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1. Integrating artificial intelligence into lung cancer screening: a randomised controlled trial protocol

Author

Paul Hofman, Sylvie Leroy, Jonathan Benzaquen, Bernard Padovani, Charles Hugo Marquette, Fontas Eric, Eric Fontas, Stephanie Lopez, Nesrine Rouis, Jacques Boutros, Allegra Maryline, Amamou-Elhani Faten, ARFI Thierry, Baque Jean, Baque-Juston Marie, Barel Remy, Barrios Baretto Deisy, Baudin Guillaume, Beck Camille, Bellmann Laurent, Benchetrit Maxime, Benkirane Mohamed-Taib, Benyoussef Sid Ali, Benzaquen Jonathan, Berthet Jean Philippe, Bonnard Eric, Bordone Olivier, Boutros Jacques, Boyer Guy-René, Bulsei Julie, Caillon Cynthia, Castelnau Olivier, Chalmin Jérémy, Chebib Ralph, Cohen Charlotte, Cruzel Coralie, Degoutte Aurélien, Delin Margot, Diascorn Yann, Doux Nathalie, Durand Lorraine, Duval Yannick, El Hemweh Omar, Fayada Julien, Felderhoof Eric, Feliciello Stéphane:, Femenia Richard, Ferrari Victoria, Francisci Marc Paul, Ghalloussi Hannah, Gomez-Caro-Andres Abel, Gora Assia, Griffonnet Jennifer, Gubeno Marie Christine, Guigay Joël, Hamila Marame, Harrathi Mohamed-Ali, Henaut Quentin, Herin Edouard, Hofman Paul, Hofman Véronique, ILIE Marius, Korzeniewski Sylvia, Lalvee Salomé, Lassalle Sandra, Le Heron Charles, Leray Loïc, Leriche Julien, Lerousseau Lionel, Leroy Sylvie, Lespinet Fabre Virginie, Lestrez Roxane, Leyssalle Axelle, Long Mira Elodie, Lopez Stephanie, Mahler Valentin, Maniel Charlotte, Marcano Xavier, Marco Roucayrol Sabine, Marquette Charles-Hugo, Martin Nicolas, Mistri Aurélie, Nicolle Isabelle, Novellas Sébastien, Oddo Frédéric, Otto Josiane, Padovani Bernard, PERQUIS Marie Pierre, Philibert Lorène, Pop Daniel, Pottier Héloïse, Raguin Olivier, Rolland Fabien, Rouis Nesrine, Rousset Johanna, Ruitort Frédéric, Sanfiorenzo Céline, Selva Eric, Tanga Virginie, Tardy Magalie, Thomas Olivier, Varenio Sophie, Verdoire Paul, Vigny Isabelle, Washetine Kévin, Zurlinden Olivier, Tarhini Adam, and Perrotin Cédric

Subjects
Medicine
Abstract

Introduction Lung cancer (LC) is the most common cause of cancer-related deaths worldwide. Its early detection can be achieved with a CT scan. Two large randomised trials proved the efficacy of low-dose CT (LDCT)-based lung cancer screening (LCS) in high-risk populations. The decrease in specific mortality is 20%–25%.Nonetheless, implementing LCS on a large scale faces obstacles due to the low number of thoracic radiologists and CT scans available for the eligible population and the high frequency of false-positive screening results and the long period of indeterminacy of nodules that can reach up to 24 months, which is a source of prolonged anxiety and multiple costly examinations with possible side effects.Deep learning, an artificial intelligence solution has shown promising results in retrospective trials detecting lung nodules and characterising them. However, until now no prospective studies have demonstrated their importance in a real-life setting.Methods and analysis This open-label randomised controlled study focuses on LCS for patients aged 50–80 years, who smoked more than 20 pack-years, whether active or quit smoking less than 15 years ago. Its objective is to determine whether assisting a multidisciplinary team (MDT) with a 3D convolutional network-based analysis of screening chest CT scans accelerates the definitive classification of nodules into malignant or benign. 2722 patients will be included with the aim to demonstrate a 3-month reduction in the delay between lung nodule detection and its definitive classification into benign or malignant.Ethics and dissemination The sponsor of this study is the University Hospital of Nice. The study was approved for France by the ethical committee CPP (Comités de Protection des Personnes) Sud-Ouest et outre-mer III (No. 2022-A01543-40) and the Agence Nationale du Medicament et des produits de Santé (Ministry of Health) in December 2023. The findings of the trial will be disseminated through peer-reviewed journals and national and international conference presentations.Trial registration number NCT05704920.

Published
2024
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2. Activation of the P2RX7/IL-18 pathway in immune cells attenuates lung fibrosis

Author

Serena Janho dit Hreich, Thierry Juhel, Sylvie Leroy, Alina Ghinet, Frederic Brau, Veronique Hofman, Paul Hofman, and Valerie Vouret-Craviari

Subjects
purinergic signaling, P2X7 receptor, lung fibrosis, Medicine, Science, Biology (General), QH301-705.5
Abstract

Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease associated with progressive and irreversible deterioration of respiratory functions that lacks curative therapies. Despite IPF being associated with a dysregulated immune response, current antifibrotics aim only at limiting fibroproliferation. Transcriptomic analyses show that the P2RX7/IL18/IFNG axis is downregulated in IPF patients and that P2RX7 has immunoregulatory functions. Using our positive modulator of P2RX7, we show that activation of the P2RX7/IL-18 axis in immune cells limits lung fibrosis progression in a mouse model by favoring an antifibrotic immune environment, with notably an enhanced IL-18-dependent IFN-γ production by lung T cells leading to a decreased production of IL-17 and TGFβ. Overall, we show the ability of the immune system to limit lung fibrosis progression by targeting the immunomodulator P2RX7. Hence, treatment with a small activator of P2RX7 may represent a promising strategy to help patients with lung fibrosis.

Published
2024
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3. Feasibility of home initiation of an airway clearance device (SIMEOX) by telecare in people with non-cystic fibrosis bronchiectasis: a pilot study

Author

Jean-Christian Borel, Nathalie Arnol, Sylvie Leroy, Marlène Murris-Espin, Rebecca Hamidfar, Marie Mahot, Raphael Abouly, Hughes Gauchez, Sophie Jacques, Eloise Joffray, and Laurent Morin

