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6. Contributors

Author

B. Binder, Elisabeth, primary, Bale, Tracy L., additional, Baram, Tallie Z., additional, Barrière, David André, additional, Bolton, Jessica L., additional, Bowers, Mallory E., additional, Charney, Dennis S., additional, Chen, Alon, additional, Cranshaw, Matthew, additional, Cryan, John F., additional, de Kloet, E. Ron, additional, Deussing, Jan M., additional, Engmann, Olivia, additional, Epperson, C. Neill, additional, Ganz, Edward, additional, Hartmann, Jakob, additional, Henckens, Marloes J.A.G., additional, Herman, James P., additional, Hill, Matthew N., additional, Hill, S.B., additional, Iacoviello, Brian M., additional, Issler, Orna, additional, Jay, Thérèse M., additional, Joëls, Marian, additional, King, C.D., additional, Lightman, Stafford L., additional, Likhtik, Ekaterina, additional, Lorsch, Zachary S., additional, Lyons, David M., additional, Magalhães, Ricardo, additional, Mansuy, Isabelle M., additional, McEwen, Bruce S., additional, Mériaux, Sébastien, additional, Morató, Laia, additional, Morrison, Kathleen E., additional, Müller, Iris, additional, Nemeroff, Charles B., additional, Nestler, Eric J., additional, O'Leary, Olivia F., additional, Papst, Lilia, additional, Patel, Sachin, additional, Paz, Rony, additional, Ressler, K.J., additional, Richter-Levin, Gal, additional, Rodrigues, Mariana, additional, Sandi, Carmen, additional, Sarabdjitsingh, R. Angela, additional, Schatzberg, Alan F., additional, Schmidt, Mathias V., additional, Seligowski, A.V., additional, Short, Annabel K., additional, Sousa, Nuno, additional, Spiga, Francesca, additional, Stork, Oliver, additional, Syed, Shariful A., additional, Tripathi, Kuldeep, additional, Vinkers, Christiaan H., additional, Wingo, A.P., additional, and Yehuda, Rachel, additional

Published
2020
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10. A systematic review of the reporting quality of studies that use Mendelian randomisation in UK Biobank

Author

Gibson, Mark, Spiga, Francesca, Campbell, Amy, Richmond, Rebecca, and Munafo, Marcus

Subjects
replication, UK Biobank, Tobacco and Alcohol Research Group, reporting standards, Life Sciences, Psychological Science, TARG, systematic review, @BristolTARG, Medicine and Health Sciences, reporting quality, Mendelian randomisation, University of Bristol, reproducibility
Abstract

The aim of this systematic review is to assess whether studies which conduct Mendelian randomisation (MR) in UK Biobank give all the information needed to perform a direct replication. The findings will highlight which specific characteristics of MR analyses are omitted and how this pattern differs across subgroups (e.g. Journal Impact Factor, Journal open access policy, Journal word limit, whether the authors claimed to follow STROBE-MR and article type). As MR is a rapidly expanding field it is vital we make sure the research is being accurately reported so its replicability can be checked. This will lead to work in the field being more robust which in turn will lead to a reduction in wasted resources and an increase in impact.

Published
2022
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12. Interventions to prevent obesity in children aged 5 to 11 years old

Author

Moore, Theresa HM, additional, Tomlinson, Eve, additional, Spiga, Francesca, additional, Higgins, Julian PT, additional, Gao, Yang, additional, Caldwell, Deborah M, additional, Nobles, James, additional, Dawson, Sarah, additional, Ijaz, Sharea, additional, Savovic, Jelena, additional, Hodder, Rebecca K, additional, Wolfenden, Luke, additional, Jago, Russell, additional, Phillips, Sophie, additional, Hillier-Brown, Frances, additional, and Summerbell, Carolyn D, additional

Published
2022
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13. Interventions to prevent obesity in children aged 12 to 18 years old

Author

Moore, Theresa HM, additional, Tomlinson, Eve, additional, Spiga, Francesca, additional, Higgins, Julian PT, additional, Gao, Yang, additional, Caldwell, Deborah M, additional, Nobles, James, additional, Dawson, Sarah, additional, Ijaz, Sharea, additional, Savovic, Jelena, additional, Hodder, Rebecca K, additional, Wolfenden, Luke, additional, Jago, Russell, additional, Phillips, Sophie, additional, Hillier-Brown, Frances, additional, and Summerbell, Carolyn D, additional

Published
2022
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17. Tools for assessing quality and risk of bias in Mendelian randomization studies: a systematic review.

