipid ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Cell Membrane ,030302 biochemistry & molecular biology ,Dengue Virus ,Biological Sciences ,biochemical phenomena, metabolism, and nutrition ,Lipid Metabolism ,medicine.disease ,dengue ,metabolomics ,3. Good health ,Cell biology ,[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,medicine.anatomical_structure ,chemistry ,Insect Proteins ,RNA, Viral ,RNA Interference ,lipids (amino acids, peptides, and proteins) ,Viral genome replication ,Metabolic Networks and Pathways - Abstract
Dengue virus (DENV) subdues cell membranes for its cellular cycle by reconfiguring phospholipids in humans and mosquitoes. Here, we determined how and why DENV reconfigures phospholipids in the mosquito vector. By inhibiting and activating the de novo phospholipid biosynthesis, we demonstrated the antiviral impact of de novo–produced phospholipids. In line with the virus hijacking lipids for its benefit, metabolomics analyses indicated that DENV actively inhibited the de novo phospholipid pathway and instead triggered phospholipid remodeling. We demonstrated the early induction of remodeling during infection by using isotope tracing in mosquito cells. We then confirmed in mosquitoes the antiviral impact of de novo phospholipids by supplementing infectious blood meals with a de novo phospholipid precursor. Eventually, we determined that phospholipid reconfiguration was required for viral genome replication but not for the other steps of the virus cellular cycle. Overall, we now propose that DENV reconfigures phospholipids through the remodeling cycle to modify the endomembrane and facilitate formation of the replication complex. Furthermore, our study identified de novo phospholipid precursor as a blood determinant of DENV human-to-mosquito transmission.
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- 2020
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31. A Comprehensive Gridded Dataset Associated to the Climate Change Effect on the Water Resources in the Grand Est Region, France
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Ionel Haidu, Cristina Ştefan, Ştefan Dezsi, Mărgărit-Mircea Nistor, Earthresearch Company, Centre de Recherche en Géographie (LOTERR), Université de Lorraine (UL), Universitatea Babeş-Bolyai [Cluj-Napoca], and Duke-NUS Medical School [Singapore]
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Atmospheric Science ,010504 meteorology & atmospheric sciences ,Climate change ,Land cover ,lcsh:QC851-999 ,010501 environmental sciences ,Environmental Science (miscellaneous) ,01 natural sciences ,Effects of global warming ,climate models ,dataset ,terrain morphology ,0105 earth and related environmental sciences ,Land use ,Groundwater recharge ,[SHS.GEO]Humanities and Social Sciences/Geography ,6. Clean water ,Water resources ,hydrogeology ,13. Climate action ,Geographical Information Systems (GIS) ,lcsh:Meteorology. Climatology ,Climate model ,Water resource management ,Surface runoff ,Grand Est - Abstract
Water resources and environment quality are nowadays under high pressure because of climate change, land use practices, as well as human actions. A comprehensive gridded dataset becomes a necessary instrument to assess the risk level at regional scale, and also for territorial planning, the defining strategies to address future natural and anthropological challenges. In order to obtain a complete database with the most important parameters at spatial scale, this study is constructed as a preparation of layers used for various environmental risks, but mostly with the climate change effect on the water resources from the Grand Est region, France. In addition, geological formations, terrain data, and land cover were harmonized as grid format for the study area. Thus, the temperature and precipitation parameters, related to the 1961&ndash, 1990 (1990s), 2011&ndash, 2040 (2020s), and 2041&ndash, 2070 (2050s), become useful data for evapotranspiration, water availability, and effective precipitation calculations. The geology layer indicates the composition and types of aquifers and it contributes to the potential infiltration map (PIM). The morphology of the terrain contributes to the slope angle and PIM. Through the typology of land cover, the pollution load index (PLI) was estimated. The findings indicate intense aridization and the depletion of the effective precipitation (below 650 mm) during the present and future periods. With respect to these concerns, the surface waters and groundwater resources from the Grand Est region are experiencing the negative effects of climate change on runoff and aquifers recharge respectively. In addition, the high PLI in the industrial and agricultural areas contribute to the possibility of the increasing water resources vulnerability. The affected areas extend mainly in the western, north-central, and north-eastern parts of the region, mainly in the Rhine, Aube, and Marne Valleys. Considered as a precious resource in the region, the water management should follow best practices for vulnerability and risk assessment, and further to delineate the protection areas. As a comprehensive gridded dataset, the calculations and original maps presented in this paper represent a complex product with main environmental parameters processed at spatial scale of 1 km2 in ArcGIS. This product has the purpose to integrate the geospatial data for the Grand Est region of France.
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- 2020
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32. JNK pathway restricts DENV2, ZIKV and CHIKV infection by activating complement and apoptosis in mosquito salivary glands
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Benjamin Wong Wei Xiang, Siok Thing Tan, R. Manjunatha Kini, Julien Pompon, Cassandra M. Modahl, Thomas Vial, Avisha Chowdhury, Dorothée Missé, National University of Singapore (NUS), Duke-NUS Medical School [Singapore], Interhuman Arbovirus Transmission (MIVEGEC-iHAT), Biologie des infections virales: Emergence, DIFfusion, Impact, Contrôle, Elimination (EDIFICE), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])
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RNA viruses ,Viral Diseases ,Cell signaling ,Gene Expression ,Apoptosis ,Dengue virus ,Signal transduction ,Disease Vectors ,medicine.disease_cause ,Pathology and Laboratory Medicine ,Virus Replication ,Mosquitoes ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,Salivary Glands ,Dengue ,Medical Conditions ,Aedes ,Medicine and Health Sciences ,Biology (General) ,0303 health sciences ,Chikungunya Virus ,Cell Death ,Kinase ,Zika Virus Infection ,030302 biochemistry & molecular biology ,Microbial Genetics ,Signaling cascades ,Eukaryota ,c-Jun N-terminal kinase signaling cascade ,3. Good health ,Cell biology ,Insects ,Infectious Diseases ,[SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology ,Medical Microbiology ,Cell Processes ,Viral Pathogens ,Viruses ,Host-Pathogen Interactions ,Viral Genetics ,Insect Proteins ,Female ,Pathogens ,Anatomy ,Research Article ,Neglected Tropical Diseases ,Arthropoda ,MAP Kinase Signaling System ,QH301-705.5 ,Alphaviruses ,Immunology ,Antimicrobial peptides ,Complement factor I ,Biology ,Microbiology ,Togaviruses ,03 medical and health sciences ,Immune system ,Exocrine Glands ,stomatognathic system ,Virology ,medicine ,Genetics ,Gene silencing ,Animals ,Molecular Biology ,Microbial Pathogens ,030304 developmental biology ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,Biology and life sciences ,Flaviviruses ,Organisms ,Chikungunya Infection ,Cell Biology ,Complement System Proteins ,Zika Virus ,Dengue Virus ,RC581-607 ,Tropical Diseases ,Invertebrates ,Insect Vectors ,Species Interactions ,Viral Gene Expression ,Viral replication ,Chikungunya Fever ,Parasitology ,Immunologic diseases. Allergy ,Transcriptome ,Digestive System ,Zoology ,Entomology - Abstract
Arbovirus infection of Aedes aegypti salivary glands (SGs) determines transmission. However, there is a dearth of knowledge on SG immunity. Here, we characterized SG immune response to dengue, Zika and chikungunya viruses using high-throughput transcriptomics. We also describe a transcriptomic response associated to apoptosis, blood-feeding and lipid metabolism. The three viruses differentially regulate components of Toll, Immune deficiency (IMD) and c-Jun N- terminal Kinase (JNK) pathways. However, silencing of the Toll and IMD pathway components showed variable effects on SG infection by each virus. In contrast, regulation of the JNK pathway produced consistent responses in both SGs and midgut. Infection by the three viruses increased with depletion of the activator Kayak and decreased with depletion of the negative regulator Puckered. Virus-induced JNK pathway regulates the complement factor, Thioester containing protein-20 (TEP20), and the apoptosis activator, Dronc, in SGs. Individual and co-silencing of these genes demonstrate their antiviral effects and that both may function together. Co-silencing either TEP20 or Dronc with Puckered annihilates JNK pathway antiviral effect. Upon infection in SGs, TEP20 induces antimicrobial peptides (AMPs), while Dronc is required for apoptosis independently of TEP20. In conclusion, we revealed the broad antiviral function of JNK pathway in SGs and showed that it is mediated by a TEP20 complement and Dronc-induced apoptosis response. These results expand our understanding of the immune arsenal that blocks arbovirus transmission., Author summary Arboviral diseases caused by dengue (DENV), Zika (ZIKV) and chikungunya (CHIKV) viruses are responsible for large number of death and debilitation around the world. These viruses are transmitted to humans by the mosquito vector, Aedes aegypti. During the bites, infected salivary glands (SGs) release saliva containing viruses, which initiate human infection. As the tissue where transmitted viruses are produced, SG infection is a key determinant of transmission. To bridge the knowledge gap in vector-virus molecular interactions in SGs, we describe the transcriptome after DENV, ZIKV and CHIKV infection using RNA-sequencing and characterized the immune response in this tissue. Our study reveals the broad antiviral function of c-Jun N-terminal kinase (JNK) pathway against DENV, ZIKV and CHIKV in SGs. We further show that it is mediated by the complement system and apoptosis, identifying the mechanism. Our study adds the JNK pathway to the immune arsenal that can be harnessed to engineer refractory vectors.
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- 2020
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33. Effects of combined renin-angiotensin-aldosterone system inhibitor and beta-blocker treatment on outcomes in heart failure with reduced ejection fraction: insights fromBIOSTAT-CHFandASIAN-HFregistries
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Wataru Shimizu, Gurpreet Singh Wander, Wan Ting Tay, Leong L. Ng, Wouter Ouwerkerk, Jitendra P. S. Sawhney, Chim C. Lang, Chung-Lieh Hung, Stefan D. Anker, Dirk J. van Veldhuisen, Kenneth Dickstein, Faiez Zannad, A. Mark Richards, Inder S. Anand, John G.F. Cleland, Jasper Tromp, Carolyn S.P. Lam, Adriaan A. Voors, Nobuhisa Hagiwara, Ajay Naik, Tiew-Hwa Katherine Teng, Cardiovascular Centre (CVC), Epidemiology and Data Science, Dermatology, National Heart Centre Singapore (NHCS), Amsterdam UMC - Amsterdam University Medical Center, Duke-National University of Singapore Graduate Medical School, The University of Western Australia (UWA), Glenfield Hospital, Duke-NUS Medical School [Singapore], University Medical Center Groningen [Groningen] (UMCG), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University of Bergen (UiB), Stavanger University Hospital, University Hospitals Leicester, University of Leicester, University of Dundee, Ninewells Hospital and Medical School [Dundee], Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Charité Campus Virchow-Klinikum (CVK), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Brigham and Women’s Hospital [Boston, MA], Harvard Medical School [Boston] (HMS), Sir Gangaram Hospital, CIMS Hospital, Tokyo Women's Medical University (TWMU), Nippon Medical School [Tokyo, Japon], Dayanand Medical College and Hospital [Ludhiana], Veterans Affairs Medical Center, Cardiovascular Research Institute, National University Heart Centre, University of Otago [Dunedin, Nouvelle-Zélande], Biomedical Research Council Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT). Grant Numbers: SPF2014/005, SPF2014/004, SPF2014/003, Boston Scientific Investigator Sponsored Research Program, National Medical Research Council of Singapore. Grant Number: R-172-003-219-511, European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), and European Project
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Male ,Angiotensin-Converting Enzyme Inhibitors ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,Renin-Angiotensin System ,0302 clinical medicine ,Prospective Studies ,Registries ,ESC GUIDELINES ,Aldosterone ,ELDERLY-PATIENTS ,Ejection fraction ,Hazard ratio ,Middle Aged ,Europe ,VARIABLE SELECTION ,ENALAPRIL ,Cardiology ,Female ,TRIAL ,Cardiology and Cardiovascular Medicine ,medicine.medical_specialty ,Asia ,medicine.drug_class ,Heart failure ,Outcomes ,03 medical and health sciences ,Angiotensin Receptor Antagonists ,Reduced ejection fraction ,MORBIDITY ,Up-titration ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,LEFT-VENTRICULAR FUNCTION ,Internal medicine ,Renin–angiotensin system ,medicine ,Humans ,In patient ,cardiovascular diseases ,Beta blocker ,Aged ,CARVEDILOL ,business.industry ,MORTALITY ,Stroke Volume ,medicine.disease ,Confidence interval ,Target dose ,business ,SUDDEN CARDIAC DEATH ,Evidence-based pharmacotherapy - Abstract
Background Angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and beta-blockers are guideline-recommended first-line therapies in heart failure (HF) with reduced ejection fraction (HFrEF). Previous studies showed that individual drug classes were under-dosed in many parts of Europe and Asia. In this study, we investigated the association of combined up-titration of ACEi/ARBs and beta-blockers with all-cause mortality and its combination with hospitalization for HF. Methods and results A total of 6787 HFrEF patients (mean age 62.6 +/- 13.2 years, 77.7% men, mean left ventricular ejection fraction 27.7 +/- 7.2%) were enrolled in the prospective multinational European (BIOSTAT-CHF;n = 2100) and Asian (ASIAN-HF;n = 4687) studies. Outcomes were analysed according to achieved percentage of guideline-recommended target doses (GRTD) of combination ACEi/ARB and beta-blocker therapy, adjusted for indication bias. Only 14% (n = 981) patients achieved >= 50% GRTD for both ACEi/ARB and beta-blocker. The best outcomes were observed in patients who achieved 100% GRTD of both ACEi/ARB and beta-blocker [hazard ratio (HR) 0.32, 95% confidence interval (CI) 0.26-0.39 vs. none]. Lower dose of combined therapy was associated with better outcomes than 100% GRTD of either monotherapy. Up-titrating beta-blockers was associated with a consistent and greater reduction in hazards of all-cause mortality (HR for 100% GRTD: 0.40, 95% CI 0.25-0.63) than corresponding ACEi/ARB up-titration (HR 0.75, 95% CI 0.53-1.07). Conclusion This study shows that best outcomes were observed in patients attaining GRTD for both ACEi/ARB and beta-blockers, unfortunately this was rarely achieved. Achieving >50% GRTD of both drug classes was associated with better outcome than target dose of monotherapy. Up-titrating beta-blockers to target dose was associated with greater mortality reduction than up-titrating ACEi/ARB.