Subjects
Medicine, Diseases of the respiratory system, RC705-779
Abstract

Background Mucociliary clearance is a cornerstone of the management of people with non-cystic fibrosis bronchiectasis (NCFB). SIMEOX, an innovative device, could facilitate autonomous airway clearance, but its use requires specific training. We hypothesised that telecare would be an effective means to train people with NCFB in the handling of device and to monitor and promote device adherence.Objectives (1) To evaluate frequency of use of the SIMEOX for 10 weeks after telecare training. (2) To assess user satisfaction and clinical efficacy of the SIMEOX+telecare.Methods Multicentre, prospective, pilot study in adults with NCFB. A SIMEOX was provided to each participant at inclusion. Physiotherapists performed telecare sessions the first 2 weeks (3–5 sessions) for device training and every 10 days to reinforce motivation and provide technical support.Results 22 individuals were included, 21 analysed (38% male; mean±SD age 53±18 years; Bronchiectasis Severity Index 6.6±3.5). Fourteen participants (66.7%; 95% CI 43.1% to 84.5%) performed ≥3 SIMEOX sessions/week (self-reported adherence, primary outcome). Median (Q1; Q3) number of self-reported sessions/week for the whole group was 3.7 (1.8; 5.7). Adherence including web registration was 80.9%. At week 12, participant satisfaction rating was 9.0 (7.9; 10.0) on a 10-point visual analogue scale; respiratory function did not change but quality of life improved (COPD Assessment Test score −4.7, 95% CI −7.7 to −1.6, p=0.023; St Georges Respiratory Questionnaire −5.8, 95% CI −10.8 to −0.9, p=0.005).Conclusion Adherence to and satisfaction with the SIMEOX airway clearance device supported by telecare were high in people with NCFB. The clinical efficacy needs to be confirmed in a randomised controlled trial.Trial registration number NCT04742270.

Published
2023
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4. Development and validation of a quality of life measurement scale specific to hereditary hemorrhagic telangiectasia: the QoL-HHT

Author

Thi Thao Truc Le, Guillaume Martinent, Sophie Dupuis-Girod, Antoine Parrot, Anne Contis, Sophie Riviere, Thierry Chinet, Vincent Grobost, Olivier Espitia, Brigitte Dussardier-Gilbert, Laurent Alric, Guillaume Armengol, Hélène Maillard, Vanessa Leguy-Seguin, Sylvie Leroy, Murielle Rondeau-Lutz, Christian Lavigne, Shirine Mohamed, Laurent Chaussavoine, Pascal Magro, Julie Seguier, Mallorie Kerjouan, and Sylvie Fourdrinoy

Subjects
Disease-specific scale, Hereditary hemorrhagic telangiectasia, HHT, Instrument development, Quality of life, Rendu–Osler disease, Medicine
Abstract

Abstract Background Hereditary hemorrhagic telangiectasia (HHT) disease is a rare genetic disorder with symptoms and complications that can significantly affect patients’ daily lives. To date, no scale has been validated to assess the specific symptoms of this disease on the quality of life (QOL) of HHT patients. This makes it difficult for clinicians to accurately measure the quality of life of patients with HHT. The present study aims to develop and validate a QOL measurement tool specific to HHT disease: the QOL questionnaire in HHT (QoL-HHT). Methods A quantitative, non-interventional, multi-center study involving HHT patients in twenty French HHT expert centers was conducted. A calibration sample of 415 HHT patients and a validation sample of 228 HHT patients voluntarily participated in the study. Data were analyzed using exploratory factor analysis (EFA), confirmatory factor analysis (CFA), Exploratory Structural Equation Modeling (ESEM) analyses, reliability analyses, and correlational analyses. Results The EFA, CFA and ESEM results allowed us to provide evidence of the factorial structure of a questionnaire composed of 24 items measuring 6 domains of QOL: Physical limitations, social relationships, concern about bleeding, relationship with the medical profession, experience of symptoms, and concern about the evolution of the disease. Cronbach’s alpha coefficients (> 0.70) demonstrated reliable internal consistency of all the QoL-HHT scores (dimensions). The results of the test–retest provided further evidence of the reliability of the QOL-HHT scores over time. Correlational analyses provided evidence for the convergent validity of the QoL-HHT scores. Conclusions We developed a simple and quick self-assessment tool to measure quality of life specific to HHT disease. This study demonstrated reliability and validity of our QoL-HHT scores. It is a very promising tool to evaluate the impact of HHT disease on all aspects of the quality of life of HHT patients in order to offer them individualized medico-psycho-social support. Trial registration: ClinicalTrials, NCT03695874. Registered 04 October 2018, https://www.clinicaltrials.gov/ct2/show/NCT03695874

Published
2022
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5. Systemic sclerosis associated interstitial lung disease: a survey of current practices in France

Author

Amélie Nicolas, Sylvie Leroy, Luc Mouthon, Yurdagul Uzunhan, Vincent Cottin, Arsene Mekinian, Viviane Queyrel, Eric Hachulla, Benoit Gachet, David Launay, and Nihal Martis

Subjects
Diseases of the musculoskeletal system, RC925-935
Abstract

Background: Interstitial lung disease (ILD) is the leading cause of mortality in systemic sclerosis (SSc). Objective: We performed an overview of the diagnostic approaches, follow-up and treatment strategies used in France for the management of SSc-associated ILD (SSc-ILD). Design: Structured nationwide online survey.Methods: A structured nationwide online survey was submitted to participants via the French Medical Societies for Internal Medicine and Pneumology, and research groups on SSc-ILD from May 2018 to June 2020. The 79 multiple-choice and 9 open-ended questions covered the screening of ILD at baseline, monitoring of patients with established SSc-ILD and its management. Fourteen optional vignettes exploring different clinical phenotypes of SSc-ILD were submitted to evaluate therapeutic decisions. Results: All of the 93 participants screened SSc patients for ILD at baseline with 83 (89%) participants relying on a systematic chest computed tomography (CT) scan. Pulmonary function tests (PFT) were prescribed by 87 (94%) participants at baseline and during follow-up. Treatment was started based on abnormal PFT (95%), chest CT scan characteristics (89%), worsening dyspnoea (72%) and drop in SpO 2 during 6-min walk tests (66%). First-line therapy was cyclophosphamide (CYC) (89%), mycophenolate mofetil (MMF) (83%) and prednisone (73%). Rituximab as second-line immunosuppressive therapy (41%) was preferred to antifibrotic agents (18%), and a median daily prednisone dose of 10 mg (interquartile range, 10–15) was prescribed by 73% participants. Extensive SSc-ILD with worsening PFT (95%), regardless of diffusing capacity for carbon monoxide values and skin extension, were more likely to be treated, and CYC was favoured over MMF ( p

Published
2023
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6. The Prognosis of ART Is Not Altered in Cystic Fibrosis Women: A Case-Report Study

Author

Inès Braham, Adeline Morisot, Samir Boukaïdi, Marie Perceval, Isabelle Durieu, Christine Rousset-Jablonski, Sylvie Hieronimus, Sylvie Leroy, and Nicolas Chevalier

Subjects
cystic fibrosis, female, infertility, assisted reproductive techniques, pregnancy, pregnancy outcome, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Research QuestionUnlike in men, a very limited number of studies were focused on the specificity of ART management of cystic fibrosis (CF) in women. The purpose of this study was to determine the causes of infertility in patients, the appropriate ART treatment, and their prognosis in terms of pregnancy.DesignWe conducted a multicentre analytical case-control study including CF women who were age-matched to non-CF women. We reported the causes of infertility, the ART management type and pregnancy outcomes.Results17 cases were compared to 34 controls. There was no significant difference between the groups concerning cause infertility. There was a non-statistically significant trend with a lower antral follicle count in CF compared to controls (19.5 versus 26.8, p=0.08). IUI seemed to be as successful as IVF/ICSI in CF as opposed to controls where the IVF/ICSI was the most effective (in CF group for HCG >100 UI/L: 38.8% vs. 36.8%, p=0.4175). There were more embryos obtained in CF than in controls (3.1 versus 1.6, p=0.02). The number of oocytes and embryos obtained and pregnancy outcomes remained similar between DF508 homozygous group and others CFTR mutations group. The results of ART procedures and pregnancy evolution were not influenced by FEV1. ConclusionIn absence of any other pathology, IUI may be first option for CF women. If insemination fails, IVF with a low dose of gonadotropins may be more appropriate to prevent the risk of hyperstimulation syndrome. FEV1 and genetic do not seem to be contributing factors in the prognosis of ART.

