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5. RpoS contributes in a host-dependent manner to Salmonella colonization of the leaf apoplast during plant disease

Author

Lovelace, AH, Chen, H-C, Lee, S, Soufi, Z, Bota, P, Preston, GM, and Kvitko, BH

Subjects
Microbiology (medical), Microbiology
Abstract

Contaminated fresh produce has been routinely linked to outbreaks of Salmonellosis. Multiple studies have identified Salmonella enterica factors associated with successful colonization of diverse plant niches and tissues. It has also been well documented that S. enterica can benefit from the conditions generated during plant disease by host-compatible plant pathogens. In this study, we compared the capacity of two common S. enterica research strains, 14028s and LT2 (strain DM10000) to opportunistically colonize the leaf apoplast of two model plant hosts Arabidopsis thaliana and Nicotiana benthamiana during disease. While S. enterica 14028s benefited from co-colonization with plant-pathogenic Pseudomonas syringae in both plant hosts, S. enterica LT2 was unable to benefit from Pto co-colonization in N. benthamiana. Counterintuitively, LT2 grew more rapidly in ex planta N. benthamiana apoplastic wash fluid with a distinctly pronounced biphasic growth curve in comparison with 14028s. Using allelic exchange, we demonstrated that both the N. benthamiana infection-depedent colonization and apoplastic wash fluid growth phenotypes of LT2 were associated with mutations in the S. enterica rpoS stress-response sigma factor gene. Mutations of S. enterica rpoS have been previously shown to decrease tolerance to oxidative stress and alter metabolic regulation. We identified rpoS-dependent alterations in the utilization of L-malic acid, an abundant carbon source in N. benthamiana apoplastic wash fluid. We also present data consistent with higher relative basal reactive oxygen species (ROS) in N. benthamiana leaves than in A. thaliana leaves. The differences in basal ROS may explain the host-dependent disease co-colonization defect of the rpoS-mutated LT2 strain. Our results indicate that the conducive environment generated by pathogen modulation of the apoplast niche can vary from hosts to host even with a common disease-compatible pathogen.

Published
2022

6. 1368P TALAPRO-1: Talazoparib monotherapy in metastatic castration-resistant prostate cancer (mCRPC) with DNA damage response alterations (DDRm) – Exploration of tumor genetics associated with prolonged benefit

Author

de Bono, J.S., primary, Castro Marcos, E., additional, Laird, D.A., additional, Fizazi, K., additional, Dorff, T., additional, Zhao, S., additional, van Oort, I.M., additional, Gasparro, D., additional, Calabrò, F., additional, Pignata, S., additional, Geczi, L., additional, Barthelemy, P., additional, Kilari, D., additional, Hopkins, J.F., additional, Chen, H-C., additional, Healy, C.G., additional, Chelliserry, J., additional, Scagliotti, G.V., additional, and Mehra, N., additional

Published
2022
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7. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients (vol 12, 278, 2022)

Author

Schubert, KO, Thalamuthu, A, Amare, AT, Frank, J, Streit, F, Adl, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J-M, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Marie-Claire, C, Cearns, M, Cervantes, P, Chen, H-C, Chillotti, C, Cichon, S, Clark, SR, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Degenhardt, F, Del Zompo, M, DePaulo, JR, Etain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Heilbronner, U, Herms, S, Hoffmann, P, Hou, L, Hsu, Y-H, Jamain, S, Jimenez, E, Kahn, J-P, Kassem, L, Kuo, P-H, Kato, T, Kelsoe, J, Kittel-Schneider, S, Ferensztajn-Rochowiak, E, Konig, B, Kusumi, I, Laje, G, Landen, M, Lavebratt, C, Leboyer, M, Leckband, SG, Maj, M, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nothen, MM, Novak, T, O'Donovan, C, Ozaki, N, Osby, U, Papiol, S, Pfennig, A, Pisanu, C, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shekhtman, T, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Tekola-Ayele, F, Tortorella, A, Turecki, G, Veeh, J, Vieta, E, Witt, SH, Roberts, G, Zandi, PP, Alda, M, Bauer, M, McMahon, FJ, Mitchell, PB, Schulze, TG, Rietschel, M, Baune, BT, Schubert, KO, Thalamuthu, A, Amare, AT, Frank, J, Streit, F, Adl, M, Akula, N, Akiyama, K, Ardau, R, Arias, B, Aubry, J-M, Backlund, L, Bhattacharjee, AK, Bellivier, F, Benabarre, A, Bengesser, S, Biernacka, JM, Birner, A, Marie-Claire, C, Cearns, M, Cervantes, P, Chen, H-C, Chillotti, C, Cichon, S, Clark, SR, Cruceanu, C, Czerski, PM, Dalkner, N, Dayer, A, Degenhardt, F, Del Zompo, M, DePaulo, JR, Etain, B, Falkai, P, Forstner, AJ, Frisen, L, Frye, MA, Fullerton, JM, Gard, S, Garnham, JS, Goes, FS, Grigoroiu-Serbanescu, M, Grof, P, Hashimoto, R, Hauser, J, Heilbronner, U, Herms, S, Hoffmann, P, Hou, L, Hsu, Y-H, Jamain, S, Jimenez, E, Kahn, J-P, Kassem, L, Kuo, P-H, Kato, T, Kelsoe, J, Kittel-Schneider, S, Ferensztajn-Rochowiak, E, Konig, B, Kusumi, I, Laje, G, Landen, M, Lavebratt, C, Leboyer, M, Leckband, SG, Maj, M, Manchia, M, Martinsson, L, McCarthy, MJ, McElroy, S, Colom, F, Mitjans, M, Mondimore, FM, Monteleone, P, Nievergelt, CM, Nothen, MM, Novak, T, O'Donovan, C, Ozaki, N, Osby, U, Papiol, S, Pfennig, A, Pisanu, C, Potash, JB, Reif, A, Reininghaus, E, Rouleau, GA, Rybakowski, JK, Schalling, M, Schofield, PR, Schweizer, BW, Severino, G, Shekhtman, T, Shilling, PD, Shimoda, K, Simhandl, C, Slaney, CM, Squassina, A, Stamm, T, Stopkova, P, Tekola-Ayele, F, Tortorella, A, Turecki, G, Veeh, J, Vieta, E, Witt, SH, Roberts, G, Zandi, PP, Alda, M, Bauer, M, McMahon, FJ, Mitchell, PB, Schulze, TG, Rietschel, M, and Baune, BT

Published
2022

8. P1187: END OF TREATMENT 18F FDG-PET/CT RESPONSE IS PROGNOSTIC FOR OVERALL AND PROGRESSION-FREE SURVIVAL IN PERIPHERAL T-CELL LYMPHOMA: RESULTS OF THE UK NCRI PHASE 2 RANDOMISED CHEMO-T TRIAL PET/CT SUBSTUDY

Author

Gleeson, M., primary, Arias, C., additional, Cunningham, D., additional, Peckitt, C., additional, Du, Y., additional, Hujairi, N., additional, To, Y. M., additional, Chen, H.-C., additional, Patel, S., additional, Chau, I., additional, Johnson, P., additional, Ardeshna, K. M., additional, Wotherspoon, A., additional, Attygalle, A., additional, Hawkes, E. A., additional, Macheta, M. P., additional, Collins, G. P., additional, Radford, J., additional, Forbes, A., additional, Hart, A., additional, Montoto, S., additional, McKay, P., additional, Benstead, K., additional, Morley, N., additional, Kalakonda, N., additional, Hasan, Y., additional, Turner, D., additional, and Chua, S., additional

Published
2022
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12. TALAPRO-3: A phase 3, double-blind, randomized study of enzalutamide (ENZA) plus talazoparib (TALA) vs placebo plus ENZA in patients (pts) with DDR gene mutated metastatic castration-sensitive prostate cancer (mCSPC)

Author

Agarwal, N., primary, Azad, A.A., additional, Fizazi, K., additional, Mateo, J., additional, Matsubara, N., additional, Shore, N.D., additional, Chakrabarti, J., additional, Chen, H.-C., additional, Lanzalone, S., additional, Niyazov, A., additional, and Saad, F., additional

Published
2021
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13. 645TiP TALAPRO-3: A phase III, double-blind, randomized study of enzalutamide (ENZA) plus talazoparib (TALA) vs placebo plus ENZA in patients (pts) with DDR gene mutated metastatic castration-sensitive prostate cancer (mCSPC)

Author

Agarwal, N., primary, Azad, A.A., additional, Mateo, J., additional, Shore, N.D., additional, Chakrabarti, J., additional, Chen, H-C., additional, Lanzalone, S., additional, Niyazov, A., additional, and Saad, F., additional

Published
2021
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15. 580P TALAPRO-1: Talazoparib (TALA) monotherapy in metastatic castration-resistant prostate cancer (mCRPC) with DNA damage response alterations (DDRm) - Exploration of non-DDR mutational landscape and potential associations with antitumor activity

Author

Mehra, N., primary, de Bono, J., additional, Laird, A.D., additional, Barthélémy, P., additional, Delva, R., additional, Dorff, T., additional, Maruzzo, M., additional, Stirling, A., additional, Machiels, J-P., additional, Dumez, H., additional, Renard, V., additional, Hopkins, J., additional, Albacker, L.A., additional, Chen, H-C., additional, Healy, C., additional, Chelliserry, J., additional, van Oort, I.M., additional, Scagliotti, G., additional, and Fizazi, K., additional

Published
2021
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17. Using vendor management inventory system for goods inventory management in IoT manufacturing.