Author

Spiga, Francesca, Gibson, Mark, Dawson, Sarah, Tilling, Kate, Smith, George Davey, Munafò, Marcus R, and Higgins, Julian P T

Subjects
*INSTRUMENTAL variables (Statistics), *RANDOMIZATION (Statistics), *ACQUISITION of data, *PREPRINTS, *MEDLINE
Abstract

Background The use of Mendelian randomization (MR) in epidemiology has increased considerably in recent years, with a subsequent increase in systematic reviews of MR studies. We conducted a systematic review of tools designed for assessing risk of bias and/or quality of evidence in MR studies and a review of systematic reviews of MR studies. Methods We systematically searched MEDLINE, Embase, the Web of Science, preprints servers and Google Scholar for articles containing tools for assessing, conducting and/or reporting MR studies. We also searched for systematic reviews and protocols of systematic reviews of MR studies. From eligible articles we collected data on tool characteristics and content, as well as details of narrative description of bias assessment. Results Our searches retrieved 2464 records to screen, from which 14 tools, 35 systematic reviews and 38 protocols were included in our review. Seven tools were designed for assessing risk of bias/quality of evidence in MR studies and evaluation of their content revealed that all seven tools addressed the three core assumptions of instrumental variable analysis, violation of which can potentially introduce bias in MR analysis estimates. Conclusion We present an overview of tools and methods to assess risk of bias/quality of evidence in MR analysis. Issues commonly addressed relate to the three standard assumptions of instrumental variables analyses, the choice of genetic instrument(s) and features of the population(s) from which the data are collected (particularly in two-sample MR), in addition to more traditional non-MR-specific epidemiological biases. The identified tools should be tested and validated for general use before recommendations can be made on their widespread use. Our findings should raise awareness about the importance of bias related to MR analysis and provide information that is useful for assessment of MR studies in the context of systematic reviews. [ABSTRACT FROM AUTHOR]

Published
2023
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20. Adrenal androgens, adrenarche, and zona reticularis: A human affair?

Author

Fudulu, Daniel, Horn, George, Hazell, Georgina, Lefrançois-Martinez, Anne-Marie, Martinez, Antoine, Angelini, Gianni, Lightman, Stafford, Spiga, Francesca, Dumontet, Typhanie, Génétique, Reproduction et Développement (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), and ANR-18-CE14-0012,Sex-Specs,Homeostasie tissulaire selon le sex et son impact sur les maladies surrénaliennes(2018)

Subjects
0301 basic medicine, medicine.drug_class, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Biochemistry, Transcriptome, 03 medical and health sciences, Mice, 0302 clinical medicine, Endocrinology, Lineage tracing, Cortex (anatomy), [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, Humans, Adrenarche, Molecular Biology, PRKAR1A, ComputingMilieux_MISCELLANEOUS, Adrenal cortex, Gene Expression Profiling, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Androgen, Zona Reticularis, Rats, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, medicine.anatomical_structure, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Androgens, Female, Neuroscience, Zona reticularis
Abstract

In humans, reticularis cells of the adrenal cortex fuel the production of androgen steroids, constituting the driver of numerous morphological changes during childhood. These steps are considered a precocious stage of sexual maturation and are grouped under the term "adrenarche". This review describes the molecular and enzymatic characteristics of the zona reticularis, along with the possible signals and mechanisms that control its emergence and the associated clinical features. We investigate the differences between species and discuss new studies such as genetic lineage tracing and transcriptomic analysis, highlighting the rodent inner cortex's cellular and molecular heterogeneity. The recent development and characterization of mouse models deficient for Prkar1a presenting with adrenocortical reticularis-like features prompt us to review our vision of the mouse adrenal gland maturation. We expect these new insights will help increase our understanding of the adrenarche process and the pathologies associated with its deregulation.