Published
2022
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7. Proteomic profiling of serum identifies a molecular signature that correlates with clinical outcomes in COPD.

Author

Rania Dagher, Paul Fogel, Jingya Wang, David Soussan, Chia-Chien Chiang, Jennifer Kearley, Daniel Muthas, Camille Taillé, Patrick Berger, Arnaud Bourdin, Cécile Chenivesse, Sylvie Leroy, Gary Anderson, Alison A Humbles, Michel Aubier, Roland Kolbeck, Marina Pretolani, and COBRA Consortium

Subjects
Medicine, Science
Abstract

ObjectiveNovel biomarkers related to main clinical hallmarks of Chronic obstructive pulmonary disease (COPD), a heterogeneous disorder with pulmonary and extra-pulmonary manifestations, were investigated by profiling the serum levels of 1305 proteins using Slow Off-rate Modified Aptamers (SOMA)scan technology.MethodsSerum samples were collected from 241 COPD subjects in the multicenter French Cohort of Bronchial obstruction and Asthma to measure the expression of 1305 proteins using SOMAscan proteomic platform. Clustering of the proteomics was applied to identify disease subtypes and their functional annotation and association with key clinical parameters were examined. Cluster findings were revalidated during a follow-up visit, and compared to those obtained in a group of 47 COPD patients included in the Melbourne Longitudinal COPD Cohort.ResultsUnsupervised clustering identified two clusters within COPD subjects at inclusion. Cluster 1 showed elevated levels of factors contributing to tissue injury, whereas Cluster 2 had higher expression of proteins associated with enhanced immunity and host defense, cell fate, remodeling and repair and altered metabolism/mitochondrial functions. Patients in Cluster 2 had a lower incidence of exacerbations, unscheduled medical visits and prevalence of emphysema and diabetes. These protein expression patterns were conserved during a follow-up second visit, and substanciated, by a large part, in a limited series of COPD patients. Further analyses identified a signature of 15 proteins that accurately differentiated the two COPD clusters at the 2 visits.ConclusionsThis study provides insights into COPD heterogeneity and suggests that overexpression of factors involved in lung immunity/host defense, cell fate/repair/ remodelling and mitochondrial/metabolic activities contribute to better clinical outcomes. Hence, high throughput proteomic assay offers a powerful tool for identifying COPD endotypes and facilitating targeted therapies.

Published
2022
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8. Setting-Up a Rapid SARS-CoV-2 Genome Assessment by Next-Generation Sequencing in an Academic Hospital Center (LPCE, Louis Pasteur Hospital, Nice, France)

Author

Paul Hofman, Olivier Bordone, Emmanuel Chamorey, Jonathan Benzaquen, Renaud Schiappa, Virginie Lespinet-Fabre, Elisabeth Lanteri, Patrick Brest, Baharia Mograbi, Charlotte Maniel, Virginie Tanga, Maryline Allegra, Myriam Salah, Julien Fayada, Jacques Boutros, Sylvie Leroy, Simon Heeke, Véronique Hofman, Charles-Hugo Marquette, and Marius Ilié

Subjects
COVID-19, SARS-CoV-2, next-generation sequencing (NGS), variants, Genexus, Medicine (General), R5-920
Abstract

Introduction: Aside from the reverse transcription-PCR tests for the diagnosis of the COVID-19 in routine clinical care and population-scale screening, there is an urgent need to increase the number and the efficiency for full viral genome sequencing to detect the variants of SARS-CoV-2. SARS-CoV-2 variants assessment should be easily, rapidly, and routinely available in any academic hospital.Materials and Methods: SARS-CoV-2 full genome sequencing was performed retrospectively in a single laboratory (LPCE, Louis Pasteur Hospital, Nice, France) in 103 SARS-CoV-2 positive individuals. An automated workflow used the Ion Ampliseq SARS-CoV-2 panel on the Genexus Sequencer. The analyses were made from nasopharyngeal swab (NSP) (n = 64) and/or saliva (n = 39) samples. All samples were collected in the metropolitan area of the Nice city (France) from September 2020 to March 2021.Results: The mean turnaround time between RNA extraction and result reports was 30 h for each run of 15 samples. A strong correlation was noted for the results obtained between NSP and saliva paired samples, regardless of low viral load and high (>28) Ct values. After repeated sequencing runs, complete failure of obtaining a valid sequencing result was observed in 4% of samples. Besides the European strain (B.1.160), various variants were identified, including one variant of concern (B.1.1.7), and different variants under monitoring.Discussion: Our data highlight the current feasibility of developing the SARS-CoV-2 next-generation sequencing approach in a single hospital center. Moreover, these data showed that using the Ion Ampliseq SARS-CoV-2 Assay, the SARS-CoV-2 genome sequencing is rapid and efficient not only in NSP but also in saliva samples with a low viral load. The advantages and limitations of this setup are discussed.

Published
2022
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9. Multidisciplinary management of tracheobronchial injury

Author

Jacques Boutros, Charles-Hugo Marquette, Carole Ichai, Sylvie Leroy, and Jonathan Benzaquen

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Tracheobronchial injury is a heterogeneous entity comprising multiple rare and potentially life-threatening scenarios. We performed a systematic literature review focusing on post-intubation tracheal injuries (PiTIs) and post-traumatic tracheobronchial injuries (PTTBIs). PiTIs are often longitudinal lacerations of the middle third of the membranous trachea. Subcutaneous emphysema of the face and trunk following tracheal intubation should immediately trigger the diagnosis. Diagnosis may be suspected on the chest computed tomography (CT) and should be confirmed by bronchoscopic examination. Conservative management is encouraged for a spontaneously breathing or stable patient on noninvasive ventilation. Surgical repair is mandatory when mechanical ventilation is required and if bridging of the injury is impossible. PTTBIs are often associated with other severe injuries. Patients often present with massive subcutaneous emphysema and intractable pneumothorax. Diagnosis may be suspected on the chest CT and should be confirmed by bronchoscopic examination. Early surgical repair is indicated. In selected patients, conservative management can be considered.