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- 2020
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34. Evolution of treatment paradigms in neovascular age-related macular degeneration: a review of real-world evidence
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Robert Finger, Paul Mitchell, Tien Yin Wong, James S Talks, Bora Eldem, Vincent Daien, Taiji Sakamoto, Jean-François Korobelnik, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), The University of Sydney, University of Bonn, Royal Victoria Infirmary, Newcastle upon Tyne, Singapore Eye Research Institute [Singapore] (SERI), Duke-NUS Medical School [Singapore], Kagoshima University Graduate School of Medical and Dental Sciences, Faculty of Medicine [Hacettepe University], Hacettepe University = Hacettepe Üniversitesi, Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Vascular Endothelial Growth Factor A ,medicine.medical_specialty ,Epidemiology ,Vision ,Recombinant Fusion Proteins ,Visual Acuity ,Angiogenesis Inhibitors ,Review ,Real world evidence ,Retina ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Macular Degeneration ,0302 clinical medicine ,Pro re nata ,Ranibizumab ,medicine ,Humans ,Dosing ,Intensive care medicine ,030304 developmental biology ,Aflibercept ,0303 health sciences ,Neovascularisation ,business.industry ,Macula ,Macular degeneration ,medicine.disease ,Sensory Systems ,3. Good health ,Ophthalmology ,Regimen ,Treatment Outcome ,030221 ophthalmology & optometry ,Wet Macular Degeneration ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,medicine.drug - Abstract
The aim of this work was to evaluate the contribution of real-world evidence (RWE) in changing anti-vascular endothelial growth factor (VEGF) therapy treatment practices and improving real-world treatment strategies for neovascular age-related macular degeneration (nAMD).A PubMed literature search was performed to review the large number of English-language studies conducted to investigate the real-world effectiveness of anti-VEGF (aflibercept and ranibizumab) treatment paradigms available for nAMD.The evidence for pro re nata (PRN), treat-and-extend (T&E) and fixed bimonthly dosing regimens for anti-VEGF treatment of nAMD were reviewed and findings are summarised. RWE demonstrated that T&E regimens optimise visual outcomes while reducing burden on patients, clinics and physicians, compared with both fixed-dose and PRN regimens.RWE has helped to develop and improve real-world treatment strategies in nAMD, with the aim of optimising visual outcomes and reducing treatment burden in clinical practice. Of the various regimens, a T&E regimen is most likely to adequately balance clinical outcomes and treatment burden for patients with nAMD.
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- 2020
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35. Anthropometric measures and HbA1c to detect dysglycemia in young Asian women planning conception: The S-PRESTO cohort
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Yung Seng Lee, Yap Seng Chong, Jerry Kok Yen Chan, Izzuddin M. Aris, Ngee Lek, Chin Meng Khoo, Fabian Yap, Wen Lun Yuan, Shiao-Yng Chan, Mya Thway Tint, Lynette Pei-Chi Shek, Bernard Su Min Chern, Sharon Ng, Anne H. Y. Chu, See Ling Loy, Keith M. Godfrey, Heng Hao Tan, Seng Bin Ang, Jonathan Y. Bernard, Kok Hian Tan, Melvin Khee-Shing Leow, Bodescot, Myriam, Agency for science, technology and research [Singapore] (A*STAR), National University of Singapore (NUS), Harvard Medical School [Boston] (HMS), KK Women's and Children's Hospital [Singapore], Duke-NUS Medical School [Singapore], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Southampton, Nanyang Technological University [Singapour], This work was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore - NMRC/TCR/004-NUS/2008, NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore., Lee Kong Chian School of Medicine (LKCMedicine), and Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
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endocrine system diseases ,Epidemiology ,Body Mass Index ,Cohort Studies ,0302 clinical medicine ,Odds Ratio ,Medicine ,030212 general & internal medicine ,Prediabetes ,Waist-to-height ratio ,Multidisciplinary ,Anthropometry ,Endocrine system and metabolic diseases ,Middle Aged ,3. Good health ,Area Under Curve ,Cohort ,Female ,Cohort study ,Adult ,Risk ,Waist ,Adolescent ,Science ,030209 endocrinology & metabolism ,[SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,Sensitivity and Specificity ,Article ,Prediabetic State ,03 medical and health sciences ,Young Adult ,Asian People ,Diabetes Mellitus ,Humans ,Medicine [Science] ,Author Correction ,Glycated Hemoglobin ,Waist-Height Ratio ,business.industry ,nutritional and metabolic diseases ,Diagnostic markers ,Odds ratio ,Endocrine System and Metabolic Diseases ,Glucose Tolerance Test ,medicine.disease ,Diagnostic Markers ,[SDV.MHEP.GEO] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics ,ROC Curve ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Body mass index ,Demography - Abstract
We investigated whether adding anthropometric measures to HbA1c would have stronger discriminative ability over HbA1c alone in detecting dysglycemia (diabetes and prediabetes) among Asian women trying to conceive. Among 971 Singaporean women, multiple regression models and area under receiver-operating characteristic (AUROC) curves were used to analyze associations of anthropometric (weight, height, waist/hip circumferences, 4-site skinfold thicknesses) and HbA1c z-scores with dysglycemia (fasting glucose ≥6.1 mmol/L with 2-hour glucose ≥7.8 mmol/l). The prevalence of dysglycemia was 10.9%. After adjusting for sociodemographic/medical history, BMI (Odds Ratio [OR] = 1.62 [95%CI 1.32-1.99]), waist-to-height ratio (OR = 1.74 [1.39-2.17]) and total skinfolds (OR = 2.02 [1.60-2.55]) showed the strongest associations with dysglycemia but none outperformed HbA1c (OR = 4.09 [2.81-5.94]). After adjustment for history, adding BMI, waist-to-height ratio and total skinfolds (anthropometry trio) as continuous variables to HbA1c (AUROC = 0.80 [95%CI 0.75-0.85]) performed similarly to HbA1c alone (AUROC = 0.79 [0.74-0.84]). However, using clinically-defined thresholds without considering history, as in common clinical practice, BMI ≥ 23 kg/m2 + HbA1c ≥ 5.7% (AUROC = 0.70 [0.64-0.75]) and anthropometry trio + HbA1c ≥ 5.7% (AUROC = 0.71 [0.65-0.76]) both outperformed HbA1c ≥ 5.7% alone (AUROC = 0.61 [0.57-0.65]). In a two-stage strategy, incorporating BMI ≥ 23 kg/m2 alongside HbA1c ≥ 5.7% into first-stage screening to identify high risk women for subsequent oral glucose tolerance testing improves dysglycemia detection in Asian women preconception. Agency for Science, Technology and Research (A*STAR) Ministry of Health (MOH) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version The S-PRESTO study group includes Anne Eng Neo Goh, Anne Rifkin-Graboi, Anqi Qiu, Bee Wah Lee, Bobby Cheon, Christiani Jeyakumar Henry, Ciaran Gerard Forde, Claudia Chi, Doris Fok, Elaine Quah, Elizabeth Tham, Evelyn Chung Ning Law, Evelyn Xiu Ling Loo, Faidon Magkos, Falk Mueller-Riemenschneider, George Seow Heong Yeo, Helen Yu Chen, Hugo P S van Bever, Joanne Yoong, Joao N. Ferreira., Jonathan Tze Liang Choo, Kenneth Kwek, Kuan Jin Lee, Lieng Hsi Ling, Ling Wei Chen, Lourdes Mary Daniel, Marielle V. Fortier, Mary Foong-Fong Chong, Mei Chien Chua, Michael Meaney, Neerja Karnani, Oon Hoe Teoh, Queenie Ling Jun Li, Sendhil Velan, Shephali Tagore, Shirong Cai, Shu E Soh, Sok Bee Lim, Stella Tsotsi, Stephen Chin-Ying Hsu, Sue Anne Toh, Teng Hong Tan, Tong Wei Yew, Victor Samuel Rajadurai, Wee Meng Han, Wei Wei Pang, Yin Bun Cheung, and Yiong Huak Chan. We also acknowledge the efforts of the research coordinators, admin staff, study managers and participants. This work was supported by the Singapore National Research Foundation under its Translational and Clinical Research (TCR) Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council (NMRC), Singapore - NMRC/TCR/004-NUS/2008; NMRC/TCR/012-NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research (A*STAR), Singapore.
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- 2020
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36. Multicolour imaging for the detection of polypoidal choroidal vasculopathy and age-related macular degeneration
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Louis W. Lim, Dominic S. Ting, Colin Siang Hui Tan, Lee Kong Chian School of Medicine (LKCMedicine), NationalHealthcare Group Eye Institute, TanTock Seng Hospital, and Duke-NUS Medical School,Singapore
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Indocyanine Green ,Male ,medicine.medical_specialty ,genetic structures ,Multimodal Imaging ,Sensitivity and Specificity ,complex mixtures ,Macular Degeneration ,03 medical and health sciences ,Polyps ,0302 clinical medicine ,Predictive Value of Tests ,Ophthalmology ,Age related ,Positive predicative value ,Photography ,medicine ,Humans ,False Positive Reactions ,Medicine [Science] ,Prospective Studies ,030212 general & internal medicine ,Fluorescein Angiography ,Coloring Agents ,Prospective cohort study ,Aged ,Aged, 80 and over ,Multimodal imaging ,medicine.diagnostic_test ,Choroid ,business.industry ,Fundus photography ,Reproducibility of Results ,Middle Aged ,Macular degeneration ,medicine.disease ,Choroidal Neovascularization ,eye diseases ,Vascular network ,Age-related Macular Degeneration ,030221 ophthalmology & optometry ,Imaging technology ,Female ,sense organs ,business - Abstract
Importance: Multicolour is a new imaging technology and its sensitivity for detecting polypoidal choroidal vasculopathy (PCV) and age-related macular degeneration (AMD) has not been well described. Background: To evaluate the accuracy of multicolour imaging compared to colour fundus photography (CFP) in differentiating AMD and PCV from normal eyes, and in detecting PCV. Design: Prospective cohort study at a tertiary referral centre. Participants: Fifty consecutive patients with PCV or AMD. Methods: Standardized multimodal imaging, including CFP, multicolour imaging, and fluorescein and indocyanine green angiography, were graded by a Central Reading Center using standardized grading protocols. Main outcomes and measures: Sensitivity, specificity, positive and negative predictive values (PPV and NPV). Results: Of 100 eyes, 44 had PCV, 33 had AMD, and 23 were normal. Multicolour imaging had higher specificity (73.9% vs 52.2%) and NPV (94% vs 85.7%) compared to CFP for detecting all types of AMD. For the detection of PCV, multicolour had higher sensitivity (86.4% vs 59.1%) and NPV (89.3% vs 74.3%). Polypoidal lesions were detected in 39 of 44 eyes (88.6%) using multicolour imaging, while the branching vascular network (BVN) was detected in 16 of 44 eyes (36.4%). Using BVN as a parameter, infrared imaging specificity and PPV for detecting PCV were 96.6% and 88.9%, respectively. Conclusions: Multicolour imaging is superior to standard CFP in differentiating AMD and PCV from normal eyes, and in detecting features of PCV. Specific features seen on multicolour imaging can alert ophthalmologists to the likely presence of these diseases so that additional definitive investigations can be performed. National Medical Research Council (NMRC) Research administration support was provided by the National Medical Research Council Centre Grant at Tan Tock Seng Hospital (NMRC/CG/M012/2017). Dr Tan reports grants from National Medical ResearchCouncil (NMRC/TA/0039/2015), grants from NationalHealthcare Group, honoraria and non-financial support fromBayer, non-financial support from Heidelberg Engineering,honoraria and non-financial support from Novartis, outsidethe submitted work. Dr Louis Lim and Mr Dominic Tinghave no financial interests to declare.