Published
2021
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21. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19 : a meta-analysis

Author

The WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, [missing], Domingo, Pere, Mur, Isabel, Mateo, Gracia María, Gutierrez, Maria del Mar, Pomar, Virginia, de Benito, Natividad, Corbacho, Noemí, Herrera, Silvia, Millan, Lucia, Muñoz, Jessica, Malouf, Jorge, Molas, Maria Ema, Asensi, Victor, Horcajada, Juan Pablo, Estrada, Vicente, Gutierrez, Felix, Torres, Ferran, Perez-Molina, Jose A, Fortun, Jesús, Villar, Luisa M, Hohenthal, Ulla, Marttila, Harri, Vuorinen, Tytti, Nordberg, Marika, Valtonen, Mika, Frigault, Matthew J, Mansour, Michael K, Patel, Naomi J, Fernandes, Ana, Harvey, Liam, Foulkes, Andrea S, Healy, Brian C, Shah, Ruta, Bensaci, Ana Maria, Woolley, Ann E., Nikiforow, Sarah, Lin, Nina, Sagar, Manish, Shrager, Harry, Huckins, David S., Axelrod, Matthew, Pincus, Michael D, Fleisher, Jorge, Lampa, Jon, Nowak, Piotr, Vesterbacka, Jan C., Rasmuson, Johan, Skorup, Paul, Janols, Helena, Niward, Katarina F, Chatzidionysiou, Katerina, Asgeirsson, Hilmir, Parke, Åsa, Blennow, Ola, Svensson, Anna-Karin, Aleman, Soo, Sönnerborg, Anders, Henter, Jan-Inge, Horne, Anna Carin, Al-Beidh, Farah, Angus, Derek, Annane, Djillali, Arabi, Yaseen, Beane, Abigail, Berry, Scott, Bhimani, Zahra, Bonten, Marc, Bradbury, Charlotte, Brunkhorst, Frank, Buxton, Meredith, Cheng, Allen, Cove, Matt, De Jong, Menno, Derde, Lennie, Estcourt, Lise, Goossens, Herman, Gordon, Anthony, Green, Cameron, Haniffa, Rashan, Ichihara, Nao, Lamontagne, Francois, Lawler, Patrick, Litton, Ed, Marshall, John, McArthur, Colin, McAuley, Daniel, McGuinness, Shay, McVerry, Bryan, Montgommery, Stephanie, Mouncey, Paul, Murthy, Srinivas, Nichol, Alistair, Parke, Rachael, Parker, Jane, Reyes, Felipe, Rowan, Kathryn, Saito, Hiroki, Santos, Marlene, Seymour, Chris, Shankar-Hari, Manu, Turgeon, Alexis, Turner, Anne, van Bentum-Puijk, Wilma, van de Veerdonk, Frank, Webb, Steve, Zarychanski, Ryan, Baillie, J Kenneth, Beasley, Richard, Cooper, Nichola, Fowler, Robert, Galea, James, Hills, Thomas, King, Andrew, Morpeth, Susan, Netea, Mihai, Ogungbenro, Kayode, Pettila, Ville, Tong, Steve, Uyeki, Tim, Youngstein, Taryn, Higgins, Alisa, Lorenzi, Elizabeth, Berry, Lindsay, Salama, Carlos, Rosas, Ivan O., Ruiz-Antorán, Belén, Muñez Rubio, Elena, Ramos Martínez, Antonio, Campos Esteban, José, Avendaño Solá, Cristina, Pizov, Reuven, Sanz Sanz, Jesus, Abad-Santos, Francisco, Bautista-Hernández, Azucena, García-Fraile, Lucio, Barrios, Ana, Gutiérrez Liarte, Ángela, Alonso Pérez, Tamara, Rodríguez-García, Sebastian C, Mejía-Abril, Gina, Prieto, Jose Carlos, Leon, Rafael, VEIGA, VIVIANE C., SCHEINBERG, PHILLIP, FARIAS, DANIELLE L.C., PRATS, JOÃO G., CAVALCANTI, ALEXANDRE B., MACHADO, FLAVIA R., ROSA, REGIS G., BERWANGER, OTÁVIO, AZEVEDO, LUCIANO C.P., LOPES, RENATO D., DOURADO, LETICIA K., CASTRO, CLAUDIO G., ZAMPIERI, FERNANDO G., AVEZUM, ALVARO, LISBOA, THIAGO C., ROJAS, SALOMÓN S.O., COELHO, JULIANA C., LEITE, RODRIGO T., CARVALHO, JULIO CESAR, ANDRADE, LUIS E.C., SANDES, ALEX R., PINTÃO, MARIA CAROLINA T., SANTOS, SUELI V., ALMEIDA, THIAGO M.L., COSTA, ANDRÉ N., GEBARA, OTAVIO C.E., FREITAS, FLAVIO G.R., PACHECO, EDUARDO S., MACHADO, DAVID J.B., MARTIN, JOSIANE, CONCEIÇÃO, FABIO G., SIQUEIRA, SUELLEN