Published
2022
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10. A case report of exogenous lipoid pneumonia associated with avocado/soybean unsaponifiables

Author

Jacques BOUTROS, Marine MUZZONE, Jonathan BENZAQUEN, Michael LEVRAUT, Charles-Hugo MARQUETTE, Fanny ROCHER, Yann DIASCORN, Bernard PADOVANI, Véronique HOFMAN, and Sylvie LEROY

Subjects
Exogenous lipoid pneumonia, Avocado oil, Soybean oil, Hiatal hernia, Gastroesophageal reflux disease, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Exogenous lipoid pneumonia is a rare disease resulting from intra-alveolar accumulation of lipids of mineral, vegetal, or animal origin, that induce a foreign body type of inflammatory reaction in the lungs. Gastroesophageal reflux disease and other esophageal abnormalities have often been associated with this disease. Case presentation We herein report the case of an 83-year-old patient in whom a follow-up chest computed tomography scan, for a lingular consolidation, showed multifocal ground glass and consolidative opacities with areas of low attenuation, suggestive of exogenous lipid pneumonia. The patient had been on piascledine capsules (avocado/soybean unsaponifiables) for 20 years and had a hiatal hernia with documented gastroesophageal reflux disease. After thorough history taking, no other predisposing factors were found. The diagnosis was confirmed using oil red staining of bronchoalveolar lavage showing lipid-laden macrophages and extracellular lipid droplets. Conclusions To our knowledge, this is the first case of ELP secondary to avocado/soybean unsaponifiables in the literature.

Published
2019
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11. Salivary detection of COVID-19: clinical performance of oral sponge sampling for SARS-CoV-2 testing

Author

Jacques Boutros, Jonathan Benzaquen, Charles Hugo Marquette, Marius Ilié, Mickelina Labaky, Didier Benchetrit, Thibaut Lavrut, Sylvie Leroy, Richard Chemla, Michel Carles, Virginie Tanga, Charlotte Maniel, Olivier Bordone, Maryline Allégra, Virginie Lespinet, Julien Fayada, Jennifer Griffonnet, Véronique Hofman, and Paul Hofman

Subjects
Medicine
Abstract

Background The current diagnostic standard for coronavirus disease 2019 (COVID-19) is reverse transcriptase-polymerase chain reaction (RT-PCR) testing with nasopharyngeal (NP) swabs. The invasiveness and need for trained personnel make the NP technique unsuited for repeated community-based mass screening. We developed a technique to collect saliva in a simple and easy way with the sponges that are usually used for tamponade of epistaxis. This study was carried out to validate the clinical performance of oral sponge (OS) sampling for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing. Methods Over a period of 22 weeks, we collected prospectively 409 paired NP and OS samples from consecutive subjects presenting to a public community-based free screening centre. Subjects were referred by their attending physician because of recent COVID-19 symptoms (n = 147) or by the contact tracing staff of the French public health insurance because they were considered as close contacts of a laboratory-confirmed COVID-19 case (n = 262). Results In symptomatic subjects, RT-PCR SARS-CoV-2 testing with OS showed a 96.5% (95% CI: 89.6–94.8) concordance with NP testing, and a 93.2% (95% CI: 89.1–97.3) sensitivity when using the IdyllaTM platform and a sensitivity of 76.3% (95% CI: 69.4–83.2) on the Synlab Barla laboratory platform. In close contacts the NP-OS concordance (93.8%, 95% CI: 90.9–96.7) and OS sensitivity (71.9%, 95% CI: 66.5–77.3) were slightly lower. Conclusion These results strongly suggest that OS testing is a straightforward, low-cost and high-throughput sampling method that can be used for frequent RT-PCR testing of COVID-19 patients and mass screening of populations.

Published
2021
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12. Evaluation of Sample Pooling for SARS-CoV-2 Detection in Nasopharyngeal Swab and Saliva Samples with the Idylla SARS-CoV-2 Test

Author

Paul Hofman, Maryline Allegra, Myriam Salah, Jonathan Benzaquen, Virginie Tanga, Olivier Bordone, Julien Fayada, Elodie Long-Mira, Sandra Lassalle, Elisabeth Lanteri, Virginie Lespinet-Fabre, Patrick Brest, Baharia Mograbi, Charlotte Maniel, Jacques Boutros, Sylvie Leroy, Simon Heeke, Véronique Hofman, Charles-Hugo Marquette, and Marius Ilié

Subjects
COVID-19, pooling, SARS-CoV-2, Idylla test, Microbiology, QR1-502
Abstract

ABSTRACT Due to increased demand for testing, as well as restricted supply chain resources, testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continues to face many hurdles. Pooling several samples has been proposed as an alternative approach to address these issues. We investigated the feasibility of pooling nasopharyngeal swab (NPS) or saliva samples for SARS-CoV-2 testing with a commercial assay (Idylla SARS-CoV-2 test; Biocartis). We evaluated the 10-pool and 20-pool approaches for 149 subjects, with 30 positive samples and 119 negative samples. The 10-pool approach had sensitivity of 78.95% (95% confidence interval [CI], 54.43% to 93.95%) and specificity of 100% (95% CI, 71.51% to 100%), whereas the 20-pool approach had sensitivity of 55.56% (95% CI, 21.20% to 86.30%) and specificity of 100% (95% CI, 25% to 100%). No significant difference was observed between the results obtained with pooled NPS and saliva samples. Given the rapidity, full automation, and practical advantages of the Idylla SARS-CoV-2 assay, pooling of 10 samples has the potential to significantly increase testing capacity for both NPS and saliva samples, with good sensitivity. IMPORTANCE To control outbreaks of coronavirus disease 2019 (COVID-19) and to avoid reagent shortages, testing strategies must be adapted and maintained for the foreseeable future. We analyzed the feasibility of pooling NPS and saliva samples for SARS-CoV-2 testing with the Idylla SARS-CoV-2 test, and we found that sensitivity was dependent on the pool size. The SARS-CoV-2 testing capacity with both NPS and saliva samples could be significantly expanded by pooling 10 samples; however, pooling 20 samples resulted in lower sensitivity.

Published
2021
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13. Margin-to-Margin Seafloor Spreading in the Eastern Gulf of Aden: A 16 Ma-Long History of Deformation and Magmatism from Seismic Reflection, Gravity and Magnetic Data

Author

Morgane Gillard, Sylvie Leroy, Mathilde Cannat, and Heather Sloan

Subjects
oceanic spreading, gulf of aden, seismic reflection, magmatism, sheba ridge, Science
Abstract

In this paper we present and analyze spreading-parallel seismic transects that image the oceanic crust in the eastern Gulf of Aden, from the Oman to the Socotra margins, across the active Sheba mid-oceanic ridge and between the Socotra-Hadbeen and Eastern Gulf of Aden Fracture Zones. The correlation of potential field data sets and gravity modelling allow us to document the spreading history of this oceanic basin from the onset of seafloor spreading ∼16 Ma-ago to the present. Two main oceanic sub-domains display distinct structural characteristics associated with different magmatic budgets at this mid-ocean ridge. In addition, we document the occurrence of a magmatic pulse at the Sheba Ridge around 11 Ma leading to the construction of a magmatic plateau in the western part of the studied area. This event led to substantial deformation and additional magmatism in previously formed oceanic crust. It could be related to an off-axis magmatic event previously identified in the adjacent Sheba segment, itself possibly related to the Afar plume.

