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1. Telestroke network to robotic telestroke network: How to upgrade regional stroke care to include remote robotics?

Author: Guillaume Charbonnier, Arturo Consoli, Louise Bonnet, Alessandra Biondi, Fabrice Vuillier, Kanty Rabenorosoa, Vitor Mendes Pereira, and Thierry Moulin
Subjects: Computer applications to medicine. Medical informatics, R858-859.7
Abstract: Objective Selected patients with large vessel occlusion (LVO) strokes can benefit from endovascular therapy (EVT). However, the effectiveness of EVT is largely dependent on how quickly the patient receives treatment. Recent technological developments have led to the first neurointerventional treatments using robotic assistance, opening up the possibility of performing remote stroke interventions. Existing telestroke networks provide acute stroke care, including remote administration of intravenous thrombolysis (IVT). Therefore, the introduction of remote EVT in distant stroke centers requires an adaptation of the existing telestroke networks. The aim of this work was to propose a framework for centers that are potential candidates for telerobotics according to the resources currently available in these centers. Methods In this paper, we highlight the future challenges for including remote robotics in telestroke networks. A literature review provides potential solutions. Results Existing telestroke networks need to determine which centers to prioritize for remote robotic technologies based on objective criteria and cost-effectiveness analysis. Organizational challenges include regional coordination and specific protocols. Technological challenges mainly concern telecommunication networks. Conclusions Specific adaptations will be necessary if regional telestroke networks are to include remote robotics. Some of these can already be put in place, which could greatly help the future implementation of the technology.
Published: 2024
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2. P319: IL7-RECEPTOR EXPRESSION IS FREQUENT IN T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA AND PREDICTS SENSITIVITY TO JAK-INHIBITION

Author: Lucien Courtois, Aurélie Cabannes-Hamy, Rathana Kim, Marine Delecourt, Antoine Pinton, Guillaume Charbonnier, Melanie Feroul, Charlotte Smith, Giulia Tueur, Cecile Pivert, Estelle Balducci, Mathieu Simonin, Salvatore Spicuglia, Nicolas Boissel, Guillaume Andrieu, Vahid Asnafi, Philippe Rousselot, and Ludovic Lhermitte
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2023
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3. P321: TNF-MEDIATED CELL DEATH: AN ACTIONABLE TARGET FOR IMMUNOTHERAPY IN T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA

Author: Marie-Emilie Dourthe, Etienne Lengline, Guillaume Charbonnier, Mehdi Latiri, Chaimae Saji, Agata Cieslak, Mathieu Simonin, Norbert Ifrah, Hervé Dombret, Olivier Hermine, Nicolas Boissel, André Baruchel, Jacques Ghysdael, Elizabeth Macintyre, Christine Tran-Quang, Guillaume Andrieu, and Vahid Asnafi
Subjects: Diseases of the blood and blood-forming organs, RC633-647.5
Published: 2023
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4. Epromoters function as a hub to recruit key transcription factors required for the inflammatory response

Author: David Santiago-Algarra, Charbel Souaid, Himanshu Singh, Lan T. M. Dao, Saadat Hussain, Alejandra Medina-Rivera, Lucia Ramirez-Navarro, Jaime A. Castro-Mondragon, Nori Sadouni, Guillaume Charbonnier, and Salvatore Spicuglia
Subjects: Science
Abstract: Some promoters, termed Epromoters, can display enhancer activity and regulate distal genes in their endogenous context. Here the authors report the broad involvement of Epromoters in the coordinated activation of interferon (IFN) response. They show activation of a number of IFN-inducible genes is a result of Epromoters regulating expression of an entire IFN response gene cluster.
Published: 2021
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5. Does Intravenous Thrombolysis Influence the Time of Recanalization and Success of Mechanical Thrombectomy during the Acute Phase of Cerebral Infarction?

Author: Guillaume Charbonnier, Louise Bonnet, Benjamin Bouamra, Fabrice Vuillier, Giovanni Vitale, Thierry Moulin, Elisabeth Medeiros De Bustos, and Alessandra Biondi
Subjects: stroke, thrombectomy, revascularization time, revascularization, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract: Objectives: Mechanical thrombectomy (MT) is an effective treatment for acute ischemic stroke (AIS) caused by large vessel occlusion. Recanalization time is a key factor in the treatment of AIS. It has previously been suggested that intravenous thrombolysis (IVT) may be associated with a shorter recanalization time. The aim of our study was to investigate whether IVT or other factors could be associated with shorter or longer MT procedure times. Methods: We performed a retrospective analysis of a local cohort of patients treated by MT. We collected procedure time (puncture to recanalization and clot visualization to recanalization), demographic data, localization of the thrombus, antithrombotic treatment at arrival, IVT infusion, and stroke subtype at discharge according to the TOAST classification. We planned to analyze the full cohort and the successful revascularization subgroup. Results: There was no difference in procedure times between patients who received IVT and those who did not. In the successful revascularization subgroup, patients presenting with cardioembolic stroke had a significantly shorter time between clot visualizations and revascularization than the other patients (41 vs. 56 min, p = 0.024), but this was not the case in the full cohort. Also in the successful revascularization subgroup, the revascularization time was 76 vs. 61 min (p = 0.075) in patients presenting with tandem occlusion vs. the others, but there was no difference between these groups in the full cohort. Conclusions: There was no difference in terms of procedure times in patients treated by IVT and MT vs. patients treated by MT alone either in the full cohort or in the successful revascularization subgroup. The data from the successful revascularization subgroup may be useful for studying revascularization times, provided that data from procedures that were stopped prematurely by the operator due to the length of time since symptom onset is removed.
Published: 2020
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6. Factors That Influence Susceptibility Vessel Sign in Patients With Acute Stroke Referred for Mechanical Thrombectomy

Author: Manon Dillmann, Louise Bonnet, Fabrice Vuillier, Thierry Moulin, Alessandra Biondi, and Guillaume Charbonnier
Subjects: stroke, ischemic stroke, susceptibility vessel sign, mechanical thrombectomy, magnetic resonance imaging, thrombus, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background and PurposeThe presence of a Susceptibility Vessel Sign (SVS) in the acute phase of proximal occlusion ischemic stroke indicates the presence of deoxyhemoglobin in the thrombus. Thrombi composition changes over time. The aim of this study was to investigate whether the absence of SVS is associated with a shorter symptom onset to imaging time.MethodsWe retrospectively analyzed all patients referred for mechanical thrombectomy at Besançon University Hospital between 1 January 2015 and 31 December 2020 for whom readable T2*-weighted imaging was available. We compared patient characteristics according to the presence or absence of an SVS. We also studied the subgroup for whom the exact symptom onset time was known. We performed a univariate statistical analysis, then a multivariate analysis on the variables that were statistically significant in the univariate analysis.ResultsOf the 389 patients included, 309 (79.4%) were SVS+. We found no significant relationship between SVS– and the time between symptom onset and imaging in the whole cohort. In the multivariate analysis, SVS– was associated with anticoagulant treatment (p < 0.01), and SVS+ with age (p = 0.023) and carotid terminus occlusion (p = 0.042). In the known symptom onset subgroup, SVS– was significantly associated with a shorter symptom onset -imaging time (p < 0.001), and this was confirmed in the multivariate analysis (p = 0.011; OR 0.911; 95% CI [0.844; 0.972]).ConclusionIn the acute phase of proximal occlusion ischemic stroke, absence of SVS was associated with a shorter symptom onset–imaging time for patients with a known symptom onset time.
Published: 2022
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7. Timing and Spectrum of Neurological Complications After Flow Diverter Implantation for Intracranial Aneurysms

Author: Guillaume Charbonnier, Jean-Philippe Desilles, Simon Escalard, Benjamin Maier, Gabriele Ciccio, Stanislas Smajda, Robert Fahed, François Delvoye, Hocine Redjem, Raphaël Blanc, Michel Piotin, and Mikael Mazighi
Subjects: intracranial aneurysm, stents, platelet aggregation inhibitors, stroke, cerebral hemorrhage, subarachnoid hemorrhage, Neurology. Diseases of the nervous system, RC346-429
Abstract: Background and Purpose: The aim of this study was to characterize neurological complications after flow diverter (FD) treatment on a long follow-up cohort and identify predictive factors associated with these complications.Methods: This study was conducted on a monocentric cohort of patients treated for intracranial aneurysms by FD.Results: Between September 2008 and July 2018, 413 patients were treated for 514 aneurysms: 18% of the patients presented with at least one neurological complication during a median follow-up of 446 days (IQR 186–1,210). Sixty-one patients presented with ischemic complications, 13 with hemorrhagic ones and 10 with compressive processes. Among 89 neurological complications 64.5% were peri-operative (occurring within the 30 days following the procedure) and 35.5% were delayed after 1 month.Conclusions: Overall, neurological complications after FD implantation were overrepresented by cerebrovascular ischemic events occurring during the peri-operative period, but also in a delayed manner after 1 year. Long-term follow-up is relevant after aneurysm intervention using FD.
Published: 2021
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8. Direct transfer to angiosuite for patients with severe acute stroke treated with thrombectomy: the multicentre randomised controlled DIRECT ANGIO trial protocol

Author: Sebastien Soize, Isabelle Serre, Pierre-François Manceau, Laurent Pierot, Marine Beaumont, Thierry Moulin, Francis Guillemin, Serge Bracard, Mikael Mazighi, Raphaël Blanc, Michel Piotin, Bertrand Lapergue, Hocine Redjem, Gabriele Ciccio, Stanislas Smajda, Arturo Consoli, Oguzhan Coskun, Federico Di Maria, Adrien Wang, Maya Tchikviladze, Serge Evrard, Benjamin Gory, Charbel Mounayer, Vincent Costalat, Grégory Gascou, Cyril Dargazanli, Romain Tonnelet, René Anxionnat, Jérome Berge, Xavier Barreau, Alessandra Biondi, Louis Veunac, François Zhu, Emmanuelle Schmitt, Gioia Mione, Lisa Humbertjean, Jean-Christophe Lacour, Sébastien Richard, Aymeric Rouchaud, Anne-Laure Derelle, Isabelle Mourand, Nicolas Gaillard, Caroline Arquizan, Fernando Pico, Guillaume Charbonnier, Candice Sabben, Simon Escalard, Suzana Saleme, Gaultier Marnat, Jean-Philippe Desilles, Imad Derraz, Mariano Musacchio, Igor Sibon, Malek Ben Maacha, Pierre-Henri Lefevre, Carlos Riquelme, Gabriela Hossu, Aboubaker Cherifi, Sonia Alamowitch, Nolwenn Riou-Comte, Solene Moulin, Morgan Leguen, Olivier Ille, Giovanni Vitale, Lucas Corti, Gérard Audibert, Florent Gariel, Liang Liao, Ovide Corabianu, Thomas de Broucker, Didier Smadja, Eric Manchon, Pierre-Yves Garcia, Guillaume Taylor, David Weisenburger, Lucas Gorza, Georges Rodesh, Julie Gratieux, Haja Rakotoharinandrasana, Philippe Tassan, Roxanna Poll, Sylvie Marinier, Patrice Menegon, Ludovic Lucas, Stéphane Olindo, Pauline Renou, Sharmila Sagnier, Mathilde Poli, Sabrina Debruxelles, Marc Braun, Sophie Planel, Lionel Nace, Hamza Achit, Olivier Beaufils, Thomas Loeb, Francisco Macian, Dominique Cailloce, Thibaut Desmettre, Xavier Combes, Ariel Pablo Lebedinsky, Francis Vuillemet, Nicolas Kempf, Philippe Lemmel, Eric Schluck, Isabelle Costa, Mitchelle Bailang, Marie Reitter, Agnès Masson, Lionel Alb, Adriana Tabarna, Marcela Voicu, Iona Podar, Madalina Brezeanu, Fortunato Di Caterino, Panagiotis Primikiris, Elisabeth de Bustos Medeiros, Benjamin Bouamra, Louise Bonnet, Fabrice Vuillier, Pablo A Lebedinsky, Frederico Bolognini, Elie Cohen-Khallas, Andreas Fickl, Mathilde Goudot, Sylvie Courtois, Sohrab Mostoufizadehghalamfarsa, Alessandro La Porta, Maher Sahnoun, Christophe Gelmini, Nathalie Caucheteux, Vi Tuan Hua, Mickaël Hoang, Catherine Pradeau, Jean-Marc Mene, Musa Sesay, Mikael Obadia, Nadia Ajili, Aymerci Rouchaud, and Francisco Macian-Montoro
Subjects: Medicine
Abstract: Introduction Mechanical thrombectomy (MT) increases functional independence in patients with acute ischaemic stroke with anterior circulation large vessel occlusion (LVO), and the probability to achieve functional independence decreases by 20% for each 1-hour delay to reperfusion. Therefore, we aim to investigate whether direct angiosuite transfer (DAT) is superior to standard imaging/emergency department-based management in achieving 90-day functional independence in patients presenting with an acute severe neurological deficit likely due to LVO and requiring emergent treatment with MT.Methods and analysis DIRECT ANGIO (Effect of DIRECT transfer to ANGIOsuite on functional outcome in patient with severe acute stroke treated with thrombectomy: the randomised DIRECT ANGIO Trial) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) study. Eligibility requires a patient ≤75 years, pre-stroke modified Rankin Scale (mRS) 0–2, presenting an acute severe neurological deficit and admitted within 5 hours of symptoms onset in an endovascular-capable centre. A total of 208 patients are randomly allocated in a 1:1 ratio to DAT or standard management. The primary outcome is the rate of patients achieving a functional independence, assessed as mRS 0–2 at 90 days. Secondary endpoints include patients presenting confirmed LVO, patients eligible to intravenous thrombolysis alone, patients with intracerebral haemorrhage and stroke-mimics, intrahospital time metrics, early neurological improvement (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1 at 24 hours) and mRS overall distribution at 90 days and 12 months. Safety outcomes are death and intracerebral haemorrhage transformation. Medico-economics analyses include health-related quality of life and cost utility assessment.Ethics and dissemination The DIRECT ANGIO trial was approved by the ethics committee of Ile de France 1. Study began in April 2020. Results will be published in an international peer-reviewed medical journal.Trial registration number NCT03969511.
Published: 2021
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9. Intracranial Bleeding After Reperfusion Therapy in Acute Ischemic Stroke

Author: Guillaume Charbonnier, Louise Bonnet, Alessandra Biondi, and Thierry Moulin
Subjects: stroke, intracranial bleeding, brain hemorrhage, hemorrhagic transformation, reperfusion, intravenous thrombolysis, Neurology. Diseases of the nervous system, RC346-429
Abstract: Intracranial hemorrhage is one of the most feared complications following brain infarct. Ischemic tissues have a natural tendency to bleed. Moreover, the first recanalization trials using intravenous thrombolysis have shown an increase in mild to severe intracranial hemorrhage. Symptomatic intracerebral hemorrhage is strongly associated with poor outcomes and is an important factor in recanalization decisions. Stroke physicians have to weigh the potential benefit of recanalization therapies, first, with different risks of intracranial hemorrhage described in randomized controlled trials, and second with numerous risk markers that have been found to be associated with intracranial hemorrhage in retrospective series. These decisions have become quite complex with different intravenous thrombolytics and mechanical thrombectomy. This review aims to outline some elements of the pathophysiological mechanisms and classifications, describe most of the risk factors identified for each reperfusion therapy, and finally suggest future research directions that could help physicians dealing with these complications.
Published: 2021
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10. Effect of Intense Weathering and Postdepositional Degradation of Organic Matter on Hg/TOC Proxy in Organic‐rich Sediments and its Implicationsfor Deep‐Time Investigations

