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1. Structural brain alterations associated with suicidal thoughts and behaviors in young people: results from 21 international studies from the ENIGMA Suicidal Thoughts and Behaviours consortium

Author

van Velzen, Laura, Dauvermann, Maria, Colic, Lejla, Villa, Luca, Savage, Hannah, Toenders, Yara, Zhu, Alyssa, Bright, Joanna, Campos, Adrián, Salminen, Lauren, Ambrogi, Sonia, Ayesa-Arriola, Rosa, Banaj, Nerisa, Başgöze, Zeynep, Bauer, Jochen, Blair, Karina, Blair, Robert James, Brosch, Katharina, Cheng, Yuqi, Colle, Romain, Connolly, Colm, Corruble, Emmanuelle, Couvy-Duchesne, Baptiste, Crespo-Facorro, Benedicto, Cullen, Kathryn, Dannlowski, Udo, Davey, Christopher, Dohm, Katharina, Fullerton, Janice, Gonul, Ali Saffet, Gotlib, Ian, Grotegerd, Dominik, Hahn, Tim, Harrison, Ben, He, Mengxin, Hickie, Ian, Ho, Tiffany, Iorfino, Frank, Jansen, Andreas, Jollant, Fabrice, Kircher, Tilo, Klimes-Dougan, Bonnie, Klug, Melissa, Leehr, Elisabeth, Lippard, Elizabeth, Mclaughlin, Katie, Meinert, Susanne, Miller, Adam Bryant, Mitchell, Philip, Mwangi, Benson, Nenadić, Igor, Ojha, Amar, Overs, Bronwyn, Pfarr, Julia-Katharina, Piras, Fabrizio, Ringwald, Kai, Roberts, Gloria, Romer, Georg, Sanches, Marsal, Sheridan, Margaret, Soares, Jair, Spalletta, Gianfranco, Stein, Frederike, Teresi, Giana, Tordesillas-Gutiérrez, Diana, Uyar-Demir, Aslihan, van der Wee, Nic, van der Werff, Steven, Vermeiren, Robert, Winter, Alexandra, Wu, Mon-Ju, Yang, Tony, Thompson, Paul, Rentería, Miguel, Jahanshad, Neda, Blumberg, Hilary, van Harmelen, Anne-Laura, Schmaal, Lianne, Instituto de Investigación Marqués de Valdecilla, German Research Foundation, National Institutes of Health (US), European Commission, van Velzen, Laura S [0000-0002-6003-5227], Dauvermann, Maria R [0000-0002-2873-8512], Villa, Luca M [0000-0001-5091-6410], Toenders, Yara J [0000-0002-4117-1143], Campos, Adrián I [0000-0003-3468-8619], Ambrogi, Sonia [0000-0002-2897-358X], Ayesa-Arriola, Rosa [0000-0003-0570-5352], Başgöze, Zeynep [0000-0002-0306-4849], Bauer, Jochen [0000-0001-9345-2126], Brosch, Katharina [0000-0002-0526-8095], Connolly, Colm G [0000-0002-4051-3682], Cullen, Kathryn R [0000-0001-9631-3770], Dannlowski, Udo [0000-0001-7117-2908], Davey, Christopher G [0000-0003-1431-3852], Fullerton, Janice M [0000-0003-4014-4490], Gonul, Ali Saffet [0000-0003-3522-1359], Hahn, Tim [0000-0001-6541-3795], He, Mengxin [0000-0003-2714-3565], Hickie, Ian B [0000-0001-8832-9895], Ho, Tiffany C [0000-0002-4500-6364], Ojha, Amar [0000-0002-1038-0225], Overs, Bronwyn J [0000-0002-7138-5556], Piras, Fabrizio [0000-0003-3566-5494], Ringwald, Kai G [0000-0001-5886-6745], Sanches, Marsal [0000-0002-6993-6822], Soares, Jair C [0000-0002-5466-5628], Spalletta, Gianfranco [0000-0002-7432-4249], Tordesillas-Gutiérrez, Diana [0000-0003-1458-3932], Uyar-Demir, Aslihan [0000-0002-0856-4260], Winter, Alexandra [0000-0003-3759-1425], Wu, Mon-Ju [0000-0002-0540-8027], Rentería, Miguel E [0000-0003-4626-7248], Blumberg, Hilary P [0000-0002-6363-4698], Apollo - University of Cambridge Repository, Neurology, Developmental Neuroscience in Society, University of Melbourne, University of Cambridge [UK] (CAM), Yale School of Medicine [New Haven, Connecticut] (YSM), University of Southern California (USC), University of Queensland [Brisbane], Fondazione Santa Lucia [IRCCS], Clinical and Behavioral Neurology [IRCCS Santa Lucia], Universidad de Cantabria [Santander], University of Minnesota Medical School, University of Minnesota System, Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Boys Town National Research Hospital [Omaha], Philipps Universität Marburg = Philipps University of Marburg, Kunming Medical University (KMU), Université Paris-Saclay, Florida State University [Tallahassee] (FSU), 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, Algorithms, models and methods for images and signals of the human brain (ARAMIS), Sorbonne Université (SU)-Inria de Paris, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Institut du Cerveau = Paris Brain Institute (ICM), 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)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-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)-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Bioscience, Universidad de Sevilla / University of Sevilla, University of New South Wales [Kensington], Ege University [Izmir], Stanford University, The University of Sydney, University of Texas at Austin [Austin], Harvard University, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Neuroscience Research Australia (NeuRA), Hospital Universitario Marqués de Valdecilla [Santander], Leiden University Medical Center (LUMC), Universiteit Leiden, University of California [San Francisco] (UC San Francisco), University of California (UC), and Keck School of Medicine [Los Angeles]