Published
2021
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14. Are there specific clinical characteristics associated with physician’s treatment choices in COPD?

Author

Nicolas Roche, Anestis Antoniadis, David Hess, Pei Zhi Li, Eric Kelkel, Sylvie Leroy, Christophe Pison, Pierre-Régis Burgel, Bernard Aguilaniu, and COLIBRI COPD Research Group

Subjects
COPD, Treatment, Clinical impact, Exacerbations, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background The number of pharmacological agents and guidelines available for COPD has increased markedly but guidelines remain poorly followed. Understanding underlying clinical reasoning is challenging and could be informed by clinical characteristics associated with treatment prescriptions. Methods To determine whether COPD treatment choices by respiratory physicians correspond to specific patients’ features, this study was performed in 1171 patients who had complete treatment and clinical characterisation data. Multiple statistical models were applied to explain five treatment categories: A: no COPD treatment or short-acting bronchodilator(s) only; B: one long-acting bronchodilator (beta2 agonist, LABA or anticholinergic agent, LAMA); C: LABA+LAMA; D: a LABA or LAMA + inhaled corticosteroid (ICS); E: triple therapy (LABA+LAMA+ICS). Results Mean FEV1 was 60% predicted. Triple therapy was prescribed to 32.9% (treatment category E) of patients and 29.8% received a combination of two treatments (treatment categories C or D); ICS-containing regimen were present for 44% of patients altogether. Single or dual bronchodilation were less frequently used (treatment categories B and C: 19% each). While lung function was associated with all treatment decisions, exacerbation history, scores of clinical impact and gender were associated with the prescription of > 1 maintenance treatment. Statistical models could predict treatment decisions with a

Published
2019
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15. Lower Crustal Earthquakes in the March 2018 Sequence Along the Western Margin of Afar

Author

Alessandro La Rosa, Derek Keir, Cecile Doubre, Federico Sani, Giacomo Corti, Sylvie Leroy, Atalay Ayele, and Carolina Pagli

Subjects
Afar, deep seismicity, rift margins, Geophysics. Cosmic physics, QC801-809, Geology, QE1-996.5
Abstract

Abstract During the evolution of continental rift systems, extension is thought to progressively focus in‐rift to the future breakup boundary while faults along the rift margins progressively deactivate. However, observational constraints on how strain is partitioned between rift axis and rift margins are still lacking. The Afar rift records the latest stages of rifting and incipient continental breakup. Here, we analyzed the recent MW 5.2 earthquake on the Western Afar Margin on March 24, 2018 and the associated seismic sequence of >500 earthquakes using 24 temporary seismic stations deployed during 2017–2018. We show seismicity occurring at lower crustal depths, from ∼15 to ∼30 km, with focal mechanisms and relocated earthquakes highlighting both west‐dipping and east‐dipping normal faults. We tested earthquake depth using InSAR by processing six independent interferograms using Sentinel‐1 data acquired from both ascending and descending tracks. None of them shows evidence of surface deformation. We tested possible ranges of depth by producing forward models for a fault located at progressively increasing depths. Models show that surface deformation is not significant for fault slip at depths greater than 15 km, in agreement with the hypocentral depth of 19 km derived from seismic data for the largest earthquake. Due to the localized nature of deep earthquakes near hot springs coupled with subsurface evidence for magmatism, we favor an interpretation of seismicity induced by migrating fluids such as magma or CO2. We suggest that deep fluid migration can occur at the rifted‐margin influencing seismicity during incipient continental rupture.

Published
2021
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16. Versatile and flexible microfluidic qPCR test for high-throughput SARS-CoV-2 and cellular response detection in nasopharyngeal swab samples.

Author

Julien Fassy, Caroline Lacoux, Sylvie Leroy, Latifa Noussair, Sylvain Hubac, Aurélien Degoutte, Georges Vassaux, Vianney Leclercq, David Rouquié, Charles-Hugo Marquette, Martin Rottman, Patrick Touron, Antoinette Lemoine, Jean-Louis Herrmann, Pascal Barbry, Jean-Louis Nahon, Laure-Emmanuelle Zaragosi, and Bernard Mari

Subjects
Medicine, Science
Abstract

The emergence and quick spread of SARS-CoV-2 has pointed at a low capacity response for testing large populations in many countries, in line of material, technical and staff limitations. The traditional RT-qPCR diagnostic test remains the reference method and is by far the most widely used test. These assays are limited to a few probe sets, require large sample PCR reaction volumes, along with an expensive and time-consuming RNA extraction step. Here we describe a quantitative nanofluidic assay that overcomes some of these shortcomings, based on the BiomarkTM instrument from Fluidigm. This system offers the possibility of performing 4608 qPCR end-points in a single run, equivalent to 192 clinical samples combined with 12 pairs of primers/probe sets in duplicate, thus allowing the monitoring of SARS-CoV-2 including the detection of specific SARS-CoV-2 variants, as well as the detection other pathogens and/or host cellular responses (virus receptors, response markers, microRNAs). The 10 nL-range volume of BiomarkTM reactions is compatible with sensitive and reproducible reactions that can be easily and cost-effectively adapted to various RT-qPCR configurations and sets of primers/probe. Finally, we also evaluated the use of inactivating lysis buffers composed of various detergents in the presence or absence of proteinase K to assess the compatibility of these buffers with a direct reverse transcription enzymatic step and we propose several protocols, bypassing the need for RNA purification. We advocate that the combined utilization of an optimized processing buffer and a high-throughput real-time PCR device would contribute to improve the turn-around-time to deliver the test results to patients and increase the SARS-CoV-2 testing capacities.

Published
2021
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17. Internal Structure of the Oceanic Lithosphere at a Melt‐Starved Ultraslow‐Spreading Mid‐Ocean Ridge: Insights From 2‐D Seismic Data

Author

Ekeabino Momoh, Mathilde Cannat, and Sylvie Leroy

Subjects
Detachment faulting, Ultra‐slow spreading, Serpentinization, Geophysics. Cosmic physics, QC801-809, Geology, QE1-996.5
Abstract

Abstract Extensive outcrops of serpentinized peridotite in melt‐starved spreading corridors of the ultraslow easternmost Southwest Indian Ridge are hypothesized to be due to slip on successive long‐offset normal faults that alternate polarity (flip‐flop detachment faults). We investigate the nature of the oceanic crust which forms under these conditions, using seismic reflection data acquired during the SISMOSMOOTH 2014 cruise. Using 3‐D binning, the seismic profiles were binned elastically, while three of the profiles shot closely were merged into one to take advantage of the larger air gun source volume. Using a poststack imaging sequence, we observe several types of reflectors at crustal and infracrustal depths, in the axial valley and off‐axis. Correlating our seismic observations with Residual Mantle Bouguer gravity anomalies and seafloor observations, we find that our results are explicable in the framework of the flip‐flop hypothesis of detachment faulting. Reflectors imaged down to 5 km into the basement and interpreted as due to damaged zones outlining the detachment faults dip 50° at the early stages, while at late stages after developing offsets >10 km, they dip 25°. Other reflectors observed in the crust are interpreted as moderate offset (

Published
2020
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18. Blood co-expression modules identify potential modifier genes of diabetes and lung function in cystic fibrosis.