Author

Fang, Xiaodong and Chen, H-C

Subjects
INVENTORY management systems, INVENTORY control, PRODUCTION management (Manufacturing), STOCK transfer, SUPPLY chains, PURCHASE orders
Abstract

The revolution in the digital economy is forcing the manufacturing industry to develop new business models to achieve operational excellence. Vendor Management Inventory (VMI) is a key measure, aimed at increasing supply chain efficiency and mitigating the bullwhip effects on the Internet of Things (IoT). The problems encountered by the manufacturing supplier are the difficulty of obtaining inventory information at the hub, and being unable to easily integrate relevant inventory information in the IoT. The proposed method is to implement an integrated Hub VMI system to solve the inventory problem. This case study aims to implement an all-in-one integrated Hub VMI in an electronic manufacturing business. This proposal has two models: one comprises an Stock Transfer Order (STO)/Sales Order (SO) structure in which the purchase order is accepted and the product is manufactured onsite; the other consists of a Purchase Order (PO)/SO structure, whereby the PO is accepted onsite but the product is manufactured at another site. This case study designs an intelligent Radio Frequency Identified (RFID) system to extract product information from an inventory, and to provide a product, as recommended by customer services. The result and the contributions of this research include inventory management operation enhancements, a reduction in the cost and the total execution time, a reduction in the response time for the benefit of the customer and an increase in system performance efficiency. [ABSTRACT FROM AUTHOR]

Published
2022
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20. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author

Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. Pearson, Stefan Ehrlich, Geòrgia Escaramís, Thomas Espeseth, Xavier Estivill, Anne Farmer, Angela Favaro, Krista Fischer, James A.B. Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Christopher S. Franklin, Giovanni Gambaro, Johanna Giuranna, Paola Giusti-Rodríquez, Fragiskos Gonidakis, Scott Gordon, Monica Gratacos Mayora, Sébastien Guillaume, Ken B. Hanscombe, Konstantinos Hatzikotoulas, Johannes Hebebrand, Sietske G. Helder, Anjali K. Henders, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, L. John Horwood, Christopher Hübel, Liselotte V. Petersen, Kirstin L. Purves, Anu Raevuori, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Filip Rybakowski, Paolo Santonastaso, André Scherag, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op ‘t Landt, Agnieszka Slopien, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar W. Steen, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Jennifer Jordan, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, Martin A. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Katherine M. Kirk, Lars Klareskog, Gun Peggy S. Knudsen, Janne T. Larsen, Stephanie Le Hellard, Virpi M. Leppä, Paul Lichtenstein, Bochao Danae Lin, Astri Lundervold, Jurjen Luykx, Mario Maj, Katrin Mannik, Sara Marsal, Garret D. Stuber, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Tracey D. Wade, Gudrun Wagner, Esther Walton, H. Erich Wichmann, Elisabeth Widen, Shuyang Yao, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Martin Jungkunz, Lydie Dietl, Cornelia E. Schwarze, Norbert Dahmen, Björn H. Schott, Arian Mobascher, Silvia Crivelli, Michelle F. Dennis, Phillip D. Harvey, Bruce W. Carter, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Maren K. Olsen, John Pestian, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Jean Beckham, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James Breeling, Grant Huang, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, Mihaela Aslan, Todd Connor, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Clement J. Zablocki, Jeffrey Whittle, Frank Jacono, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Douglas Ivins, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Florez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Scott Sherman, George Ross, Philip Tsao, Patrick Strollo, Edward Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Robert Striker, Dietl, Lydie, Schwarze, Cornelia E., Dahmen, Norbert, Schott, Björn H., Nöthen, Markus M., Ripke, Stephan, Mobascher, Arian, Rujescu, Dan, Lieb, Klaus, Roepke, Stefan, Schmahl, Christian, Bohus, Martin, Rietschel, Marcella, Crivelli, Silvia, Dennis, Michelle F., Harvey, Phillip D., Carter, Bruce W., Huffman, Jennifer E., Jacobson, Daniel, Madduri, Ravi, Olsen, Maren K., Pestian, John, Gaziano, J. Michael, Muralidhar, Sumitra, Ramoni, Rachel, Beckham, Jean, Chang, Kyong-Mi, O'Donnell, Christopher J., Tsao, Philip S., Breeling, James, Huang, Grant, Romero, J. P. Casas, Moser, Jennifer, Whitbourne, Stacey B., Brewer, Jessica V., Aslan, Mihaela, Connor, Todd, Argyres, Dean P., Stephens, Brady, Brophy, Mary T., Humphries, Donald E., Selva, Luis E., Do, Nhan, Shayan, Shahpoor, Cho, Kelly, Pyarajan, Saiju, Hauser, Elizabeth, Sun, Yan, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Mattocks, Kristin, Harley, John, Zablocki, Clement J., Whittle, Jeffrey, Jacono, Frank, Gutierrez, Salvador, Gibson, Gretchen, Hammer, Kimberly, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Mathew, Roy, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Ivins, Douglas, Mastorides, Stephen, Moorman, Jonathan, Gappy, Saib, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Okusaga, Olaoluwa, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Tandon, Neeraj, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Liangpunsakul, Suthat, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Constans, Joseph, Meyer, Paul, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Gaddy, Melinda, Wallbom, Agnes, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Ross, George, Tsao, Philip, Strollo, Patrick, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Huq, Mostaqul, Fayad, Joseph, Hung, Adriana, Lichy, Jack, Hurley, Robin, Robey, Brooks, Striker, Robert, Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R. I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A. F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Penninx, Brenda W. J. H., Perlis, Roy H., Porteous, David J., Potash, James B., Preisig, Martin, Schaefer, Catherine, Schulze, Thomas G., Smoller, Jordan W., Stefansson, Kari, Tiemeier, Henning, Uher, Rudolf, Völzke, Henry, Weissman, Myrna M., Werge, Thomas, Lewis, Cathryn M., Levinson, Douglas F., Breen, Gerome, Børglum, Anders D., Sullivan, Patrick F., O'Connell, Kevin S., Coombes, Brandon, Qiao, Zhen, Als, Thomas D., Børte, Sigrid, Charney, Alexander W., Drange, Ole Kristian, Gandal, Michael J., Hagenaars, Saskia P., Ikeda, Masashi, Kamitaki, Nolan, Kim, Minsoo, Krebs, Kristi, Panagiotaropoulou, Georgia, Schilder, Brian M., Sloofman, Laura G., Winsvold, Bendik S., Won, Hong-Hee, Abramova, Liliya, Adorjan, Kristina, Al Eissa, Mariam, Albani, Diego, Alliey-Rodriguez, Ney, Anjorin, Adebayo, Antilla, Verneri, Antoniou, Anastasia, Awasthi, Swapnil, Baek, Ji Hyun, Bass, Nicholas, Bauer, Michael, Beins, Eva C., Bergen, Sarah E., Birner, Armin, Bøen, Erlend, Boks, Marco P., Bosch, Rosa, Brum, Murielle, Brumpton, Ben M., Brunkhorst-Kanaan, Nathalie, Budde, Monika, Byerley, William, Cairns, Murray, Casas, Miquel, Cervantes, Pablo, Cruceanu, Cristiana, Cuellar-Barboza, Alfredo, Cunningham, Julie, Curtis, David, Czerski, Piotr M., Dale, Anders M., Dalkner, Nina, David, Friederike S., Djurovic, Srdjan, Dobbyn, Amanda L., Douzenis, Athanassios, Elvsåshagen, Torbjørn, Ferrier, I. Nicol, Fiorentino, Alessia, Foroud, Tatiana M., Forty, Liz, Frei, Oleksandr, Freimer, Nelson B., Frisén, Louise, Gade, Katrin, Garnham, Julie, Gelernter, Joel, Gizer, Ian R., Gordon-Smith, Katherine, Greenwood, Tiffany A., Guzman-Parra, José, Ha, Kyooseob, Haraldsson, Magnus, Hautzinger, Martin, Heilbronner, Urs, Hellgren, Dennis, Holmans, Peter A., Huckins, Laura, Jamain, Stéphane, Johnson, Jessica S., Kalman, Janos L., Kamatani, Yoichiro, Kennedy, James L., Kittel-Schneider, Sarah, Kogevinas, Manolis, Koromina, Maria, Kranz, Thorsten M., Kranzler, Henry R., Kubo, Michiaki, Kupka, Ralph, Kushner, Steven A., Lavebratt, Catharina, Lawrence, Jacob, Leber, Markus, Lee, Heon-Jeong, Lee, Phil H., Levy, Shawn E., Lewis, Catrin, Liao, Calwing, Lundberg, Martin, Magnusson, Sigurdur H., Maihofer, Adam, Malaspina, Dolores, Maratou, Eirini, Martinsson, Lina, McGregor, Nathaniel W., McKay, James D., Medeiros, Helena, Millischer, Vincent, Moran, Jennifer L., Morris, Derek W., Mühleisen, Thomas W., O'Brien, Niamh, O'Donovan, Claire, Olde Loohuis, Loes M., Oruc, Lilijana, Papiol, Sergi, Pardiñas, Antonio F., Perry, Amy, Pfennig, Andrea, Porichi, Evgenia, Quested, Digby, Raj, Towfique, Rapaport, Mark H., Regeer, Eline J., Rivas, Fabio, Roth, Julian, Roussos, Panos, Ruderfer, Douglas M., Sánchez-Mora, Cristina, Senner, Fanny, Sharp, Sally, Shilling, Paul D., Sirignano, Lea, Slaney, Claire, Smeland, Olav B., Sobell, Janet L., Artigas, Maria Soler, Spijker, Anne T., Stein, Dan J., Strauss, John S., Świątkowska, Beata, Terao, Chikashi, Toma, Claudio, Tooney, Paul, Tsermpini, Evangelia-Eirini, Vawter, Marquis P., Vedder, Helmut, Walters, James T. R., Xi, Simon, Xu, Wei, Kay Yang, Jessica Mei, Young, Allan H., Young, Hannah, Zandi, Peter P., Zhou, Hang, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Babadjanova, Gulja, Backlund, Lena, Bellivier, Frank, Bengesser, Susanne, Berrettini, Wade H., Blackwood, Douglas H. R., Boehnke, Michael, Carr, Vaughan J., Catts, Stanley, Corvin, Aiden, Craddock, Nicholas, Dikeos, Dimitris, Etain, Bruno, Ferentinos, Panagiotis, Frye, Mark, Fullerton, Janice M., Gawlik, Micha, Gershon, Elliot S., Green, Melissa J., Grigoroiu-Serbanescu, Maria, Hauser, Joanna, Henskens, Frans, Hillert, Jan, Hong, Kyung Sue, Hultman, Christina M., Hveem, Kristian, Iwata, Nakao, Jablensky, Assen V., Kahn, René S., Kelsoe, John R., Kirov, George, Landén, Mikael, Leboyer, Marion, Lissowska, Jolanta, Lochner, Christine, Loughland, Carmel, Mathews, Carol A., Mayoral, Fermin, McElroy, Susan L., McMahon, Francis J., Melle, Ingrid, Michie, Patricia, Mitchell, Philip B., Morken, Gunnar, Mowry, Bryan, Myers, Richard M., Neale, Benjamin M., Nievergelt, Caroline M., Oedegaard, Ketil J., Olsson, Tomas, Pantelis, Chris, Pato, Carlos, Pato, Michele T., Patrinos, George P., Ramos-Quiroga, Josep Antoni, Reif, Andreas, Reininghaus, Eva Z., Ribasés, Marta, Rouleau, Guy A., Saito, Takeo, Schall, Ulrich, Schalling, Martin, Schofield, Peter R., Scott, Laura J., Scott, Rodney J., Serretti, Alessandro, Weickert, Cynthia Shannon, Stordal, Eystein, Turecki, Gustavo, Vaaler, Arne E., Vieta, Eduard, Vincent, John B., Waldman, Irwin D., Weickert, Thomas W., Zwart, John-Anker, Biernacka, Joanna M., Nurnberger, John I., Edenberg, Howard J., Stahl, Eli A., McQuillin, Andrew, Di Florio, Arianna, Ophoff, Roel A., Andreassen, Ole A., Adan, Roger A. H., Ando, Tetsuya, Aschauer, Harald, Baker, Jessica H., Bencko, Vladimir, Bergen, Andrew W., Birgegård, Andreas, Boden, Joseph M., Boehm, Ilka, Boni, Claudette, Perica, Vesna Boraska, Brandt, Harry, Buehren, Katharina, Bulik, Cynthia M., Burghardt, Roland, Carlberg, Laura, Cassina, Matteo, Clementi, Maurizio, Cone, Roger D., Courtet, Philippe, Crawford, Steven, Crow, Scott, Crowley, James J., Danner, Unna N., Davis, Oliver S. P., de Zwaan, Martina, Dedoussis, George, Degortes, Daniela, DeSocio, Janiece E., Dick, Danielle M., Dina, Christian, Dmitrzak-Weglarz, Monika, Martinez, Elisa Docampo, Duncan, Laramie E., Egberts, Karin, Marshall, Christian R., Mattingsdal, Morten, McDevitt, Sara, Meulenbelt, Ingrid, Micali, Nadia, Mitchell, James, Mitchell, Karen, Monteleone, Palmiero, Monteleone, Alessio Maria, Munn-Chernoff, Melissa A., Nacmias, Benedetta, Navratilova, Marie, Ntalla, Ioanna, Olsen, Catherine M., O'Toole, Julie K., Padyukov, Leonid, Palotie, Aarno, Pantel, Jacques, Papezova, Hana, Parker, Richard, Pearson, John F., Ehrlich, Stefan, Escaramís, Geòrgia, Espeseth, Thomas, Estivill, Xavier, Farmer, Anne, Favaro, Angela, Fernández-Aranda, Fernando, Fichter, Manfred M., Fischer, Krista, Floyd, James A. B., Föcker, Manuel, Foretova, Lenka, Forzan, Monica, Franklin, Christopher S., Gallinger, Steven, Gambaro, Giovanni, Giegling, Ina, Giuranna, Johanna, Giusti-Rodríquez, Paola, Gonidakis, Fragiskos, Gordon, Scott, Gorwood, Philip, Mayora, Monica Gratacos, Guillaume, Sébastien, Guo, Yiran, Hakonarson, Hakon, Halmi, Katherine A., Hanscombe, Ken B., Hatzikotoulas, Konstantinos, Hebebrand, Johannes, Helder, Sietske G., Henders, Anjali K., Herpertz-Dahlmann, Beate, Herzog, Wolfgang, Hinney, Anke, Horwood, L. John, Hübel, Christopher, Petersen, Liselotte V., Pinto, Dalila, Purves, Kirstin L., Raevuori, Anu, Ramoz, Nicolas, Reichborn-Kjennerud, Ted, Ricca, Valdo, Ripatti, Samuli, Ritschel, Franziska, Roberts, Marion, Rybakowski, Filip, Santonastaso, Paolo, Scherag, André, Scherer, Stephen W., Schmidt, Ulrike, Schork, Nicholas J., Schosser, Alexandra, Seitz, Jochen, Slachtova, Lenka, Slagboom, P. Eline, Slof-Op 't Landt, Margarita C. T., Slopien, Agnieszka, Soranzo, Nicole, Sorbi, Sandro, Southam, Lorraine, Steen, Vidar W., Strober, Michael, Huckins, Laura M., Hudson, James I., Imgart, Hartmut, Inoko, Hidetoshi, Janout, Vladimir, Jiménez-Murcia, Susana, Johnson, Craig, Jordan, Jennifer, Julià, Antonio, Kalsi, Gursharan, Kaminská, Deborah, Kaplan, Allan S., Kaprio, Jaakko, Karhunen, Leila, Karwautz, Andreas, Kas, Martien J. H., Kaye, Walter H., Kennedy, Martin A., Keski-Rahkonen, Anna, Kiezebrink, Kirsty, Kim, Youl-Ri, Kirk, Katherine M., Klareskog, Lars, Klump, Kelly L., Knudsen, Gun Peggy S., Larsen, Janne T., Le Hellard, Stephanie, Leppä, Virpi M., Li, Dong, Lichtenstein, Paul, Lilenfeld, Lisa, Lin, Bochao