Subjects
Cortical Thickness, History, Adolescent, Volume, Mood Disorders, [SCCO.NEUR]Cognitive science/Neuroscience, Brain, Suicide, Attempted, Neuroimaging, Adolescents, Reliability, Suicidal Ideation, Sample, Regions, Cellular and Molecular Neuroscience, Psychiatry and Mental health, SDG 3 - Good Health and Well-being, Bipolar, Adults, Humans, Molecular Biology, Gray
Abstract

Funder: MQ Brighter Futures Award MQBFC/2 and the U.S. National Institute of Mental Health under Award Number R01MH117601. National Suicide Prevention Research Fund, managed by Suicide Prevention Australia, Funder: MQ Brighter Futures Award MQBFC/2. Interdisziplinäres Zentrum für Klinische Forschung, UKJ, Funder: Italian Ministry of Health grant RC17-18-19-20-21/A, Funder: Instituto de Salud Carlos III through the projects PI14/00639, PI14/00918 and PI17/01056 (Co-funded by European Regional Development Fund/European Social Fund "Investing in your future") and Fundación Instituto de Investigación Marqués de Valdecilla (NCT0235832 and NCT02534363), Funder: National Institute of Mental Health (K23MH090421), the National Alliance for Research on Schizophrenia and Depression, the University of Minnesota Graduate School, the Minnesota Medical Foundation, and the Biotechnology Research Center (P41 RR008079 to the Center for Magnetic Resonance Research), University of Minnesota, and the Deborah E. Powell Center for Women’s Health Seed Grant, University of Minnesota, Funder: Medical Leader Foundation of Yunnan Province (L2019011) and Famous Doctors Project of Yunnan Province Plan (YNWR-MY-2018-041), Funder: CJ Martin Fellowship (NHMRC app 1161356). “Investissements d’avenir” ANR-10-IAIHU-06, Funder: German Research Foundation (DFG, grant FOR2107-DA1151/5-1 and DA1151/5-2 to UD, and DFG grants HA7070/2-2, HA7070/3, HA7070/4 to TH), Funder: Australian National Health and Medical Research Council of Australia (NHMRC) Project Grants 1024570 NHMRC Career Development Fellowships (1061757), Funder: Medical Faculty Münster, Innovative Medizinische Forschung (Grant IMF KO 1218 06), Funder: Australian National Medical and Health Research Council (Program Grant 1037196 and Investigator Grant 1177991 to PBM, Project Grant 1066177 to JMF), the Lansdowne Foundation, Good Talk and the Keith Pettigrew Family Bequest (PM) Janette Mary O’Neil Research Fellowship. IHG is supported in part by R37MH101495, Funder: Australian National Health and Medical Research Council of Australia (NHMRC) Project Grants 1064643 (principal investigator, BJH) NHMRC Career Development Fellowships (1124472), Funder: National Institute of Mental Health (K01MH106805). Klingenstein Third Generation Foundation, the National Institute of Mental Health (K01MH117442), the Stanford Maternal Child Health Research Institute, and the Stanford Center for Cognitive and Neurobiological Imaging. TCH receives partial support from the Ray and Dagmar Dolby Family Fund, Funder: German Research Foundation (DFG, grant FOR2107-JA 1890/7-1 and JA 1890/7-2 to AJ, and DFG, grant FOR2107-KI588/14-1 and FOR2107-KI588/14-2 to TK), Funder: NIAAA (K01AA027573, R21AA027884) and the American Foundation for Suicide Prevention, Funder: National Institute of Mental Health (R01-MH103291), Funder: National Center for Complementary and Integrative Health (NCCIH) R21AT009173 and R61AT009864 National Center for Advancing Translational Sciences (CTSI), National Institutes of Health, through UCSF-CTSI UL1TR001872 American Foundation for Suicide Prevention (AFSP) SRG-1-141-18 UCSF Research Evaluation and Allocation Committee (REAC) and J. Jacobson Fund to TTY; by the National Institute of Mental Health (NIMH) R01MH085734 and the Brain and Behavior Research Foundation (formerly NARSAD), Funder: MQ Brighter Futures Award MQBFC/2 R61MH111929RC1MH088366, R01MH070902, R01MH069747, American Foundation for Suicide Prevention, International Bipolar Foundation, Brain and Behavior Research Foundation, For the Love of Travis Foundation and Women’s Health Research at Yale, Funder: MQ Brighter Futures Award MQBFC/2 Social Safety and Resilience