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- 2019
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37. Lamina Cribrosa Curvature in Healthy Korean Eyes
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Tan, Nicholas, Tham, Yih-Chung, Thakku, Sri Gowtham, Wang, Xiaofei, Baskaran, Mani, Tan, Marcus, Mari, Jean-Martial, Strouthidis, NIcholas, Aung, Tin, Cheng, Ching-Yu, Lee, Seung Hyen, Kim, Tae-Woo, Lee, Eun Ji, Girard, Michaël, Laboratoire de Chimie des Processus Biologiques (LCPB), Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Géopôle du Pacifique Sud (GePaSUD), Université de la Polynésie Française (UPF), and Duke-NUS Medical School [Singapore]
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Lamina ,genetic structures ,Optic Disk ,Glaucoma ,lcsh:Medicine ,Curvature ,Article ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Optical coherence tomography ,Ophthalmology ,[INFO.INFO-IM]Computer Science [cs]/Medical Imaging ,Humans ,Medicine ,lcsh:Science ,ComputingMilieux_MISCELLANEOUS ,Aged ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Healthy population ,lcsh:R ,Healthy subjects ,Middle Aged ,medicine.disease ,eye diseases ,030104 developmental biology ,medicine.anatomical_structure ,Biological Variation, Population ,Population Surveillance ,Female ,lcsh:Q ,Enhanced depth imaging ,sense organs ,Factor Analysis, Statistical ,business ,Tomography, Optical Coherence ,030217 neurology & neurosurgery ,Optic disc - Abstract
Given that posterior bowing of the lamina cribrosa (LC) is a principle event in the development of glaucomatous damage, assessment of the LC morphology may have clinical utility in diagnosing and managing glaucoma patients. LC curvature has been suggested as an index to evaluate the LC morphology. To apply LC morphology in clinical practice, it is necessary to know normal profiles of LC curvature in healthy population. This study was performed to investigate the characteristics of LC curvature in healthy eyes using enhanced depth imaging spectral-domain optical coherence tomography in a total of 250 eyes of 125 healthy Korean subjects. The lamina cribrosa curvature index (LCCI) values at seven locations spaced equidistantly across the vertical optic disc diameter were measured on serial horizontal B-scan images. The mean value of the seven measurements was defined as the average LCCI. The average LCCI was 7.46 ± 1.22 (range, 4.29–10.48) and did not differ significantly between the right and left eyes. There was a strong inter-eye correlation within subjects. LCCI was significantly larger in eyes with shorter axial length (P
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- 2019
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38. Global transmission, spatial segregation, and recombination determine the long-term evolution and epidemiology of bovine coronaviruses
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Vijaykrishna Dhanasekaran, Hervé Cassard, Sarah Maman, Mariette F. Ducatez, Elias Salem, Ben M. Hause, Gilles Meyer, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Monash University [Melbourne], Duke-NUS Medical School [Singapore], Emerging Infectious Diseases Program, Kansas State University, Department of Diagnostic Medicine and Pathobiology, Système d'Information des GENomes des Animaux d'Elevage (SIGENAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and This work was supported by the 'RESPICARE' grant of the Institut Carnot Sante Animale (ICSA), and by the French Ministry of Agriculture. Elias Salem was supported by a PhD scholarship of the Lebanese University.
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0301 basic medicine ,Gastrointestinal Diseases ,040301 veterinary sciences ,lcsh:QR1-502 ,Cattle Diseases ,Genome, Viral ,Biology ,Genome ,Article ,lcsh:Microbiology ,Virus ,Evolution, Molecular ,0403 veterinary science ,03 medical and health sciences ,Phylogenetics ,Virology ,Animals ,Selection, Genetic ,Molecular clock ,Respiratory Tract Infections ,Gene ,Phylogeny ,Bovine coronavirus ,Coronavirus, Bovine ,Genetic diversity ,Geography ,molecular clock ,04 agricultural and veterinary sciences ,[SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM] ,recombination ,3. Good health ,Genetic divergence ,bovine coronavirus ,geographic clustering ,Viral Tropism ,030104 developmental biology ,Infectious Diseases ,Evolutionary biology ,Cattle ,France ,Coronavirus Infections - Abstract
Bovine coronavirus (BCoV) is widespread in cattle and wild ruminant populations throughout the world. The virus causes neonatal calf diarrhea and winter dysentery in adult cattle, as well as upper and lower respiratory tract infection in young cattle. We isolated and deep sequenced whole genomes of BCoV from calves with respiratory distress in the south&ndash, west of France and conducted a comparative genome analysis using globally collected BCoV sequences to provide insights into the genomic characteristics, evolutionary origins, and global diversity of BCoV. Molecular clock analyses allowed us to estimate that the BCoV ancestor emerged in the 1940s, and that two geographically distinct lineages diverged from the 1960s&ndash, 1970s. A recombination event in the spike gene (breakpoint at nt 1100) may be at the origin of the genetic divergence sixty years ago. Little evidence of genetic mixing between the spatially segregated lineages was found, suggesting that BCoV genetic diversity is a result of a global transmission pathway that occurred during the last century. However, we found variation in evolution rates between the European and non-European lineages indicating differences in virus ecology.
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- 2020
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39. A network analysis to identify pathophysiological pathways distinguishing ischaemic from non-ischaemic heart failure
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Kenneth Dickstein, Faiez Zannad, Marco Metra, Nilesh J. Samani, Jozine M. ter Maaten, Stefan D. Anker, Dirk J. van Veldhuisen, Rebecca J. Woolley, Peter van der Meer, John G.F. Cleland, Iziah E Sama, Carolyn S.P. Lam, Jasper Tromp, Leong L. Ng, Hans L. Hillege, Adriaan A. Voors, Simon P. R. Romaine, Jan F. Nauta, Chim C. Lang, University Medical Center Groningen [Groningen] (UMCG), University of Leicester, Glenfield Hospital, National Heart Centre Singapore (NHCS), Duke-NUS Medical School [Singapore], University of Glasgow, National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, University of Brescia, University of Bergen (UiB), Stavanger University Hospital, Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Centre for Cardiovascular Research (DZHK) partner site Berlin, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Ninewells Hospital and Medical School [Dundee], This work was supported by a grant from the European Commission (FP7‐242209‐BIOSTAT‐CHF), European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Kidney Center (GKC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), BOZEC, Erwan, and A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure - BIOSTAT-CHF - - EC:FP7:HEALTH2010-04-01 - 2015-03-31 - 242209 - VALID
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Male ,Heart disease ,Cardiomyopathy ,Angiotensin-Converting Enzyme Inhibitors ,030204 cardiovascular system & hematology ,Bioinformatics ,Ventricular Function, Left ,0302 clinical medicine ,Medicine ,FIBROSIS ,Myocardial infarction ,Endothelial dysfunction ,Middle Aged ,Pathophysiology ,3. Good health ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,SYSTEMS BIOLOGY ,SURVIVAL ,Female ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,Research Article ,UROKINASE PLASMINOGEN-ACTIVATOR ,Physical protein-protein interaction ,Physical protein–protein interaction ,PROTEINS ,Ischaemic heart failure ,Pathway ,Inflammation ,DIAGNOSIS ,03 medical and health sciences ,Angiotensin Receptor Antagonists ,Percutaneous Coronary Intervention ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Humans ,Aged ,Heart Failure ,RECEPTOR ,business.industry ,BETA-BLOCKERS ,Stroke Volume ,medicine.disease ,Urokinase receptor ,ATHEROSCLEROSIS ,Heart failure ,INTERACTION DATABASE ,business - Abstract
International audience; Aims: Heart failure (HF) is frequently caused by an ischaemic event (e.g. myocardial infarction) but might also be caused by a primary disease of the myocardium (cardiomyopathy). In order to identify targeted therapies specific for either ischaemic or non-ischaemic HF, it is important to better understand differences in underlying molecular mechanisms.Methods and results: We performed a biological physical protein-protein interaction network analysis to identify pathophysiological pathways distinguishing ischaemic from non-ischaemic HF. First, differentially expressed plasma protein biomarkers were identified in 1160 patients enrolled in the BIOSTAT-CHF study, 715 of whom had ischaemic HF and 445 had non-ischaemic HF. Second, we constructed an enriched physical protein-protein interaction network, followed by a pathway over-representation analysis. Finally, we identified key network proteins. Data were validated in an independent HF cohort comprised of 765 ischaemic and 100 non-ischaemic HF patients. We found 21/92 proteins to be up-regulated and 2/92 down-regulated in ischaemic relative to non-ischaemic HF patients. An enriched network of 18 proteins that were specific for ischaemic heart disease yielded six pathways, which are related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. We identified five key network proteins: acid phosphatase 5, epidermal growth factor receptor, insulin-like growth factor binding protein-1, plasminogen activator urokinase receptor, and secreted phosphoprotein 1. Similar results were observed in the independent validation cohort.Conclusions: Pathophysiological pathways distinguishing patients with ischaemic HF from those with non-ischaemic HF were related to inflammation, endothelial dysfunction superoxide production, coagulation, and atherosclerosis. The five key pathway proteins identified are potential treatment targets specifically for patients with ischaemic HF.
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- 2020
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40. Presence of Recombinant Bat Coronavirus GCCDC1 in Cambodian Bats
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Feng Zhu, Veasna Duong, Xiao Fang Lim, Vibol Hul, Tanu Chawla, Lucy Keatts, Tracey Goldstein, Alexandre Hassanin, Vuong Tan Tu, Philippe Buchy, October M. Sessions, Lin-Fa Wang, Philippe Dussart, Danielle E. Anderson, Duke-NUS Medical School [Singapore], Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Wildlife Conservation Society (WCS), University of California [Davis] (UC Davis), University of California (UC), Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Vietnam Academy of Science and Technology (VAST), University of Melbourne, and DEA and L-FW were supported by Grants NRF2012NRFCRP001-056 and NRF2016NRF-NSFC002-013 from the Singapore National Research Foundation. This study was made possible by the generous support of the American people through the United States Agency for International Development (USAID) Emerging Pandemic Threats PREDICT project (cooperative agreement number GHN-A-OO-09-00010-00 and AID-OAA-A-14-00102). The contents of this paper are the responsibility of the authors and do not necessarily reflect the views of the US Agency for International Development or the US Government. The fieldwork was supported in part by the National Authority for Preah Vihear, UNESCO, 'Société des amis du Muséum et du Jardin des Plantes', and the Muséum national d’Histoire naturelle.
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Recombination, Genetic ,China ,Coronaviridae ,Coronaviridae Infections ,[SDV]Life Sciences [q-bio] ,viruses ,bats ,coronavirus ,virus diseases ,cross-species transmission ,Genome, Viral ,zoonosis ,recombination ,respiratory tract diseases ,Evolution, Molecular ,Phylogeography ,co-infection ,Infectious Diseases ,Chiroptera ,Virology ,Animals ,GCCDC1 ,Cambodia ,Phylogeny ,Disease Reservoirs - Abstract
International audience; Bats have been recognized as an exceptional viral reservoir, especially for coronaviruses. At least three bat zoonotic coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2) have been shown to cause severe diseases in humans and it is expected more will emerge. One of the major features of CoVs is that they are all highly prone to recombination. An extreme example is the insertion of the P10 gene from reoviruses in the bat CoV GCCDC1, first discovered in Rousettus leschenaultii bats in China. Here, we report the detection of GCCDC1 in four different bat species (Eonycteris spelaea, Cynopterus sphinx, Rhinolophus shameli and Rousettus sp.) in Cambodia. This finding demonstrates a much broader geographic and bat species range for this virus and indicates common cross-species transmission. Interestingly, one of the bat samples showed a co-infection with an Alpha CoV most closely related to RsYN14, a virus recently discovered in the same genus (Rhinolophus) of bat in Yunnan, China, 2020. Taken together, our latest findings highlight the need to conduct active surveillance in bats to assess the risk of emerging CoVs, especially in Southeast Asia.