Danae, Lundervold, Astri, Luykx, Jurjen, Magistretti, Pierre J., Maj, Mario, Mannik, Katrin, Marsal, Sara, Stuber, Garret D., Szatkiewicz, Jin P., Tachmazidou, Ioanna, Tenconi, Elena, Thornton, Laura M., Tortorella, Alfonso, Tozzi, Federica, Treasure, Janet, Tsitsika, Artemis, Tyszkiewicz-Nwafor, Marta, Tziouvas, Konstantinos, van Elburg, Annemarie A., van Furth, Eric F., Wade, Tracey D., Wagner, Gudrun, Walton, Esther, Watson, Hunna J., Whiteman, David C., Wichmann, H. Erich, Widen, Elisabeth, Woodside, D. Blake, Yao, Shuyang, Yilmaz, Zeynep, Zeggini, Eleftheria, Zerwas, Stephanie, Zipfel, Stephan, Jungkunz, Martin, Mullins, N., Kang, J., Campos, A. I., Coleman, J. R. I., Edwards, A. C., Galfalvy, H., Levey, D. F., Lori, A., Shabalin, A., Starnawska, A., Su, M. -H., Watson, H. J., Adams, M., Awasthi, S., Gandal, M., Hafferty, J. D., Hishimoto, A., Kim, M., Okazaki, S., Otsuka, I., Ripke, S., Ware, E. B., Bergen, A. W., Berrettini, W. H., Bohus, M., Brandt, H., Chang, X., Chen, W. J., Chen, H. -C., Crawford, S., Crow, S., Diblasi, E., Duriez, P., Fernandez-Aranda, F., Fichter, M. M., Gallinger, S., Glatt, S. J., Gorwood, P., Guo, Y., Hakonarson, H., Halmi, K. A., Hwu, H. -G., Jain, S., Jamain, S., Jimenez-Murcia, S., Johnson, C., Kaplan, A. S., Kaye, W. H., Keel, P. K., Kennedy, J. L., Klump, K. L., Li, D., Liao, S. -C., Lieb, K., Lilenfeld, L., Liu, C. -M., Magistretti, P. J., Marshall, C. R., Mitchell, J. E., Monson, E. T., Myers, R. M., Pinto, D., Powers, A., Ramoz, N., Roepke, S., Rozanov, V., Scherer, S. W., Schmahl, C., Sokolowski, M., Strober, M., Thornton, L. M., Treasure, J., Tsuang, M. T., Witt, S. H., Woodside, D. B., Yilmaz, Z., Zillich, L., Adolfsson, R., Agartz, I., Air, T. M., Alda, M., Alfredsson, L., Andreassen, O. A., Anjorin, A., Appadurai, V., Soler Artigas, M., Van der Auwera, S., Azevedo, M. H., Bass, N., Bau, C. H. D., Baune, B. T., Bellivier, F., Berger, K., Biernacka, J. M., Bigdeli, T. B., Binder, E. B., Boehnke, M., Boks, M. P., Bosch, R., Braff, D. L., Bryant, R., Budde, M., Byrne, E. M., Cahn, W., Casas, M., Castelao, E., Cervilla, J. A., Chaumette, B., Cichon, S., Corvin, A., Craddock, N., Craig, D., Degenhardt, F., Djurovic, S., Edenberg, H. J., Fanous, A. H., Foo, J. C., Forstner, A. J., Frye, M., Fullerton, J. M., Gatt, J. M., Gejman, P. V., Giegling, I., Grabe, H. J., Green, M. J., Grevet, E. H., Grigoroiu-Serbanescu, M., Gutierrez, B., Guzman-Parra, J., Hamilton, S. P., Hamshere, M. L., Hartmann, A., Hauser, J., Heilmann-Heimbach, S., Hoffmann, P., Ising, M., Jones, I., Jones, L. A., Jonsson, L., Kahn, R. S., Kelsoe, J. R., Kendler, K. S., Kloiber, S., Koenen, K. C., Kogevinas, M., Konte, B., Krebs, M. -O., Landen, M., Lawrence, J., Leboyer, M., Lee, P. H., Levinson, D. F., Liao, C., Lissowska, J., Lucae, S., Mayoral, F., Mcelroy, S. L., Mcgrath, P., Mcguffin, P., Mcquillin, A., Medland, S. E., Mehta, D., Melle, I., Milaneschi, Y., Mitchell, P. B., Molina, E., Morken, G., Mortensen, P. B., Muller-Myhsok, B., Nievergelt, C., Nimgaonkar, V., Nothen, M. M., O'Donovan, M. C., Ophoff, R. A., Owen, M. J., Pato, C., Pato, M. T., Penninx, B. W. J. H., Pimm, J., Pistis, G., Potash, J. B., Power, R. A., Preisig, M., Quested, D., Ramos-Quiroga, J. A., Reif, A., Ribases, M., Richarte, V., Rietschel, M., Rivera, M., Roberts, A., Roberts, G., Rouleau, G. A., Rovaris, D. L., Rujescu, D., Sanchez-Mora, C., Sanders, A. R., Schofield, P. R., Schulze, T. G., Scott, L. J., Serretti, A., Shi, J., Shyn, S. I., Sirignano, L., Sklar, P., Smeland, O. B., Smoller, J. W., Sonuga-Barke, E. J. S., Spalletta, G., Strauss, J. S., Swiatkowska, B., Trzaskowski, M., Turecki, G., Vilar-Ribo, L., Vincent, J. B., Volzke, H., Walters, J. T. R., Shannon Weickert, C., Weickert, T. W., Weissman, M. M., Williams, L. M., Wray, N. R., Zai, C. C., Ashley-Koch, A. E., Beckham, J. C., Hauser, E. R., Hauser, M. A., Kimbrel, N. A., Lindquist, J. H., Mcmahon, B., Oslin, D. W., Qin, X., Mattheisen, M., Abdellaoui, A., Adams, M. J., Agerbo, E., Andlauer, T. F. M., Bacanu, S. -A., Baekvad-Hansen, M., Beekman, A. T. F., Bryois, J., Buttenschon, H. N., Bybjerg-Grauholm, J., Cai, N., Christensen, J. H., Clarke, T. -K., Colodro-Conde, L., Couvy-Duchesne, B., Crawford, G. E., Davies, G., Derks, E. M., Direk, N., Dolan, C. V., Dunn, E. C., Eley, T. C., Escott-Price, V., Hassan Kiadeh, F. F., Finucane, H. K., Frank, J., Gaspar, H. A., Gill, M., Goes, F. S., Gordon, S. D., Weinsheimer, S. M., Wellmann, J., Willemsen, G., Wu, Y., Xi, H. S., Yang, J., Zhang, F., Arolt, V., Boomsma, D. I., Dannlowski, U., Depaulo, J. 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A., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Kirk, K. M., Klareskog, L., Knudsen, G. P. S., Larsen, J. T., Le Hellard, S., Leppa, V. M., Lichtenstein, P., Lin, B. D., Lundervold, A., Luykx, J., Maj, M., Mannik, K., Marsal, S., Stuber, G. D., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wade, T. D., Wagner, G., Walton, E., Whiteman, D. C., Wichmann, H. E., Widen, E., Yao, S., Zeggini, E., Zerwas, S., Zipfel, S., Jungkunz, M., Dietl, L., Schwarze, C. E., Dahmen, N., Schott, B. H., Mobascher, A., Crivelli, S., Dennis, M. F., Harvey, P. D., Carter, B. W., Huffman, J. E., Jacobson, D., Madduri, R., Olsen, M. K., Pestian, J., Gaziano, J. M., Muralidhar, S., Ramoni, R., Beckham, J., Chang, K. -M., O'Donnell, C. J., Tsao, P. S., Breeling, J., Huang, G., Romero, J. P. C., Moser, J., Whitbourne, S. B., Brewer, J. V., Aslan, M., Connor, T., Argyres, D. P., Stephens, B., Brophy, M. T., Humphries, D. E., Selva, L. E., Do, N., Shayan, S., Cho, K., Pyarajan, S., Hauser, E., Sun, Y., Zhao, H., Wilson, P., Mcardle, R., Dellitalia, L., Mattocks, K., Harley, J., Zablocki, C. J., Whittle, J., Jacono, F., Gutierrez, S., Gibson, G., Hammer, K., Kaminsky, L., Villareal, G., Kinlay, S., Xu, J., Hamner, M., Mathew, R., Bhushan, S., Iruvanti, P., Godschalk, M., Ballas, Z., Ivins, D., Mastorides, S., Moorman, J., Gappy, S., Klein, J., Ratcliffe, N., Florez, H., Okusaga, O., Murdoch, M., Sriram, P., Yeh, S. S., Tandon, N., Jhala, D., Aguayo, S., Cohen, D., Sharma, S., Liangpunsakul, S., Oursler, K. A., Whooley, M., Ahuja, S., Constans, J., Meyer, P., Greco, J., Rauchman, M., Servatius, R., Gaddy, M., Wallbom, A., Morgan, T., Stapley, T., Sherman, S., Ross, G., Tsao, P., Strollo, P., Boyko, E., Meyer, L., Gupta, S., Huq, M., Fayad, J., Hung, A., Lichy, J., Hurley, R., Robey, B., Striker, R., Erlangsen, A., Kessler, R. C., Porteous, D., Ursano, R. J., Wasserman, D., Coon, H., Demontis, D., Docherty, A. R., Kuo, P. -H., Mann, J. J., Renteria, M. E., Stein, M. B., Willour, V., Psychiatry, Biological Psychology, APH - Methodology, APH - Mental Health, APH - Health Behaviors & Chronic Diseases, AMS - Sports, AMS - Ageing & Vitality, APH - Personalized Medicine, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Institute for Molecular Medicine Finland, Centre of Excellence in Complex Disease Genetics, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, HUS Psychiatry, Department of Public Health, Clinicum, Nuorisopsykiatria, Faculty Common Matters (Faculty of Social Sciences), Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Anna Keski-Rahkonen / Principal Investigator, Elisabeth Ingrid Maria Widen / Principal Investigator, Genomic Discoveries and Clinical Translation, Internal medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, Mullins N., Kang J., Campos A.I., Coleman J.R.I., Edwards 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Maratou E., Martinsson L., McGregor N.W., McKay J.D., Medeiros H., Millischer V., Moran J.L., Morris D.W., Muhleisen T.W., O'Brien N., O'Donovan C., Olde Loohuis L.M., Oruc L., Papiol S., Pardinas A.F., Perry A., Pfennig A., Porichi E., Raj T., Rapaport M.H., Regeer E.J., Rivas F., Roth J., Roussos P., Ruderfer D.M., Senner F., Sharp S., Shilling P.D., Slaney C., Sobell J.L., Artigas M.S., Spijker A.T., Stein D.J., Terao C., Toma C., Tooney P., Tsermpini E.-E., Vawter M.P., Vedder H., Xi S., Xu W., Kay Yang J.M., Young A.H., Young H., Zandi P.P., Zhou H., HUNT All-In Psychiatry, Babadjanova G., Backlund L., Bengesser S., Blackwood D.H.R., Carr V.J., Catts S., Dikeos D., Etain B., Ferentinos P., Gawlik M., Gershon E.S., Henskens F., Hillert J., Hong K.S., Hultman C.M., Hveem K., Iwata N., Jablensky A.V., Kirov G., Lochner C., Loughland C., Mathews C.A., McMahon F.J., Michie P., Mowry B., Neale B.M., Nievergelt C.M., Oedegaard K.J., Olsson T., Pantelis C., Patrinos G.P., Reininghaus E.Z., Saito T., Schall U., Schalling M., Scott R.J., Weickert C.S., Stordal E., Vaaler A.E., Vieta E., Waldman I.D., Zwart J.-A., Nurnberger J.I., Stahl E.A., Di Florio A., Adan R.A.H., Ando T., Aschauer H., Baker J.H., Bencko V., Birgegard A., Boden J.M., Boehm I., Boni C., Perica V.B., Buehren K., Bulik C.M., Burghardt R., Carlberg L., Cassina M., Clementi M., Cone R.D., Courtet P., Crowley J.J., Danner U.N., Davis O.S.P., de Zwaan M., Dedoussis G., Degortes D., DeSocio J.E., Dick D.M., Dina C., Dmitrzak-Weglarz M., Martinez E.D., Duncan L.E., Egberts K., Mattingsdal M., McDevitt S., Meulenbelt I., Micali N., Mitchell J., Mitchell K., Monteleone P., Monteleone A.M., Munn-Chernoff M.A., Nacmias B., Navratilova M., Ntalla I., Olsen C.M., O'Toole J.K., Padyukov L., Palotie A., Pantel J., Papezova H., Parker R., Pearson J.F., Ehrlich S., Escaramis G., Espeseth T., Estivill X., Farmer A., Favaro A., Fischer K., Floyd J.A.B., Focker M., Foretova L., Forzan M., Franklin C.S., Gambaro G., Giuranna J., Giusti-Rodriquez P., Gonidakis F., Gordon S., Mayora M.G., Guillaume S., Hanscombe K.B., Hatzikotoulas K., Hebebrand J., Helder S.G., Henders A.K., Herpertz-Dahlmann B., Herzog W., Hinney A., Horwood L.J., Hubel C., Petersen L.V., Purves K.L., Raevuori A., Reichborn-Kjennerud T., Ricca V., Ripatti S., Ritschel F., Roberts M., Rybakowski F., Santonastaso P., Scherag A., Schmidt U., Schork N.J., Schosser A., Seitz J., Slachtova L., Slagboom P.E., Slof-Op 't Landt M.C.T., Slopien A., Soranzo N., Sorbi S., Southam L., Steen V.W., Huckins L.M., Hudson J.I., Imgart H., Inoko H., Janout V., Jordan J., Julia A., Kalsi G., Kaminska D., Kaprio J., Karhunen L., Karwautz A., Kas M.J.H., Kennedy M.A., Keski-Rahkonen A., Kiezebrink K., Kim Y.-R., Kirk K.M., Klareskog L., Knudsen G.P.S., Larsen J.T., Le Hellard S., Leppa V.M., Lichtenstein P., Lin B.D., Lundervold A., Luykx J., Maj M., Mannik K., Marsal S., Stuber G.D., Szatkiewicz J.P., Tachmazidou I., Tenconi E., Tortorella A., Tozzi F., Tsitsika A., Tyszkiewicz-Nwafor M., Tziouvas K., van Elburg A.A., van Furth E.F., Wade T.D., Wagner G., Walton E., Whiteman D.C., Wichmann H.E., Widen E., Yao S., Zeggini E., Zerwas S., Zipfel S., Jungkunz M., Dietl L., Schwarze C.E., Dahmen N., Schott B.H., Mobascher A., Crivelli S., Dennis M.F., Harvey P.D., Carter B.W., Huffman J.E., Jacobson D., Madduri R., Olsen M.K., Pestian J., Gaziano J.M., Muralidhar S., Ramoni R., Beckham J., Chang K.-M., O'Donnell C.J., Tsao P.S., Breeling J., Huang G., Romero J.P.C., Moser J., Whitbourne S.B., Brewer J.V., Aslan M., Connor T., Argyres D.P., Stephens B., Brophy M.T., Humphries D.E., Selva L.E., Do N., Shayan S., Cho K., Pyarajan S., Hauser E., Sun Y., Zhao H., Wilson P., McArdle R., Dellitalia L., Mattocks K., Harley J., Zablocki C.J., Whittle J., Jacono F., Gutierrez S., Gibson G., Hammer K., Kaminsky L., Villareal G., Kinlay S., Xu J., Hamner M., Mathew R., Bhushan S., Iruvanti P., Godschalk M., Ballas Z., Ivins D., Mastorides S., Moorman J., Gappy S., Klein J., Ratcliffe N., Florez H., Okusaga O., Murdoch M., Sriram P., Yeh S.S., Tandon N., Jhala D., Aguayo S., Cohen D., Sharma S., Liangpunsakul S., Oursler K.A., Whooley M., Ahuja S., Constans J., Meyer P., Greco J., Rauchman M., Servatius R., Gaddy M., Wallbom A., Morgan T., Stapley T., Sherman S., Ross G., Tsao P., Strollo P., Boyko E., Meyer L., Gupta S., Huq M., Fayad J., Hung A., Lichy J., Hurley R., Robey B., Striker R., Erlangsen A., Kessler R.C., Porteous D., Ursano R.J., Wasserman D., Coon H., Demontis D., Docherty A.R., Kuo P.-H., Mann J.J., Renteria M.E., Stein M.B., and Willour V.