programme of Leiden University, Funder: MQ Brighter Futures Award MQBFC/2 National Institute of Mental Health under Award Number R01MH117601 NHMRC Career Development Fellowship (1140764), Identifying brain alterations associated with suicidal thoughts and behaviors (STBs) in young people is critical to understanding their development and improving early intervention and prevention. The ENIGMA Suicidal Thoughts and Behaviours (ENIGMA-STB) consortium analyzed neuroimaging data harmonized across sites to examine brain morphology associated with STBs in youth. We performed analyses in three separate stages, in samples ranging from most to least homogeneous in terms of suicide assessment instrument and mental disorder. First, in a sample of 577 young people with mood disorders, in which STBs were assessed with the Columbia Suicide Severity Rating Scale (C-SSRS). Second, in a sample of young people with mood disorders, in which STB were assessed using different instruments, MRI metrics were compared among healthy controls without STBs (HC; N = 519), clinical controls with a mood disorder but without STBs (CC; N = 246) and young people with current suicidal ideation (N = 223). In separate analyses, MRI metrics were compared among HCs (N = 253), CCs (N = 217), and suicide attempters (N = 64). Third, in a larger transdiagnostic sample with various assessment instruments (HC = 606; CC = 419; Ideation = 289; HC = 253; CC = 432; Attempt=91). In the homogeneous C-SSRS sample, surface area of the frontal pole was lower in young people with mood disorders and a history of actual suicide attempts (N = 163) than those without a lifetime suicide attempt (N = 323; FDR-p = 0.035, Cohen's d = 0.34). No associations with suicidal ideation were found. When examining more heterogeneous samples, we did not observe significant associations. Lower frontal pole surface area may represent a vulnerability for a (non-interrupted and non-aborted) suicide attempt; however, more research is needed to understand the nature of its relationship to suicide risk.

Published
2022
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2. Genetic Variants of Glucose-6-Phosphate Dehydrogenase and Their Associated Enzyme Activity: A Systematic Review and Meta-Analysis

Author

Pfeffer, DA, Satyagraha, AW, Sadhewa, A, Alam, MS, Bancone, G, Boum, Y, Brito, M, Cui, L, Deng, Z, Domingo, GJ, He, Y, Khan, WA, Kibria, MG, Lacerda, M, Menard, D, Monteiro, W, Pal, S, Parikh, S, Roca-Feltrer, A, Roh, M, Sirdah, MM, Wang, D, Huang, Q, Howes, RE, Price, RN, Ley, B, Charles Darwin University [Australia], Eijkman Institute for Molecular Biology [Jakarta], International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), Mahidol University [Bangkok], University of Oxford, Mbarara University of Science and Technology [Mbarara] (MUST), Fundação de Medicina Tropical Dr Heitor Vieira Dourado [Manaus, Brazil], University of South Florida [Tampa] (USF), Kunming Medical University (KMU), Génétique du paludisme et résistance - Malaria Genetics and Resistance, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Dynamique des interactions hôte pathogène (DIHP), Université de Strasbourg (UNISTRA), Yale School of Public Health (YSPH), University of California [San Francisco] (UC San Francisco), University of California (UC), Xiamen University, Foundation for Innovative New Diagnostics (FIND), and A.W.S. and A.S. were funded by the Ministry of Research and Technology/National Research and Innovation Agency of the Republic of Indonesia. GB and SMRU are supported by the Wellcome Trust [grant 220111]. GJD and PATH studies were funded by the United Kingdom’s Foreign, Commonwealth & Development Office (FCDO), grant number 204139 and, by the Bill & Melinda Gates Foundation [OPP1107113]. This research was funded by Wellcome Trust Senior Fellow in Clinical Science (200909 RNP) and by the Bill & Melinda Gates Foundation [SEPRA-INV-024389]. For the purpose of Open Access, the authors have applied a CC BY public copyright license to any Author Accepted Manuscript version arising from this submission.