Author

Fanny Pineau, Davide Caimmi, Milena Magalhães, Enora Fremy, Abdillah Mohamed, Laurent Mely, Sylvie Leroy, Marlène Murris, Mireille Claustres, Raphael Chiron, and Albertina De Sario

Subjects
Medicine, Science
Abstract

Cystic fibrosis (CF) is a rare genetic disease that affects the respiratory and digestive systems. Lung disease is variable among CF patients and associated with the development of comorbidities and chronic infections. The rate of lung function deterioration depends not only on the type of mutations in CFTR, the disease-causing gene, but also on modifier genes. In the present study, we aimed to identify genes and pathways that (i) contribute to the pathogenesis of cystic fibrosis and (ii) modulate the associated comorbidities. We profiled blood samples in CF patients and healthy controls and analyzed RNA-seq data with Weighted Gene Correlation Network Analysis (WGCNA). Interestingly, lung function, body mass index, the presence of diabetes, and chronic P. aeruginosa infections correlated with four modules of co-expressed genes. Detailed inspection of networks and hub genes pointed to cell adhesion, leukocyte trafficking and production of reactive oxygen species as central mechanisms in lung function decline and cystic fibrosis-related diabetes. Of note, we showed that blood is an informative surrogate tissue to study the contribution of inflammation to lung disease and diabetes in CF patients. Finally, we provided evidence that WGCNA is useful to analyze-omic datasets in rare genetic diseases as patient cohorts are inevitably small.

Published
2020
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19. Imaging Lithospheric Discontinuities Beneath the Northern East African Rift Using S‐to‐P Receiver Functions

Author

Aude Lavayssière, Catherine Rychert, Nicholas Harmon, Derek Keir, James O. S. Hammond, J.‐Michael Kendall, Cécile Doubre, and Sylvie Leroy

Subjects
East African rift, lithosphere‐asthenosphere boundary, continental rifting, receiver functions, partial melt, Geophysics. Cosmic physics, QC801-809, Geology, QE1-996.5
Abstract

Abstract Imaging the lithosphere is key to understand mechanisms of extension as rifting progresses. Continental rifting results in a combination of mechanical stretching and thinning of the lithosphere, decompression upwelling, heating, sometimes partial melting of the asthenosphere, and potentially partial melting of the mantle lithosphere. The northern East African Rift system is an ideal locale to study these processes as it exposes the transition from tectonically active continental rifting to incipient seafloor spreading. Here we use S‐to‐P receiver functions to image the lithospheric structure beneath the northernmost East African Rift system where it forms a triple junction between the Main Ethiopian rift, the Red Sea rift, and the Gulf of Aden rift. We image the Moho at 31 ± 6 km beneath the Ethiopian plateau. The crust is 28 ± 3 km thick beneath the Main Ethiopian rift and thins to 23 ± 2 km in northern Afar. We identify a negative phase, a velocity decrease with depth, at 67 ± 3 km depth beneath the Ethiopian plateau, likely associated with the lithosphere‐asthenosphere boundary (LAB), and a lack of a LAB phase beneath the rift. Using observations and waveform modeling, we show that the LAB phase beneath the plateau is likely defined by a small amount of partial melt. The lack of a LAB phase beneath the rift suggests melt percolation through the base of the lithosphere beneath the northernmost East African Rift system.

Published
2018
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20. Impact of Achromobacter xylosoxidans isolation on the respiratory function of adult patients with cystic fibrosis

Author

Macha Tetart, Frederic Wallet, Maeva Kyheng, Sylvie Leroy, Thierry Perez, Olivier Le Rouzic, Benoit Wallaert, and Anne Prevotat

Subjects
Medicine
Abstract

Background The prevalence of Achromobacter xylosoxidans lung isolation in cystic fibrosis (CF) patients has increased, but the impact on lung function is controversial. The aim of this study was to evaluate the long-term effects of A. xylosoxidans isolation on respiratory function of adult patients with CF in the first 3 years after identification of A. xylosoxidans isolation. Methods This was a case–control retrospective study performed at a single CF centre in Lille, France. Data for 36 patients with CF who had at least one sputum culture positive for A. xylosoxidans (Ax+) were evaluated and compared with control CF patients uninfected by A. xylosoxidans (Ax−). Respiratory function and exacerbation frequency were evaluated between 1 year prior to and 3 years after A. xylosoxidans isolation. Results Compared with the Ax− group, the Ax+ group had a lower forced expiratory volume in 1 s (FEV1) at baseline (median (interquartile range): 55.2% (50.6–59.8%) versus 73.8% (67.2–80.4%); p=0.005), a greater decline in FEV1 (±se) in the first year after A. xylosoxidans identification (−153.6±16.1 mL·year−1 versus −63.8±18.5 mL·year−1; p=0.0003), and more exacerbations in the first 3 years after A. xylosoxidans identification (9 (7–12) versus 7 (5–10); p=0.03). Ax+ patients co-colonised with Pseudomonas aeruginosa (n=27, 75%) had a greater FEV1 decline (p=0.003) and more exacerbations in the year after A. xylosoxidans identification (p=0.037) compared with patients colonised with A. xylosoxidans alone. Patients with chronic A. xylosoxidans isolation (n=23, 64%) had more exacerbations than intermittently colonised patients in the 3 years after A. xylosoxidans identification (p=0.012). Conclusion A. xylosoxidans isolation is associated with a decline in respiratory function in patients with CF. Chronic A. xylosoxidans isolation and P. aeruginosa co-isolation may be markers of more severe respiratory disease in Ax+ patients.