Subjects
LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract

Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551

Published
2022

22. Combining schizophrenia and depression polygenic risk scores improves the genetic prediction of lithium response in bipolar disorder patients

Author

Michael McCarthy, Claire O'Donovan, Urs Heilbronner, Ichiro Kusumi, Eduard Vieta, Liping Hou, Hsi-Chung Chen, Claire Slaney, Maria Grigoroiu-Serbanescu, Kazufumi Akiyama, Michael Bauer, Janusz K. Rybakowski, Frank Bellivier, Marion Leboyer, Katzutaka Shimoda, Palmiero Monteleone, Cristiana Cruceanu, Alessio Squassina, Stephanie H. Witt, Tadafumi Kato, Giovanni Severino, Alfonso Tortorella, J. Raymond DePaulo, Martin Alda, Louise Frisén, Mazda Adl, Martin Schalling, Per Hoffmann, Susan G. Leckband, Jean-Pierre Kahn, Jean-Michel Aubry, Francis J. McMahon, Sven Cichon, Alexandre Dayer, Tatyana Shekhtman, Franziska Degenhardt, James B. Potash, Bruno Etain, Joseph Frank, Antonio Benabarre, Bernhard T. Baune, Gloria Roberts, Ryota Hashimoto, Tomas Novak, Paul D. Shilling, Julia Veeh, Joanna M. Biernacka, Barbara König, Peter Falkai, Philip B. Mitchell, Urban Ösby, Esther Jiménez, Sébastien Gard, Mark A. Frye, Sarah Kittel-Schneider, Layla Kassem, Fasil Tekola-Ayele, Armin Birner, Cynthia Marie-Claire, Raffaella Ardau, Abesh Kumar Bhattacharjee, Stéphane Jamain, Julie Garnham, Guy A. Rouleau, Caterina Chillotti, Piotr M. Czerski, Thomas G. Schulze, Gustavo Turecki, Anbupalam Thalamuthu, Claudia Pisanu, Azmeraw T. Amare, Marina Mitjans, Sergi Papiol, Mario Maj, Bárbara Arias, Janice M. Fullerton, Nina Dalkner, Peter R. Schofield, Susanne Bengesser, Stefan Herms, Klaus Oliver Schubert, Francis M. Mondimore, Eva Z. Reininghaus, Fernando S. Goes, Lena Backlund, Francesc Colom, Catharina Lavebratt, Christian Simhandl, Marcella Rietschel, Micah Cearns, Mikael Landén, Norio Ozaki, Gonzalo Laje, Barbara W. Schweizer, Nirmala Akula, Andrea Pfennig, Yi-Hsiang Hsu, John R. Kelsoe, Lina Martinsson, Markus M. Nöthen, Caroline M. Nievergelt, Pavla Stopkova, Mirko Manchia, Susan L. McElroy, Peter P. Zandi, Scott R. Clark, Joanna Hauser, Andreas J. Forstner, Po-Hsiu Kuo, Andreas Reif, Maria Del Zompo, Paul Grof, Fabian Streit, Ewa Ferensztajn-Rochowiak, Pablo Cervantes, Thomas Stamm, APH - Mental Health, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Amsterdam Neuroscience - Complex Trait Genetics, Psychiatry, APH - Digital Health, Schubert, K. O., Thalamuthu, A., Amare, A. T., Frank, J., Streit, F., Adl, M., Akula, N., Akiyama, K., Ardau, R., Arias, B., Aubry, J. -M., Backlund, L., Bhattacharjee, A. K., Bellivier, F., Benabarre, A., Bengesser, S., Biernacka, J. M., Birner, A., Marie-Claire, C., Cearns, M., Cervantes, P., Chen, H. -C., Chillotti, C., Cichon, S., Clark, S. R., Cruceanu, C., Czerski, P. M., Dalkner, N., Dayer, A., Degenhardt, F., Del Zompo, M., Depaulo, J. R., Etain, B., Falkai, P., Forstner, A. J., Frisen, L., Frye, M. A., Fullerton, J. M., Gard, S., Garnham, J. S., Goes, F. S., Grigoroiu-Serbanescu, M., Grof, P., Hashimoto, R., Hauser, J., Heilbronner, U., Herms, S., Hoffmann, P., Hou, L., Hsu, Y. -H., Jamain, S., Jimenez, E., Kahn, J. -P., Kassem, L., Kuo, P. -H., Kato, T., Kelsoe, J., Kittel-Schneider, S., Ferensztajn-Rochowiak, E., Konig, B., Kusumi, I., Laje, G., Landen, M., Lavebratt, C., Leboyer, M., Leckband, S. G., Maj, M., Manchia, M., Martinsson, L., Mccarthy, M. J., Mcelroy, S., Colom, F., Mitjans, M., Mondimore, F. M., Monteleone, P., Nievergelt, C. M., Nothen, M. M., Novak, T., O'Donovan, C., Ozaki, N., Osby, U., Papiol, S., Pfennig, A., Pisanu, C., Potash, J. B., Reif, A., Reininghaus, E., Rouleau, G. A., Rybakowski, J. K., Schalling, M., Schofield, P. R., Schweizer, B. W., Severino, G., Shekhtman, T., Shilling, P. D., Shimoda, K., Simhandl, C., Slaney, C. M., Squassina, A., Stamm, T., Stopkova, P., Tekola-Ayele, F., Tortorella, A., Turecki, G., Veeh, J., Vieta, E., Witt, S. H., Roberts, G., Zandi, P. P., Alda, M., Bauer, M., Mcmahon, F. J., Mitchell, P. B., Schulze, T. G., Rietschel, M., and Baune, B. T.