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- 2022
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41. Distinct Pathological Pathways in Patients With Heart Failure and Diabetes
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Karla F. Arevalo Gomez, João Pedro Ferreira, Abhinav Sharma, Leong L. Ng, Carolyn S.P. Lam, Hans L. Hillege, Stefan D. Anker, Dirk J. van Veldhuisen, Wouter Ouwerkerk, Iziah E Sama, Marco Metra, Kenneth Dickstein, Faiez Zannad, Peter van der Meer, Jasper Tromp, Adriaan A. Voors, Chim C. Lang, Pim van der Harst, University Medical Center Groningen [Groningen] (UMCG), National Heart Centre Singapore (NHCS), Duke-NUS Medical School [Singapore], McGill University Health Center [Montreal] (MUHC), University of Alberta, Stanford University, Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), University of Bergen (UiB), Berlin-Brandenburg Center for Regenerative Therapies [Berlin, Germany], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), Charité Campus Virchow-Klinikum (CVK), Azienda Socio Sanitaria Territoriale Spedali Civili di Brescia [Brescia], University of Dundee, University of Leicester, Duke-National University of Singapore Graduate Medical School, The George Institute for Global Health [Sydney] (GIGH), The University of Sydney, BIOSTAT-CHF was funded by the European Commission [FP7-242209-BIOSTAT-CHF, EudraCT 2010-020808-29]. Additional funding was provided by Roche diagnostics, European Project: 242209,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,BIOSTAT-CHF(2010), European Project, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Kidney Center (GKC), Restoring Organ Function by Means of Regenerative Medicine (REGENERATE), BOZEC, Erwan, A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure - BIOSTAT-CHF - - EC:FP7:HEALTH2010-04-01 - 2015-03-31 - 242209 - VALID, EudraCT 2010–020808–29 - INCOMING, and Epidemiology and Data Science
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Male ,Oncology ,medicine.medical_specialty ,DATABASE ,heart failure ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Ventricular Function, Left ,BIOMARKER PROFILES ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Diabetes mellitus ,Internal medicine ,medicine ,Humans ,Prospective Studies ,030212 general & internal medicine ,Aged ,OUTCOMES ,Ejection fraction ,diabetes ,biology ,biomarkers ,business.industry ,EJECTION ,Paraoxonase ,Stroke Volume ,Prognosis ,medicine.disease ,[SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Diabetes Mellitus, Type 2 ,Heart failure ,SYSTEMS BIOLOGY ,Neutrophil degranulation ,biology.protein ,Biomarker (medicine) ,Female ,GDF15 ,GLYCATION END-PRODUCTS ,Cardiology and Cardiovascular Medicine ,business - Abstract
OBJECTIVES: The aims of this study were to compare the characteristics of patients with and without diabetes and to use network analyses to compare biomarker profiles and associated pathways in patients with diabetes compared with those without diabetes, which might offer new avenues for potential therapeutic targets.BACKGROUND: Diabetes adversely affects clinical outcomes and complicates treatment in patients with heart failure (HF). A clear understanding of the pathophysiological processes associated with type 2 diabetes in HF is lacking.METHODS: Network and pathway over-representation analyses were performed to identify unique pathological pathways in patients with and without diabetes using 92 biomarkers from different pathophysiological domains measured in plasma samples from 1,572 patients with HF (31% with diabetes) with reduced ejection fraction (left ventricular ejection fraction RESULTS: Biomarker profiles were first compared between patients with HF with and without diabetes. Patients with diabetes showed higher levels of galectin-4, growth differentiation factor 15, and fatty acid binding protein 4 and lower levels of paraoxonase 3. Network analyses were then performed, revealing that epidermal growth factor receptor and galectin-3 were the most prominent connecting proteins. Translation of these networks to biologic pathways revealed that diabetes was associated with inflammatory response and neutrophil degranulation. Diabetes conferred worse outcomes after correction for an established risk model (hazard ratio: 1.20; 95% confidence interval: 1.01 to 1.42).CONCLUSIONS: Concomitant diabetes in patients with HF with reduced ejection fraction is associated with distinct pathophysiological pathways related to inflammation, protein phosphorylation, and neutrophil degranulation. These data support the evaluation of anti-inflammatory therapeutic approaches, epidermal growth factor receptor in particular, for patients with HF and diabetes.
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- 2020
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42. A trans-eQTL network regulates osteoclast multinucleation and bone mass
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Jacques Behmoaras, Marie Pereira, Enrico Petretto, Peter I. Croucher, Amelia Li Min Tan, Kwon-Sik Park, Graham R. Williams, J. H. Duncan Bassett, Maxime Rotival, Jeong-Hun Ko, Hayley Protheroe, Kee-Beom Kim, John G. Logan, Imperial College London, Hammersmith Hospital NHS Imperial College Healthcare, University of Virginia, Duke-NUS Medical School [Singapore], University of New South Wales [Sydney] (UNSW), Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the Medical Research Council ‘Control of Macrophage Multinucleation in Health and Disease’ (MR/N01121X/1 to JB, GRW, JHDB), a Wellcome Trust Strategic Award (Grant Number 101123 to GRW and JHDB) and National Institutes of Health/ National Cancer Institute (NIH/NCI U01CA224293)., and Medical Research Council (MRC)
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0301 basic medicine ,Life Sciences & Biomedicine - Other Topics ,Male ,Network - organization ,Rat and human model ,Gene regulatory network ,Cell biology and structure ,Osteoclasts ,Genome-wide association study ,DETERMINANTS ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,0601 Biochemistry and Cell Biology ,Rats, Inbred WKY ,bone ,Mice ,0302 clinical medicine ,Bone Density ,genetics ,Gene Regulatory Networks ,rat ,Biology (General) ,MACROPHAGES ,Genomics and evolution ,RISK ,Mice, Knockout ,General Neuroscience ,General Medicine ,Phenotype ,Cell biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Knockout mouse ,osteoclast ,Genetics Humans ,Medicine ,PHOSPHATIDYLINOSITOL 3-KINASE ,Bone Biology ,Female ,Human - human interaction ,Life Sciences & Biomedicine ,Research Article ,Human ,Osteoclast gene ,QH301-705.5 ,Science ,Quantitative Trait Loci ,Quantitative trait locus ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Bone resorption ,03 medical and health sciences ,Osteoclast ,medicine ,genomics ,Animals ,GENOME-WIDE ASSOCIATION ,DC-STAMP ,Bone Resorption ,Gene ,METAANALYSIS ,mouse ,Science & Technology ,General Immunology and Microbiology ,COMPLEX TRAITS ,Genetics and Genomics ,Cell Biology ,Rats ,030104 developmental biology ,[SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics ,Rats, Inbred Lew ,network ,SYSTEMS GENETICS ,MINERAL DENSITY ,Genome-Wide Association Study - Abstract
International audience; Functional characterisation of cell-type-specific regulatory networks is key to establish a causal link between genetic variation and phenotype. The osteoclast offers a unique model for interrogating the contribution of co-regulated genes to in vivo phenotype as its multinucleation and resorption activities determine quantifiable skeletal traits. Here we took advantage of a trans-regulated gene network (MMnet, macrophage multinucleation network) which we found to be significantly enriched for GWAS variants associated with bone-related phenotypes. We found that the network hub gene Bcat1 and seven other co-regulated MMnet genes out of 13, regulate bone function. Specifically, global (Pik3cb-/-, Atp8b2+/-, Igsf8-/-, Eml1-/-, Appl2-/-, Deptor-/-) and myeloid-specific Slc40a1 knockout mice displayed abnormal bone phenotypes. We report opposing effects of MMnet genes on bone mass in mice and osteoclast multinucleation/resorption in humans with strong correlation between the two. These results identify MMnet as a functionally conserved network that regulates osteoclast multinucleation and bone mass.
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- 2020
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43. The longitudinal relationship between early-life screen viewing and 24-hour movement behaviours -findings from a multi-ethnic birth cohort study
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Chen, Bozhi, Bernard, Jonathan, Padmapriya, Natarajan, Ning, Yilin, Cai, Shirong, Lança, Carla, Tan, Kok Hian, Yap, Fabian, Chong, Yap-Seng, Shek, Lynette, Godfrey, Keith, Saw, Seang, Chan, Shiao-Yng, Eriksson, Johan, Tan, Chuen, Müller-Riemenschneider, Falk, Saw Swee Hock School of Public Health [Singapore, Singapore], National University of Singapore (NUS), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), Yong Loo Lin School of Medicine, National University of Singapore, NUS Graduate School of Integrative Sciences and Engineering [Singapore, Singapore], Singapore Eye Research Institute [Singapore] (SERI), KK Women’s and Children’s Hospital (KKH), Duke-NUS Graduate Medical School, Lee Kong Chian School of Medicine, Nanyang Technological University [Singapour], National University Health System, Medical Research Council, University of Southampton, Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, University of Helsinki, Berlin Institute of Health (BIH), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Duke-NUS Medical School [Singapore], Nanyang Technological University (NTU), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, and Bernard, Jonathan
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[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,[SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics ,[SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
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- 2020
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44. Three-dimensional biventricular strains in pulmonary arterial hypertension patients using hyperelastic warping
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John Carson Allen, Fei Gao, Martin Genet, Shuang Leng, Ju Le Tan, Xiaodan Zhao, Hua Zou, Ce Xi, Lik Chuan Lee, Ru San Tan, Angela S Koh, Liang Zhong, National Heart Centre Singapore (NHCS), Michigan State University [East Lansing], Michigan State University System, Duke-NUS Medical School [Singapore], Mathematical and Mechanical Modeling with Data Interaction in Simulations for Medicine (M3DISIM), Laboratoire de mécanique des solides (LMS), École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris)
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Adult ,Male ,medicine.medical_specialty ,Heart Ventricles ,Magnetic Resonance Imaging, Cine ,Health Informatics ,Models, Biological ,Article ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,Ventricular Dysfunction, Left ,0302 clinical medicine ,Imaging, Three-Dimensional ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Internal medicine ,medicine ,Image Processing, Computer-Assisted ,Humans ,cardiovascular diseases ,Image warping ,Pulmonary Arterial Hypertension ,Ejection fraction ,Cardiac cycle ,Receiver operating characteristic ,business.industry ,[SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph] ,Middle Aged ,[SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph] ,Computer Science Applications ,medicine.anatomical_structure ,Ventricle ,Hyperelastic material ,[INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV] ,Cardiology ,cardiovascular system ,Female ,Objective evaluation ,business ,Cardiac magnetic resonance ,030217 neurology & neurosurgery ,Software ,circulatory and respiratory physiology - Abstract
International audience; Background and Objective: Evaluation of biventricular function is an essential component of clinical management in pulmonary arterial hypertension (PAH). This study aims to examine the utility of biventricular strains derived from a model-to-image registration technique in PAH patients in comparison to age-and gender-matched normal controls. Methods: A three-dimensional (3D) model was reconstructed from cine short-and long-axis cardiac magnetic resonance (CMR) images and subsequently partitioned into right ventricle (RV), left ventricle (LV) and septum. The hyperelastic warping method was used to register the meshed biventricular finite element model throughout the cardiac cycle and obtain the corresponding biventricular circumferential, longitudinal and radial strains. Results: Intra-and inter-observer reproducibility of biventricular strains was excellent with all intra-class correlation coefficients > 0.84. 3D biventricular longitudinal, circumferential and radial strains for RV, LV and septum were significantly decreased in PAH patients compared with controls. Receiver operating characteristic (ROC) analysis showed that the 3D biventricular strains were better early markers (Area under the ROC curve = 0.96 for RV longitudinal strain) of ventricular dysfunction than conventional parameters such as two-dimensional strains and ejection fraction. Conclusions: Our highly reproducible methodology holds potential for extending CMR imaging to characterize 3D biventricular strains, eventually leading to deeper understanding of biventricular mechanics in PAH.
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- 2020
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45. Highly Efficient Vertical Transmission for Zika Virus in Aedes aegypti after Long Extrinsic Incubation Time
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Menchie Manuel, Julien Pompon, Dorothée Missé, Duke-NUS Medical School [Singapore], Interhuman Arbovirus Transmission (MIVEGEC-iHAT), Biologie des infections virales: Emergence, DIFfusion, Impact, Contrôle, Elimination (EDIFICE), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), and Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])
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Aedes aegypti ,Microbiology (medical) ,030231 tropical medicine ,lcsh:Medicine ,Virus ,Incubation period ,law.invention ,Zika virus ,03 medical and health sciences ,0302 clinical medicine ,law ,Immunology and Allergy ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Larva ,General Immunology and Microbiology ,biology ,lcsh:R ,biology.organism_classification ,Virology ,3. Good health ,Infectious Diseases ,Transmission (mechanics) ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,vertical transmission ,Viral load ,Horizontal transmission - Abstract
While the Zika virus (ZIKV) 2014&ndash, 2017 pandemic has subsided, there remains active transmission. Apart from horizontal transmission to humans, the main vector Aedes aegypti can transmit the virus vertically from mother to offspring. Large variation in vertical transmission (VT) efficiency between studies indicates the influence of parameters, which remain to be characterized. To determine the roles of extrinsic incubation time and gonotrophic cycle, we deployed an experimental design that quantifies ZIKV in individual progeny and larvae. We observed an early infection of ovaries that exponentially progressed. We quantified VT rate, filial infection rate, and viral load per infected larvae at 10 days post oral infection (d.p.i.) on the second gonotrophic cycle and at 17 d.p.i. on the second and third gonotrophic cycle. As compared to previous reports that studied pooled samples, we detected a relatively high VT efficiency from 1.79% at 10 d.p.i. and second gonotrophic cycle to 66% at 17 d.p.i. and second gonotrophic cycle. At 17 d.p.i., viral load largely varied and averaged around 800 genomic RNA (gRNA) copies. Longer incubation time and fewer gonotrophic cycles promoted VT. These results shed light on the mechanism of VT, how environmental conditions favor VT, and whether VT can maintain ZIKV circulation.