Author: Guillaume Charbonnier, Thierry Adatte, Karl B. Föllmi, and Guillaume Suan
Subjects: mercury, lowermost Toarcian, Cenomanian‐Turonian boundary, weathering profiles, organic‐matter degradation, Geophysics. Cosmic physics, QC801-809, Geology, QE1-996.5
Abstract: Abstract Mercury (Hg) enrichments in sediments are increasingly used as tracer for distal volcanism in deep‐time investigations. The impact of changes in organic‐matter deposition and preservation on sedimentary Hg sequestration is, however, poorly understood. In this study, we evaluate the potential role of intense weathering and postdepositional organic‐matter degradation on the Hg/TOC proxy in sediments. For this, we investigate weathering profiles in organic‐rich sediments from lowermost Toarcian sediments (T‐OAE; Lafarge cement quarry, France) and organic‐rich deposits from the uppermost Cenomanian‐lowermost Turonian Bonarelli level (OAE2; Furlo and Monte Velo, Italy; Manilva and El Chorro, Spain). The comparison of Hg data along weathering profiles in lowermost Toarcian sediments indicates that recent intense oxidation of the originally organic‐rich deposits has removed up to 89% of the Hg signal. The organic‐rich sediments of the Furlo and Manilva sections are characterized by lower Hg/total organic carbon (TOC) ratios, which suggest important Hg scavenging by organic matter (OM) deposition. At the opposite, in equivalent successions, three significant positive Hg/TOC excursions persist at El Chorro and Monte Velo. These samples exhibit low Hydrogen Index (HI) values, which plot in the field of type‐III OM. This resulted from postdepositional degradation of marine OM type II to type III, which largely modified the amount and the quality of OM. Consequently, the recorded Hg/TOC ratios do not reflect original Hg drawdown but postdepositional oxidation, suggesting that extreme care is needed in the evaluation of the history of OM preservation when using Hg as a proxy for volcanic activity.
Published: 2020
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11. Integration of high-throughput reporter assays identify a critical enhancer of the Ikzf1 gene.

Author: Jaafar Alomairi, Anne M Molitor, Nori Sadouni, Saadat Hussain, Magali Torres, Wiam Saadi, Lan T M Dao, Guillaume Charbonnier, David Santiago-Algarra, Jean Christophe Andrau, Denis Puthier, Tom Sexton, and Salvatore Spicuglia
Subjects: Medicine, Science
Abstract: The Ikzf1 locus encodes the lymphoid specific transcription factor Ikaros, which plays an essential role in both T and B cell differentiation, while deregulation or mutation of IKZF1/Ikzf1 is involved in leukemia. Tissue-specific and cell identity genes are usually associated with clusters of enhancers, also called super-enhancers, which are believed to ensure proper regulation of gene expression throughout cell development and differentiation. Several potential regulatory regions have been identified in close proximity of Ikzf1, however, the full extent of the regulatory landscape of the Ikzf1 locus is not yet established. In this study, we combined epigenomics and transcription factor binding along with high-throughput enhancer assay and 4C-seq to prioritize an enhancer element located 120 kb upstream of the Ikzf1 gene. We found that deletion of the E120 enhancer resulted in a significant reduction of Ikzf1 mRNA. However, the epigenetic landscape and 3D topology of the locus were only slightly affected, highlighting the complexity of the regulatory landscape regulating the Ikzf1 locus.
Published: 2020
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12. Nut Directs p300-Dependent, Genome-Wide H4 Hyperacetylation in Male Germ Cells

Author: Hitoshi Shiota, Sophie Barral, Thierry Buchou, Minjia Tan, Yohann Couté, Guillaume Charbonnier, Nicolas Reynoird, Fayçal Boussouar, Matthieu Gérard, Mingrui Zhu, Lisa Bargier, Denis Puthier, Florent Chuffart, Ekaterina Bourova-Flin, Sarah Picaud, Panagis Filippakopoulos, Afsaneh Goudarzi, Ziad Ibrahim, Daniel Panne, Sophie Rousseaux, Yingming Zhao, and Saadi Khochbin
Subjects: Biology (General), QH301-705.5
Abstract: Summary: Nuclear protein in testis (Nut) is a universal oncogenic driver in the highly aggressive NUT midline carcinoma, whose physiological function in male germ cells has been unclear. Here we show that expression of Nut is normally restricted to post-meiotic spermatogenic cells, where its presence triggers p300-dependent genome-wide histone H4 hyperacetylation, which is essential for the completion of histone-to-protamine exchange. Accordingly, the inactivation of Nut induces male sterility with spermatogenesis arrest at the histone-removal stage. Nut uses p300 and/or CBP to enhance acetylation of H4 at both K5 and K8, providing binding sites for the first bromodomain of Brdt, the testis-specific member of the BET family, which subsequently mediates genome-wide histone removal. Altogether, our data reveal the detailed molecular basis of the global histone hyperacetylation wave, which occurs before the final compaction of the male genome. : A transcription-independent histone hyperacetylation is associated with near-total histone replacement during mouse spermatogenesis. Shiota et al. show the oncogenic factor Nut is expressed in post-meiotic male germ cells, where it recruits p300 and/or CBP and enhances histone H4K5 and H4K8 acetylation, leading to histone-to-protamine replacement. Keywords: BRD4-NUT, protamines, transition proteins, histone variants, spermiogenesis, histone post-translational modifications, cancer testis, testis specific
Published: 2018
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13. RNA-Guided Genomic Localization of H2A.L.2 Histone Variant

Author: Naghmeh Hoghoughi, Sophie Barral, Sandrine Curtet, Florent Chuffart, Guillaume Charbonnier, Denis Puthier, Thierry Buchou, Sophie Rousseaux, and Saadi Khochbin
Subjects: histone dynamics, testis-specific histone variants, epigenetic inheritance, repetitive elements, centromere, Cytology, QH573-671
Abstract: The molecular basis of residual histone retention after the nearly genome-wide histone-to-protamine replacement during late spermatogenesis is a critical and open question. Our previous investigations showed that in postmeiotic male germ cells, the genome-scale incorporation of histone variants TH2B-H2A.L.2 allows a controlled replacement of histones by protamines to occur. Here, we highlight the intrinsic ability of H2A.L.2 to specifically target the pericentric regions of the genome and discuss why pericentric heterochromatin is a privileged site of histone retention in mature spermatozoa. We observed that the intranuclear localization of H2A.L.2 is controlled by its ability to bind RNA, as well as by an interplay between its RNA-binding activity and its tropism for pericentric heterochromatin. We identify the H2A.L.2 RNA-binding domain and demonstrate that in somatic cells, the replacement of H2A.L.2 RNA-binding motif enhances and stabilizes its pericentric localization, while the forced expression of RNA increases its homogenous nuclear distribution. Based on these data, we propose that the specific accumulation of RNA on pericentric regions combined with H2A.L.2 tropism for these regions are responsible for stabilizing H2A.L.2 on these regions in mature spermatozoa. This situation would favor histone retention on pericentric heterochromatin.
Published: 2020
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14. OLOGRAM: determining significance of total overlap length between genomic regions sets.

Author: Quentin Ferré, Guillaume Charbonnier, N. Sadouni, Frédéric Lopez, Yasmina Kermezli, Salvatore Spicuglia, Cécile Capponi, Badih Ghattas, and Denis Puthier
Published: 2020
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15. Patient Selection in a Pragmatic Study on the Management of Patients with Brain Arteriovenous Malformations

Author: Jean Raymond, Anass Benomar, Jean-Christophe Gentric, Elsa Magro, Lorena Nico, Emma Bacchus, Ruby Klink, Daniela Iancu, Alain Weill, Daniel Roy, Michel W. Bojanowski, Chiraz Chaalala, Omer Eker, Isabelle Pelissou-Guyotat, Michel Piotin, Sorin Aldea, Charlotte Barbier, Thomas Gaberel, Chrysanthi Papagiannaki, Stéphane Derrey, Thanh N. Nguyen, Mohamad Abdalkader, Christophe Cognard, Anne-Christine Januel, Jean-François Sabatier, Vincent Jecko, Xavier Barreau, Vincent Costalat, Marine Le Corre, Jean-Yves Gauvrit, Xavier Morandi, Alessandra Biondi, Laurent Thines, Hubert Desal, Romain Bourcier, Rémy Beaujeux, François Proust, Geraldine Viard, Guylaine Gevry, Tim E. Darsaut, Cian J. O'Kelly, Michael MC. Chow, J. Max Findlay, Jeremy L. Rempel, Robert Fahed, Howard Lesiuk, Brian Drake, Marlene dos Santos, Michel Nonent, Julien Ognard, Mourad Cheddad El-Aouni, Romuald Seizeur, Serge Timsit, Olivier Pradier, Romain Boursier, François Thillays, Vincent Roualdes, Raphael Blanc, Lionel Calviere, Jean Yves Gauvrit, Hélène Raoult, François Eugene, Anthony Le Bras, Jean-Christophe Ferre, Christophe Paya, Isabelle Lecouillard, Elodie Nouhaud, Thomas Ronziere, Denis Trystram, Olivier Naggara, Christine Rodriguez-Regent, Basile Kerleroux, Evelyne Emery, Emmanuel Touze, Roberto Riva, Isabelle Pellisou-Guyotat, Jacques Guyotat, Monsef Berhouma, Chloé Dumot, Nassim Bougaci, Guillaume Charbonnier, Serge Bracard, René Anxionnat, Benjamin Gory, Thierry Civit, Valérie Bernier-Chastagner, Gaultier Marnat, Guillaume Penchet, Edouard Gimbert, Aymeri Huchet, Denis Herbreteau, Grégoire Boulouis, Richard Bibi, Héloïse Ifergan, Kévin Janot, Stéphane Velut, Hervé Brunel, Pierre-Hugues Roche, Thomas Graillon, Hadrien Peyriere, Jean-Marc Kaya, Adamou Touta, Lucas Troude, Sébastien Boissonneau, Frédéric Clarençon, Eimad Shotar, Nader Sourour, Stéphanie Lenck, Kévin Premat, Anne-Laure Boch, Philippe Cornu, Aurélien Nouet, Alain Bonafe, Cyril Dargazanli, Gregory Gascou, Pierre-Henri Lefevre, Carlos Riquelme, Raoul Pop, Hélène Cebula, Irène Ollivier, Giorgio Spatola, Laurent Spell, Vanessa Chalumeau, Sophie Gallas, Léon Ikka, Cristian Mihalea, Augustin Ozanne, Jildaz Caroff, Emmanuel Chabert, Charbel Mounayer, Aymeric Rouchaud, François Caire, Frédéric Ricolfi, Pierre Thouant, Catherine Cao, Klaus-Luc Mourier, Walid Farah, Thien Huynh, Rabih G. Tawk, Andrew P. Carlson, Luciana Alves Oliveira Silva, Nayara de Lima Froio, Gisele Sampaio Silva, Francisco J.A. Mont’Alverne, Jose Luri Martins, George Nunes Mendes, and Rodrigo Rivera Miranda
Subjects: Surgery, Neurology (clinical)
Published: 2023
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16. Endovascular treatment of brain arteriovenous malformations: clinical outcomes of patients included in the registry of a pragmatic randomized trial

Author: Jean Raymond, Jean-Christophe Gentric, Elsa Magro, Lorena Nico, Emma Bacchus, Ruby Klink, Christophe Cognard, Anne-Christine Januel, Jean-François Sabatier, Daniela Iancu, Alain Weill, Daniel Roy, Michel W. Bojanowski, Chiraz Chaalala, Xavier Barreau, Vincent Jecko, Chrysanthi Papagiannaki, Stéphane Derrey, Eimad Shotar, Philippe Cornu, Omer F. Eker, Isabelle Pelissou-Guyotat, Michel Piotin, Sorin Aldea, Rémy Beaujeux, François Proust, René Anxionnat, Vincent Costalat, Marine Le Corre, Jean-Yves Gauvrit, Xavier Morandi, Hervé Brunel, Pierre-Hugues Roche, Thomas Graillon, Emmanuel Chabert, Denis Herbreteau, Hubert Desal, Denis Trystram, Charlotte Barbier, Thomas Gaberel, Thanh N. Nguyen, Geraldine Viard, Guylaine Gevry, Tim E. Darsaut, Cian J. O’Kelly, Michael M. C. Chow, J. Max Findlay, Jeremy L. Rempel, Robert Fahed, Howard Lesiuk, Brian Drake, Marlene dos Santos, Michel Nonent, Julien Ognard, Mourad Cheddad El-Aouni, Romuald Seizeur, Serge Timsit, Olivier Pradier, Romain Boursier, François Thillays, Vincent Roualdes, Raphael Blanc, Lionel Calviere, Jean Yves Gauvrit, Hélène Raoult, François Eugene, Anthony Le Bras, Jean-Christophe Ferre, Christophe Paya, Isabelle Lecouillard, Elodie Nouhaud, Thomas Ronziere, Olivier Naggara, Christine Rodriguez-Regent, Basile Kerleroux, Evelyne Emery, Emmanuel Touze, Roberto Riva, Isabelle Pellisou-Guyotat, Jacques Guyotat, Monsef Berhouma, Chloé Dumot, Alessandra Biondi, Laurent Thines, Nassim Bougaci, Guillaume Charbonnier, Serge Bracard, Benjamin Gory, Thierry Civit, Valérie Bernier-Chastagner, Gaultier Marnat, Guillaume Penchet, Edouard Gimbert, Aymeri Huchet, Grégoire Boulouis, Richard Bibi, Héloïse Ifergan, Kévin Janot, Stéphane Velut, Hadrien Peyriere, Jean-Marc Kaya, Adamou Touta, Lucas Troude, Sébastien Boissonneau, Frédéric Clarençon, Nader Sourour, Stéphanie Lenck, Kévin Premat, Anne-Laure Boch, Aurélien Nouet, Alain Bonafe, Cyril Dargazanli, Gregory Gascou, Pierre-Henri Lefevre, Carlos Riquelme, Raoul Pop, Hélène Cebula, Irène Ollivier, Giorgio Spatola, Laurent Spell, Vanessa Chalumeau, Sophie Gallas, Léon Ikka, Cristian Mihalea, Augustin Ozanne, Jildaz Caroff, Charbel Mounayer, Aymeric Rouchaud, François Caire, Frédéric Ricolfi, Pierre Thouant, Catherine Cao, Klaus-Luc Mourier, Walid Farah, Mohamad Abdalkader, Thien Huynh, Rabih G. Tawk, Andrew P. Carlson, Luciana Alves Oliveira Silva, Nayara de Lima Froio, Gisele Sampaio Silva, Francisco J. A. Mont’Alverne, Jose Luri Martins, George Nunes Mendes, and Rodrigo Rivera Miranda
Subjects: General Medicine
Abstract: OBJECTIVE The role of endovascular treatment in the management of patients with brain arteriovenous malformations (AVMs) remains uncertain. AVM embolization can be offered as stand-alone curative therapy or prior to surgery or stereotactic radiosurgery (SRS) (pre-embolization). The Treatment of Brain AVMs Study (TOBAS) is an all-inclusive pragmatic study that comprises two randomized trials and multiple registries. METHODS Results from the TOBAS curative and pre-embolization registries are reported. The primary outcome for this report is death or dependency (modified Rankin Scale [mRS] score > 2) at last follow-up. Secondary outcomes include angiographic results, perioperative serious adverse events (SAEs), and permanent treatment-related complications leading to an mRS score > 2. RESULTS From June 2014 to May 2021, 1010 patients were recruited in TOBAS. Embolization was chosen as the primary curative treatment for 116 patients and pre-embolization prior to surgery or SRS for 92 patients. Clinical and angiographic outcomes were available in 106 (91%) of 116 and 77 (84%) of 92 patients, respectively. In the curative embolization registry, 70% of AVMs were ruptured, and 62% were low-grade AVMs (Spetzler-Martin grade I or II), while the pre-embolization registry had 70% ruptured AVMs and 58% low-grade AVMs. The primary outcome of death or disability (mRS score > 2) occurred in 15 (14%, 95% CI 8%–22%) of the 106 patients in the curative embolization registry (4 [12%, 95% CI 5%–28%] of 32 unruptured AVMs and 11 [15%, 95% CI 8%–25%] of 74 ruptured AVMs) and 9 (12%, 95% CI 6%–21%) of the 77 patients in the pre-embolization registry (4 [17%, 95% CI 7%–37%] of 23 unruptured AVMs and 5 [9%, 95% CI 4%–20%] of 54 ruptured AVMs) at 2 years. Embolization alone was confirmed to occlude the AVM in 32 (30%, 95% CI 21%–40%) of the 106 curative attempts and in 9 (12%, 95% CI 6%–21%) of 77 patients in the pre-embolization registry. SAEs occurred in 28 of the 106 attempted curative patients (26%, 95% CI 18%–35%, including 21 new symptomatic hemorrhages [20%, 95% CI 13%–29%]). Five of the new hemorrhages were in previously unruptured AVMs (n = 32; 16%, 95% CI 5%–33%). Of the 77 pre-embolization patients, 18 had SAEs (23%, 95% CI 15%–34%), including 12 new symptomatic hemorrhages [16%, 95% CI 9%–26%]). Three of the hemorrhages were in previously unruptured AVMs (3/23; 13%, 95% CI 3%–34%). CONCLUSIONS Embolization as a curative treatment for brain AVMs was often incomplete. Hemorrhagic complications were frequent, even when the specified intent was pre-embolization before surgery or SRS. Because the role of endovascular treatment remains uncertain, it should preferably, when possible, be offered in the context of a randomized trial.
Published: 2022
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17. Surgical treatment of brain arteriovenous malformations: clinical outcomes of patients included in the registry of a pragmatic randomized trial