Subjects
Oncology, Multifactorial Inheritance, Treatment response, medicine.medical_specialty, Lithium (medication), Bipolar disorder, Poor responder, Neurosciences. Biological psychiatry. Neuropsychiatry, Lithium, DISEASE, Article, Cellular and Molecular Neuroscience, Risk Factors, Internal medicine, medicine, Humans, Manic-depressive illness, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Depressió psíquica, METAANALYSIS, Biological Psychiatry, Depression (differential diagnoses), MANIA, Depressive Disorder, Depressive Disorder, Major, Trastorn bipolar, Depression, business.industry, Major, medicine.disease, Pathway analysis, Liti, COMPARATIVE EFFICACY, Psychiatry and Mental health, Mental depression, Schizophrenia, Polygenic risk score, Esquizofrènia, Pharmacogenomics, business, RC321-571, medicine.drug
Abstract

Lithium is the gold standard therapy for Bipolar Disorder (BD) but its effectiveness differs widely between individuals. The molecular mechanisms underlying treatment response heterogeneity are not well understood, and personalized treatment in BD remains elusive. Genetic analyses of the lithium treatment response phenotype may generate novel molecular insights into lithium’s therapeutic mechanisms and lead to testable hypotheses to improve BD management and outcomes. We used fixed effect meta-analysis techniques to develop meta-analytic polygenic risk scores (MET-PRS) from combinations of highly correlated psychiatric traits, namely schizophrenia (SCZ), major depression (MD) and bipolar disorder (BD). We compared the effects of cross-disorder MET-PRS and single genetic trait PRS on lithium response. For the PRS analyses, we included clinical data on lithium treatment response and genetic information for n = 2283 BD cases from the International Consortium on Lithium Genetics (ConLi+Gen; www.ConLiGen.org). Higher SCZ and MD PRSs were associated with poorer lithium treatment response whereas BD-PRS had no association with treatment outcome. The combined MET2-PRS comprising of SCZ and MD variants (MET2-PRS) and a model using SCZ and MD-PRS sequentially improved response prediction, compared to single-disorder PRS or to a combined score using all three traits (MET3-PRS). Patients in the highest decile for MET2-PRS loading had 2.5 times higher odds of being classified as poor responders than patients with the lowest decile MET2-PRS scores. An exploratory functional pathway analysis of top MET2-PRS variants was conducted. Findings may inform the development of future testing strategies for personalized lithium prescribing in BD.

Published
2021

23. The combination of three CD4-induced antibodies targeting highly conserved Env regions with a small CD4-mimetic achieves potent ADCC activity.

Author

Marchitto L, Richard J, Prévost J, Tauzin A, Yang D, Chiu T-J, Chen H-C, Díaz-Salinas MA, Nayrac M, Benlarbi M, Beaudoin-Bussières G, Anand SP, Dionne K, Bélanger É, Chatterjee D, Medjahed H, Bourassa C, Tolbert WD, Hahn BH, Munro JB, Pazgier M, Smith AB 3rd, and Finzi A

Abstract

The majority of naturally elicited antibodies against the HIV-1 envelope glycoproteins (Env) are non-neutralizing (nnAbs) because they are unable to recognize the Env trimer in its native "closed" conformation. Nevertheless, it has been shown that nnAbs have the potential to eliminate HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC) provided that Env is present on the cell surface in its "open" conformation. This is because most nnAbs recognize epitopes that become accessible only after Env interaction with CD4 and the exposure of epitopes that are normally occluded in the closed trimer. HIV-1 limits this vulnerability by downregulating CD4 from the surface of infected cells, thus preventing a premature encounter of Env with CD4. Small CD4-mimetics (CD4mc) sensitize HIV-1-infected cells to ADCC by opening the Env glycoprotein and exposing CD4-induced (CD4i) epitopes. There are two families of CD4i nnAbs, termed anti-cluster A and anti-CoRBS Abs, which are known to mediate ADCC in the presence of CD4mc. Here, we performed Fab competition experiments and found that anti-gp41 cluster I antibodies comprise a major fraction of the plasma ADCC activity in people living with HIV (PLWH). Moreover, addition of gp41 cluster I antibodies to cluster A and CoRBS antibodies greatly enhanced ADCC-mediated cell killing in the presence of a potent indoline CD4mc, CJF-III-288. This cocktail outperformed broadly neutralizing antibodies and even showed activity against HIV-1-infected monocyte-derived macrophages. Thus, combining CD4i antibodies with different specificities achieves maximal ADCC activity, which may be of utility in HIV cure strategies.IMPORTANCEThe elimination of HIV-1-infected cells remains an important medical goal. Although current antiretroviral therapy decreases viral loads below detection levels, it does not eliminate latently infected cells that form the viral reservoir. Here, we developed a cocktail of non-neutralizing antibodies targeting highly conserved Env regions and combined it with a potent indoline CD4mc. This combination exhibited potent ADCC activity against HIV-1-infected primary CD4 + T cells as well as monocyte-derived macrophages, suggesting its potential utility in decreasing the size of the viral reservoir.

Published
2024
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24. Three families of CD4-induced antibodies are associated with the capacity of plasma from people living with HIV to mediate ADCC in the presence of CD4-mimetics.

Author

Tauzin A, Marchitto L, Bélanger É, Benlarbi M, Beaudoin-Bussières G, Prévost J, Yang D, Chiu T-J, Chen H-C, Bourassa C, Medjahed H, Korzeniowski MK, Gottumukkala S, Tolbert WD, Richard J, Smith AB 3rd, Pazgier M, and Finzi A

Abstract

CD4-mimetics (CD4mcs) are small molecule compounds that mimic the interaction of the CD4 receptor with HIV-1 envelope glycoproteins (Env). Env from primary viruses normally samples a "closed" conformation that occludes epitopes recognized by CD4-induced (CD4i) non-neutralizing antibodies (nnAbs). CD4mcs induce conformational changes on Env resulting in the exposure of these otherwise inaccessible epitopes. Here, we evaluated the capacity of plasma from a cohort of 50 people living with HIV to recognize HIV-1-infected cells and eliminate them by antibody-dependent cellular cytotoxicity (ADCC) in the presence of a potent indoline CD4mc. We observed a marked heterogeneity among plasma samples. By measuring the levels of different families of CD4i Abs, we found that the levels of anti-cluster A, anti-coreceptor binding site, and anti-gp41 cluster I antibodies are responsible for plasma-mediated ADCC in the presence of CD4mc., Importance: There are several reasons that make it difficult to target the HIV reservoir. One of them is the capacity of infected cells to prevent the recognition of HIV-1 envelope glycoproteins (Env) by commonly elicited antibodies in people living with HIV. Small CD4-mimetic compounds expose otherwise occluded Env epitopes, thus enabling their recognition by non-neutralizing antibodies (nnAbs). A better understanding of the contribution of these antibodies to eliminate infected cells in the presence of CD4mc could lead to the development of therapeutic cure strategies.

Published
2024
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26. UV-A radiation increases biomass yield by enhancing energy flow and carbon assimilation in the edible cyanobacterium Nostoc sphaeroides .