R.R., DAMIANI, LUCAS P., ISHIHARA, LUCIANA M., SCHNEIDER, DANIEL, DE SOUZA, DENISE, Hermine, Olivier, Mariette, Xavier, Tharaux, Pierre Louis, Resche Rigon, Matthieu, Porcher, Raphael, Ravaud, Philippe, Azoulay, Elie, Cadranel, Jacques, Emmerich, Joseph, Fartoukh, Muriel, Guidet, Bertrand, Humbert, Marc, Lacombe, Karine, Mahevas, Matthieu, Pene, Frédéric, Pourchet-Martinez, Valérie, Schlemmer, Frédéric, Tibi, Annick, Yazdanpanah, Yazdan, Dougados, Maxime, Bureau, Serge, Horby, Peter W, Landray, Martin J, Baillie, Kenneth J, Buch, Maya H, Chappell, Lucy C, Day, Jeremy N, Faust, Saul N, Haynes, Richard, Jaki, Thomas, Jeffery, Katie, Juszczak, Edmund, Lim, Wei Shen, Mafham, Marion, Montgomery, Alan, Mumford, Andrew, Thwaites, Guy, Kamarulzaman, Adeeba, Syed Omar, Sharifah Faridah, Ponnampalavanar, Sasheela, Raja Azwa, Raja Iskandar Syah, Wong, Pui Li, Kukreja, Anjanna, Ong, Hang Cheng, Sulaiman, Helmi, Basri, Sazali, Ng, Rong Xiang, Megat Johari, Bushra, Rajasuriar, Reena, Chong, Meng Li, Neelamegam, Malinee, Syed Mansor, Syed Mukhtar, Zulhaimi, Nurul Syuhada, Lee, Cheng Siang, Altice, Frederick, Price, Christina, Malinis, Maricar, Hasan, Mohd Shahnaz, Wong, Chee Kuan, Chidambaram, Suresh, Misnan, Nor Arisah, Mohd Thabit, Alif Adlan, Sim, Benedict, Bidin, Farah Nadiah, Mohd Abd Rahim, Mohd Abd Hafiz, Saravanamuttu, Sujana, Tuang, Wei Xuan, Mohamed Gani, Yasmin, Thangavelu, Suvintheran, Tay, Kim Heng, Ibrahim, Nur Munirah, Halid, Luqman Alhakim, Tan, Kok Tong, Mukri, Mohd Noor Azreet, Arip, Masita, Koh, Hui Moon, Syed Badaruddin, Syarifah Nurul Ain, Raja Sureja, Letchumi, Chun, Geok Ying, TORRE-CISNEROS, JULIAN, MERCHANTE, NICOLAS, LEON, RAFAEL, CARCEL, SHEILA, GARRIDO, JOSE CARLOS, Galun, Eitan, Soriano, Alex, Martínez, José Antonio, Castán, Clara, Paredes, Roger, Dalmau, David, Carbonell, Cristina, Espinosa, Gerard, Castro, Pedro, Muñóz, José, Almuedo, Alex, Prieto, Sergio, Pacheco, Iván, Ratain, Mark, Pisano, Jennifer, Strek, Mary, Adegunsoye, Ayodeji, Karrison, Theodore, Declercq, Jozefien, Van Damme, Karel, De Leeuw, Elisabeth, Bosteels, Cedric, Maes, Bastiaan, Vale, Claire L., Godolphin, Peter J., Fisher, David, Higgins, Julian P. T., Spiga, Francesca, Savovic, Jelena, Tierney, Jayne, Baron, Gabriel, Benbenishty, Julie S., Berry, Lindsay R., Broman, Niklas, Cavalcanti, Alexandre Biasi, Colman, Roos, De Buyser, Stefanie, Derde, Lennie P. G., Omar, Sharifah Faridah, Fernandez-Cruz, Ana, Feuth, Thijs, Garcia, Felipe, Garcia-Vicuna, Rosario, Gonzalez-Alvaro, Isidoro, Gordon, Anthony C., Horby, Peter W., Horick, Nora K., Kumar, Kuldeep, Lambrecht, Bart, Landray, Martin J., Leal, Lorna, Lederer, David J., Merchante, Nicolas, Mohan, Shalini V., Nivens, Michael C., Oksi, Jarmo, Perez-Molina, Jose A., Postma, Simone, Ramanan, Athimalaipet V., Reid, Pankti D., Rutgers, Abraham, Sancho-Lopez, Aranzazu, Seto, Todd B., Sivapalasingam, Sumathi, Soin, Arvinder Singh, Staplin, Natalie, Stone, John H., Strohbehn, Garth W., Sunden-Cullberg, Jonas, Torre-Cisneros, Julian, Tsai, Larry W., van Hoogstraten, Hubert, van Meerten, Tom, Veiga, Viviane Cordeiro, Westerweel, Peter E., Diaz, Janet V., Marshall, John C., Sterne, Jonathan A. C., Translational Immunology Groningen (TRIGR), Stem Cell Aging Leukemia and Lymphoma (SALL), World Health Organization, and Group, WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working