Author: Tim E. Darsaut, Elsa Magro, Michel W. Bojanowski, Chiraz Chaalala, Lorena Nico, Emma Bacchus, Ruby Klink, Daniela Iancu, Alain Weill, Daniel Roy, Jean-Francois Sabatier, Christophe Cognard, Anne-Christine Januel, Isabelle Pelissou-Guyotat, Omer Eker, Pierre-Hugues Roche, Thomas Graillon, Hervé Brunel, Francois Proust, Rémy Beaujeux, Sorin Aldea, Michel Piotin, Philippe Cornu, Eimad Shotar, Thomas Gaberel, Charlotte Barbier, Marine Le Corre, Vincent Costalat, Vincent Jecko, Xavier Barreau, Xavier Morandi, Jean-Yves Gauvrit, Stéphane Derrey, Chrysanthi Papagiannaki, Thanh N. Nguyen, Mohamad Abdalkader, Rabih G. Tawk, Thien Huynh, Geraldine Viard, Guylaine Gevry, Jean-Christophe Gentric, Jean Raymond, Jeremy L. Rempel, Cian J. O’Kelly, Michael M. C. Chow, J. Max Findlay, Robert Fahed, Howard Lesiuk, Brian Drake, Marlene dos Santos, Romuald Seizeur, Michel Nonent, Serge Timsit, Olivier Pradier, Julien Ognard, Mourad Cheddad El-Aouni, Hubert Desal, Romain Boursier, François Thillays, Vincent Roualdes, Raphael Blanc, Jean-François Sabatier, Lionel Calviere, Jean Yves Gauvrit, Isabelle Lecouillard, Elodie Nouhaud, Hélène Raoult, François Eugene, Anthony Le Bras, Jean-Christophe Ferre, Christophe Paya, Thomas Ronziere, Denis Trystram, Olivier Naggara, Christine Rodriguez-Regent, Basile Kerleroux, Evelyne Emery, Emmanuel Touze, Stephane Derrey, Isabelle Pellisou-Guyotat, Jacques Guyotat, Monsef Berhouma, Roberto Riva, Chloé Dumot, Alessandra Biondi, Laurent Thines, Guillaume Charbonnier, Nassim Bougaci, Serge Bracard, René Anxionnat, Valérie Bernier-Chastagner, Thierry Civit, Benjamin Gory, Guillaume Penchet, Edouard Gimbert, Gaulthier Marnat, Aymeri Huchet, Denis Herbreteau, Grégoire Boulouis, Stéphane Velut, Richard Bibi, Héloïse Ifergan, Kévin Janot, Hadrien Peyriere, Jean-Marc Kaya, Adamou Touta, Lucas Troude, Sébastien Boissonneau, Anne-Laure Boch, Frédéric Clarençon, Nader Sourour, Aurélien Nouet, Stéphanie Lenck, Kévin Premat, Alain Bonafe, Cyril Dargazanli, Gregory Gascou, Pierre-Henri Lefevre, Carlos Riquelme, Hélène Cebula, Irène Ollivier, Raoul Pop, Giorgio Spatola, Laurent Spelle, Vanessa Chalumeau, Sophie Gallas, Léon Ikka, Cristian Mihalea, Augustin Ozanne, Jildaz Caroff, Emmanuel Chabert, Charbel Mounayer, Aymeric Rouchaud, Francois Caire, Frédéric Ricolfi, Catherine Cao, Klaus-Luc Mourier, Pierre Thouant, Walid Farah, Andrew P. Carlson, Luciana Alves Oliveira Silva, Nayara de Lima Froio, Gisele Sampaio Silva, Francisco J. A. Mont’Alverne, Jose Luri Martins, George Nunes Mendes, and Rodrigo Rivera Miranda
Subjects: General Medicine
Abstract: OBJECTIVE The Treatment of Brain Arteriovenous Malformations Study (TOBAS) is a pragmatic study that includes 2 randomized trials and registries of treated or conservatively managed patients. The authors report the results of the surgical registry. METHODS TOBAS patients are managed according to an algorithm that combines clinical judgment and randomized allocation. For patients considered for curative treatment, clinicians selected from surgery, endovascular therapy, or radiation therapy as the primary curative method, and whether observation was a reasonable alternative. When surgery was selected and observation was deemed unreasonable, the patient was not included in the randomized controlled trial but placed in the surgical registry. The primary outcome of the trial was mRS score > 2 at 10 years (at last follow-up for the current report). Secondary outcomes include angiographic results, perioperative serious adverse events, and permanent treatment-related complications leading to mRS score > 2. RESULTS From June 2014 to May 2021, 1010 patients were recruited at 30 TOBAS centers. Surgery was selected for 229/512 patients (44%) considered for curative treatment; 77 (34%) were included in the surgery versus observation randomized trial and 152 (66%) were placed in the surgical registry. Surgical registry patients had 124/152 (82%) ruptured and 28/152 (18%) unruptured arteriovenous malformations (AVMs), with the majority categorized as low-grade Spetzler-Martin grade I–II AVM (118/152 [78%]). Thirteen patients were excluded, leaving 139 patients for analysis. Embolization was performed prior to surgery in 78/139 (56%) patients. Surgical angiographic cure was obtained in 123/139 all-grade (89%, 95% CI 82%–93%) and 105/110 low-grade (95%, 95% CI 90%–98%) AVM patients. At the mean follow-up of 18.1 months, 16 patients (12%, 95% CI 7%–18%) had reached the primary safety outcome of mRS score > 2, including 11/16 who had a baseline mRS score ≥ 3 due to previous AVM rupture. Serious adverse events occurred in 29 patients (21%, 95% CI 15%–28%). Permanent treatment-related complications leading to mRS score > 2 occurred in 6/139 patients (4%, 95% CI 2%–9%), 5 (83%) of whom had complications due to preoperative embolization. CONCLUSIONS The surgical treatment of brain AVMs in the TOBAS registry was curative in 88% of patients. The participation of more patients, surgeons, and centers in randomized trials is needed to definitively establish the role of surgery in the treatment of unruptured brain AVMs. Clinical trial registration no.: NCT02098252 (ClinicalTrials.gov)
Published: 2022
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18. Short tandem repeats are important contributors to silencer elements in T cells

Author: Saadat Hussain, Nori Sadouni, Dominic van Essen, Lan T M Dao, Quentin Ferré, Guillaume Charbonnier, Magali Torres, Frederic Gallardo, Charles-Henri Lecellier, Tom Sexton, Simona Saccani, Salvatore Spicuglia, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Méthodes et Algorithmes pour la Bioinformatique (MAB), Laboratoire d'Informatique de Robotique et de Microélectronique de Montpellier (LIRMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), and Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics
Abstract: The action of cis-regulatory elements with either activation or repression functions underpins the precise regulation of gene expression during normal development and cell differentiation. Gene activation by the combined activities of promoters and distal enhancers has been extensively studied in normal and pathological contexts. In sharp contrast, gene repression by cis-acting silencers, defined as genetic elements that negatively regulate gene transcription in a position-independent fashion, is less well understood. Here, we repurpose the STARR-seq approach as a novel high-throughput reporter strategy to quantitatively assess silencer activity in mammals. We assessed silencer activity from DNase hypersensitive I sites in a mouse T cell line. Identified silencers were associated with either repressive or active chromatin marks and enriched for binding motifs of known transcriptional repressors. CRISPR-mediated genomic deletions validated the repressive function of distinct silencers involved in the repression of non-T cell genes and genes regulated during T cell differentiation. Finally, we unravel an association of silencer activity with short tandem repeats, highlighting the role of repetitive elements in silencer activity. Our results provide a general strategy for genome-wide identification and characterization of silencer elements.
Published: 2023
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19. Antithrombotic therapies for neurointerventional surgery: a 2021 French comprehensive national survey

Author: Jildaz, Caroff, Laurent, Aubert, Cécile, Lavenu-Bombled, Samy, Figueiredo, Kamelia, Habchi, Jonathan, Cortese, Francois, Eugene, Julien, Ognard, Florence, Tahon, Géraud, Forestier, Heloise, Ifergan, François, Zhu, Jean-Francois, Hak, Anthony, Reyre, Morgane, Laubacher, Abdoulaye, Traore, Jean Philippe, Desilles, Imad, Derraz, Ricardo, Moreno, Marc, Bintner, Guillaume, Charbonnier, Anthony, Le Bras, Louis, Veunac, Florent, Gariel, Hocine, Redjem, Jacques, Sedat, Guillaume, Tessier, Victor, Dumas, Maxime, Gauberti, Cyril, Chivot, Arturo, Consoli, Nicolas, Bricout, Titien, Tuilier, Alexis, Guedon, Raoul, Pop, Pierre, Thouant, Guillaume, Bellanger, Riccardo, Zannoni, Sebastien, Soize, Johann Sebastian, Richter, Olivier, Heck, Cristian, Mihalea, Julien, Burel, Jean-Baptiste, Girot, Eimad, Shotar, Sebastian, Gazzola, Gregoire, Boulouis, Basile, Kerleroux, Laurent, Spelle, Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Neuroradiologie [Rennes], CHU Pontchaillou [Rennes], CHRU Brest - Service d'Imagerie médicale (CHU - Brest - HM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Optimisation Continue des Actions Thérapeutiques par l'Intégration d'Informations Multimodales, Université de Brest (UBO)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Privé Clairval [Marseille], CHU Limoges, Service de neuroradiologie [Tours], Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hospices Civils de Lyon (HCL), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Neurologie [Hôpitaux Civils de Colmar], Hôpitaux Civils Colmar, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Clermont-Ferrand, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Service de Neuroradiologie Interventionnelle [CHU Besançon], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Le CHCB, Centre Hospitalier de la Côte Basque, CHU de Bordeaux Pellegrin [Bordeaux], Clinique des Cèdres, Centre Hospitalier Universitaire de Nice (CHU Nice), Département de Neuroradiologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Amiens-Picardie, Service Neuroradiologie diagnostique et interventionnelle [Hôpital Foch], Hôpital Foch [Suresnes], CHU Lille, CHU Henri Mondor, Hôpital Lariboisière-Fernand-Widal [APHP], CHU Strasbourg, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Toulouse [Toulouse], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre hospitalier de Pau, Centre Hospitalier Universitaire [Grenoble] (CHU), CHU Rouen, Normandie Université (NU), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Neuroradiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Saint Anne Military Teaching Hospital [Toulon, France], CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Centre Hospitalier Saint-Anne (GHU Paris)
Subjects: Surgery, Neurology (clinical), General Medicine, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: BackgroundNeurointerventionists lack guidelines for the use of antithrombotic therapies in their clinical practice; consequently, there is likely to be significant heterogeneity in antithrombotic use between centers. Through a nationwide survey, we aimed to obtain an exhaustive cross-sectional overview of antithrombotic use in neurointerventional procedures in France.MethodsIn April 2021, French neurointerventional surgery centers were invited to participate in a nationwide 51-question survey disseminated through an active trainee-led research collaborative network (the JENI-RC).ResultsAll 40 centers answered the survey. Fifty-one percent of centers reported using ticagrelor and 43% used clopidogrel as premedication before intracranial stenting. For flow diversion treatment, dual antiplatelet therapy was maintained for 3 or 6 months in 39% and 53% of centers, respectively, and aspirin was prescribed for 12 months or more than 12 months in 63% and 26% of centers, respectively. For unruptured aneurysms, the most common heparin bolus dose was 50 IU/kg (59%), and only 35% of centers monitored heparin activity for dose adjustment. Tirofiban was used in 64% of centers to treat thromboembolic complications. Fifteen percent of these comprehensive stroke centers reported using tenecteplase to treat acute ischemic strokes. Cangrelor appeared as an emergent drug in specific indications.ConclusionThis nationwide survey highlights the important heterogeneity in clinical practices across centers. There is a pressing need for trials and guidelines to further evaluate and harmonize antithrombotic regimens in the neurointerventional field.
Published: 2022
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20. Astrochronology of the Aptian stage and evidence for the chaotic orbital motion of Mercury