Author

Chen Z, Yuan Z-W, Luo W-X, Wu X, Pan J-L, Yin Y-Q, Shao H-C, Xu K, Li W-Z, Hu Y-L, Wang Z, Gao K-S, and Chen X-W

Subjects
Humans, Biomass, Carbon metabolism, Carbon Dioxide metabolism, Photosynthesis physiology, Ultraviolet Rays, Nostoc metabolism
Abstract

Ultraviolet (UV) A radiation (315-400 nm) is the predominant component of solar UV radiation that reaches the Earth's surface. However, the underlying mechanisms of the positive effects of UV-A on photosynthetic organisms have not yet been elucidated. In this study, we investigated the effects of UV-A radiation on the growth, photosynthetic ability, and metabolome of the edible cyanobacterium Nostoc sphaeroides . Exposures to 5-15 W m -2 (15-46 µmol photons m -2 s -1 ) UV-A and 4.35 W m -2 (20 μmol photons m -2 s -1 ) visible light for 16 days significantly increased the growth rate and biomass production of N. sphaeroides cells by 18%-30% and 15%-56%, respectively, compared to the non-UV-A-acclimated cells. Additionally, the UV-A-acclimated cells exhibited a 1.8-fold increase in the cellular nicotinamide adenine dinucleotide phosphate (NADP) pool with an increase in photosynthetic capacity (58%), photosynthetic efficiency (24%), Q A re-oxidation, photosystem I abundance, and cyclic electron flow (87%), which further led to an increase in light-induced NADPH generation (31%) and ATP content (83%). Moreover, the UV-A-acclimated cells showed a 2.3-fold increase in ribulose-1,5-bisphosphate carboxylase/oxygenase activity, indicating an increase in their carbon-fixing capacity. Gas chromatography-mass spectrometry-based metabolomics further revealed that UV-A radiation upregulated the energy-storing carbon metabolism, as evidenced by the enhanced accumulation of sugars, fatty acids, and citrate in the UV-A-acclimated cells. Therefore, our results demonstrate that UV-A radiation enhances energy flow and carbon assimilation in the cyanobacterium N. sphaeroides .IMPORTANCEUltraviolet (UV) radiation exerts harmful effects on photo-autotrophs; however, several studies demonstrated the positive effects of UV radiation, especially UV-A radiation (315-400 nm), on primary productivity. Therefore, understanding the underlying mechanisms associated with the promotive effects of UV-A radiation on primary productivity can facilitate the application of UV-A for CO 2 sequestration and lead to the advancement of photobiological sciences. In this study, we used the cyanobacterium Nostoc sphaeroides , which has an over 1,700-year history of human use as food and medicine, to explore its photosynthetic acclimation response to UV-A radiation. As per our knowledge, this is the first study to demonstrate that UV-A radiation increases the biomass yield of N. sphaeroides by enhancing energy flow and carbon assimilation. Our findings provide novel insights into UV-A-mediated photosynthetic acclimation and provide a scientific basis for the application of UV-A radiation for optimizing light absorption capacity and enhancing CO 2 sequestration in the frame of a future CO 2 neutral, circular, and sustainable bioeconomy., Competing Interests: The authors declare no conflict of interest.

Published
2024
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27. Pantailocins: phage-derived bacteriocins from Pantoea ananatis and Pantoea stewartii subsp. indologenes .

Author

Stice SP, Jan H-H, Chen H-C, Nwosu L, Shin GY, Weaver S, Coutinho T, Kvitko BH, and Baltrus DA

Subjects
Plant Diseases microbiology, Bacteriocins, Pantoea genetics
Abstract

Importance: Phage-derived bacteriocins (tailocins) are ribosomally synthesized structures produced by bacteria in order to provide advantages against competing strains under natural conditions. Tailocins are highly specific in their target range and have proven to be effective for the prevention and/or treatment of bacterial diseases under clinical and agricultural settings. We describe the discovery and characterization of a new tailocin locus encoded within genomes of Pantoea ananatis and Pantoea stewartii subsp. indologenes , which may enable the development of tailocins as preventative treatments against phytopathogenic infection by these species., Competing Interests: The authors declare no conflict of interest.

Published
2023
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28. Genomic analysis of penicillin-binding proteins and recombination events in an emerging amoxicillin- and meropenem-resistant PMEN3 (Spain 9V -3, ST156) variant in Taiwan and comparison with global descendants of this lineage.

Author

Chen Y-Y, Chi H, Liao W-C, Li S-W, Yang Y-C, Lin H-C, Chang H-P, Pan Y-J, Chiang R-L, and Hsieh Y-C

Subjects
Humans, Penicillin-Binding Proteins genetics, Penicillin-Binding Proteins metabolism, Meropenem, Spain epidemiology, Ceftriaxone, Taiwan epidemiology, Vaccines, Conjugate metabolism, Streptococcus pneumoniae, Serogroup, beta-Lactams, Microbial Sensitivity Tests, Genomics, Recombination, Genetic, Polysaccharides metabolism, Amoxicillin pharmacology, Pneumococcal Infections epidemiology
Abstract

From 2008 to 2020, the Taiwan National Notifiable Disease Surveillance System database demonstrated that the incidence of non-vaccine serotype 23A invasive pneumococcal disease (IPD) approximately doubled. In this study, 276 non-repetitive pneumococcal clinical isolates were collected from two medical centers in Taiwan between 2019 and 2021. Of these 267 pneumococci, 60 were serotype 23A. Among them, 50 (83%) of serotype 23A isolates belonged to the sequence type (ST) 166 variant of the Spain 9V -3 clone. Pneumococcal 23A-ST166 isolates were collected to assess their evolutionary relationships using whole-genome sequencing. All 23A-ST166 isolates were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299, the newly identified PBP2x-299 in Taiwan. Transformation of the pbp1a , pbp2b , and pbp2x alleles into the β-lactam-susceptible R6 strain revealed that PBP2x-299 and PBP2b-11 increased the MIC of ceftriaxone and meropenem by 16-fold, respectively. Prediction analysis of recombination sites in PMEN3 descendants (23A-ST166 in Taiwan, 35B-ST156 in the United States, and 11A-ST838/ST6521 in Europe) showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM , and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displayed an evolutionary capacity for global dissemination and persistence, increasing IPD incidence, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases, and contributing to high antibiotic resistance. A clonal shift with a highly β-lactam-resistant non-vaccine serotype 23A, from ST338 to ST166, increased in Taiwan. ST166 is a single-locus variant of the Spain 9V -3 clone, which is also called the PMEN3 lineage. All 23A-ST166 isolates, in this study, were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299. PBP2x-299 and PBP2b-11 contributed to the increasing MIC of ceftriaxone and meropenem, respectively. Prediction analysis of recombination sites in PMEN3 descendants showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM , and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displays the evolutionary capacity for dissemination, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases and contributing to high antibiotic resistance., Competing Interests: The authors declare no conflict of interest.

Published
2023
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29. Soluble CD4 and low molecular weight CD4-mimetic compounds sensitize cells to be killed by anti-HIV cytotoxic immunoconjugates.

Author

Pincus SH, Stackhouse M, Watt C, Ober K, Cole FM, Chen H-C, Smith Iii AB, and Peters T

Subjects
Humans, Cell Line, Molecular Weight, CD4 Antigens chemistry, CD4 Antigens immunology, CD4 Antigens therapeutic use, HIV Infections drug therapy, HIV Infections immunology, HIV Infections pathology, HIV Infections virology, HIV-1 drug effects, HIV-1 immunology, Immunoconjugates chemistry, Immunoconjugates immunology, Immunoconjugates therapeutic use, HIV Antibodies chemistry, HIV Antibodies immunology, HIV Antibodies therapeutic use, Cytotoxins chemistry, Cytotoxins therapeutic use
Abstract

Importance: HIV infection can be effectively treated to prevent the development of AIDS, but it cannot be cured. We have attached poisons to anti-HIV antibodies to kill the infected cells that persist even after years of effective antiviral therapy. Here we show that the killing of infected cells can be markedly enhanced by the addition of soluble forms of the HIV receptor CD4 or by mimics of CD4., Competing Interests: The authors declare no conflict of interest.

Published
2023
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30. [A prospective study on application of human umbilical cord mesenchymal stem cells combined with autologous Meek microskin transplantation in patients with extensive burns].

Author

Yan TT, Xiao R, Wang Y, Lin GA, Zheng Y, Zhao H, Li WJ, Shang XZ, Meng JS, Hu DS, Li S, Wang C, Lin ZC, Chen HC, Zhao DY, and Tang D

Subjects
Female, Humans, Male, Eosine Yellowish-(YS), Hyaluronic Acid therapeutic use, Hyperplasia, Ki-67 Antigen, Prospective Studies, Umbilical Cord, Vimentin, Young Adult, Adult, Middle Aged, Burns surgery, Cicatrix
Abstract

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990 th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P <0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group ( t =-3.68, P <0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P <0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group ( t =4.39, P <0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups ( P >0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.

Published
2023
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31. Associations between Various Sleep-Wake-Related Indicators and Nutritional Status in Community-Dwelling Older Adults: The Yilan Study, Taiwan.

Author

Lin RA, Pan PJ, Hsu NW, and Chen HC

Subjects
Humans, Female, Aged, Aged, 80 and over, Male, Independent Living, Nutritional Status, Taiwan epidemiology, Cross-Sectional Studies, Sleep, Sleep Initiation and Maintenance Disorders epidemiology, Malnutrition complications, Malnutrition epidemiology, Sleep Wake Disorders epidemiology
Abstract

Objectives: To elucidate the relationship between various sleep-wake-related indicators and nutritional status., Design: Cross-sectional study., Setting: Community-based survey between 2017 and 2022 in Yilan City, Taiwan., Participants: 1,905 community-dwelling older adults aged ≥65 years., Measurements: Nutritional status was evaluated using the Mini Nutritional Assessment, and participants were classified into normal nutritional status and undernutrition groups. Regarding sleep-wake-related indicators, specific items or component scores of the Pittsburgh Sleep Quality Index were used to assess sleep-wake schedule, subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, presence of sleep disturbances, hypnotic use, and dysfunction in maintaining enthusiasm. The 5-item Athens Insomnia Scale and the Epworth Sleepiness Scale were used to evaluate insomnia and excessive daytime sleepiness, respectively., Results: Of the 1,905 participants, the mean age was 75.6±7.1, with 52.2% being ≥75 years old, 58.9% were women, and 11.4% had undernutrition. After controlling for covariates, short sleepers were less likely to have undernutrition (OR: 0.63; 95% CI: 0.41-0.97); in contrast, long sleepers were more likely to exhibit undernutrition (OR: 1.52; 95% CI: 1.06-2.17). In addition, poor habitual sleep efficiency (OR:1.69; 95% CI:1.15-2.50), taking hypnotics in the past month (OR: 1.58; 95% CI: 1.12-2.24), and dysfunction in maintaining enthusiasm (OR: 1.93; 95% CI: 1.24-2.99) were associated with increased risk of undernutrition., Conclusions: Among older adults, various sleep-wake-related indicators differed in their relationships with nutritional status. Specific sleep-wake disturbances may indicate undernutrition in this population., Competing Interests: None declared.