Subjects
Male, medicine.medical_specialty, Randomization, Secondary infection, Placebo, Antibodies, Monoclonal, Humanized, Internal medicine, Cause of Death, Medicine and Health Sciences, Medicine, Humans, Prospective Studies, Prospective cohort study, Glucocorticoids, METAANALYSIS, Cause of death, Aged, Randomized Controlled Trials as Topic, business.industry, Coinfection, Interleukin-6, COVID-19, Odds ratio, General Medicine, Middle Aged, Respiration, Artificial, COVID-19 Drug Treatment, Clinical trial, Hospitalization, Meta-analysis, Disease Progression, Drug Therapy, Combination, Female, business
Abstract

[Importance] Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm., [Objective] To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes., [Data Sources] Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts., [Study Selection] Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria., [Data Extraction and Synthesis] In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance–weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality., [Main Outcomes and Measures] The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days., [Results] A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P, [Conclusions and Relevance] In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality., [Trial Registration] PROSPERO Identifier: CRD42021230155., Funding for administrative and communications support was provided by the World Health Organization.

Published
2021

23. Reporting and methodological quality of studies that use Mendelian randomisation in UK Biobank: a meta-epidemiological study

Author

Gibson, Mark J, Spiga, Francesca, Campbell, Amy, Khouja, Jasmine N, Richmond, Rebecca C, and Munafò, Marcus R

Abstract

ObjectivesTo identify whether Mendelian randomisation (MR) studies are appropriately conducted and reported in enough detail for other researchers to accurately replicate and interpret them.DesignCross-sectional meta-epidemiological study.Data sourcesWeb of Science, EMBASE, PubMed and PsycINFO were searched on 15 July 2022 for literature.Eligibility criteriaFull research articles that conducted an MR analysis exclusively using individual-level UK Biobank data to obtain a causal estimate of the exposure–outcome relationship (for no more than ten exposures or outcomes).Methods and analysisData were extracted using a 25-item checklist relating to reporting and methodological quality (based on the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)-MR reporting guidelines and the guidelines for performing MR investigations). Article characteristics, such as 2021 Journal Impact Factor, publication year, journal word limit/recommendation, whether the MR analysis was the primary analysis, open access status and whether reporting guidelines were followed, were also extracted. Descriptive statistics were calculated for each item, and whether article characteristics predicted overall article completeness was investigated with linear regression.Results116 articles were included in this review. The proportion of articles which reported complete information/adequate methodology ranged from 3% to 100% across the different items. Palindromic variants, variant replication, missing data, associations of the instrumental variable with the exposure or outcome and bias introduced by two-sample methods used on a single sample were often not completely addressed (<11%). There was no clear evidence that article characteristics predicted overall completeness except for primary analysis status.ConclusionsThe results identify areas in which the reporting and conducting of MR studies needs to be improved and also suggest researchers do not make use of supplementary materials to sufficiently report secondary analyses. Future research should focus on the quality of code and analyses, attempt direct replications and investigate the impact of the STROBE-MR specifically.Study registrationhttps://osf.io/nwrdj

Published
2023
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24. MGMTpromoter methylation testing to predict overall survival in people with glioblastoma treated with temozolomide: a comprehensive meta-analysis based on a Cochrane Systematic Review

Author

Brandner, Sebastian, primary, McAleenan, Alexandra, additional, Kelly, Claire, additional, Spiga, Francesca, additional, Cheng, Hung-Yuan, additional, Dawson, Sarah, additional, Schmidt, Lena, additional, Faulkner, Claire L, additional, Wragg, Christopher, additional, Jefferies, Sarah, additional, Higgins, Julian P T, additional, and Kurian, Kathreena M, additional