Author: Guillaume Charbonnier, Slah Boulila, Jorge E. Spangenberg, Jean Vermeulen, Bruno Galbrun, Institut des Sciences de la Terre de Paris (iSTeP), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Mécanique Céleste et de Calcul des Ephémérides (IMCCE), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Lille-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut des Dynamiques de la Surface Terrestre [Lausanne] (IDYST), Université de Lausanne = University of Lausanne (UNIL), n.a., particulier, ERC AstroGeo, and ANR-19-CE31-0002,AstroMeso,Solution astronomique pour le Mésozoïque(2019)
Subjects: Vocontian Basin, Geophysics, Space and Planetary Science, Geochemistry and Petrology, astrochronology, Earth and Planetary Sciences (miscellaneous), Aptian, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Mercury, OAEs, astronomical chaos
Abstract: International audience; The Aptian stage, between ∼113 and ∼121 million years ago (Ma), was punctuated by a succession of Oceanic Anoxic Events (OAEs), recording extreme global warmings, dramatic expansions of the ocean's oxygen minimum zones, along with perturbations to the biotic and carbon cycles. However, the chronology of the Aptian stage is poorly constrained, impacting the duration and timing of OAEs. Using a greatly expanded sedimentary composite record (380 m) of key outcropping sections in the Vocontian Basin (SE France) combined with available radiometric dates and correlations to a set of astronomical solutions, we provide a constrained absolute astrochronology of the Aptian stage. The 405 kyr (gVenus–gJupiter) eccentricity astronomical timescale indicates a minimal duration of ∼9.4 Myr for the Aptian stage and an age of 122.6 ± 0.3 Ma for the base of the Aptian, consistent with radioisotope dating. We find a deviation in the periodicity of gMercury–gJupiter eccentricity term in the mid-Aptian stage, at ca. 117.19 ± 0.3 Ma, that we ascribe as an expression of the resonance transition σ = (gMercury – gJupiter) – (sMercury – sVenus), in relation with a strong chaotic orbital motion of Mercury. Such a geological observation is supported by a concomitant resonant transition in the La2004 astronomical model.
Published: 2023
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21. IL7-receptor expression is frequent in T-cell acute lymphoblastic leukemia and predicts sensitivity to JAK-inhibition

Author: Lucien Courtois, Aurelie Cabannes-Hamy, Rathana Kim, Marine Delecourt, Antoine Pinton, Guillaume Charbonnier, Mélanie Féroul, Charlotte Smith, Giulia Tueur, Cecile Pivert, Estelle Balducci, Mathieu Simonin, Laure Hélène Angel, Salvatore Spicuglia, Nicolas Boissel, Guillaume P Andrieu, Vahid Asnafi, Philippe Rousselot, and Ludovic Lhermitte
Subjects: Immunology, Cell Biology, Hematology, Biochemistry
Abstract: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy with a dismal prognosis related to refractory/relapsing diseases, raising the need for new targeted-therapies. Activating mutations of the IL7-receptor pathway genes (IL7Rp) play a proven leukemia-supportive role in T-ALL. JAK-inhibitors such as ruxolitinib have recently demonstrated preclinical efficacy. However, prediction markers for sensitivity to JAK-inhibitors are still lacking. Herein, we show that IL7R (CD127) expression is more frequent (~70%) than IL7Rp-mutations in T-ALL (~30%). We compared the so-called non-expressers (no IL7R-expression/IL7Rp-mutation), expressers (IL7R-expression without IL7Rp-mutation) and mutants (IL7Rp-mutations). Integrative multi-omics analysis outlined IL7R-deregulation in virtually all T-ALL subtypes, at the epigenetic-level in non-expressers, genetic-level in mutants, and post-transcriptional level in expressers. Ex-vivo data using primary-derived xenografts support that IL7Rp is functional whenever the IL7R is expressed, regardless of the IL7Rp mutational status. Consequently, ruxolitinib impaired T-ALL survival in both expressers and mutants. Interestingly, we show that expressers displayed ectopic IL7R-expression and IL7Rp-addiction conferring a deeper sensitivity to ruxolitinib. Conversely, mutants were more sensitive to venetoclax than expressers. Overall, combination of ruxolitinib and venetoclax resulted in synergistic effects in both groups. We illustrate the clinical relevance of this association by reporting achievement of complete remission in two patients with refractory/relapsed-T-ALL. This provides proof of concept for translation of this strategy into clinics as bridge to transplant. Altogether, IL7R-expression can be used as a biomarker for sensitivity to JAK-inhibition, thereby expanding the fraction of T-ALL patients eligible to ruxolitinib up to nearly ~70% of T-ALL.
Published: 2023
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22. Defining the optimal size of an aspiration catheter in relation to the arterial diameter during mechanical thrombectomy for stroke

Author: Guillaume Charbonnier, Panagiotis Primikiris, Maxime Desmarets, Gregory Tio, Sergio Vancheri, Fortunato Di Caterino, Giovanni Vitale, and Alessandra Biondi
Subjects: Radiological and Ultrasound Technology, Radiology, Nuclear Medicine and imaging, Neurology (clinical)
Published: 2023
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23. A 20‐million‐year Early Jurassic cyclostratigraphic record and its implications for the chaotic inner Solar System and sea‐level changes

Author: Guillaume Charbonnier, Slah Boulila, Bruno Galbrun, Jacques Laskar, Silvia Gardin, Isabelle Rouget, Institut des Sciences de la Terre de Paris (iSTeP), Institut national des sciences de l'Univers (INSU - CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Mécanique Céleste et de Calcul des Ephémérides (IMCCE), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Lille-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de recherche sur la Paléobiodiversité et les Paléoenvironnements (CR2P), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Paléontologie - Paris (CR2P), and Muséum national d'Histoire naturelle (MNHN)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: sea-level change, Early Jurassic, [SDU.STU.ST]Sciences of the Universe [physics]/Earth Sciences/Stratigraphy, Geology, [SDU.STU.PG]Sciences of the Universe [physics]/Earth Sciences/Paleontology
Abstract: International audience; We present high-resolution (every 2 cm) magnetic susceptibility (MS) data from the Sancerre-Couy drill core (Paris Basin), spanning the latest Sinemurian to the earliest Aalenian (Early Jurassic). This record allows to build a 20-million-year cyclostratigraphic interval using the stable 405 kyr (g2–g5) orbital eccentricity cycle and to focus on long-period cyclicities and their potential implications for the chaotic diffusion in the inner Solar System and sea-level changes. Time series analysis indicates evidence of two long-period cyclicities of 1.6 and 3.4 Myr. These Early Jurassic cyclicities likely correspond to the Cenozoic orbital cyclicities of 2.4 Myr (g4–g3) and 4.7 Myr eccentricity terms. Shortening of eccentricity terms during the Early Jurassic is potentially related to the chaotic orbital motion of the inner planets expressed in the resonant argument θ = 2(g4–g3) − (s4–s3). The 1.6 Myr (g4–g3) cycle matches the third-order eustatic sequences, whereas the 3.4 Myr cycle has no equivalent in the reference eustatic chart. These cycles of several million years are superimposed a cyclicity of ca. 7.5 Myr, which may correspond to the eccentricity term of 9.5 Myr, previously detected in the Cenozoic. Such cyclicity matches the global, ‘shorter’ second-order sea-level sequences and is strongly documented in the sedimentological and mineralogical proxy data, hence supporting the potential key role of orbitally paced climate and sea-level changes at this timescale.
Published: 2023
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24. Correspondence on H3K4 methylation at enhancers and broad promoters concerning the issues raised by Shah et al. in “Examining the Roles of H3K4 Methylation States with Systematically Characterized Antibodies”

Author: Pękowska, Aleksandra, primary, Guillaume, Charbonnier, additional, Jean-Christophe, Andrau, additional, and Spicuglia, Salvatore, additional
Published: 2023
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25. Explore, edit and leverage genomic annotations using Python GTF toolkit.

Author: Frédéric Lopez, Guillaume Charbonnier, Yasmina Kermezli, Mohamed Belhocine, Quentin Ferré, N. Zweig, Mourad Aribi, Aitor González, Salvatore Spicuglia, and Denis Puthier
Published: 2019
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26. Transcriptomic Studies of Antidepressant Action in Rodent Models of Depression: A First Meta-Analysis

Author: El Chérif Ibrahim, Victor Gorgievski, Pilar Ortiz-Teba, Raoul Belzeaux, Gustavo Turecki, Etienne Sibille, Guillaume Charbonnier, Eleni T. Tzavara, Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Fondation FondaMental [Créteil], Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre Neurosciences intégratives et Cognition (INCC - UMR 8002), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Laboratory of Neuropharmacology, Department of Medicine and Life Sciences, Universitat Pompeu Fabra, Pôle Universitaire de Psychiatrie, CHU de Montpellier, Douglas Mental Health University Institute [Montréal], McGill University = Université McGill [Montréal, Canada], Department of Psychiatry, University of Toronto, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), ANR-19-NEUR-0005,ANTaRES,Biomarkers of ANTidepressant RESponse : early indicators and novel targets(2019), and ANR-19-CE37-0017,GeBra,Approches translationelles, profilage transcriptomique, et imagerie cérébrale: vers des nouveaux biomarqueurs et réseaux biologiques dans la resilience au stress(2019)
Subjects: Depressive Disorder, Major, antidepressant, Depression, hippocampus, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Organic Chemistry, fluoxetine, Rodentia, General Medicine, major depression, transcriptomics, Antidepressive Agents, Catalysis, Computer Science Applications, Inorganic Chemistry, Animals, Physical and Theoretical Chemistry, Transcriptome, Molecular Biology, Spectroscopy
Abstract: Antidepressants (ADs) are, for now, the best everyday treatment we have for moderate to severe major depressive episodes (MDEs). ADs are among the most prescribed drugs in the Western Hemisphere; however, the trial-and-error prescription strategy and side-effects leave a lot to be desired. More than 60% of patients suffering from major depression fail to respond to the first AD they are prescribed. For those who respond, full response is only observed after several weeks of treatment. In addition, there are no biomarkers that could help with therapeutic decisions; meanwhile, this is already true in cancer and other fields of medicine. For years, many investigators have been working to decipher the underlying mechanisms of AD response. Here, we provide the first systematic review of animal models. We thoroughly searched all the studies involving rodents, profiling transcriptomic alterations consecutive to AD treatment in naïve animals or in animals subjected to stress-induced models of depression. We have been confronted by an important heterogeneity regarding the drugs and the experimental settings. Thus, we perform a meta-analysis of the AD signature of fluoxetine (FLX) in the hippocampus, the most studied target. Among genes and pathways consistently modulated across species, we identify both old players of AD action and novel transcriptional biomarker candidates that warrant further investigation. We discuss the most prominent transcripts (immediate early genes and activity-dependent synaptic plasticity pathways). We also stress the need for systematic studies of AD action in animal models that span across sex, peripheral and central tissues, and pharmacological classes.
Published: 2022
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27. Pre-Interventional 3D-Printing-Assisted Planning of Flow Disrupter Implantation for the Treatment of an Intracranial Aneurysm

Author: Guillaume Charbonnier, Panagiotis Primikiris, Benjamin Billottet, Aurélien Louvrier, Sergio Vancheri, Serine Ferhat, and Alessandra Biondi
Subjects: aneurysm, 3D printing, interventional neuroradiology, stroke, web, contour, General Medicine
Abstract: Intrasaccular flow disrupter devices (ISFD) have opened up new ways to treat intracranial aneurysms but choosing the correct size of ISFD can be challenging. We describe the first use of 3D printing to assist in the choice of ISFD, and we report an illustrative case. We developed a technique that uses preoperative angiography to make a plastic model of the aneurysm. We tested the deployment of different sizes of intrasaccular flow disruptor on the 3D model under fluoroscopy. The best devices were then used as the first-line strategy to treat the patient. The preoperative 3D printing helped in the successful selection of a first-line ISFD, which was not the one recommended by the manufacturer. Three-dimensional printing can provide interesting information regarding the treatment of intracranial aneurysms using ISFD. Further studies are needed to fully assess its benefits.
Published: 2022

28. Venous balloon test occlusion for pulsatile tinnitus assessment: A clinical feasibility study

Author: Guillaume Charbonnier, Nicole Mariantonia Cancelliere, Arianna Rustici, André Araújo, Irene Vanek, John Rutka, Jose Danilo Bengzon Diestro, Tom Marotta, Julian Spears, and Vitor Mendes Pereira
Subjects: General Medicine
Abstract: Background Pulsatile tinnitus (PT) can have huge impact on the patients’ quality of life and can be associated with curable vascular anomalies. In the present study, we aim firstly to describe our protocol for venous BTO and secondly to report possible predictors for a positive BTO test. Methods All consecutive PT patients undergoing BTO for the purpose of determining eligibility for venous neuro-intervention were included. We recommend BTO for patients when there is uncertainty in the association of the venous pathology identified on non-invasive cross-sectional imaging (CTV or MRV) and the patient's symptoms. Results Between May 2016 and October 2022, we recorded 29 venous balloon test occlusions fulfilling our inclusions criteria. Over the 29 procedures scheduled, 8 finally did not lead to a successful balloon test occlusion. The main reason was that the patient did not hear the PT on the day the angiogram was performed. Two patients could not have the BTO due to difficulties in venous navigation. After BTO, only four patients of our cohort were scheduled for an endovascular treatment. Conclusion We describe a technique and present a single cohort of venous BTO in severe PT patients with unclear anatomical cause. This angiographic test was useful to exclude patients from endovascular surgery and discuss the most probable cause of the PT. Complexity of vascular PT should support a patient-based approach when discussing interventional treatment.
Published: 2023
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29. Deep learning-based cerebral aneurysm segmentation and morphological analysis with three-dimensional rotational angiography

Author: Hidehisa Nishi, Nicole M Cancelliere, Ariana Rustici, Guillaume Charbonnier, Vanessa Chan, Julian Spears, Thomas R Marotta, and Vitor Mendes Pereira
Subjects: Surgery, Neurology (clinical), General Medicine
Abstract: BackgroundThe morphological assessment of cerebral aneurysms based on cerebral angiography is an essential step when planning strategy and device selection in endovascular treatment, but manual evaluation by human raters only has moderate interrater/intrarater reliability.MethodsWe collected data for 889 cerebral angiograms from consecutive patients with suspected cerebral aneurysms at our institution from January 2017 to October 2021. The automatic morphological analysis model was developed on the derivation cohort dataset consisting of 388 scans with 437 aneurysms, and the performance of the model was tested on the validation cohort dataset consisting of 96 scans with 124 aneurysms. Five clinically important parameters were automatically calculated by the model: aneurysm volume, maximum aneurysm size, neck size, aneurysm height, and aspect ratio.ResultsOn the validation cohort dataset the average aneurysm size was 7.9±4.6 mm. The proposed model displayed high segmentation accuracy with a mean Dice similarity index of 0.87 (median 0.93). All the morphological parameters were significantly correlated with the reference standard (all PConclusionThe automatic aneurysm analysis model based on angiography data exhibited high accuracy for evaluating the morphological characteristics of cerebral aneurysms.
Published: 2023
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30. Rescue intracranial permanent stenting for refractory occlusion following thrombectomy: a propensity matched analysis