Published
2019
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21. Cost-effectiveness of lung volume reduction coil treatment in patients with severe emphysema: results from the 2-year follow-up crossover REVOLENS study (REVOLENS-2 study)

Author

Julie Bulsei, Sylvie Leroy, Jeanne-Marie Perotin, Hervé Mal, Charles-Hugo Marquette, Hervé Dutau, Arnaud Bourdin, Jean-Michel Vergnon, Christophe Pison, Romain Kessler, Vincent Jounieaux, Mathieu Salaün, Armelle Marceau, Sylvain Dukic, Coralie Barbe, Margaux Bonnaire, Gaëtan Deslee, Isabelle Durand-Zaleski, and the REVOLENS study group

Subjects
Coil treatment, Severe emphysema, Cost-effectiveness, QALY, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background The REVOLENS study compared lung volume reduction coil treatment to usual care in patients with severe emphysema at 1 year, resulting in improved quality-adjusted life-year (QALY) and higher costs. Durability of the coil treatment benefit and its cost-effectiveness at 2 years are now assessed. Methods After one year, the REVOLENS trial’s usual care group patients received coil treatment (second-line coil treatment group). Costs and QALYs were assessed in both arms at 2 years and an incremental cost-effectiveness ratio in cost per QALY gained was calculated. The uncertainty of the results was estimated by probabilistic bootstrapping. Results The average cost of coil treatment in both groups was estimated at €24,356. The average total cost at 2 years was €9655 higher in the first-line coil treatment group (p = 0.07) and the difference in QALY between the two groups was 0.127 (p = 0.12) in favor of first-line coil treatment group. The 2-year incremental cost-effectiveness ratio (ICER) was €75,978 / QALY. The scatter plot of the probabilistic bootstrapping had 92% of the replications in the top right-hand quadrant. Conclusion First-line coil treatment was more expensive but also more effective than second-line coil treatment at 2 years, with a 2-year ICER of €75,978 / QALY. Trial registration ClinicalTrials.gov Identifier NCT01822795.

Published
2018
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22. Rituximab for auto-immune alveolar proteinosis, a real life cohort study

Author

Berenice Soyez, Raphael Borie, Cedric Menard, Jacques Cadranel, Leonidas Chavez, Vincent Cottin, Emmanuel Gomez, Sylvain Marchand-Adam, Sylvie Leroy, Jean-Marc Naccache, Hilario Nunes, Martine Reynaud-Gaubert, Laurent Savale, Abdellatif Tazi, Lidwine Wemeau-Stervinou, Marie-Pierre Debray, and Bruno Crestani

Subjects
Whole lung lavage, GM-CSF, Surfactant, Interstitial lung disease, Therapy, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Whole lung lavage is the current standard therapy for pulmonary alveolar proteinosis (PAP) that is characterized by the alveolar accumulation of surfactant. Rituximab showed promising results in auto-immune PAP (aPAP) related to anti-GM-CSF antibody. Methods We aimed to assess efficacy of rituximab in aPAP in real life and all patients with aPAP in France that received rituximab were retrospectively analyzed. Results Thirteen patients were included. No patients showed improvement 6 months after treatment, but, 4 patients (30%) presented a significant decrease of alveolar-arterial difference in oxygen after 1 year. One patient received lung transplantation and one patient was lost of follow-up within one year. Although a spontaneous improvement cannot be excluded in these 4 patients, improvement was more frequent in patients naïve to prior specific therapy and with higher level of anti-GM-CSF antibodies evaluated by ELISA. No serious adverse event was evidenced. Conclusions These data do not support rituximab as a second line therapy for patients with refractory aPAP.

Published
2018
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23. Seismic Ambient Noise Imaging of a Quasi-Amagmatic Ultra-Slow Spreading Ridge

Author

Mohamadhasan Mohamadian Sarvandani, Emanuel Kästle, Lapo Boschi, Sylvie Leroy, and Mathilde Cannat

Subjects
seismic interferometry, phase velocity measurement, cross-correlation, S-wave model, Science
Abstract

Passive seismic interferometry has become very popular in recent years in exploration geophysics. However, it has not been widely applied in marine exploration. The purpose of this study is to investigate the internal structure of a quasi-amagmatic portion of the Southwest Indian Ridge by interferometry and to examine the performance and reliability of interferometry in marine explorations. To reach this goal, continuous vertical component recordings from 43 ocean bottom seismometers were analyzed. The recorded signals from 200 station pairs were cross-correlated in the frequency domain. The Bessel function method was applied to extract phase–velocity dispersion curves from the zero crossings of the cross-correlations. An average of all the dispersion curves was estimated in a period band 1–10 s and inverted through a conditional neighborhood algorithm which led to the final 1D S-wave velocity model of the crust and upper mantle. The obtained S-wave velocity model is in good agreement with previous geological and geophysical studies in the region and also in similar areas. We find an average crustal thickness of 7 km with a shallow layer of low shear velocities and high Vp/Vs ratio. We infer that the uppermost 2 km are highly porous and may be strongly serpentinized.

Published
2021
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24. The initiation of segmented buoyancy-driven melting during continental breakup

Author

Ryan J. Gallacher, Derek Keir, Nicholas Harmon, Graham Stuart, Sylvie Leroy, James O. S. Hammond, J-Michael Kendall, Atalay Ayele, Berhe Goitom, Ghebrebrhan Ogubazghi, and Abdulhakim Ahmed

Subjects
Science
Abstract

Our understanding of melt production during early continental breakup remains poorly constrained. Using the Afar triple junction as an example, Gallacher et al. generate a 3D velocity model suggesting that melt production is highest during early continental breakup due to localised thinning of the crust.

Published
2016
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25. The airway microbiota in cystic fibrosis: a complex fungal and bacterial community--implications for therapeutic management.

Author

Laurence Delhaes, Sébastien Monchy, Emilie Fréalle, Christine Hubans, Julia Salleron, Sylvie Leroy, Anne Prevotat, Frédérick Wallet, Benoit Wallaert, Eduardo Dei-Cas, Telesphore Sime-Ngando, Magali Chabé, and Eric Viscogliosi

Subjects
Medicine, Science
Abstract

BackgroundGiven the polymicrobial nature of pulmonary infections in patients with cystic fibrosis (CF), it is essential to enhance our knowledge on the composition of the microbial community to improve patient management. In this study, we developed a pyrosequencing approach to extensively explore the diversity and dynamics of fungal and prokaryotic populations in CF lower airways.Methodology and principal findingsFungi and bacteria diversity in eight sputum samples collected from four adult CF patients was investigated using conventional microbiological culturing and high-throughput pyrosequencing approach targeting the ITS2 locus and the 16S rDNA gene. The unveiled microbial community structure was compared to the clinical profile of the CF patients. Pyrosequencing confirmed recently reported bacterial diversity and observed complex fungal communities, in which more than 60% of the species or genera were not detected by cultures. Strikingly, the diversity and species richness of fungal and bacterial communities was significantly lower in patients with decreased lung function and poor clinical status. Values of Chao1 richness estimator were statistically correlated with values of the Shwachman-Kulczycki score, body mass index, forced vital capacity, and forced expiratory volume in 1 s (p = 0.046, 0.047, 0.004, and 0.001, respectively for fungal Chao1 indices, and p = 0.010, 0.047, 0.002, and 0.0003, respectively for bacterial Chao1 values). Phylogenetic analysis showed high molecular diversities at the sub-species level for the main fungal and bacterial taxa identified in the present study. Anaerobes were isolated with Pseudomonas aeruginosa, which was more likely to be observed in association with Candida albicans than with Aspergillus fumigatus.ConclusionsIn light of the recent concept of CF lung microbiota, we viewed the microbial community as a unique pathogenic entity. We thus interpreted our results to highlight the potential interactions between microorganisms and the role of fungi in the context of improving survival in CF.