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- 2020
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46. Editorial: Monocyte Heterogeneity and Function
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Florent Ginhoux, Alexander Mildner, Emmanuel L. Gautier, Andreas Schlitzer, Claudia Jakubzick, Chen Varol, Calum Bain, Pierre Guermonprez, Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Agency for science, technology and research [Singapore] (A*STAR), Shanghai Jiao Tong University School of Medicine, Max Delbrück Center for Molecular Medicine [Berlin] (MDC), Helmholtz-Gemeinschaft = Helmholtz Association, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Bonn, Geisel School of Medicine at Dartmouth, Sackler Faculty of Medicine, Tel Aviv University [Tel Aviv], University of Edinburgh, King‘s College London, Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Tel Aviv University (TAU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Gestionnaire, Hal Sorbonne Université, Gautier, Emmanuel, Duke-NUS Medical School [Singapore], German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), AP-HP - Hôpital Bichat - Claude Bernard [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
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lcsh:Immunologic diseases. Allergy ,MESH: Inflammation ,Cancer Research ,[SDV]Life Sciences [q-bio] ,Immunology ,Inflammation ,010402 general chemistry ,Chronic inflammatory disease ,MESH: Monocytes ,01 natural sciences ,03 medical and health sciences ,immunology [Monocytes] ,Inflammation resolution ,immunology [Inflammation] ,Fibrosis ,cardiovascular disease ,medicine ,Immunology and Allergy ,Humans ,cancer ,ddc:610 ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,0303 health sciences ,MESH: Humans ,business.industry ,Monocyte ,fibrosis ,Cancer ,MESH: Macrophages ,chronic inflammatory disease ,immunology [Macrophages] ,medicine.disease ,0104 chemical sciences ,macrophages ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,inflammation ,inflammation resolution ,medicine.symptom ,lcsh:RC581-607 ,business ,monocytes ,Function (biology) - Abstract
International audience; No abstract available
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- 2020
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47. Decreased microglial Wnt/β-catenin signalling drives microglial pro-inflammatory activation in the developing brain
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Amélie Montané, Vincent Degos, Rebecca K. Holloway, Valérie C. Besson, Olivier Baud, David H. Rowitch, Pierre Gressens, A. David Edwards, Rahma Hassan-Abdi, Henrik Hagberg, Bobbi Fleiss, Nadia Soussi-Yanicostas, Sophie Lebon, Enrico Petretto, Gareth Ball, Tifenn Le Charpentier, Fabrice Chrétien, Andrée Delahaye-Duriez, Olivier Hennebert, Zsolt Csaba, Paul Aljabar, Anne-Laure Schang, Alka Saxena, Juliette Van Steenwinckel, Veronique E. Miron, Michelle L. Krishnan, Stéphanie Sigaut, Claire Leconte, Franck Verdonk, Cindy Bokobza, Leslie Schwendimann, Walter Birchmeier, Rowitch, David [0000-0002-0079-0060], Apollo - University of Cambridge Repository, Maladies neurodéveloppementales et neurovasculaires (NeuroDiderot (UMR_S_1141 / U1141)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), PremUp Foundation, Institut de Recherche pour le Développement (IRD)-CHI Créteil-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Paris (UP), Laboratoire de Chimie et Toxicologie Analytique et Cellulaire (EA 4463), Université Paris Descartes - Paris 5 (UPD5), King‘s College London, Service d'Anesthésie réanimation [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), UFR Santé, Médecine et Biologie Humaine (UFR SMBH), Université Sorbonne Paris Nord, Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Conservatoire National des Arts et Métiers [CNAM] (CNAM), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, Queen's Medical Researche Institute, University of Edinburgh, Max Delbrueck Center for Molecular Medicine, Helmholtz-Gemeinschaft = Helmholtz Association, University of Cambridge [UK] (CAM), Centre Hospitalier Sainte Anne [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Pharmacologie de la circulation cérébrale (EA 4475), Duke-NUS Medical School [Singapore], University of Gothenburg (GU), Royal Melbourne Institute of Technology University (RMIT University), This study was supported by grants from Inserm, Université Paris Diderot, Université Sorbonne-Paris-Cité, Investissement d'Avenir (ANR-11-INBS-0011, NeurATRIS), ERA-NET Neuron (Micromet), DHU PROTECT, Association Robert Debré, PremUP, Fondation de France, Fondation pour la Recherche sur le Cerveau, Fondation des Gueules Cassées, Roger de Spoelberch Foundation, Grace de Monaco Foundation, Leducq Foundation, Action Medical Research, Cerebral Palsy Alliance Research Foundation Australia, Wellcome Trust (WSCR P32674) and The Swedish Research Council (2015-02493). We wish to acknowledge the support of the Department of Perinatal Imaging and Health, King’s College London. In addition, the authors acknowledge financial support from the National Institute for Health Research (NIHR) Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust and King's College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health., ANR-11-INBS-0011,NeurATRIS,Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences(2011), Soussi-Yanicostas, Nadia, Infrastructures - Infrastructure de Recherche Translationnelle pour les Biothérapies en Neurosciences - - NeurATRIS2011 - ANR-11-INBS-0011 - INBS - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche pour le Développement (IRD)-CHI Créteil-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris-Saclay-Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM), Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Jean Verdier [AP-HP], Laboratoire de dynamique des systèmes neuroendocriniens, Service des Soins Intensifs [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Zealand University Hospital, Physiopathologie et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Computing [London], Biomedical Image Analysis Group [London] (BioMedIA), Imperial College London-Imperial College London, Physiopathologie, conséquences fonctionnelles et neuroprotection des atteintes du cerveau en développement, Université Paris Diderot - Paris 7 (UPD7)-IFR2-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Henri Mondor, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Cardiovascular and Metabolic Disorders, Imperial College London, Perinatal Center, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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0301 basic medicine ,[SDV]Life Sciences [q-bio] ,neuroinflammation ,Animals, Genetically Modified ,[SCCO]Cognitive science ,Mice ,0302 clinical medicine ,Neuroinflammation ,Zebrafish ,[SDV.BDD]Life Sciences [q-bio]/Development Biology ,innate immunity ,Wnt Signaling Pathway ,Cells, Cultured ,Innate immunity ,biology ,Microglia ,Inflammation/metabolism ,neonatal encephalopathy ,Wnt signaling pathway ,Brain ,Human brain ,Neuroprotection ,3. Good health ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,Blood-Brain Barrier ,[SDV.IMM]Life Sciences [q-bio]/Immunology ,neuroprotection ,Signal transduction ,Wnt Signaling Pathway/physiology ,Blood-Brain Barrier/metabolism ,[SDV.IMM] Life Sciences [q-bio]/Immunology ,3DNA ,Neonatal encephalopathy ,Microglia/metabolism ,03 medical and health sciences ,[SDV.BDD] Life Sciences [q-bio]/Development Biology ,medicine ,[SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Brain/metabolism ,Animals ,Humans ,[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology ,Inflammation ,Innate immune system ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,Computational Biology ,Original Articles ,[SCCO] Cognitive science ,biology.organism_classification ,030104 developmental biology ,Neurology (clinical) ,Neuroscience ,030217 neurology & neurosurgery - Abstract
International audience; Microglia of the developing brain have unique functional properties but how their activation states are regulated is poorly understood. Inflammatory activation of microglia in the still-developing brain of preterm-born infants is associated with permanent neurological sequelae in 9 million infants every year. Investigating the regulators of microglial activation in the developing brain across models of neuroinflammation-mediated injury (mouse, zebrafish) and primary human and mouse microglia we found using analysis of genes and proteins that a reduction in Wnt/b-catenin signalling is necessary and sufficient to drive a microglial phenotype causing hypomyelination. We validated in a cohort of preterm-born infants that genomic variation in the Wnt pathway is associated with the levels of connectivity found in their brains. Using a Wnt agonist delivered by a blood-brain barrier penetrant microglia-specific targeting nanocarrier we prevented in our animal model the pro-inflammatory microglial activation, white matter injury and behavioural deficits. Collectively, these data validate that the Wnt pathway regulates microglial activation, is critical in the evolution of an important form of human brain injury and is a viable therapeutic target.
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- 2019
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48. Associations of autozygosity with a broad range of human phenotypes
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Dennis O. Mook-Kanamori, Salma M. Wakil, Lisa R. Yanek, Dominique P.V. de Kleijn, Gert J. de Borst, Alison D. Murray, Kamran Guity, Vincent W. V. Jaddoe, Mario Pirastu, Carole Ober, Giuseppe Matullo, Charles N. Rotimi, Daniela Ruggiero, Teresa Tusié-Luna, Wolfgang Lieb, Chew-Kiat Heng, John R. B. Perry, Hortensia Moreno-Macías, Jie Zhou, John M. Starr, Juhani Junttila, Lei Yu, Danielle Posthuma, Marcus Dörr, Yingchang Lu, Jonathan P. Bradfield, Einat Granot-Hershkovitz, Karina Meidtner, Wouter van Rheenen, T Esko, Maris Alver, Wen-Jane Lee, Zhengming Chen, Jennifer A. Brody, Paolo Gasparini, Yii-Der Ida Chen, Cinzia Sala, Peter P. Pramstaller, Gauri Prasad, Nana Matoba, Natalie Terzikhan, Simonetta Guarrera, Bjarke Feenstra, Peter Vollenweider, Smeeta Shrestha, Yi-Jen Hung, Lilja Stefansdottir, David R. Weir, Felix R. Day, Antonietta Robino, Liang Zhang, Lluis Quintana-Murci, Nicholas J. Timpson, Robyn E Wootton, Xue W. Mei, Dharambir K. Sanghera, Gisli Masson, Debbie A Lawlor, Thomas Meitinger, Sharon L.R. Kardia, Peter K. Joshi, Frank J. A. van Rooij, Claude Bouchard, Cassandra N. Spracklen, Ken K. Ong, Taulant Muka, Guanjie Chen, Laura J. Scott, Walter Palmas, Daniel I. Chasman, Sarah E. Medland, Krista Fischer, Blair H. Smith, Jon K. Sigurdsson, Leon Straker, Clara Viberti, Yuan Shi, Louis Pérusse, Peter J. van der Most, Timo Tõnis Sikka, Chris Haley, Kuang Lin, Leif Groop, Hester M. den Ruijter, Hakon Hakonarson, Masato Akiyama, Stephan J. L. Bakker, Sonja I. Berndt, Jeffery R. O'Connell, Cisca Wijmenga, Daniele Cusi, Lorena Orozco, Kristjan H. S. Moore, Kevin Sandow, Stephen S. Rich, Stephanie J. Loomis, George Davey Smith, Cornelia M. van Duijn, Sharvari Rahul Shukla, Agnar Helgason, Thorsten Kessler, Anuj Goel, Dan Mason, David W. Clark, James S. Pankow, Simona Vaccargiu, Uwe Völker, Tamara B. Harris, Matthew A. Allison, Clicerio Gonzalez, Sarju Ralhan, I-Te Lee, Matthias Laudes, Yen-Feng Chiu, Neil Poulter, Benjamin Lehne, John Wright, Lawrence F. Bielak, Philip L. De Jager, Reinhold Schmidt, Ya Xing Wang, Matthias Nauck, Diana L. Cousminer, Patrick Deelen, Ani Manichaikul, Stephen J. Chanock, Anders Hamsten, Barry I. Freedman, Gudmar Thorleifsson, Peter Kraft, Ozren Polasek, Jie Yao, Yoshinori Murakami, Paul M. Ridker, Anubha Mahajan, Struan F.A. Grant, Claudia Schurmann, Bjarni Gunnarsson, Catriona L. K. Barnes, Jessica van Setten, Sandosh Padmanabhan, Alena Stančáková, Markus M. Lerch, Anuradha Jagadeesan, Franco Giulianini, Daniel F. Gudbjartsson, Dwaipayan Bharadwaj, Shengchao Alfred Li, Peter S. Sever, Trevor A. Mori, Albertine J. Oldehinkel, Koichi