Author: Heloise Ifergan, Cyril Dargazanli, Wagih Ben Hassen, Jean-Francois Hak, Benjamin Gory, Julien Ognard, Kevin Premat, Gaultier Marnat, Basile Kerleroux, François Zhu, Guillaume Bellanger, Peter B Sporns, Guillaume Charbonnier, Géraud Forestier, Jildaz Caroff, Cédric Fauché, Frédéric Clarençon, Kevin Janot, Bertrand Lapergue, and Gregoire Boulouis
Subjects: Surgery, Neurology (clinical), General Medicine
Abstract: BackgroundRescue intracranial stenting (RIS) can be used in refractory large vessel occlusion (LVO) after mechanical thrombectomy (MT). We aimed to assess the safety and efficacy of RIS versus a propensity matched sample of patients with persistent LVO.MethodsWe retrospectively analysed a multicenter retrospective pooled cohort of patients with anterior LVO (2015−2021) treated with MT, and identified patients with at least three passes and a modified Thrombolysis In Cerebral Infarction (mTICI) score of 0 to 2a. Propensity score matching was used to account for determinants of outcome in patients with or without RIS. The study outcomes included 3 months modified Rankin Scale (mRS) and symptomatic hemorrhagic transformation (HT).Results420 patients with a refractory anterior occlusion were included, of which 101 were treated with RIS (mean age 69 years). Favorable outcome (mRS 0–2) was more frequent in patients with a patent stent at day 1 (53% vs 6%, PConclusionIn selected patients with a refractory intracranial occlusion despite at least three thrombectomy passes, RIS may be associated with an overall shift towards more favorable clinical outcome, and no significant increase in the odds of symptomatic HT or death.
Published: 2023
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31. Potential encoding of coupling between Milankovitch forcing and Earth's interior processes in the Phanerozoic eustatic sea-level record

Author: Nathan Hara, Bruno Galbrun, Guillaume Charbonnier, Slah Boulila, Bilal U. Haq, R. Dietmar Müller, Institut de Mécanique Céleste et de Calcul des Ephémérides (IMCCE), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Lille-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Observatoire Astronomique de l'Université de Genève (ObsGE), Université de Genève (UNIGE), Institut des Sciences de la Terre de Paris (iSTeP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and Université de Genève = University of Geneva (UNIGE)
Subjects: Milankovitch, Biogeochemical cycle, Milankovitch cycles, 010504 meteorology & atmospheric sciences, multi-million year timescales, Climate change, Forcing (mathematics), Geophysics, sea level, 010502 geochemistry & geophysics, 01 natural sciences, Physics::Geophysics, Earth system science, Tectonics, Earth's climate, 13. Climate action, [SDU]Sciences of the Universe [physics], General Earth and Planetary Sciences, tectonics, Sedimentary rock, Astrophysics::Earth and Planetary Astrophysics, Sea level, Geology, 0105 earth and related environmental sciences
Abstract: International audience; The driving mechanisms of Earth's climate system at a multi-Myr timescale have received considerable attention since the 1980's as they are deemed to control largeamplitude climatic variations that result in severe biogeochemical disruptions, major sea-level variations, and the evolution of Earth's land-and seascapes through geological time. The commonly accepted mechanism for these changes derives from the evolution of Earth's coupled plate-mantle system. Connection between Earth's interior and external climate drivers, e.g., Milankovitch insolation forcing, has not been investigated at multi-Myr timescale, because tectonics and astronomical influences at these longer timescales have long been thought as independent pacemakers in the evolution of the Earth system. Here we have analyzed time-series from multiple geological datasets and found common periodicities of 10 and 35 Myr. Additionally, we have highlighted the modulation in amplitude of the 10 Myr cycle band by the 35 Myr cyclicity in sedimentary sea-level data. We then demonstrate the same physical amplitude modulation relationship between these two cyclicities in astronomical (Milankovitch) variations, and establish correlation between Milankovitch and sea-level variations at these two frequency bands. The 10 and 35 Myr cycles are prominent in the geological records, suggesting either unresolved fundamental Milankovitch periodicities, or reflecting a sedimentary energy-transfer process from higher to lower Milankovitch frequencies, as argued here via amplitude modulation analysis in both astronomical and sea-level data. Finally, we find a coherent correlation, at the 35 Myr cycle band, between Milankovitch, sea-level and geodynamic (plate subduction rate) variations, hinting at a coupling between Earth's interior and surface processes via Milankovitch paced climate. Thus, our findings point to a coupling between Milankovitch and Earth's internal forcings, at 10 to 10s of Myr. The most likely scenario that could link insolation-driven climate change to Earth's interior processes is Earth's interior feedbacks to astro-climatically driven mass changes on Earth's surface. We suggest that Earth's interior processes may drive largeamplitude sea-level changes, especially during greenhouse periods, by resonating to astroclimatically driven Earth's surface perturbations.
Published: 2021
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32. Étude rétrospective multicentrique pour évaluer l'efficacité et la sécurité de la prise en charge thérapeutique des anévrysmes fusiformes et dolichoectasies du tronc basilaire. cohorte collaborative du jeni

Author: Héloïse Ifergan, Jean-François Hak, Jean Darcourt, Guillaume Charbonnier, Alessandra Biondi, Alexis Guedon, Emmanuel Houdart, Jean-Philippe Desilles, Quentin Holay, Eimad Shotar, Baptiste Bonnet, Basile Kerleroux, Paul Janvier, Géraud Forestier, Aymeric Rouchaud, Jon Cortese, Peter Sporns, Victor Schulze-Zachau, Gaultier Marnat, Jean Papaxanthos, Benoît Testud, Raoul Pop, Julien Burel, Margaux Lefebvre, Guillaume Tessier, Richard Bibi, Denis Herbreteau, Kevin Janot, Julien Labreuche, Francis Turjman, and Grégoire Boulouis
Subjects: Radiological and Ultrasound Technology, Radiology, Nuclear Medicine and imaging, Neurology (clinical)
Published: 2022
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33. Stenting intra-crânien comme stratégie de sauvetage pour les sténoses intra-crâniennes refractaires chez les patients pris en charge pour une occlusion artérielle proximale. cohorte collaborative du jeni et du registre etis

Author: Héloïse Ifergan, Cyril Dargazanli, Amel Benali, Julien Ognard, Kevin Premat, Laure Bottin, Gaultier Marnat, Basile Kerleroux, Christine Rodriguez, François Zhu, Guillaume Bellanger, Jean Darcourt, Peter Sporns, Marios Psychogios, Guillaume Charbonnier, Alessandra Biondi, Géraud Forestier, Jildaz Caroff, Cédric Fauche, Kevin Janot, Richard Bibi, Denis Herbreteau, Bertrand Lapergue, Jean-François Hak, and Grégoire Boulouis
Subjects: Radiological and Ultrasound Technology, Radiology, Nuclear Medicine and imaging, Neurology (clinical)
Published: 2022
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34. New evidences of subaerial volcanism as a trigger for the Kilian event (Aptian-Albian transition) and major climatic changes from offshore Morocco (DSDP Site 545)

Author: Elodie Bracquart, Guillaume Charbonnier, Sylvain Garel, Thomas Munier, Thierry Adatte, and Julien Danzelle
Subjects: Global and Planetary Change, Oceanography
Published: 2022
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35. Timing and Spectrum of Neurological Complications After Flow Diverter Implantation for Intracranial Aneurysms

Author: Stanislas Smajda, Michel Piotin, Hocine Redjem, Jean-Philippe Desilles, François Delvoye, Simon Escalard, Raphaël Blanc, Mikael Mazighi, Guillaume Charbonnier, Benjamin Maïer, Gabriele Ciccio, and Robert Fahed
Subjects: medicine.medical_specialty, cerebral hemorrhage, Subarachnoid hemorrhage, business.industry, Neurological complication, subarachnoid hemorrhage, medicine.disease, intracranial aneurysm, stroke, Surgery, Aneurysm, Neurology, stents, Cohort, Medicine, Platelet aggregation inhibitor, Neurology (clinical), Neurology. Diseases of the nervous system, business, RC346-429, platelet aggregation inhibitors, Stroke, Flow diverter, Original Research
Abstract: Background and Purpose: The aim of this study was to characterize neurological complications after flow diverter (FD) treatment on a long follow-up cohort and identify predictive factors associated with these complications.Methods: This study was conducted on a monocentric cohort of patients treated for intracranial aneurysms by FD.Results: Between September 2008 and July 2018, 413 patients were treated for 514 aneurysms: 18% of the patients presented with at least one neurological complication during a median follow-up of 446 days (IQR 186–1,210). Sixty-one patients presented with ischemic complications, 13 with hemorrhagic ones and 10 with compressive processes. Among 89 neurological complications 64.5% were peri-operative (occurring within the 30 days following the procedure) and 35.5% were delayed after 1 month.Conclusions: Overall, neurological complications after FD implantation were overrepresented by cerebrovascular ischemic events occurring during the peri-operative period, but also in a delayed manner after 1 year. Long-term follow-up is relevant after aneurysm intervention using FD.
Published: 2021

36. Endosaccular flow disruption with the Contour Neurovascular System: angiographic and clinical results in a single-center study of 60 unruptured intracranial aneurysms

Author: Alessandra Biondi, Panagiotis Primikiris, Giovanni Vitale, and Guillaume Charbonnier
Subjects: Surgery, Neurology (clinical), General Medicine
Abstract: BackgroundThe Contour Neurovascular System is a novel device designed to treat intracranial aneurysms by intrasaccular flow disruption. We report our experience and mid-term follow-up in a series of patients treated with the Contour.MethodsThe patients were divided into an intention to treat and a per protocol population, the latter defined by the successful implantation of the Contour device. The intention to treat population included 53 patients (30 women, mean age 56 years) with 60 unruptured intracranial aneurysms (53 in the anterior circulation and seven in the posterior circulation). There was clinical and angiographic follow-up immediate postoperatively and at 24 hours, 3 months and 1 year using the Raymond–Roy classification and the O’Kelly–Marotta grading scale.ResultsThe Contour was successfully implanted in 54/60 (90%) aneurysms. With regard to the angiographic follow-up, there was adequate occlusion (defined as complete occlusion or presence of a neck remnant) in 31.5% of 54 aneurysms immediately postoperatively, 62.3% (in 53/54 aneurysms) at 24 hours, 81.4% (in 43/54 aneurysms) at 3 months, and 89.3% (in 28/54 aneurysms) at 1 year. Technical complications in 60 aneurysms of the intention to treat population included two (3.3%) inadvertent detachments of the device. Thromboembolic events were observed in four of the 60 aneurysms (6.7%), with no clinical symptoms in three patients and transient morbidity in one (1.7%). No aneurysm bleeding was observed and no patient was retreated during the 1-year follow-up period. There was no permanent morbidity or mortality.ConclusionsThe Contour device is effective and safe in the treatment of intracranial aneurysms. However, more experience and long-term follow-up are needed.
Published: 2022
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37. PRC2 loss of function confers a targetable vulnerability to BET proteins in T-ALL

Author: Vahid Asnafi, Mathieu Simonin, Guillaume Charbonnier, Carlos Graux, Guillaume P. Andrieu, Philippe Rousselot, Françoise Huguet, Charlotte L. Smith, Milena Kohn, Agata Cieslak, Véronique Lhéritier, Salvatore Spicuglia, Marie-Emilie Dourthe, Nicolas Boissel, Hervé Dombret, UCL - (MGD) Service d'hématologie, UCL - SSS/IREC/MONT - Pôle Mont Godinne, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Spinelli, Lionel, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Catholique de Louvain = Catholic University of Louvain (UCL), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Coordination du Groupe GRAALL [CH Lyon-Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier de Versailles André Mignot (CHV), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, BLOOD COMMENTARY, [SDV]Life Sciences [q-bio], Mice, SCID, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Biochemistry, Epigenesis, Genetic, Histones, 0302 clinical medicine, Loss of Function Mutation, Tumor Cells, Cultured, Medicine, 0303 health sciences, Lymphoid Neoplasia, biology, Gene Expression Regulation, Leukemic, Polycomb Repressive Complex 2, JAK-STAT signaling pathway, Hematology, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Stem cell, PRC2, Adult, Adolescent, Antineoplastic Agents, Hormonal, Immunology, [SDV.CAN]Life Sciences [q-bio]/Cancer, macromolecular substances, 03 medical and health sciences, Young Adult, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Humans, Epigenetics, Interleukin-7 receptor, Loss function, 030304 developmental biology, business.industry, Cell Biology, Minimal residual disease, Bromodomain, biology.protein, Cancer research, Prednisone, business, Transcription Factors
Abstract: T-cell acute lymphoblastic leukemia (T-ALL) is a group of aggressive hematological cancers with dismal outcomes that are in need of new therapeutic options. Polycomb repressor complex 2 (PRC2) loss-of-function alterations were reported in pediatric T-ALL, yet their clinical relevance and functional consequences remain elusive. Here, we extensively analyzed PRC2 alterations in a large series of 218 adult T-ALL patients. We found that PRC2 genetic lesions are frequent events in T-ALL and are not restricted to early thymic precursor ALL. PRC2 loss of function associates with activating mutations of the IL7R/JAK/STAT pathway. PRC2-altered T-ALL patients respond poorly to prednisone and have low bone marrow blast clearance and persistent minimal residual disease. Furthermore, we identified that PRC2 loss of function profoundly reshapes the genetic and epigenetic landscapes, leading to the reactivation of stem cell programs that cooperate with bromodomain and extraterminal (BET) proteins to sustain T-ALL. This study identifies BET proteins as key mediators of the PRC2 loss of function-induced remodeling. Our data have uncovered a targetable vulnerability to BET inhibition that can be exploited to treat PRC2-altered T-ALL patients.
Published: 2021
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38. Direct transfer to angiosuite for patients with severe acute stroke treated with thrombectomy: the multicentre randomised controlled DIRECT ANGIO trial protocol