Published
2021
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26. Prognostic value of test(s) for O6-methylguanine–DNA methyltransferase (MGMT) promoter methylation for predicting overall survival in people with glioblastoma treated with temozolomide

Author

McAleenan, Alexandra, additional, Kelly, Claire, additional, Spiga, Francesca, additional, Kernohan, Ashleigh, additional, Cheng, Hung-Yuan, additional, Dawson, Sarah, additional, Schmidt, Lena, additional, Robinson, Tomos, additional, Brandner, Sebastian, additional, Faulkner, Claire L, additional, Wragg, Christopher, additional, Jefferies, Sarah, additional, Howell, Amy, additional, Vale, Luke, additional, Higgins, Julian P T, additional, and Kurian, Kathreena M, additional

Published
2021
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32. Involvement of CREB-regulated transcription coactivators (CRTC) in transcriptional activation of steroidogenic acute regulatory protein (Star) by ACTH

Author

Smith, Lorna I.F., primary, Huang, Victoria, additional, Olah, Mark, additional, Trinh, Loc, additional, Liu, Ying, additional, Hazell, Georgina, additional, Conway-Campbell, Becky, additional, Zhao, Zidong, additional, Martinez, Antoine, additional, Lefrançois-Martinez, Anne-Marie, additional, Lightman, Stafford, additional, Spiga, Francesca, additional, and Aguilera, Greti, additional

Published
2020
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33. CORRIGENDUM FOR 'Dynamics of ACTH-Mediated Regulation of Gene Transcription in ATC1 and ATC7 Adrenal Zona Fasciculata Cell Lines'

Author

Spiga, Francesca and University of Bristol [Bristol]

Subjects
[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019
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36. Association Between Administration of IL-6 Antagonists and Mortality Among Patients Hospitalized for COVID-19: A Meta-analysis.

Author

Shankar-Hari, Manu, Vale, Claire L., Godolphin, Peter J., Fisher, David, Higgins, Julian P. T., Spiga, Francesca, Savović, Jelena, Tierney, Jayne, Baron, Gabriel, Benbenishty, Julie S., Berry, Lindsay R., Broman, Niklas, Cavalcanti, Alexandre Biasi, Colman, Roos, De Buyser, Stefanie L., Derde, Lennie P. G., Domingo, Pere, Omar, Sharifah Faridah, Fernandez-Cruz, Ana, and Feuth, Thijs

Subjects
DRUG efficacy, INTERLEUKIN-6 receptors, MORTALITY risk factors, COVID-19, PLACEBOS, ADRENOCORTICAL hormones, META-analysis
Abstract

Importance: Clinical trials assessing the efficacy of IL-6 antagonists in patients hospitalized for COVID-19 have variously reported benefit, no effect, and harm.Objective: To estimate the association between administration of IL-6 antagonists compared with usual care or placebo and 28-day all-cause mortality and other outcomes.Data Sources: Trials were identified through systematic searches of electronic databases between October 2020 and January 2021. Searches were not restricted by trial status or language. Additional trials were identified through contact with experts.Study Selection: Eligible trials randomly assigned patients hospitalized for COVID-19 to a group in whom IL-6 antagonists were administered and to a group in whom neither IL-6 antagonists nor any other immunomodulators except corticosteroids were administered. Among 72 potentially eligible trials, 27 (37.5%) met study selection criteria.Data Extraction and Synthesis: In this prospective meta-analysis, risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool. Inconsistency among trial results was assessed using the I2 statistic. The primary analysis was an inverse variance-weighted fixed-effects meta-analysis of odds ratios (ORs) for 28-day all-cause mortality.Main Outcomes and Measures: The primary outcome measure was all-cause mortality at 28 days after randomization. There were 9 secondary outcomes including progression to invasive mechanical ventilation or death and risk of secondary infection by 28 days.Results: A total of 10 930 patients (median age, 61 years [range of medians, 52-68 years]; 3560 [33%] were women) participating in 27 trials were included. By 28 days, there were 1407 deaths among 6449 patients randomized to IL-6 antagonists and 1158 deaths among 4481 patients randomized to usual care or placebo (summary OR, 0.86 [95% CI, 0.79-0.95]; P = .003 based on a fixed-effects meta-analysis). This corresponds to an absolute mortality risk of 22% for IL-6 antagonists compared with an assumed mortality risk of 25% for usual care or placebo. The corresponding summary ORs were 0.83 (95% CI, 0.74-0.92; P < .001) for tocilizumab and 1.08 (95% CI, 0.86-1.36; P = .52) for sarilumab. The summary ORs for the association with mortality compared with usual care or placebo in those receiving corticosteroids were 0.77 (95% CI, 0.68-0.87) for tocilizumab and 0.92 (95% CI, 0.61-1.38) for sarilumab. The ORs for the association with progression to invasive mechanical ventilation or death, compared with usual care or placebo, were 0.77 (95% CI, 0.70-0.85) for all IL-6 antagonists, 0.74 (95% CI, 0.66-0.82) for tocilizumab, and 1.00 (95% CI, 0.74-1.34) for sarilumab. Secondary infections by 28 days occurred in 21.9% of patients treated with IL-6 antagonists vs 17.6% of patients treated with usual care or placebo (OR accounting for trial sample sizes, 0.99; 95% CI, 0.85-1.16).Conclusions and Relevance: In this prospective meta-analysis of clinical trials of patients hospitalized for COVID-19, administration of IL-6 antagonists, compared with usual care or placebo, was associated with lower 28-day all-cause mortality.Trial Registration: PROSPERO Identifier: CRD42021230155. [ABSTRACT FROM AUTHOR]