Subjects
Microbiology (medical), G6PD genotype, G6PD activity, Infectious Diseases, General Immunology and Microbiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, G6PD deficiency, glucose-6-phosphate dehydrogenase, Immunology and Allergy, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Molecular Biology
Abstract

Low glucose-6-phosphate dehydrogenase enzyme (G6PD) activity is a key determinant of drug-induced haemolysis. More than 230 clinically relevant genetic variants have been described. We investigated the variation in G6PD activity within and between different genetic variants. In this systematic review, individual patient data from studies reporting G6PD activity measured by spectrophotometry and corresponding the G6PD genotype were pooled (PROSPERO: CRD42020207448). G6PD activity was converted into percent normal activity applying study-specific definitions of 100%. In total, 4320 individuals from 17 studies across 10 countries were included, where 1738 (40.2%) had one of the 24 confirmed G6PD mutations, and 61 observations (3.5%) were identified as outliers. The median activity of the hemi-/homozygotes with A-(c.202G>A/c.376A>G) was 29.0% (range: 1.7% to 76.6%), 10.2% (range: 0.0% to 32.5%) for Mahidol, 16.9% (range 3.3% to 21.3%) for Mediterranean, 9.0% (range: 2.9% to 23.2%) for Vanua Lava, and 7.5% (range: 0.0% to 18.3%) for Viangchan. The median activity in heterozygotes was 72.1% (range: 16.4% to 127.1%) for A-(c.202G>A/c.376A>G), 54.5% (range: 0.0% to 112.8%) for Mahidol, 37.9% (range: 20.7% to 80.5%) for Mediterranean, 53.8% (range: 10.9% to 82.5%) for Vanua Lava, and 52.3% (range: 4.8% to 78.6%) for Viangchan. A total of 99.5% of hemi/homozygotes with the Mahidol mutation and 100% of those with the Mediterranean, Vanua Lava, and Viangchan mutations had A/c.376A>G), 55% of hemi/homozygotes had

Published
2022
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3. Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice

Author

Emilie Heuillard, Mourad Bouhadjar, Eric Robinet, Thierry F. Vandamme, Thomas Baumert, Philippe Choquet, Christophe Ferrand, Eugénie Dalimier, Céline Giraudeau, Mihaela Ignat, Véronique Lindner, Patrick Pessaux, Cynthia Calligaro, Ghina Bou About, Franck Blindauer, Michele Diana, Nicolas Anton, Gael Fouré, Hussein El-Saghire, Tao Wu, Tania Sorg, Jacques Marescaux, Jean-Philippe Dillenseger, Francine Gossé, Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Kunming Medical University (KMU), L'Institut hospitalo-universitaire de Strasbourg (IHU Strasbourg), Institut National de Recherche en Informatique et en Automatique (Inria)-l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD)-Les Hôpitaux Universitaires de Strasbourg (HUS)-La Fédération des Crédits Mutuels Centre Est (FCMCE)-L'Association pour la Recherche contre le Cancer (ARC)-La société Karl STORZ, CHU Strasbourg, Institut Clinique de la Souris, Les Hôpitaux Universitaires de Strasbourg (HUS), l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg (UNISTRA), Conception et application de molécules bioactives (CAMB), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), LLTech SAS Paris, Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS BFC)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)

Subjects
Male, 0301 basic medicine, Sorafenib, Carcinoma, Hepatocellular, metabolism, pathology, Sciences du Vivant [q-bio]/Médecine humaine et pathologie, Multimodal Imaging, Article, methods, Mice, 03 medical and health sciences, Optical coherence tomography, In vivo, Cell Line, Tumor, medicine, Animals, Humans, Doxorubicin, Luciferases, Ultrasonography, Multidisciplinary, medicine.diagnostic_test, business.industry, Liver Neoplasms, Magnetic resonance imaging, Hep G2 Cells, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Transplantation, Disease Models, Animal, 030104 developmental biology, Hepatocellular carcinoma, Cancer research, Female, business, Neoplasm Transplantation, Preclinical imaging, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging.

Published
2016
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