Author: Isabelle Serre, Thierry Moulin, Guillaume Charbonnier, Mariano Musacchio, Aboubaker Cherifi, Solene Moulin, Giovanni Vitale, Lionel Nace, Hamza Achit, Olivier Beaufils, Thomas Loeb, Dominique Cailloce, Thibaut Desmettre, Xavier Combes, Ariel Pablo Lebedinsky, Francis Vuillemet, Nicolas Kempf, Philippe Lemmel, Eric Schluck, Fortunato Di Caterino, Panagiotis Primikiris, Elisabeth de Bustos Medeiros, Benjamin Bouamra, Louise Bonnet, Fabrice Vuillier, Pablo A Lebedinsky, Frederico Bolognini, Elie Cohen-Khallas, Andreas Fickl, Mathilde Goudot, Sylvie Courtois, Sohrab Mostoufizadehghalamfarsa, Alessandro La Porta, Nathalie Caucheteux, Vi Tuan Hua, Mickaël Hoang, Catherine Pradeau, Jean-Marc Mene, Musa Sesay, Aymerci Rouchaud, BIRKER, Juliette, Service de neurologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre d'Investigation Clinique - Innovation Technologique [Nancy] (CIC-IT), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service de Réanimation Médicale [CHRU Nancy], Centre d'investigation clinique - Epidémiologie clinique [Nancy] (CIC-EC), Département de Neuroradiologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Département de neurologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service Neuroradiologie diagnostique et interventionnelle [Hôpital Foch], Hôpital Foch [Suresnes], SAMU 92 [Garches], Hôpital Raymond Poincaré [AP-HP], Service de Neuroradiologie interventionnelle [CHU Limoges], CHU Limoges, Service de Neurologie [CHU Limoges], SAMU/SMUR [Limoges], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHU Bordeaux [Bordeaux], CH Colmar, Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Rothschild [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Groupe hospitalier de la région de Mulhouse Sud-Alsace (GHRMSA), and Hôpital Gui de Chauliac [Montpellier]-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)
Subjects: medicine.medical_specialty, medicine.medical_treatment, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Direct transfer, Brain Ischemia, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 03 medical and health sciences, 0302 clinical medicine, Quality of life, Modified Rankin Scale, interventional radiology, medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Multicenter Studies as Topic, 030212 general & internal medicine, Prospective Studies, Acute stroke, Randomized Controlled Trials as Topic, Thrombectomy, clinical trials, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, medicine.diagnostic_test, business.industry, Endovascular Procedures, Interventional radiology, General Medicine, Emergency department, Thrombolysis, 3. Good health, Clinical trial, Stroke, Treatment Outcome, Neurology, Emergency medicine, Quality of Life, stroke medicine, Medicine, France, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: IntroductionMechanical thrombectomy (MT) increases functional independence in patients with acute ischaemic stroke with anterior circulation large vessel occlusion (LVO), and the probability to achieve functional independence decreases by 20% for each 1-hour delay to reperfusion. Therefore, we aim to investigate whether direct angiosuite transfer (DAT) is superior to standard imaging/emergency department-based management in achieving 90-day functional independence in patients presenting with an acute severe neurological deficit likely due to LVO and requiring emergent treatment with MT.Methods and analysisDIRECT ANGIO (Effect of DIRECT transfer to ANGIOsuite on functional outcome in patient with severe acute stroke treated with thrombectomy: the randomised DIRECT ANGIO Trial) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) study. Eligibility requires a patient ≤75 years, pre-stroke modified Rankin Scale (mRS) 0–2, presenting an acute severe neurological deficit and admitted within 5 hours of symptoms onset in an endovascular-capable centre. A total of 208 patients are randomly allocated in a 1:1 ratio to DAT or standard management. The primary outcome is the rate of patients achieving a functional independence, assessed as mRS 0–2 at 90 days. Secondary endpoints include patients presenting confirmed LVO, patients eligible to intravenous thrombolysis alone, patients with intracerebral haemorrhage and stroke-mimics, intrahospital time metrics, early neurological improvement (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1 at 24 hours) and mRS overall distribution at 90 days and 12 months. Safety outcomes are death and intracerebral haemorrhage transformation. Medico-economics analyses include health-related quality of life and cost utility assessment.Ethics and disseminationThe DIRECT ANGIO trial was approved by the ethics committee of Ile de France 1. Study began in April 2020. Results will be published in an international peer-reviewed medical journal.Trial registration numberNCT03969511.
Published: 2021
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39. European Multicenter Study of ET-COVID-19

Author: Federico Cagnazzo, Michel Piotin, Simon Escalard, Benjamin Maier, Marc Ribo, Manuel Requena, Raoul Pop, Anca Hasiu, Roberto Gasparotti, Dikran Mardighian, Mariangela Piano, Amedeo Cervo, Omer Faruk Eker, Vincent Durous, Nader-Antoine Sourour, Mahmoud Elhorany, Andrea Zini, Luigi Simonetti, Simona Marcheselli, Nuzzi Nunzio Paolo, Emmanuel Houdart, Alexis Guédon, Noémie Ligot, Benjamin Mine, Arturo Consoli, Bertrand Lapergue, Pere Cordona Portela, Xabier Urra, Alejandro Rodriguez, Federico Bolognini, Pablo Ariel Lebedinsky, Anne Pasco-Papon, Sophie Godard, Gaultier Marnat, Igor Sibon, Nicola Limbucci, Patrizia Nencini, Sergio Nappini, Valentina Saia, Valentina Caldiera, Daniele Romano, Giulia Frauenfelder, Ivan Gallesio, Giuliano Gola, Roberto Menozzi, Antonio Genovese, Alberto Terrana, Andrea Giorgianni, Manuel Cappellari, Raffaele Augelli, Paolo Invernizzi, Marco Pavia, Elvis Lafe, Anna Cavallini, Alessia Giossi, Michele Besana, Luca Valvassori, Antonio Macera, Lucio Castellan, Giancarlo Salsano, Fortunato Di Caterino, Alessandra Biondi, Caroline Arquizan, Julien Lebreuche, Gianluca Galvano, Alfio Cannella, Mirco Cosottini, Guido Lazzarotti, Giuseppe Guizzardi, Alessandro Stecco, Rossana Tassi, Sandra Bracco, Elena Bianchini, Camilla Micieli, Rosario Pascarella, Manuela Napoli, Francesco Causin, Hubert Desal, François Cotton, Vincent Costalat, François Delvoye, Gabriele Ciccio, Stanislas Smajda, Hocine Redjem, Solène Hébert, Raphaël Blanc, Mikael Mazighi, Jean-Philippes Desilles, Dan Mihoc, Monica Manisor, Rémy Beaujeux, Véronique Quenardelle, Roxana Gheoca, Valérie Wolff, Guiglielmo Pero, Giussani Giuditta, Ceresa Chiara, Roberto Riva, Matteo Cappucci, Morgane Laubacher, Celia Tuttle, Lorenzo Piergallini, Francis Turjman, Frédéric Clarençon, Eimad Shotar, Stéphanie Lenck, Kevin Premat, Vincent Degos, Yves Samson, Charlotte Rosso, Sonia Alamowitch, Luigi Cirillo, Mauro Gentile, Ludovica Migliaccio, Salvatore Isceri, Simone Rossi, Tommaso Baldini, Massimo Dall’Olio, Martino Cellerini, Jean-Pierre Saint-Maurice, Vittorio Civelli, Matteo Fantoni, Naeije Gilles, Jodaïtis Lise, Lubicz Boris, Stephanie Elens, Bonnet Thomas, Guenego Adrien, Sadeghi Niloufar, Van Nuffelen Marc, Federico Di Maria, Oguzhan Coskun, Georges Rodesch, Sergio Zimatore, Gariel Florent, Jérôme Berge, Patrice Menegon, Xavier Barreau, Thomas Tourdias, Stéphane Olindo, Ludovic Lucas, Jean-Sebastien Liegey, Sharmila Sagnier, Pauline Renou, Marie Couture, Sabrina Debruxelles, Mathilde Poli, Mariano Musacchio, Mariette Delaitre, Riccardo Padolecchia, Giuseppe Ganci, Annalisa Sugo, Barbero Stefano, Taverna Giacomo Giovanni, Umberto Scoditti, Paola Castellini, Lilia Latte, Ilaria Grisendi, Enrico Epifani, Francesco Vizzari, Stefano Molinaro, Luca Nativo, Gabriele Vinacci, Bruno Bonetti, Nicola Micheletti, Giampaolo Tomelleri, Piergiuseppe Zampieri, Mauro Plebani, Andrea Grazioli, Giuseppe Kenneth Ricciardi, Alessandra Polistena, Sgreccia Alessando, Giuseppina Sanfilippo, Alessandra Persico, William Boadu, Maria Giovanna Cuzzoni, Serena Magno, Gianpaolo Toscano, Maria Federica Denaro, Piera Tosi, Bruno Censori, Valentina Puglisi, Luisa Vinciguerra, Valeria De Giuli, Nicola Mavillo, Leonardo Renieri, Enrico Fainardi, Giovanni Vitale, Primikiris Panagiotis, Guillaume Charbonnier, Moratti Claudio, Fabrizio Sallustio, Andrea Wlderk, Riccardo Russo, Mauro Bergui, Chiara Comelli, Andrea Boghi, Marinette Moynier, Elisa Francesca Maria Ciceri, Danilo Toni, Julien Frandon, Isabelle Mourand, Nicolas Gaillard, Salvatore Mangiafico, Imad Derraz, Cyril Dargazanli, Pierre-Henri Lefevre, Carlos Riquelme, Gregory Gascou, Alain Bonafe, Cagnazzo F., Piotin M., Escalard S., Maier B., Ribo M., Requena M., Pop R., Hasiu A., Gasparotti R., Mardighian D., Piano M., Cervo A., Eker O.F., Durous V., Sourour N.-A., Elhorany M., Zini A., Simonetti L., Marcheselli S., Paolo N.N., Houdart E., Guedon A., Ligot N., Mine B., Consoli A., Lapergue B., Cordona Portela P., Urra X., Rodriguez A., Bolognini F., Lebedinsky P.A., Pasco-Papon A., Godard S., Marnat G., Sibon I., Limbucci N., Nencini P., Nappini S., Saia V., Caldiera V., Romano D., Frauenfelder G., Gallesio I., Gola G., Menozzi R., Genovese A., Terrana A., Giorgianni A., Cappellari M., Augelli R., Invernizzi P., Pavia M., Lafe E., Cavallini A., Giossi A., Besana M., Valvassori L., MacEra A., Castellan L., Salsano G., Di Caterino F., Biondi A., Arquizan C., Lebreuche J., Galvano G., Cannella A., Cosottini M., Lazzarotti G., Guizzardi G., Stecco A., Tassi R., Bracco S., Bianchini E., Micieli C., Pascarella R., Napoli M., Causin F., Desal H., Cotton F., Costalat V., Luigi Cirillo, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Strasbourg, Hospices Civils de Lyon (HCL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Hôpital Foch [Suresnes], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CH Colmar, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Bordeaux [Bordeaux], CHU Lille, Université de Lille, and Centre hospitalier universitaire de Nantes (CHU Nantes)
Subjects: Registrie, Male, MESH: Registries, [SDV]Life Sciences [q-bio], Brain ischemia, Cohort Studies, MESH: Aged, 80 and over, MESH: Risk Factors, Risk Factors, Epidemiology, Medicine, MESH: Thrombectomy, MESH: COVID-19, Registries, MESH: Cohort Studies, MESH: Treatment Outcome, Thrombectomy, MESH: Aged, Aged, 80 and over, MESH: Middle Aged, Cerebral infarction, Endovascular Procedures, Middle Aged, cerebral infarction, COVID-19, intracranial hemorrhage, lymphocyte count, thrombectomy, Europe, Treatment Outcome, Cardiology, Female, Cardiology and Cardiovascular Medicine, COVID-19/*complications/epidemiology Cohort Studies *Endovascular Procedures/mortality Europe Female Humans Ischemic Stroke/*complications/mortality/*surgery Male Middle Aged Registries Risk Factors SARS-CoV-2 *Thrombectomy/mortality Treatment Outcome Covid-19 cerebral infarction intracranial hemorrhage lymphocyte count thrombectomy, Cohort study, MESH: Ischemic Stroke, Human, medicine.medical_specialty, MESH: Endovascular Procedures, Coronavirus disease 2019 (COVID-19), Internal medicine, Humans, MESH: SARS-CoV-2, Risk factor, Aged, Ischemic Stroke, Advanced and Specialized Nursing, Endovascular Procedure, MESH: Humans, business.industry, SARS-CoV-2, Risk Factor, medicine.disease, MESH: Male, Clinical trial, Neurology (clinical), MESH: Europe, Cohort Studie, business, Complication, MESH: Female
Abstract: Background and Purpose: Acute ischemic stroke and large vessel occlusion can be concurrent with the coronavirus disease 2019 (COVID-19) infection. Outcomes after mechanical thrombectomy (MT) for large vessel occlusion in patients with COVID-19 are substantially unknown. Our aim was to study early outcomes after MT in patients with COVID-19. Methods: Multicenter, European, cohort study involving 34 stroke centers in France, Italy, Spain, and Belgium. Data were collected between March 1, 2020 and May 5, 2020. Consecutive laboratory-confirmed COVID-19 cases with large vessel occlusion, who were treated with MT, were included. Primary investigated outcome: 30-day mortality. Secondary outcomes: early neurological improvement (National Institutes of Health Stroke Scale improvement ≥8 points or 24 hours National Institutes of Health Stroke Scale 0–1), successful reperfusion (modified Thrombolysis in Cerebral Infarction grade ≥2b), and symptomatic intracranial hemorrhage. Results: We evaluated 93 patients with COVID-19 with large vessel occlusion who underwent MT (median age, 71 years [interquartile range, 59–79]; 63 men [67.7%]). Median pretreatment National Institutes of Health Stroke Scale and Alberta Stroke Program Early CT Score were 17 (interquartile range, 11–21) and 8 (interquartile range, 7–9), respectively. Anterior circulation acute ischemic stroke represented 93.5% of cases. The rate modified Thrombolysis in Cerebral Infarction 2b to 3 was 79.6% (74 patients [95% CI, 71.3–87.8]). Thirty-day mortality was 29% (27 patients [95% CI, 20–39.4]). Early neurological improvement was 19.5% (17 patients [95% CI, 11.8–29.5]), and symptomatic intracranial hemorrhage was 5.4% (5 patients [95% CI, 1.7–12.1]). Patients who died at 30 days exhibited significantly lower lymphocyte count, higher levels of aspartate, and LDH (lactate dehydrogenase). After adjustment for age, initial National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, and successful reperfusion, these biological markers remained associated with increased odds of 30-day mortality (adjusted odds ratio of 2.70 [95% CI, 1.21–5.98] per SD-log decrease in lymphocyte count, 2.66 [95% CI, 1.22–5.77] per SD-log increase in aspartate, and 4.30 [95% CI, 1.43–12.91] per SD-log increase in LDH). Conclusions: The 29% rate of 30-day mortality after MT among patients with COVID-19 is not negligible. Abnormalities of lymphocyte count, LDH and aspartate may depict a patient’s profiles with poorer outcomes after MT. Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT04406090.
Published: 2020
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40. Mechanical thrombectomy practices in France: Exhaustive survey of centers and individual operators