Matsuda, Xueling Sim, Evangelos Evangelou, André G. Uitterlinden, Pekka Jousilahti, Yukihide Momozawa, Ioanna Tzoulaki, Chao A. Hsiung, Ginevra Biino, Murielle Bochud, Hannele Mattsson, Ilja M. Nolte, Sarah H. Wild, Patricia B. Munroe, Jianjun Liu, Bruce M. Psaty, Giriraj R. Chandak, Masahiro Kanai, Tony R. Merriman, Teemu Palviainen, Rodney A. Lea, Janie Corley, Nicholas J. Wareham, Alan B. Zonderman, Makoto Hirata, Matthew J. Bixley, Caroline Hayward, Nora Franceschini, Kristel R van Eijk, Etienne Patin, Daniel Shriner, Niek Verweij, Xiuqing Guo, Fredrik Karpe, Ruth J. F. Loos, Tiinamaija Tuomi, Ashley van der Spek, Patricia A. Peyser, Jessica D. Faul, Christian Fuchsberger, David Cesarini, Alex S. F. Doney, Janine F. Felix, Cornelius A. Rietveld, Jagadish Vangipurapu, Tanguy Corre, Line Skotte, Rajkumar Dorajoo, Catherine Igartua, Meena Kumari, Nona Sotoodehnia, Leonard H. van den Berg, Najaf Amin, Dale R. Nyholt, Harry Campbell, Massimiliano Cocca, Scott D. Gordon, Patrik K. E. Magnusson, John C. Chambers, Traci M. Bartz, Mike A. Nalls, Tin Aung, Nduna Dzimiri, Colin N. A. Palmer, Rob M. van Dam, Johanna Kuusisto, Russell P. Tracy, Anna Damulina, Pierre-Emmanuel Morange, Sylvain Foisy, Jing Hua Zhao, Nicholas G. Martin, Ching-Yu Cheng, Mariaelisa Graff, Rashmi B. Prasad, Alice Stanton, David-Alexandre Trégouët, Yu Guo, Helen R. Warren, Lyn R. Griffiths, Weihua Meng, Annika Tillander, Christa Meisinger, Albert V. Smith, Mark I. McCarthy, Jingyun Yang, Marine Germain, Neil Small, Linda Broer, Vilmundur Gudnason, Gunnar K. Pálsson, Michele K. Evans, Alexander Teumer, Mark J. Caulfield, Giorgia Girotto, Thomas Lumley, Tinca J. C. Polderman, Wei Zhao, Carlos A. Aguilar-Salinas, Jari Lahti, Matthew L. Albert, Yechiel Friedlander, Veikko Salomaa, Iona Y Millwood, Jan H. Veldink, Archie Campbell, Andres Metspalu, Ulf Gyllensten, Grant W. Montgomery, Veronique Vitart, Jai Rup Singh, Saima Afaq, Alan R. Shuldiner, Miao-Li Chee, Adebowale Adeyemo, Jennifer A. Smith, David A. van Heel, Jaspal S. Kooner, Daniela Toniolo, Cristian Pattaro, Jerome I. Rotter, John Whitfield, Melissa C. Smart, Kari E. North, Salman M. Tajuddin, Tallapragada Divya Sri Priyanka, Christopher A. Haiman, Diane M. Becker, Bernhard K. Krämer, Paul Elliott, Lihua Wang, He Gao, Patrick Sulem, Jinyan Huang, Chiea Chuen Khor, Ruifang Li-Gao, Åsa Johansson, Winfried März, Shai Carmi, Ilaria Gandin, Eric Boerwinkle, Gardar Sveinbjornsson, Saskia P. Hagenaars, Sander W. van der Laan, Gerard Pasterkamp, E-Shyong Tai, Hagit Hochner, Yih Chung Tham, Kent D. Taylor, Kari Stefansson, Matt J. Neville, Craig E. Pennell, Yanchun Bao, Annelot M. Dekker, Helena Schmidt, Mehdi Hedayati, Joshua Elliott, Ian J. Deary, Iris E. Jansen, Judith B. Borja, Edith Hofer, Martin Gögele, Igor Rudan, Lude Franke, Matthias Munz, Folkert W. Asselbergs, Bengt Sennblad, Imo Hofer, John D. Rioux, Pim van der Harst, Bahareh Sedaghati-khayat, Giovanni Cugliari, Morris A. Swertz, Francine Grodstein, Erwin P. Bottinger, Carol A. Wang, Andre Franke, Brian F. Meyer, Adele M. Taylor, Klodian Dhana, Jian'an Luan, Constance Turman, Robert A. Scott, May E. Montasser, Alison Pattie, Marco Brumat, Liming Li, Heiner Boeing, Karen L. Mohlke, Clemens Baumbach, Bishwa Raj Sapkota, Unnur Thorsteinsdottir, Naveed Sattar, Amy R. Bentley, Matthias B. Schulze, Ivana Kolcic, Stella Trompet, Sarah E. Harris, Ayo P. Doumatey, Charumathi Sabanayagam, David Eccles, Mary F. Feitosa, Jost B. Jonas, Massimo Mezzavilla, Mark O. Goodarzi, David Ellinghaus, Heribert Schunkert, Christian Gieger, Heikki V. Huikuri, Lingyao Zeng, Johan G. Eriksson, Woon-Puay Koh, Yucheng Jia, Gurpreet Singh Wander, James F. Wilson, Torgny Karlsson, Steven C. Hunt, Weihua Zhang, Maria Pina Concas, Zoltán Kutalik, Rebecca Rohde, Chittaranjan S. Yajnik, Yasaman Saba, Dabeeru C. Rao, Robin G. Walters, Reedik Mägi, Marie Loh, Eero Vuoksimaa, Josyf C. Mychaleckyj, Katri Räikkönen, Philippe Goyette, M. Arfan Ikram, Alicia Huerta-Chagoya, David J. Porteous, Teresa Nutile, J. Wouter Jukema, Noha A. Yousri, Yoichiro Kamatani, Maryam S. Daneshpour, Babette S. Zemel, Rona J. Strawbridge, Tien Yin Wong, Claudia Langenberg, Amy Moore, Marcus E. Kleber, Fereidoun Azizi, Avner Halevy, Erika Salvi, Francis S. Collins, Markku Laakso, Tim Kacprowski, S. Sunna Ebenesersdóttir, William R. Scott, Michael Boehnke, Jin-Fang Chai, Markus Perola, Nicola Pirastu, Wayne Huey-Herng Sheu, Robert Karlsson, Lenore J. Launer, Lili Milani, Renée de Mutsert, Fernando Rivadeneira, David A. Bennett, Nicola D. Kerrison, Paolo Manunta, Graciela E. Delgado, Magnus Johannesson, Carolina Medina-Gomez, Alanna C. Morrison, Kay-Tee Khaw, Jian-Min Yuan, Jaakko Kaprio, Melanie Waldenberger, Ralf Ewert, Hugoline G. de Haan, Andrew A. Hicks, Yukinori Okada, Maria Sabater-Lleal, Marilyn C. Cornelis, Stephanie J. London, Federica Rizzi, Jeanette Erdmann, Marina Ciullo, Michiaki Kubo, University of Edinburgh, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Osaka University Graduate School of Medicine, Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE genetics [Reykjavik], Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Area Science Park, Università degli studi di Trieste = University of Trieste, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Harbor UCLA Medical Center [Torrance, Ca.], Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Pop. Genetics, CNR, Sassari, Shardna life science Pula Cagliari, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Medstar Research Institute, Florida State University [Tallahassee] (FSU), University Medical Center [Utrecht], Centre for Population Health Sciences, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), California State University [Sacramento], Department of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Medical University Graz, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Frederick National Laboratory for Cancer Research (FNLCR), Wellcome Trust Centre of Human Genetics, University of Oxford, Department of Epidemiology, German Institute of Human Nutrition, University Medical Center Groningen [Groningen] (UMCG), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Department of Medicine, Surgery, and Dentistry, University of Milano, Icelandic Heart Association, Kopavogur, Iceland., Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Glasgow, Department of Cardiology, Leiden University Medical Center, Leiden, Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, Queen Mary University of London (QMUL), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Genentech, Inc., Genentech, Inc. [San Francisco], University of Tartu, Duke-NUS Medical School [Singapore], Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Human Genome Sequencing Center, Baylor College of Medicine, Baylor College of Medicine (BCM), Baylor University-Baylor University, University of San Carlos, Office of Population Studies Foundation, Icahn School of Medicine at Mount Sinai [New York] (MSSM), King‘s College London, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of Oxford, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, University of Chicago, University of Huddersfield, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Section on Nephrology [Winston-Salem, NC, USA] (Department of Internal Medicine), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, Radcliffe Department of Medicine [Oxford], Harvard School of Public Health, Kunming University of Science and Technology (KMUST), Sans affiliation, University of Southern California (USC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival, University of Cambridge [UK] (CAM), National University of Singapore (NUS), Experimental Cardiology Laboratory (ECL), Unirversity Medical Center, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, Department of Medical Genetics, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Capital Normal University [Beijing], Saw Swee Hock School of Public Health, National Institute for Environmental Health Sciences Research Triangle Park, Brown University, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Toyota Research Institute, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Metacohorts Consortium, Universiteit Leiden, Institute of Clinical Chemistry and Laboratory Medicine, University of Groningen [Groningen], Medical Research Concil Epidemiology Unit, Institute of Medical Science, Faculty of Medicine, Genetics and Pathology, Imperial College London, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Brigham and Women's Hospital [Boston], Erasmus University Rotterdam, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Stockholm Bioinformatics Center (SBC), Stockholm University, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, INRH, Department of Genetics, Los Angeles Biomedical Research Institute (LA BioMed), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Western General Hospital, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Medical Research Council, Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute-University of Pittsburgh Graduate School of Public Health, Zhengzhou University of Light Industry, Department of Electrical and Electronic Engineering [Niigata Univ.], Niigata University, Genetic Epidemiology Unit, University College of London [London] (UCL), Aston Business School, Aston University [Birmingham], Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], Centre Hospitalier Universitaire Vaudois (CHUV), Pennington Biomedical Research Center, University of Washington [Seattle], Guy's and St Thomas' Hospitals, Northwestern Polytechnical University [Xi'an] (NPU), Department of Social Medicine, University of Bristol [Bristol], Department of Genomics of Common Disease [London, UK], Imperial College London-Hammersmith Hospital NHS Imperial College Healthcare, Department of Internal Medicine, Institute of Clinical Molecular Biology, Kiel University, Medizinische Klinik II, Universität zu Lübeck = University of Lübeck [Lübeck], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina, Institute for Social Research, University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Department of Physics, RISSC-Lab-University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Medical Research Center Oulu, University of Oulu, University of Utah School of Medicine [Salt Lake City], The Generation R Study, Pediatrics, Epidemiology, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], Universität Heidelberg [Heidelberg] = Heidelberg University, Interuniversity Cardiology Institute Netherlands, School of Public Health, University of Michigan [Dearborn], Department of Epidemiology and Public Health, University of Kuopio, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institute of Epidemiology and Biobank PopGen, Department of Biostatistics, University of Washington, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Clinical Institute of Medical and Chemical Laboratory Diagnostics, Karl-Franzens-Universität Graz, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), QIMR Berghofer Medical Research Institute, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, University of Illinois [Chicago] (UIC), University of Illinois System, Experimental Cardiology Laboratory, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Functional Genomics, Erasmus Medical Centre, National Human Genome Research Institute (NHGRI), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Pathological Biochemistry, Royal Infirmary, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institute of Metabolic Science, MRC, University of Maryland School of Medicine [Baltimore, MD, USA], Centre for Molecular Epidemiology, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, IRCCS San Raffaele Scientific Institute [Milan, Italie], U937, Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Michigan System, HMNC Brain Health, Singapore Eye Research Institute, Partenaires INRAE, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Groningen, Department of Genomics of Common Disease, Department of Microbiology, The Freeman Hospital, Department