Published
2021
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41. Activation and expression of endogenous CREB‐regulated transcription coactivators (CRTC) 1, 2 and 3 in the rat adrenal gland.

Author

Smith, Lorna I. F., Zhao, Zidong, Walker, Jamie, Lightman, Stafford, and Spiga, Francesca

Subjects
STEROIDOGENIC acute regulatory protein, ADRENAL glands, CREB protein, WESTERN immunoblotting, NUCLEAR proteins
Abstract

The activation and nuclear translocation of cAMP‐response element binding protein (CREB)‐regulated transcription coactivator (CRTC)2 occurs in the rat adrenal gland, in response to adrenocorticotrophic hormone (ACTH) and stressors, and has been implicated in the transcriptional regulation of steroidogenic acute regulatory protein (StAR). We have recently demonstrated the activation of CRTC isoforms, CRTC1 and CRTC3, in adrenocortical cell lines. In the present study, we aimed to determine the activation and expression of the three CRTC isoforms in vivo in relation to Star transcription, under basal conditions and following a robust endotoxic stress challenge. Rat adrenal glands and blood plasma were collected following i.v. administration of either an ultradian‐sized pulse of ACTH or administration of lipopolysaccharide, as well as under unstressed conditions across the 24‐hour period. Plasma ACTH and corticosterone (CORT) were measured and the adrenal glands were processed for measurement of protein by western immunoblotting, RNA by a quantitative reverse transcriptase‐polymerase chain reaction and association of CRTC2 and CRTC3 with the Star promoter by chromatin immunoprecipitation. An increase in nuclear localisation of CRTC2 and CRTC3 followed increases in both ultradian and endotoxic stress‐induced plasma ACTH, and this was associated with increased CREB phosphorylation and corresponding increases in Star transcription. Both CRTC2 and CRTC3 were shown to associate with the Star promoter, with the dynamics of CRTC3 binding corresponding to that of nuclear changes in protein levels. CRTC isoforms show little variation in ultradian expression or variation across 24 hours, although evidence of long‐term down‐regulation following endotoxic stress was found. We conclude that co‐transcription factors CRTC2 and, more clearly, CRTC3 appear to act alongside phosphorylated CREB in the generation of ultradian pulses of Star transcription, essential for the maintenance of basal StAR expression. Similarly, our findings suggest CRTC2 and CRTC3 mediate Star transcriptional initiation following an endotoxic stressor; however, other transcription factors are likely to be responsible for the long‐term up‐regulation of adrenal Star transcription. [ABSTRACT FROM AUTHOR]

Published
2021
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47. The Role of Hippocampal NMDA Receptors in Long-Term Emotional Responses following Muscarinic Receptor Activation

Author

Hoeller, Alexandre A., primary, Costa, Ana Paula R., additional, Bicca, Maíra A., additional, Matheus, Filipe C., additional, Lach, Gilliard, additional, Spiga, Francesca, additional, Lightman, Stafford L., additional, Walz, Roger, additional, Collingridge, Graham L., additional, Bortolotto, Zuner A., additional, and de Lima, Thereza C. M., additional

Published
2016
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