Author: A. Kastler, Christophe Paya, Romain Bourcier, J. Sedat, O. Zurlinden, Alexis Guédon, A. Marchal, Pierre Thouant, Thomas Personnic, Sébastien Soize, Aymeric Rouchaud, Florent Gariel, Olivier Naggara, Kevin Premat, Kevin Janot, Hubert Desal, Mohamed Aggour, Eimad Shotar, R. Hanafi, J.-B. Veyrieres, O. Heck, Pierre-François Manceau, Guillaume Charbonnier, X. Carle, C. Bogey, T. Tuilier, J. Le Moa, Géraud Forestier, Emmanuel Chabert, Simon Escalard, M. Mejdoubi, Nicolas Raynaud, Gregoire Boulouis, Cyril Dargazanli, Omer Eker, Pierre-Olivier Comby, P. Lebedinsky, Raoul Pop, Denis Herbreteau, Jérôme Berge, Victor Dumas, Vincent L'Allinec, Stéphane Velasco, Frédéric Clarençon, J.S. Richter, E. Ducouret, Jean-Christophe Gentric, Arturo Consoli, Caterina Michelozzi, Lili Detraz, Jean-François Hak, Marc Bintner, François Eugène, Charlotte Barbier, J. Caroff, Imad Derraz, Robert Fahed, Jean Darcourt, Jean-Baptiste Girot, Benjamin Gory, Alessandra Biondi, C. Papagiannaki, François Zhu, Gautier Marnat, Julien Ognard, Wagih Ben Hassen, F. Di-Maria, Basile Kerleroux, A. Le Bras, C. Arteaga, Vanessa Chalumeau, P. Guedin, V. Civelli, Service de Radiologie et Imagerie Médicale [CHU Limoges], CHU Limoges, Institut de psychiatrie et neurosciences de Paris (IPNP - U1266 Inserm), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de neuroradiologie [Tours], Imagerie Adaptative Diagnostique et Interventionnelle (IADI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), CHU Marseille, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Reims Champagne-Ardenne (URCA), Centre Hospitalier Universitaire de Reims (CHU Reims), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, XLIM (XLIM), Université de Limoges (UNILIM)-Centre National de la Recherche Scientifique (CNRS), Service de Neuroradiologie interventionnelle [CHU Limoges], CHU Amiens-Picardie, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Neuroradiologie [Brest], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Clermont-Ferrand, Hôpital pasteur [Colmar], CHU Henri Mondor [Créteil], Service de neuroradiologie, imagerie des urgences [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire de Martinique [Fort-de-France, Martinique], Service de neuroradiologie [Grenoble], CHU Grenoble, Service de Neuroradiologie [CHU de Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Services de neuroradiologie [Lille], Hôpital Roger Salengro [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de neuroradiologie [Lyon], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Service de neuroradiologie diagnostique et interventionnelle, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Neuroradiologie [Hôpital Gui de Chauliac], Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Département de neuroradiologie diagnostique et thérapeutique [CHRU Nancy], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre hospitalier territorial Gaston-Bourret [Nouméa], Hôpital de la Fondation Ophtalmologique Adolphe de Rothschild [AP-HP], Service de Neuroradiologie [CHU Lariboisière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Centre Hospitalier de Polynésie Française, Département de Radiologie [CHU de Rennes], Université de Rennes (UR), Service de Radiologie [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), CHU Sud Saint Pierre [Ile de la Réunion], Département de Neuroradiologie [Strasbourg], Les Hôpitaux Universitaires de Strasbourg (HUS), Hôpital Foch [Suresnes], Hopital d'instruction des armées Sainte-Anne [Toulon] (HIA), Service Neuroradiologie Diagnostique et Thérapeutique [CHU Toulouse], Pôle imagerie médicale [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre hospitalier de Vannes, Service de Neuroradiologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Henri Mondor, Hôpital Gui de Chauliac [Montpellier], Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Neuroradiologie Diagnostique et Thérapeutique [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Service de neuroradiologie diagnostique et fonctionnelle [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
Subjects: Male, medicine.medical_specialty, [INFO.INFO-IM] Computer Science [cs]/Medical Imaging, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Suction, Stroke care, Radiography, Interventional, Nationwide survey, [SDV.IB.MN] Life Sciences [q-bio]/Bioengineering/Nuclear medicine, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, Humans, Medicine, Radiology, Nuclear Medicine and imaging, Practice Patterns, Physicians', Stroke, ComputingMilieux_MISCELLANEOUS, Aged, Ischemic Stroke, Thrombectomy, Neuroradiology, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Radiological and Ultrasound Technology, business.industry, Public health, Continuity of Patient Care, Middle Aged, medicine.disease, Magnetic Resonance Imaging, 3. Good health, Mechanical thrombectomy, Female, Stents, Continuity of care, France, Neurology (clinical), Medical emergency, business, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background and purpose Mechanical thrombectomy (MT) has dramatically changed the landscape of stroke care as well as stroke care organization. Public health institutions are faced with the challenge of swiftly providing equal access to this high technical level procedure with rapidly broadening indications, and constantly developing techniques. The aim of this study was to present a current nationwide overview of technical MT practices in France as well as local organizations. Materials and methods Thrombectomy capable French stroke centers, and physicians performing MT were invited to participate to a nationwide survey, disseminated through an existing trainee-led research network (the JENI-RC) under the aegis of the French Society of Neuroradiology. The survey was composed of 64 questions to collect both individual practices and general center-based information. Results All French centers (100%) answered the survey, and 74% (110/148) of active interventional neuroradiologists (INR) performing MT completed individual questionnaires. The mean number of INR per center performing MT was 3.7 ± 1.85, and 85% of the centers were organized for 24/7 continuity of care. MRI was the most commonly used imaging modality for stroke diagnosis and patients’ selection, and perfusion imaging was routinely available in 85% of the centers. Half of centers performed yearly between 100 and 200 MT. Anesthesiologic, and technical considerations are also developed in the manuscript. Conclusions This nationwide survey highlights the impressive response to the challenge of reorganization of stroke care with regards to mechanical thrombectomy in France. Technical and management disparities remain. Most centers remain understaffed to properly function in the long term, but the inflow of INT trainees is substantial.
Published: 2020
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41. [Interest of telemedicine for hospitals with no stroke unit]

Author: Élisabeth, Medeiros-de Bustos, Guillaume, Charbonnier, Benjamin, Bouamra, and Thierry, Moulin
Subjects: Stroke, Humans, Hospitals, Telemedicine
Published: 2020

42. Alternative Enhancer Usage and Targeted Polycomb Marking Hallmark Promoter Choice during T Cell Differentiation

Author: Frederic Koch, Olivier Joffre, Amal Zine El Aabidine, Tom Sexton, Romain Fenouil, Jean-Christophe Andrau, Anne Molitor, Lan T.M. Dao, Muhammad Ahmad Maqbool, Nezih Karasu, Léo Pioger, Georges Lacaud, Salvatore Spicuglia, Francois van Laethem, Ivo Gut, Guillaume Charbonnier, Marta Gut, Sebastian Amigorena, University of Manchester [Manchester], Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universitat Pompeu Fabra [Barcelona] (UPF), Barcelona Institute of Science and Technology (BIST), Institut Curie [Paris], Immunité et cancer (U932), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, 0301 basic medicine, Gene isoform, CapSTARR-seq, T-Lymphocytes, [SDV]Life Sciences [q-bio], Polycomb-Group Proteins, macromolecular substances, Computational biology, General Biochemistry, Genetics and Molecular Biology, Mice, enhancer and promoter usage, long-distance enhancer-promoter interactions, 03 medical and health sciences, 0302 clinical medicine, enhancer redundancy, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Animals, Enhancer, Gene, Epigenomics, biology, Manchester Cancer Research Centre, ResearchInstitutes_Networks_Beacons/mcrc, Cell Differentiation, Promoter, Phenotype, 3. Good health, 030104 developmental biology, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, PRC2, 030217 neurology & neurosurgery, Function (biology), T cell enhancerome
Abstract: During thymic development and upon peripheral activation, T cells undergo extensive phenotypic and functional changes coordinated by lineage-specific developmental programs. To characterize the regulatory landscape controlling T cell identity, we perform a wide epigenomic and transcriptional analysis of mouse thymocytes and naive CD4 differentiated T helper cells. Our investigations reveal a dynamic putative enhancer landscape, and we could validate many of the enhancers using the high-throughput CapStarr sequencing (CapStarr-seq) approach. We find that genes using multiple promoters display increased enhancer usage, suggesting that apparent "enhancer redundancy" might relate to isoform selection. Furthermore, we can show that two Runx3 promoters display long-range interactions with specific enhancers. Finally, our analyses suggest a novel function for the PRC2 complex in the control of alternative promoter usage. Altogether, our study has allowed for the mapping of an exhaustive set of active enhancers and provides new insights into their function and that of PRC2 in controlling promoter choice during T cell differentiation. This work was supported in J.-C.A.’s lab by grants from Fondation pour la Recherche Médicale (FRM) “Amorçage Jeunes Equipes” AJE20130728183, Agence Nationale de la Recherche (ANR) isplice (ANR-11-BSV8-0013), ANR ChromaTin (ANR-10-BLAN-1326), ITMO INCA “Dys3Dpoly,” ESGI 2011 (FP7 funding for high-throughput sequencing), and Ligue Régionale contre le Cancer (Hérault). L.P. was supported by a grant from FRM (4eme année thèse FDT201904007910). The T.S. lab was supported by funds from the European Research Council (ERC) (H2020, Starting Grant 678624 - CHROMTOPOLOGY), the ATIP-Avenir program, and the grant ANR-10-LABX-0030-INRT, under program ANR-10-IDEX-0002-02. A.M.M. is supported by funds from IDEX (University of Strasbourg) and the Institut National Du Cancer.
Published: 2020
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43. Dynamics of broad H3K4me3 domains uncover an epigenetic switch between cell identity and cancer-related genes

Author: Mathieu Simonin, Denis Puthier, Guillaume Charbonnier, Iris Manosalva, Aneta Mikulasova, Eve-Lyne Mathieu, Pierre Ferrier, Charlotte Smith, José David Abad Flores, Mohamed Belhocine, Lydie Pradel, Vahid Asnafi, Salvatore Spicuglia, Daniel Rico, Lisa J. Russell, Hendrik G. Stunnenberg, Joost H.A. Martens, Muhammad Ahmad Maqbool, Agata Cieslak, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Radboud University [Nijmegen], University of Manchester [Manchester], Newcastle University [Newcastle], Centre d'Immunologie de Marseille - Luminy (CIML), and Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: biology, T cell, [SDV]Life Sciences [q-bio], Oncogenes, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Cell biology, Epigenesis, Genetic, Histones, medicine.anatomical_structure, T cell differentiation, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, biology.protein, medicine, Demethylase, H3K4me3, Humans, Ectopic expression, Epigenetics, Gene, Transcription factor, Molecular Biology, Genetics (clinical)
Abstract: International audience; Broad domains of H3K4 methylation have been associated with consistent expression of tissue-specific, cell identity, and tumor suppressor genes. Here, we identified broad domain–associated genes in healthy human thymic T cell populations and a collection of T cell acute lymphoblastic leukemia (T-ALL) primary samples and cell lines. We found that broad domains are highly dynamic throughout T cell differentiation, and their varying breadth allows the distinction between normal and neoplastic cells. Although broad domains preferentially associate with cell identity and tumor suppressor genes in normal thymocytes, they flag key oncogenes in T-ALL samples. Moreover, the expression of broad domain–associated genes, both coding and noncoding, is frequently deregulated in T-ALL. Using two distinct leukemic models, we showed that the ectopic expression of T-ALL oncogenic transcription factor preferentially impacts the expression of broad domain–associated genes in preleukemic cells. Finally, an H3K4me3 demethylase inhibitor differentially targets T-ALL cell lines depending on the extent and number of broad domains. Our results show that the regulation of broad H3K4me3 domains is associated with leukemogenesis, and suggest that the presence of these structures might be used for epigenetic prioritization of cancer-relevant genes, including long noncoding RNAs.
Published: 2020
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44. Neuro-lupus révélé par une hémiparésie et des mouvements anormaux chez une adolescente

Author: Elisabeth Medeiros de Bustos, Matthieu Bereau, Thierry Moulin, Guillaume Charbonnier, Fabrice Vuillier, and Louise Bonnet
Subjects: Gynecology, medicine.medical_specialty, business.industry, medicine, General Medicine, business
Published: 2019
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45. Mechanical Thrombectomy for Acute Ischemic Stroke Amid the COVID-19 Outbreak: Decreased Activity, and Increased Care Delays

Author: Basile Kerleroux, Thibaut Fabacher, Nicolas Bricout, Martin Moïse, Benoit Testud, Sivadji Vingadassalom, Héloïse Ifergan, Kévin Janot, Arturo Consoli, Wagih Ben Hassen, Eimad Shotar, Julien Ognard, Guillaume Charbonnier, Vincent L’Allinec, Alexis Guédon, Federico Bolognini, Gaultier Marnat, Géraud Forestier, Aymeric Rouchaud, Raoul Pop, Nicolas Raynaud, François Zhu, Jonathan Cortese, Vanessa Chalumeau, Jérome Berge, Simon Escalard, Grégoire Boulouis, Cyril Chivot, Riyad Hanafi, Anne Pasco, Jean-Baptiste Girot, Alessandra Biondi, Fortunato Di Caterino, Panagiotis Primikiris, Giovanni Vitale, Louise Bonnet, Florent Gariel, Xavier Barreau, Sabrina Debruxelles, Ludovic Lucas, Patrice Menegon, Stéphane Olindo, Mathilde Poli, Pauline Renou, Sharmila Sagnier, Igor Sibon, Louis Veunac, Jean-Christophe Gentric, Charlotte Barbier, Marion Boulanger, Julien Cogez, Sophie Guettier, Romain Schneckenburger, Emmanuel Touze, Mariette Delaitre, Pablo Lebendinsky, Mariano Musacchio, Frédéric Ricolfi, Pierre Thouant, François Caparros, Barbara Casolla, Lucie Della Schiava, Nelly Dequatre, Hilde Henon, Marco Pasi, Apolline Kazemi, Fouzi Bala, Laurent Estrade, Charbel Mounayer, Susanna Saleme, Francisco Macian-Montoro, Omer Eker, François Cotton, Karine Blanc-Lasserre, Serkan Cakmak, Tae-Hee Cho, Laurent Derex, Anne-Claire Lukaszewicz, Laura Mechtouff, Norbert Nighoghossian, Frédéric Philippeau, Roberto Riva, Francis Turjman, Anne-Evelyne Vallet, Xavier Carle, Philippe Dory-Lautrec, Anthony Reyre, Jean-François Hak, Hervé Brunel, Amel Benali, François-Louis Collemiche, Cyril Dargazanli, Frederico Cagnazzo, Imad Derraz, Caroline Arquizan, Lucas Corti, Vincent Costalat, Nicolas Gaillard, Grégory Gascou, Pierre-Henri Lefèvre, Isabelle Mourand, Carlos Riquelme, Anne Laure Derelle, Benjamin Gory, Liang Liao, Romain Tonnelet, René Anxionnat, Mathieu Bonnerot, Serge Bracard, Marc Braun, Lisa Humbertjean, Jean-Christophe Lacour, Gioia Mione, Sophie Planel, Sébastien Richard, Nolwenn Riou-Comte, Emmanuelle Schmitt, Romain Bourcier, Lili Detraz, Hubert Desal, Pierre-Louis Alexandre, Benjamin Daumas-Duport, Cédric Lenoble, Monica Roy, Oghuzan Coskun, Frederico Di Maria, Bertrand Lapergue, Georges Rodesch, Adrien Wang, David Weisenburger-Lile, Sergio Zimatore, Nadia Ajili, Géraldine Buard, Serge Evrard, Lucas Gorza, Julie Gratieux, Morgan Leguen, Sylvie Marinier, Fernando Pico, Roxanna Poll, Haja Rakotoharinandrasana, Philippe Tassan, Maya Tchikviladze, François Delvoye, Solène Hebert, Raphaël Blanc, Gabriele Ciccio, Jean-Philippe Desilles, Benjamin Maier, Mikael Mazighi, Michel Piotin, Hocine Redjem, Stanislas Smajda, Malek Ben Maacha, Ovide Corabianu, Thomas De Broucker, Olivier Ille, Eric Manchon, Michael Obadia, Mickael Obadia, Igor Raynouard, Roxanne Peres, Candice Sabben, Didier Smadja, Guillaume Taylor, Laurie-Anne Thion, Augustin Lecler, Laurent Spelle, Christian Denier, Jildaz Caroff, Olivier Chassin, laurent Spelle, Laura Venditti, Armand Aymard, Jean Betty, Vittorio Civelli, Michael Eliezer, Matteo Fantoni, Emmanuel Houdart, Marc-Antoine Labeyrie, Jean-Pierre Saint Maurice, Erwah Kalsoum, Aurelien Pacini, Chawkat Ramadane, Titien Tuilier, Adrien Villain, Frédéric Clarencon, Vincent Degos, Ahmed Elhfnawy, Mahmoud Elhorany, Stéphanie Lenck, Kevin Premat, Nader-Antoine Sourour, Sonia Alamowitch, Flore Baronnet, Sophie Crozier, Sandrine Deltour, Anne Leger, Charlotte Rosso, Nadya Pyatigorskaya, Christine Rodriguez Regent, Denis Trystram, Olivier Naggara, Pierre Seners, Guillaume Turc, Myriam Edjlali, Rémi Agbonon, Mohammed Alotaibi, Antoine Sonchet, Catherine Oppenheim, Jean François Meder, Joseph Benzakoun, Laurence Legrand, Cédric Fauché, Stéphane Velasco, Pierre François Manceau, Sebastien Solène Soize Moulin, François Eugene, Jean-Christophe Ferre, Christophe Paya, Jean-Yves Gauvrit, Sophie Langnier-Lemercier, Maria Lassale, helene Raoult, thomas Ronziere, Clément Tracol, Stéphane Vannier, Julien Burel, Julien Le Moal, Chrysanthi Papagiannaki, Mohamed Aggour, Marina Sachet, Claire Boutet, Remy Beaujeux, Anca Hasiu, Monica Manisor, Dan Mihoc, Stéphane Kremer, Charles Arteaga, Sébastien Gazzola, Jean Darcourt, Christophe Cognard, Fabrice Bonneville, Anne Christine Januel, Jean-Marc Olivot, Nicolas Raposo, Alain Viguier, Richard Bibi, Fakhreddine Boustia, Denis Herbreteau, Igor Maldonado, and Ana-Paula Narata
Subjects: Male, 2019-20 coronavirus outbreak, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Mechanical Thrombolysis, Pneumonia, Viral, 030204 cardiovascular system & hematology, medicine.disease_cause, Brain Ischemia, Time-to-Treatment, 03 medical and health sciences, Betacoronavirus, 0302 clinical medicine, Patient Admission, Pandemic, Medicine, Humans, Prospective Studies, Acute ischemic stroke, Pandemics, Coronavirus, Aged, Advanced and Specialized Nursing, Aged, 80 and over, business.industry, SARS-CoV-2, Outbreak, COVID-19, Middle Aged, 3. Good health, Mechanical thrombectomy, Hospitalization, Stroke, Emergency medicine, Female, Neurology (clinical), France, Cardiology and Cardiovascular Medicine, business, Coronavirus Infections, Delivery of Health Care, 030217 neurology & neurosurgery, Procedures and Techniques Utilization
Abstract: Background and Purpose: The efficiency of prehospital care chain response and the adequacy of hospital resources are challenged amid the coronavirus disease 2019 (COVID-19) outbreak, with suspected consequences for patients with ischemic stroke eligible for mechanical thrombectomy (MT). Methods: We conducted a prospective national-level data collection of patients treated with MT, ranging 45 days across epidemic containment measures instatement, and of patients treated during the same calendar period in 2019. The primary end point was the variation of patients receiving MT during the epidemic period. Secondary end points included care delays between onset, imaging, and groin puncture. To analyze the primary end point, we used a Poisson regression model. We then analyzed the correlation between the number of MTs and the number of COVID-19 cases hospitalizations, using the Pearson correlation coefficient (compared with the null value). Results: A total of 1513 patients were included at 32 centers, in all French administrative regions. There was a 21% significant decrease (0.79; [95%CI, 0.76–0.82]; P P P R 2 −0.51; P =0.04). Patients treated during the COVID outbreak were less likely to receive intravenous thrombolysis and to have unwitnessed strokes (both P Conclusions: Our study showed a significant decrease in patients treated with MTs during the first stages of the COVID epidemic in France and alarming indicators of lengthened care delays. These findings prompt immediate consideration of local and regional stroke networks preparedness in the varying contexts of COVID-19 pandemic evolution.
Published: 2020