Biostatistics University of North Carolina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Clark, D. W., Okada, Y., Moore, K. H. S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C. L. K., Lin, K., Zhao, J. H., Deelen, P., Rohde, R., Schurmann, C., Guo, X., Giulianini, F., Zhang, W., Medina-Gomez, C., Karlsson, R., Bao, Y., Bartz, T. M., Baumbach, C., Biino, G., Bixley, M. J., Brumat, M., Chai, J. -F., Corre, T., Cousminer, D. L., Dekker, A. M., Eccles, D. A., van Eijk, K. R., Fuchsberger, C., Gao, H., Germain, M., Gordon, S. D., de Haan, H. G., Harris, S. E., Hofer, E., Huerta-Chagoya, A., Igartua, C., Jansen, I. E., Jia, Y., Kacprowski, T., Karlsson, T., Kleber, M. E., Li, S. A., Li-Gao, R., Mahajan, A., Matsuda, K., Meidtner, K., Meng, W., Montasser, M. E., van der Most, P. J., Munz, M., Nutile, T., Palviainen, T., Prasad, G., Prasad, R. B., Priyanka, T. D. S., Rizzi, F., Salvi, E., Sapkota, B. R., Shriner, D., Skotte, L., Smart, M. C., Smith, A. V., van der Spek, A., Spracklen, C. N., Strawbridge, R. J., Tajuddin, S. M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H. R., Wootton, R. E., Yanek, L. R., Yao, J., Yousri, N. A., Zhao, W., Adeyemo, A. A., Afaq, S., Aguilar-Salinas, C. A., Akiyama, M., Albert, M. L., Allison, M. A., Alver, M., Aung, T., Azizi, F., Bentley, A. R., Boeing, H., Boerwinkle, E., Borja, J. B., de Borst, G. J., Bottinger, E. P., Broer, L., Campbell, H., Chanock, S., Chee, M. -L., Chen, G., Chen, Y. -D. I., Chen, Z., Chiu, Y. -F., Cocca, M., Collins, F. S., Concas, M. P., Corley, J., Cugliari, G., van Dam, R. M., Damulina, A., Daneshpour, M. S., Day, F. R., Delgado, G. E., Dhana, K., Doney, A. S. F., Dorr, M., Doumatey, A. P., Dzimiri, N., Ebenesersdottir, S. S., Elliott, J., Elliott, P., Ewert, R., Felix, J. F., Fischer, K., Freedman, B. I., Girotto, G., Goel, A., Gogele, M., Goodarzi, M. O., Graff, M., Granot-Hershkovitz, E., Grodstein, F., Guarrera, S., Gudbjartsson, D. F., Guity, K., Gunnarsson, B., Guo, Y., Hagenaars, S. P., Haiman, C. A., Halevy, A., Harris, T. B., Hedayati, M., van Heel, D. A., Hirata, M., Hofer, I., Hsiung, C. A., Huang, J., Hung, Y. -J., Ikram, M. A., Jagadeesan, A., Jousilahti, P., Kamatani, Y., Kanai, M., Kerrison, N. D., Kessler, T., Khaw, K. -T., Khor, C. C., de Kleijn, D. P. V., Koh, W. -P., Kolcic, I., Kraft, P., Kramer, B. K., Kutalik, Z., Kuusisto, J., Langenberg, C., Launer, L. J., Lawlor, D. A., Lee, I. -T., Lee, W. -J., Lerch, M. M., Li, L., Liu, J., Loh, M., London, S. J., Loomis, S., Lu, Y., Luan, J., Magi, R., Manichaikul, A. W., Manunta, P., Masson, G., Matoba, N., Mei, X. W., Meisinger, C., Meitinger, T., Mezzavilla, M., Milani, L., Millwood, I. Y., Momozawa, Y., Moore, A., Morange, P. -E., Moreno-Macias, H., Mori, T. A., Morrison, A. C., Muka, T., Murakami, Y., Murray, A. D., de Mutsert, R., Mychaleckyj, J. C., Nalls, M. A., Nauck, M., Neville, M. J., Nolte, I. M., Ong, K. K., Orozco, L., Padmanabhan, S., Palsson, G., Pankow, J. S., Pattaro, C., Pattie, A., Polasek, O., Poulter, N., Pramstaller, P. P., Quintana-Murci, L., Raikkonen, K., Ralhan, S., Rao, D. C., van Rheenen, W., Rich, S. S., Ridker, P. M., Rietveld, C. A., Robino, A., van Rooij, F. J. A., Ruggiero, D., Saba, Y., Sabanayagam, C., Sabater-Lleal, M., Sala, C. F., Salomaa, V., Sandow, K., Schmidt, H., Scott, L. J., Scott, W. R., Sedaghati-Khayat, B., Sennblad, B., van Setten, J., Sever, P. J., Sheu, W. H. -H., Shi, Y., Shrestha, S., Shukla, S. R., Sigurdsson, J. K., Sikka, T. T., Singh, J. R., Smith, B. H., Stancakova, A., Stanton, A., Starr, J. M., Stefansdottir, L., Straker, L., Sulem, P., Sveinbjornsson, G., Swertz, M. A., Taylor, A. M., Taylor, K. D., Terzikhan, N., Tham, Y. -C., Thorleifsson, G., Thorsteinsdottir, U., Tillander, A., Tracy, R. P., Tusie-Luna, T., Tzoulaki, I., Vaccargiu, S., Vangipurapu, J., Veldink, J. H., Vitart, V., Volker, U., Vuoksimaa, E., Wakil, S. M., Waldenberger, M., Wander, G. S., Wang, Y. X., Wareham, N. J., Wild, S., Yajnik, C. S., Yuan, J. -M., Zeng, L., Zhang, L., Zhou, J., Amin, N., Asselbergs, F. W., Bakker, S. J. L., Becker, D. M., Lehne, B., Bennett, D. A., van den Berg, L. H., Berndt, S. I., Bharadwaj, D., Bielak, L. F., Bochud, M., Boehnke, M., Bouchard, C., Bradfield, J. P., Brody, J. A., Campbell, A., Carmi, S., Caulfield, M. J., Cesarini, D., Chambers, J. C., Chandak, G. R., Cheng, C. -Y., Ciullo, M., Cornelis, M., Cusi, D., Smith, G. D., Deary, I. J., Dorajoo, R., van Duijn, C. M., Ellinghaus, D., Erdmann, J., Eriksson, J. G., Evangelou, E., Evans, M. K., Faul, J. D., Feenstra, B., Feitosa, M., Foisy, S., Franke, A., Friedlander, Y., Gasparini, P., Gieger, C., Gonzalez, C., Goyette, P., Grant, S. F. A., Griffiths, L. R., Groop, L., Gudnason, V., Gyllensten, U., Hakonarson, H., Hamsten, A., van der Harst, P., Heng, C. -K., Hicks, A. A., Hochner, H., Huikuri, H., Hunt, S. C., Jaddoe, V. W. V., De Jager, P. L., Johannesson, M., Johansson, A., Jonas, J. B., Jukema, J. W., Junttila, J., Kaprio, J., Kardia, S. L. R., Karpe, F., Kumari, M., Laakso, M., van der Laan, S. W., Lahti, J., Laudes, M., Lea, R. A., Lieb, W., Lumley, T., Martin, N. G., Marz, W., Matullo, G., Mccarthy, M. I., Medland, S. E., Merriman, T. R., Metspalu, A., Meyer, B. F., Mohlke, K. L., Montgomery, G. W., Mook-Kanamori, D., Munroe, P. B., North, K. E., Nyholt, D. R., O'Connell, J. R., Ober, C., Oldehinkel, A. J., Palmas, W., Palmer, C., Pasterkamp, G. G., Patin, E., Pennell, C. E., Perusse, L., Peyser, P. A., Pirastu, M., Polderman, T. J. C., Porteous, D. J., Posthuma, D., Psaty, B. M., Rioux, J. D., Rivadeneira, F., Rotimi, C., Rotter, J. I., Rudan, I., Den Ruijter, H. M., Sanghera, D. K., Sattar, N., Schmidt, R., Schulze, M. B., Schunkert, H., Scott, R. A., Shuldiner, A. R., Sim, X., Small, N., Smith, J. A., Sotoodehnia, N., Tai, E. -S., Teumer, A., Timpson, N. J., Toniolo, D., Tregouet, D. -A., Tuomi, T., Vollenweider, P., Wang, C. A., Weir, D. R., Whitfield, J. B., Wijmenga, C., Wong, T. -Y., Wright, J., Yang, J., Yu, L., Zemel, B. S., Zonderman, A. B., Perola, M., Magnusson, P. K. E., Uitterlinden, A. G., Kooner, J. S., Chasman, D. I., Loos, R. J. F., Franceschini, N., Franke, L., Haley, C. S., Hayward, C., Walters, R. G., Perry, J. R. B., Esko, T., Helgason, A., Stefansson, K., Joshi, P. K., Kubo, M., Wilson, J. 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[0000-0002-3352-4500], Cocca, Massimiliano [0000-0002-1127-7596], Collins, Francis S [0000-0002-1023-7410], Cugliari, Giovanni [0000-0002-6080-0718], Damulina, Anna [0000-0001-8241-2727], Day, Felix R [0000-0003-3789-7651], Dhana, Klodian [0000-0002-6397-7009], Dzimiri, Nduna [0000-0003-3395-5754], Elliott, Paul [0000-0002-7511-5684], Felix, Janine F [0000-0002-9801-5774], Freedman, Barry I [0000-0003-0275-5530], Girotto, Giorgia [0000-0003-4507-6589], Goel, Anuj [0000-0003-2307-4021], Goodarzi, Mark O [0000-0001-6364-5103], Gudbjartsson, Daniel F [0000-0002-5222-9857], Guity, Kamran [0000-0002-8379-9668], van Heel, David A [0000-0002-0637-2265], Hirata, Makoto [0000-0002-9994-9958], Ikram, M Arfan [0000-0003-0372-8585], Kamatani, Yoichiro [0000-0001-8748-5597], Kanai, Masahiro [0000-0001-5165-4408], Khor, Chiea Chuen [0000-0002-1128-4729], Kolcic, Ivana [0000-0001-7918-6052], Langenberg, Claudia [0000-0002-5017-7344], Lawlor, Deborah A [0000-0002-6793-2262], Liu, Jianjun [0000-0002-3255-3019], London, Stephanie J [0000-0003-4911-5290], Luan, Jian’an [0000-0003-3137-6337], Matoba, Nana [0000-0001-5329-0134], Mei, Xue W [0000-0002-6279-4884], Mezzavilla, Massimo [0000-0002-9000-4595], Milani, Lili [0000-0002-5323-3102], Mori, Trevor A [0000-0002-5264-9229], Murakami, Yoshinori [0000-0002-2826-4396], Murray, Alison D [0000-0003-4915-4847], Mychaleckyj, Josyf C [0000-0003-2595-0005], Neville, Matt J [0000-0002-6004-5433], Nolte, Ilja M [0000-0001-5047-4077], Ong, Ken K [0000-0003-4689-7530], Pálsson, Gunnar [0000-0002-8231-3961], Pankow, James S [0000-0001-7076-483X], Pattaro, Cristian [0000-0002-4119-0109], Quintana-Murci, Lluis [0000-0003-2429-6320], van Rheenen, Wouter [0000-0002-5860-1533], Rich, Stephen S [0000-0003-3872-7793], Rietveld, Cornelius A [0000-0003-4053-1861], Ruggiero, Daniela [0000-0003-3898-7827], Sabanayagam, Charumathi [0000-0002-4042-4719], Sabater-Lleal, Maria [0000-0002-0128-379X], Sala, Cinzia Felicita [0000-0003-2514-2075], 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Mark J [0000-0001-9295-3594], Smith, George Davey [0000-0002-1407-8314], Dorajoo, Rajkumar [0000-0001-6608-2051], Ellinghaus, David [0000-0002-4332-6110], Erdmann, Jeanette [0000-0002-4486-6231], Evangelou, Evangelos [0000-0002-5488-2999], Feenstra, Bjarke [0000-0003-1478-649X], Feitosa, Mary [0000-0002-0933-2410], Franke, Andre [0000-0003-1530-5811], Grant, Struan F A [0000-0003-2025-5302], Griffiths, Lyn R [0000-0002-6774-5475], Groop, Leif [0000-0002-0187-3263], Gudnason, Vilmundur [0000-0001-5696-0084], van der Harst, Pim [0000-0002-2713-686X], Heng, Chew-Kiat [0000-0002-7309-9473], Hicks, Andrew A [0000-0001-6320-0411], Jaddoe, Vincent W V [0000-0003-2939-0041], De Jager, Philip L [0000-0002-8057-2505], Johannesson, Magnus [0000-0001-8759-6393], Johansson, Åsa [0000-0002-2915-4498], Jonas, Jost B [0000-0003-2972-5227], Jukema, J Wouter [0000-0002-3246-8359], Kaprio, Jaakko [0000-0002-3716-2455], Laakso, Markku [0000-0002-3394-7749], van der Laan, Sander W [0000-0001-6888-1404], Lahti, Jari [0000-0002-4310-5297], Martin, Nicholas G [0000-0003-4069-8020], Medland, Sarah E [0000-0003-1382-380X], Merriman, Tony R [0000-0003-0844-8726], Metspalu, Andres [0000-0002-3718-796X], Mohlke, Karen L [0000-0001-6721-153X], Montgomery, Grant W [0000-0002-4140-8139], Munroe, Patricia B [0000-0002-4176-2947], Nyholt, Dale R [0000-0001-7159-3040], Ober, Carole [0000-0003-4626-9809], Oldehinkel, Albertine J [0000-0003-3925-3913], Palmer, Colin [0000-0002-6415-6560], Perusse, Louis [0000-0001-6440-9698], Polderman, Tinca J. C. [0000-0001-5564-301X], Porteous, David J [0000-0003-1249-6106], Rioux, John D [0000-0001-7560-8326], Rivadeneira, Fernando [0000-0001-9435-9441], Rotimi, Charles [0000-0001-5759-053X], Rotter, Jerome I [0000-0001-7191-1723], Rudan, Igor [0000-0001-6993-6884], Sattar, Naveed [0000-0002-1604-2593], Sim, Xueling [0000-0002-1233-7642], Smith, Jennifer A [0000-0002-3575-5468], Teumer, Alexander [0000-0002-8309-094X], Timpson, Nicholas J [0000-0002-7141-9189], Tuomi, Tiinamaija [0000-0002-8306-6202], Wang, Carol A [0000-0002-4301-3974], Weir, David R [0000-0002-1661-2402], Whitfield, John B [0000-0002-1103-0876], Magnusson, Patrik K. E. [0000-0002-7315-7899], Uitterlinden, André G [0000-0002-7276-3387], Loos, Ruth J. F. [0000-0002-8532-5087], Franke, Lude [0000-0002-5159-8802], Haley, Chris S [0000-0002-9811-0210], Hayward, Caroline [0000-0002-9405-9550], Walters, Robin G [0000-0002-9179-0321], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Apollo - University of Cambridge Repository, Moore, Kristjan HS [0000-0002-9579-4362], Luan, Jian'an [0000-0003-3137-6337], Grant, Struan FA [0000-0003-2025-5302], Jaddoe, Vincent WV [0000-0003-2939-0041], Polderman, Tinca JC [0000-0001-5564-301X], Magnusson, Patrik KE [0000-0002-7315-7899], Loos, Ruth JF [0000-0002-8532-5087], Neurology, Human genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Stem Cell Aging Leukemia and Lymphoma (SALL), Institute for Molecular Medicine Finland, Department of Psychology and Logopedics, University Management, Developmental Psychology Research Group, Staff Services, Cognitive and Brain Aging, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Clinicum, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Genetic Epidemiology, Helsinki Collegium for Advanced Studies, HUS Abdominal Center, Endokrinologian yksikkö, Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Trieste, Université de Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], University of Oxford [Oxford], Medical Genetics, Dept. RSD and Public Health, IRCCS-Burlo Garofolo/University of Trieste, sans affiliation, Helmholtz-Zentrum München (HZM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Cardiovascular Science, University College London, Hammersmith Hospital NHS Imperial College Healthcare-Imperial College London, Universität zu Lübeck [Lübeck], University of Ioannina Medical School, Università degli studi di Napoli Federico II-RISSC-Lab, Universität Heidelberg [Heidelberg], University of Turin, University of California-University of California, Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Université de Nantes (UN)-Université de Rennes 1 (UR1), Erasmus MC other, Internal Medicine, and Applied Economics