Published
2023
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32. [Detection and clinical application of HIV-1 DNA].

Author

Dong LJ, Chen HC, Ma YL, and Xing W

Subjects
Humans, DNA, Polymerase Chain Reaction, HIV-1 genetics, HIV Infections diagnosis, HIV Seropositivity
Abstract

The persistence of the HIV-1 reservoir is still the main obstacle to the cure of HIV. In clinical research, reliable biomarkers are needed to label it. HIV-1 DNA can be continuously detected in the HIV-1 reservoir. It has significant application value in diagnosing HIV-1 infection, the timing of antiretroviral therapy, the prediction of virus rebound, and monitoring treatment effects. The detection technology based on polymerase chain reaction (PCR) is the most commonly used HIV-1 DNA detection method in clinical practice. The continuous innovation and advancement of technology can accurately detect the total, integrated, and unintegrated HIV-1 DNA in infected cells using qualitative or quantitative methods. Different forms of HIV-1 DNA in infected cells have been increasingly reported as biomarkers in HIV infection monitoring and AIDS treatment-related research. This article reviews the progress of HIV-1 DNA.

Published
2022
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33. Gastroepiploic vascularized lymph node transfer for extremities' lymphedema: Is two better than one? A retrospective case-control study.

Author

Elia R, Chen HC, Taranto GD, Ciudad P, Torto FL, Nacchiero E, Giudice G, and Maruccia M

Subjects
Case-Control Studies, Cellulitis, Humans, Lower Extremity surgery, Lymph Nodes surgery, Retrospective Studies, Lymphedema pathology, Lymphedema surgery, Quality of Life
Abstract

Single (SG-VLN) and double gastroepiploic vascularized lymph node transfer (DG-VLN) have shown promising results for the treatment of extremities' lymphedema. The literature search yields only few other cases describing outcomes following double VLN transfers, but no comparative studies have been produced so far. The aim of this study was to retrospectively examine and compare the effects of SG-VLN versus DG-VLN transfer. All patients diagnosed with extremities' stage II and III lymphedema who had undergone SG-VLN or DG-VLN between January 2012 and December 2018 were identified from two institutions' databases. Demographic and surgical data were collected. The primary endpoint was the comparison of the reduction in limb circumference (CRR) within 12 months post-surgery. Secondary endpoints included the reduction of cellulitis episodes and patients' quality of life improvement. Eighty-nine patients met the inclusion criteria. At 12 months of follow-up, higher CRR values were observed in the double inset group (p<0.05*) both at above elbow/above knee (AE/AK) level (SG-VLN: 70.6% ± 0.6%; DG-VLN: 72.2% ± 0.7%) and at below elbow/below knee level (SG-VLN: 59.1% ± 1.3%; DG-VLN: 61.6% ± 3.7%). Subgroup analyses of the involved limb (upper vs lower) were consistent with the primary treatment effects. The reduction of cellulitis episodes did not differ between the two groups, while the DG-VLN group showed better results in the overall satisfaction function, symptoms, and mood domains of the LYMQoL questionnaire (p=0.04). The study suggests that either single or double transfer can produce excellent results, but double inset of the gastroepiploic VLNT flap may produce greater volume reductions both at 12 and 24 months. Further studies with a larger sample size are warranted to corroborate our results., Competing Interests: Conflict of Interest None, (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Published
2022
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34. Use of Second Window ICG in spinal cord biopsy of a mildly contrast-enhancing lesion: Technical note and review of the literature.

Author

Mensah-Brown KG, Germi JW, Quattrone F, Maloney-Wilensky E, Lee JYK, Chen HI, and Schuster JM

Subjects
Adult, Biopsy, Female, Humans, Indocyanine Green, Young Adult, Brain Neoplasms diagnostic imaging, Brain Neoplasms surgery, Spinal Cord Neoplasms diagnostic imaging, Spinal Cord Neoplasms surgery
Abstract

Introduction: Indocyanine green (ICG) is commonly used to visualize cerebral vasculature, particularly in the management of cerebral aneurysms. There have also been attempts to use ICG for visualization of tumors. Injection of ICG followed by immediate fluorescence microscopy is limited by the short time window for imaging and administration and restricted depth of imaging. Second Window Indocyanine Green (SWIG) addresses these issues by allowing for longer contrast times and the imaging of deeper regions of brain tissue. Biopsy of spinal cord lesions is often difficult for a variety of reasons, including the delicate nature of the tissue and differentiating normal from lesional tissue visually, especially in lesions with heterogeneous enhancement., Methods: In this case report, we describe the use of second window ICG to facilitate the visualization of a spinal cord lesion and subsequent biopsy of the lesion., Results: This patient is a 24-year-old female who had recurrence of a suprasellar germinoma. An MRI of the rest of the neuraxis was performed to assess for the presence of drop metastases. The spinal cord from C2-5 was expanded with areas of patchy enhancement; however, this lesion was asymptomatic. The patient's oncologist requested a biopsy of this lesion to help direct subsequent care of her recurrent germinoma. The day before surgery, the patient had an intravenous injection of ICG dye. She then underwent a C3-5 laminectomy for biopsy of her cervical intramedullary lesion. After opening of the dura, no visible abnormality of the spinal cord could be identified. A Stryker endoscope showed an area of ICG uptake in the cord at approximately the C3-4 level. A midline myelotomy was centered over the ICG demarcated area and several samples were taken for pathology. Final biopsy results determined the lesion to be spinal cord parenchyma with perivascular and intraparenchymal lymphocytes - not consistent with spinal cord tumor or germinoma., Conclusion: Second Window ICG is effective in visualizing otherwise visually unremarkable spinal cord lesions. This technology can facilitate biopsy of these lesions and possibly their surgical resection., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Published
2022
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35. [HCV and Treponema pallidum infection status in HIV/AIDS cases in Yunnan province, January-June, 2020].

Author

Li DF, Chen HC, Jin XM, Dai J, Zeng ZJ, Yang M, Sun PY, Dong LJ, Han Y, Ma YL, Chen M, and Song ZZ

Subjects
China epidemiology, Cross-Sectional Studies, Female, Homosexuality, Male, Humans, Male, Middle Aged, Prevalence, Risk Factors, Treponema pallidum, HIV Infections epidemiology, Hepatitis C epidemiology, Sexual and Gender Minorities
Abstract

Objective: To understand the infection status of HCV and Treponema pallidum (TP) in HIV/AIDS cases in Yunnan province,and identify the risk factors. Methods: Between January 1 and June 30 in 2020,a cross-sectional survey was conducted in Yunnan. Two enzyme-linked immunosorbent assay (ELISA) kits were used to detect anti-HCV, the positive results of both two kits indicated HCV infection. ELISA and syphilis toluidine red untreated serum test were applied to identify TP infection. Both Excel 2016 and SPSS 22.0 software were used for statistical analysis, and logistic regression model was conducted to identify the relevant factors of HCV and TP infection. Results: A total of 5 922 HIV/AIDS cases were included in this study, the infection rates of HCV and TP were 6.5% (383/5 922) and 5.8% (344/5 922) respectively. The co-infection rate of HCV and TP was 0.4% (22/5 922). The risk for HCV infection in HIV/AIDS cases was higher in younger age groups compared with age group ≥50 years (15-19:a OR =3.53;20-29:a OR =3.02;30-39:a OR =2.91;40-49:a OR =3.61), in males than in females (a OR =2.31), in the married and unmarried than in the divorced or widowed (married:a OR =1.61;unmarried:a OR =1.63), in other ethnic groups than in Han ethnic group (a OR =1.70), in people with lower education level than in people with education level of college and above (primary school degree and below:a OR =4.69;middle school:a OR =3.96), in people living in the central and western Yunnan than in people living in eastern Yunnan (central Yunnan:a OR =2.46; western Yunnan:a OR =7.08), in injection drug users than in MSM (a OR =131.08). The risk of TP infection in HIV/AIDS cases was higher in people with education level of college and primary school than in middle school degree (primary school and below:a OR =1.73;college and above:a OR =1.77), in people with other occupations than in farmers (a OR =1.39), in people living in eastern Yunnan than in people living in western Yunnan (a OR =1.75); in MSM than in people with heterosex (a OR =9.75). Conclusions: A certain proportion of HIV/AIDS cases reported between January and June in 2020 in Yunnan were co-infected with HCV and TP, many factors were associated with the co-infection. It is suggested to strengthen HCV and TP tests in HIV/AIDS cases and conduct active treatment of the co-infection.

Published
2021
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