46. OLOGRAM : Determining significance of total overlap length between genomic regions sets

Author: Cécile Capponi, Frédéric Lopez, Nori Sadouni, Badih Ghattas, Denis Puthier, Salvatore Spicuglia, Yasmina Kermezli, Guillaume Charbonnier, Quentin Ferré, Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Informatique et Systèmes (LIS), Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de Mathématiques de Marseille (I2M), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Centre National de la Recherche Scientifique (CNRS), éQuipe d'AppRentissage de MArseille (QARMA), Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS), Spinelli, Lionel, and Aix Marseille Université (AMU)-Université de Toulon (UTLN)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Statistics and Probability, 0303 health sciences, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer science, [SDV]Life Sciences [q-bio], computer.software_genre, Biochemistry, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Computer Science Applications, Functional relation, [STAT]Statistics [stat], [SDV] Life Sciences [q-bio], 03 medical and health sciences, Computational Mathematics, 0302 clinical medicine, Computational Theory and Mathematics, [INFO.INFO-LG]Computer Science [cs]/Machine Learning [cs.LG], Data mining, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], Molecular Biology, computer, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: Motivation Various bioinformatics analyses provide sets of genomic coordinates of interest. Whether two such sets possess a functional relation is a frequent question. This is often determined by interpreting the statistical significance of their overlaps. However, only few existing methods consider the lengths of the overlap, and they do not provide a resolutive P-value. Results Here, we introduce OLOGRAM, which performs overlap statistics between sets of genomic regions described in BEDs or GTF. It uses Monte Carlo simulation, taking into account both the distributions of region and inter-region lengths, to fit a negative binomial model of the total overlap length. Exclusion of user-defined genomic areas during the shuffling is supported. Availability and implementation This tool is available through the command line interface of the pygtftk toolkit. It has been tested on Linux and OSX and is available on Bioconda and from https://github.com/dputhier/pygtftk under the GNU GPL license. Contact denis.puthier@univ-amu.fr Supplementary information Supplementary data are available at Bioinformatics online.
Published: 2020
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47. The expression of early Aptian to latest Cenomanian oceanic anoxic events in the sedimentary record of the Briançonnais domain

Author: Guillaume Charbonnier, Karl B. Föllmi, Jorge E. Spangenberg, and Thierry Adatte
Subjects: Total organic carbon, Global and Planetary Change, 010504 meteorology & atmospheric sciences, Aptian, Geochemistry, 15. Life on land, 010502 geochemistry & geophysics, Oceanography, 01 natural sciences, Anoxic waters, Cretaceous, Bottom water, Water column, 13. Climate action, Sedimentary rock, 14. Life underwater, Cenomanian, Geology, 0105 earth and related environmental sciences
Abstract: The Brianconnais domain is an important paleogeographic unit in the Alps, which represents a structural high within the former Alpine Tethys Ocean. Expressions of the most important Cretaceous oceanic anoxic events (OAE1a-d and OAE2) are exceptionally well preserved in the Subbrianconnais unit at Roter Sattel in the Fribourg Prealps, Switzerland. The main objective of this study was to reconstruct oxygen contents and trophic levels in the water column for each OAE. To accomplish this we used an integrated multi-proxy approach, including total organic carbon (TOC), phosphorus (P), and redox and productivity-sensitive trace-element contents (RSTE, PSTE). RSTE enrichments associated with the highest TOC values (up to 5.4 and 4.8 wt%) and with the lowest Mn contents in sediments equivalent to the Selli and Paquier OAEs (1a and 1b) indicate the presence of intermittent anoxic to euxinic conditions during these events. Sediments equivalent to Bonarelli OAE2 near the Cenomanian-Turonian (CT) boundary are also characterized by significant trace-element enrichments in comparison to average shale values. Mo and U enrichment factors (EFs) in the lower Aptian and lower Albian intervals are characteristic of an unrestricted marine environment, and in the Cenomanian-Turonian boundary interval they indicate a relationship with a particulate Fe-Mn-oxyhydroxide shuttle within the water column. In the OAE1a interval the elevated total P content associated with higher Corg/Ptot ratios and maxima in TOC values suggests that a part of the remobilized P remained trapped in the sediments. By contrast, the lower Ptot values associated with RSTE and Corg/Ptot enrichments in the OAE1b and OAE2 intervals indicate that a significant part of P was remobilized and escaped to the bottom water. Our results highlight the combined roles of regional and global parameters in the development of oxygen-deficient conditions that may lead to anoxia and increase in organic matter preservation during the OAEs. The differentiated topography of the Brianconnais domain associated with global climate and sea-level change and its influence on weathering in general, and more specifically on the mobilization of sediments on the adjacent ridge, modulated nutrient availability in different proportions during the different “mid”-Cretaceous OAEs.
Published: 2018
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48. Effect of Intense Weathering and Postdepositional Degradation of Organic Matter on Hg/TOC Proxy in Organic‐rich Sediments and its Implicationsfor Deep‐Time Investigations

Author: Karl B. Föllmi, Thierry Adatte, Guillaume Charbonnier, Guillaume Suan, Laboratoire de Géologie de Lyon - Terre, Planètes, Environnement (LGL-TPE), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Université Jean Monnet - Saint-Étienne (UJM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: chemistry.chemical_classification, weathering profiles, mercury, 010504 meteorology & atmospheric sciences, lowermost Toarcian, chemistry.chemical_element, Weathering, 010502 geochemistry & geophysics, 01 natural sciences, Mercury (element), Geophysics, organic-matter degradation, chemistry, [SDU]Sciences of the Universe [physics], Geochemistry and Petrology, Environmental chemistry, Cenomanian-Turonian boundary, Organic matter, Geology, 0105 earth and related environmental sciences
Abstract: International audience; Mercury (Hg) enrichments in sediments are increasingly used as tracer for distal volcanism in deep-time investigations. The impact of changes in organic-matter deposition and preservation on sedimentary Hg sequestration is, however, poorly understood. In this study, we evaluate the potential role of intense weathering and postdepositional organic-matter degradation on the Hg/TOC proxy in sediments. For this, we investigate weathering profiles in organic-rich sediments from lowermost Toarcian sediments (T-OAE; Lafarge cement quarry, France) and organic-rich deposits from the uppermost Cenomanian-lowermost Turonian Bonarelli level (OAE2; Furlo and Monte Velo, Italy; Manilva and El Chorro, Spain). The comparison of Hg data along weathering profiles in lowermost Toarcian sediments indicates that recent intense oxidation of the originally organic-rich deposits has removed up to 89% of the Hg signal. The organic-rich sediments of the Furlo and Manilva sections are characterized by lower Hg/total organic carbon (TOC) ratios, which suggest important Hg scavenging by organic matter (OM) deposition. At the opposite, in equivalent successions, three significant positive Hg/TOC excursions persist at El Chorro and Monte Velo. These samples exhibit low Hydrogen Index (HI) values, which plot in the field of type-III OM. This resulted from postdepositional degradation of marine OM type II to type III, which largely modified the amount and the quality of OM. Consequently, the recorded Hg/TOC ratios do not reflect original Hg drawdown but postdepositional oxidation, suggesting that extreme care is needed in the evaluation of the history of OM preservation when using Hg as a proxy for volcanic activity.
Published: 2020
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49. Blueprint of human thymopoiesis reveals molecular mechanisms of stage-specific TCR enhancer activation

Author: Joost H.A. Martens, Guillaume Hypolite, Guillaume Andrieu, Charlotte Smith, Melania Tesio, Denis Puthier, Eva M. Janssen-Megens, Guillaume Charbonnier, Hendrik G. Stunnenberg, Ivo Gut, Salvatore Spicuglia, Marta Gut, Mohamed Belhocine, Nicolas Boissel, Eve-Lyne Mathieu, Vahid Asnafi, Elizabeth Macintyre, Arnaud Petit, Aurore Touzart, Agata Cieslak, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Theories and Approaches of Genomic Complexity (TAGC), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Radboud university [Nijmegen], Universitat Pompeu Fabra [Barcelona] (UPF), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Plan Cancer2015 (C15076AS), PlBio-INCA, and Equipe Labelis ́ee Ligue contrele Cancer, ANR-11-IDEX-0001,Amidex,INITIATIVE D'EXCELLENCE AIX MARSEILLE UNIVERSITE(2011), European Project: 282510,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,BLUEPRINT(2011), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Radboud University [Nijmegen]
Subjects: Lymphoma, Cellular differentiation, [SDV]Life Sciences [q-bio], T-Lymphocytes, Lymphocyte Activation, Histones, Epigenome, Mice, 0302 clinical medicine, Immunology and Allergy, Epigenomics, 0303 health sciences, Thymocytes, Leukemia, Stem Cells, Cell Differentiation, Chromatin, 3. Good health, Cell biology, DNA Demethylation, medicine.anatomical_structure, Enhancer Elements, Genetic, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Protein Binding, T cell, Immunology, Receptors, Antigen, T-Cell, Thymus Gland, Biology, Gene Rearrangement, T-Lymphocyte, Article, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Animals, Humans, Enhancer, Transcription factor, Molecular Biology, 030304 developmental biology, Cell Nucleus, Homeodomain Proteins, T-cell receptor, DNA Methylation, Hematopoiesis, Leukemia & Lymphoma, Gene Expression Regulation, T cell differentiation, Apoptosis Regulatory Proteins, Protein Processing, Post-Translational
Abstract: This manuscript presents a comprehensive epigenomic analysis of human thymocyte development and provides new molecular insights into the mechanism by which the TCRA enhancer is activated during thymic maturation by developmentally programmed repression of HOXA factors., Cell differentiation is accompanied by epigenetic changes leading to precise lineage definition and cell identity. Here we present a comprehensive resource of epigenomic data of human T cell precursors along with an integrative analysis of other hematopoietic populations. Although T cell commitment is accompanied by large scale epigenetic changes, we observed that the majority of distal regulatory elements are constitutively unmethylated throughout T cell differentiation, irrespective of their activation status. Among these, the TCRA gene enhancer (Eα) is in an open and unmethylated chromatin structure well before activation. Integrative analyses revealed that the HOXA5-9 transcription factors repress the Eα enhancer at early stages of T cell differentiation, while their decommission is required for TCRA locus activation and enforced αβ T lineage differentiation. Remarkably, the HOXA-mediated repression of Eα is paralleled by the ectopic expression of homeodomain-related oncogenes in T cell acute lymphoblastic leukemia. These results highlight an analogous enhancer repression mechanism at play in normal and cancer conditions, but imposing distinct developmental constraints., Graphical Abstract
Published: 2020
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50. Mechanical Thrombectomy for Acute Ischemic Stroke Amid the COVID-19 Outbreak in France: Decreased Activity, and Increased Care Delays

Author: Alexis Guédon, Julien Ognard, Géraud Forestier, Nicolas Bricout, Basile Kerleroux, Guillaume Charbonnier, Martin Moise, Wagih Ben Hassen, Simon Escalard, Gregoire Boulouis, Gaultier Marnat, Aymeric Rouchaud, Nicolas Raynaud, Raoul Pop, Jérôme Berge, Vanessa Chalumeau, Arturo Consolli, Sivadji Vingadassalom, Benoit Testud, Héloïse Ifergan, Eimad Shotar, Vincent L'Allinec, Jonathan Cortese, Kevin Janot, Federico Bolognini, François Zhu, and Thibaut Fabacher
Subjects: Mechanical thrombectomy, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Emergency medicine, Epidemiology, medicine, Outbreak, medicine.disease, business, Acute ischemic stroke, Stroke
Published: 2020
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