- Subjects
0301 basic medicine ,631/208/1397 ,Chemistry(all) ,Health Status ,[SDV]Life Sciences [q-bio] ,LOCI ,General Physics and Astronomy ,MESH: Haplotype ,MESH: Cognition ,030105 genetics & heredity ,Runs of Homozygosity ,Biochemistry ,Consanguinity ,Cognition ,Inbreeding depression ,2.1 Biological and endogenous factors ,Body Size ,Inbreeding ,Skyldleikarækt ,Aetiology ,Human phenotypes ,lcsh:Science ,MESH: Health Status ,Genetics ,Multidisciplinary ,Inbreeding Depression ,Confounding ,Homozygote ,RUNS ,631/208/205 ,631/208/721 ,3. Good health ,genomic inbreeding coefficients ,MESH: Risk-Taking ,631/208/730 ,Autozygosit ,homozygosity ,Erfðarannsóknir ,Medical Genetics ,genomic inbreeding coefficient ,MESH: Homozygote ,Offspring ,Science ,Autozygosity ,Blóðsifjar ,610 Medicine & health ,Biology ,INBREEDING DEPRESSION ,HOMOZYGOSITY ,FERTILITY ,QUANTIFICATION ,Physics and Astronomy(all) ,General Biochemistry, Genetics and Molecular Biology ,Article ,Association ,03 medical and health sciences ,Risk-Taking ,360 Social problems & social services ,Journal Article ,Humans ,ddc:610 ,Allele ,Alleles ,Medicinsk genetik ,Genetic association study ,MESH: Consanguinity ,MESH: Body Size ,MESH: Humans ,Biochemistry, Genetics and Molecular Biology(all) ,MESH: Alleles ,Haplotype ,MESH: Fertility ,General Chemistry ,Brain Disorders ,MESH: Inbreeding Depression ,030104 developmental biology ,Fertility ,Haplotypes ,Genetic markers ,lcsh:Q ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,3111 Biomedicine ,Genetics and Molecular Biology(all) - Abstract
Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.
- Published
- 2019
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49. A peridomestic Aedes malayensis population in Singapore can transmit yellow fever virus
- Author
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Anna-Bella Failloux, Cheong H. Tan, Lee C. Ng, Stéphanie Dabo, Paul T. Brey, Julien Pompon, Fabien Aubry, Sébastien Marcombe, Ian H. Mendenhall, Louis Lambrechts, Elliott F. Miot, Interactions Virus-Insectes - Insect-Virus Interactions (IVI), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur du Laos, Réseau International des Instituts Pasteur (RIIP), Duke-NUS Medical School [Singapore], Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), EFM was supported by a Calmette and Yersin doctoral fellowship of the Institut Pasteur International Network. This work was funded by Agence Nationale de la Recherche (grant ANR-17-ERC2-0016-01 to LL), the French Government’s Investissement d’Avenir program Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases (grant ANR-10-LABX-62-IBEID to LL), the European Union’s Horizon 2020 research and innovation program under ZikaPLAN grant agreement no. 734584 (to LL), and the City of Paris Emergence(s) program in Biomedical Research (to LL)., We thank Catherine Lallemand for assistance with mosquito rearing and three anonymous reviewers for constructive comments on an earlier version of the manuscript. We are grateful to the blood donor volunteers for participation in this study and the ICAReB staff for its support. We thank the National Park Board Singapore for their permission to collect in their parks and Jeffrey C. Hertz for his support and advice with the mosquito collections., ANR-17-ERC2-0016,GxG,Base génétique de la spécificité génotype-génotype dans l'interaction naturelle entre un virus et son insecte vecteur(2017), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 734584,ZikaPLAN, and Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris]
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RNA viruses ,0301 basic medicine ,Viral vectors ,Physiology ,RC955-962 ,Disease Vectors ,Pathology and Laboratory Medicine ,medicine.disease_cause ,Mosquitoes ,Dengue fever ,Geographical Locations ,0302 clinical medicine ,Aedes aegypti ,Aedes ,Arctic medicine. Tropical medicine ,Medicine and Health Sciences ,Chikungunya ,education.field_of_study ,Singapore ,biology ,Yellow fever ,Eukaryota ,Body Fluids ,3. Good health ,Insects ,Infectious Diseases ,Blood ,Medical Microbiology ,Viral Pathogens ,Host-Pathogen Interactions ,Viruses ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Female ,Public aspects of medicine ,RA1-1270 ,Yellow fever virus ,Anatomy ,Pathogens ,Chikungunya virus ,Research Article ,Asia ,Arthropoda ,Alphaviruses ,030231 tropical medicine ,Population ,Zoology ,Mosquito Vectors ,Microbiology ,Arbovirus ,Togaviruses ,03 medical and health sciences ,Virology ,Yellow Fever ,Infectious disease control ,medicine ,Animals ,Humans ,Saliva ,education ,Microbial Pathogens ,Organisms ,Public Health, Environmental and Occupational Health ,Biology and Life Sciences ,Outbreak ,medicine.disease ,biology.organism_classification ,Invertebrates ,Insect Vectors ,Species Interactions ,030104 developmental biology ,Vector (epidemiology) ,People and Places ,Viral Transmission and Infection ,Arboviruses - Abstract
The case-fatality rate of yellow fever virus (YFV) is one of the highest among arthropod-borne viruses (arboviruses). Although historically, the Asia-Pacific region has remained free of YFV, the risk of introduction has never been higher due to the increasing influx of people from endemic regions and the recent outbreaks in Africa and South America. Singapore is a global hub for trade and tourism and therefore at high risk for YFV introduction. Effective control of the main domestic mosquito vector Aedes aegypti in Singapore has failed to prevent re-emergence of dengue, chikungunya and Zika viruses in the last two decades, raising suspicions that peridomestic mosquito species untargeted by domestic vector control measures may contribute to arbovirus transmission. Here, we provide empirical evidence that the peridomestic mosquito Aedes malayensis found in Singapore can transmit YFV. Our laboratory mosquito colony recently derived from wild Ae. malayensis in Singapore was experimentally competent for YFV to a similar level as Ae. aegypti controls. In addition, we captured Ae. malayensis females in one human-baited trap during three days of collection, providing preliminary evidence that host-vector contact may occur in field conditions. Finally, we detected Ae. malayensis eggs in traps deployed in high-rise building areas of Singapore. We conclude that Ae. malayensis is a competent vector of YFV and re-emphasize that vector control methods should be extended to target peridomestic vector species., Author summary Yellow fever is a dreadful disease caused by a mosquito-borne virus circulating in Africa and South America. Historically, the Asia-Pacific region has remained free of yellow fever but the ever increasing influx of travelers puts places such as Singapore at unprecedented risk of yellow fever virus introduction. The present study characterized the potential contribution of a mosquito species called Aedes malayensis to yellow fever virus transmission in Singapore. Aedes malayensis breeds in urban parks of Singapore and is suspected to have participated in the resurgence of other mosquito-borne diseases such as dengue because it is not targeted by current mosquito control measures. Not only was Ae. malayensis able to experimentally acquire and transmit yellow fever virus, but it was also found to engage in contact with humans in a field situation. This empirical evidence indicates that Ae. malayensis is a competent vector of yellow fever virus and should be targeted by mosquito control programs.
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- 2019
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50. Phylogenetic analysis revealed the co- circulation of four dengue virus serotypes in Southern Thailand
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Hamel, Rodolphe, Surasombatpattana, Pornapat, Wichit, Sineewanlaya, Dauvé, Alexandra, Donato, Celeste, Pompon, Julien, Vijaykrishna, Dhanasekaran, Liegeois, Florian, Vargas, Ronald Morales, Luplertlop, Natthanej, Missé, Dorothée, Interhuman Arbovirus Transmission (MIVEGEC-iHAT), Biologie des infections virales: Emergence, DIFfusion, Impact, Contrôle, Elimination (EDIFICE), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Mahidol University [Bangkok], Prince of Songkla University (PSU), Monash University [Clayton], Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Duke-NUS Medical School [Singapore], Zoonoses virales et MTN (MIVEGEC-VIROZ), and ANR-16-IDEX-0006,MUSE,MUSE(2016)
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RNA viruses ,Male ,viruses ,Pathology and Laboratory Medicine ,Polymerase Chain Reaction ,Geographical Locations ,Dengue ,Database and Informatics Methods ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Medicine and Health Sciences ,Child ,Phylogeny ,Data Management ,Geography ,Reverse Transcriptase Polymerase Chain Reaction ,virus diseases ,Phylogenetic Analysis ,Genomics ,Middle Aged ,Thailand ,Phylogenetics ,Phylogeography ,Biogeography ,Medical Microbiology ,Viral Pathogens ,Viruses ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,Medicine ,Female ,Pathogens ,Sequence Analysis ,Research Article ,Adult ,Computer and Information Sciences ,Multiple Alignment Calculation ,Asia ,Adolescent ,Genotype ,Bioinformatics ,Science ,Sequence Databases ,Research and Analysis Methods ,Serogroup ,Microbiology ,Computational Techniques ,Genetics ,Humans ,Evolutionary Systematics ,Microbial Pathogens ,Taxonomy ,Evolutionary Biology ,Sequence Assembly Tools ,Biology and life sciences ,Flaviviruses ,Population Biology ,Ecology and Environmental Sciences ,Organisms ,Computational Biology ,Dengue Virus ,biochemical phenomena, metabolism, and nutrition ,Genome Analysis ,Split-Decomposition Method ,Coculture Techniques ,Biological Databases ,People and Places ,Earth Sciences ,Population Genetics - Abstract
International audience; Dengue fever is caused by dengue viruses (DENV) from the Flavivirus genus and is the most prevalent arboviral disease. DENV exists in four immunogenically distinct and genetically related serotypes (DENV-1 to 4), each subdivided in genotypes. Despite the endemic-ity of all four DENV serotypes in Thailand, no prior study has characterized the circulation of DENV in the southern provinces of the country. To determine the genetic diversity of DENV circulating in Southern Thailand in 2015 and 2016, we investigated 46 viruses from 182 patients' sera confirmed positive for DENV by serological and Nested RT-PCR tests. Our dataset included 2 DENV-1, 20 DENV-2, 9 DENV-3 and 15 DENV-4. Phylogenetic analysis was performed on viral envelop sequences. This revealed that part of the identified genotypes from DENV-1 and DENV-4 had been predominant in Asia (genotype I for both sero-types), while genotype II for DENV-4 and the Cosmopolitan genotype DENV-2 were also circulating. Whereas DENV-3 genotype II had been predominantly detected in South East Asia during the previous decades, we found genotype III and genotype I in Southern Thai-land. All DENV genotype identified in this study were closely related to contemporary strains circulating in Southeast Asian countries, emphasizing the regional circulation of DENV. These results provide new insights into the co-circulation of all four DENV serotypes in Southern Thailand, confirming the hyperendemicity of DENV in the region. These findings also suggest a new trend of dissemination for some DENV serotypes with a possible shift in genotype distribution; as recently observed in other Asian countries.
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- 2019
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