Published
2012
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27. The East-Mayotte new volcano in the Comoros Archipelago: structure and timing of magmatic phases inferred from seismic reflection data

Author

Charles Masquelet, Sylvie Leroy, Matthias Delescluse, Nicolas Chamot-Rooke, Isabelle Thinon, Anne Lemoine, Dieter Franke, Louise Watremez, Philippe Werner, Fabien Paquet, Carole Berthod, Victor Cabiativa Pico, Daniel Sauter, 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), Laboratoire de géologie de l'ENS (LGENS), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Bundesanstalt für Geowissenschaften und Rohstoffe (BGR), Laboratoire d’Océanologie et de Géosciences (LOG) - UMR 8187 (LOG), Institut national des sciences de l'Univers (INSU - CNRS)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Nord]), Institut Terre Environnement Strasbourg (ITES), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Magmas et Volcans (LMV-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-SPIN-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Magmas et Volcans (LMV), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement et la société-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Observatoire de Physique du Globe de Clermont-Ferrand (OPGC), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement et la société-Université Clermont Auvergne (UCA)-Observatoire de Physique du Globe de Clermont-Ferrand (OPGC), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Ecole et Observatoire des Sciences de la Terre (EOST), Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), and ANR-19-CE31-0018,COYOTES,COmores & maYotte : vOlcanisme, TEctonique et Sismicité(2019)

Subjects
Volcanism, Comoros Archipelago, [SDU.STU.ST]Sciences of the Universe [physics]/Earth Sciences/Stratigraphy, Mayotte, [SDU.STU.VO]Sciences of the Universe [physics]/Earth Sciences/Volcanology, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, General Earth and Planetary Sciences, Fani Maore volcano, FaniMaore volcano, Seismic reflection, General Environmental Science
Abstract

A multichannel seismic reflection profile acquired during the SISMAORE cruise (2021) provides the first in-depth image of the submarine volcanic edifice, named Fani Maore, that formed 50 km east of Mayotte Island (Comoros Archipelago) in 2018–2019. This new edifice sits on a ∼140 m thick sedimentary layer, which is above a major, volcanic layer up to ∼1 km thick and extends over 120 km along the profile. This volcanic unit is made of several distinct seismic facies that indicate successive volcanic phases. We interpret this volcanic layer as witnessing the main phase of construction of the Mayotte Island volcanic edifice. A ∼2.2–2.5 km thick sedimentary unit is present between this volcanic layer and the top of the crust. A complex magmatic feeder system is observed within this unit, composed of saucer-shape sills and seal bypass systems. The deepest tip of this volcanic layer lies below the top-Oligocene seismic horizon, indicating that the volcanism ofMayotte Island likely began around 26.5Ma, earlier than previously assumed., Un profil de sismique réflexion multitrace acquis lors de la campagne océanographique SISMAORE (2021) apporte la première image en profondeur du volcan sous-marin Fani Maore, qui s’est formé à 50 km à l’est de l’île de Mayotte (archipel des Comores) en 2018–2019. Ce nouvel édifice repose sur une première couche sédimentaire d’environ 140 m d’épaisseur au-dessus d’une couche volcanique majeure épaisse de 1 km et qui s’étend sur 120 km le long du profil. Cette dernière unité volcanique est constituée de plusieurs faciès sismiques distincts qui indiquent des phases volcaniques successives. Nous interprétons cette couche volcanique comme le témoin de la phase principale de construction de l’édifice volcanique de l’île de Mayotte. Une couverture sédimentaire de 2.2–2.5 km d’épaisseur est présente entre cette couche volcanique et le toit de la croûte. On y observe de nombreux sills en forme de soucoupe ainsi que des zones à faciès de remontées de fluides, dessinant un système d’alimentation magmatique complexe sous la principale couche volcanique. L’extrémité la plus profonde de cette couche volcanique se place en dessous de l’horizon sismique de l’Oligocène supérieur et indique que le volcanisme de l’île de Mayotte a probablement commencé vers 26.5 Ma, plus tôt que ce qui était supposé auparavant.

Published
2023
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28. Antiviral drugs in hospitalized patients with COVID-19 - the DisCoVeRy trial

Author

Bruno Mourvillier, François-Xavier Lescure, Dominique Costagliola, Alain Makinson, Valérie Pourcher, Odile Launay, Clément Dubost, Saad Nseir, Emmanuel Faure, Yazdan Yazdanpanah, Jean-Christophe Richard, Lila Bouadma, Kevin Bouiller, Juliette Saillard, Jean Reignier, Claire Andrejak, Alpha Diallo, Lionel Piroth, Jean-Philippe Lanoix, Violaine Tolsma, Christelle Delmas, Gilles Peytavin, André Cabié, Marion Noret, Karine Lacombe, Elisabeth Botelho-Nevers, Thérèse Staub, Johan Courjon, Florence Ader, Nathan Peiffer-Smadja, Jean-Christophe Navellou, Maya Hites, Jean Reuter, Noemie Mercier, Maude Bouscambert-Duchamp, François Danion, S. Gallien, Julien Poissy, Florent Wallet, Guillaume Martin-Blondel, Raphaël Clere-Jehl, Bruno Lina, Amandine Gagneux-Brunon, Antoine Kimmoun, Rostane Gaci, Olivier Epaulard, Axelle Dupont, François Raffi, Aline Dechanet, François Goehringer, Joy Mootien, Stéphane Jauréguiberry, Sylvie Leroy, Charles Burdet, Toni Alfaiate, Drifa Belhadi, Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), CHU Lille, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Virology and human respiratory Pathologies - Virology and human respiratory Pathologies (VirPath), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), ANRS - Maladies infectieuses émergentes (ANRS - MIE), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Santé Publique, Université de Médecine Carol Davila, Centre d'investigation Clinique [CHU Bichat] - Épidémiologie clinique (CIC 1425), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM), ANRS France Recherche Nord & sud Sida-hiv hépatites, Département d'Epidemiologie, Biostatistique et Recherche Clinique (DEBRC), Service des Maladies Infectieuses et Tropicales [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Service de Réanimation Médicale [CHRU Nancy], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Les Hôpitaux Universitaires de Strasbourg (HUS), CHU Amiens-Picardie, Agents infectieux, résistance et chimiothérapie - UR UPJV 4294 (AGIR ), and Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie

Subjects
medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), business.industry, Hospitalized patients, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Lopinavir, Hydroxychloroquine, Odds ratio, law.invention, Randomized controlled trial, law, Internal medicine, medicine, Ritonavir, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

BackgroundLopinavir/ritonavir, lopinavir/ritonavir-interferon (IFN)-β-1a and hydroxychloroquine efficacy for COVID-19 have been evaluated, but detailed evaluation is lacking.ObjectiveTo determine the efficacy of lopinavir/ritonavir, lopinavir/ritonavir-IFN-β-1a, hydroxychloroquine or remdesivir for improving the clinical, virological outcomes in COVID-19 inpatients.DesignOpen-label, randomized, adaptive, controlled trial.SettingMulti-center trial with patients from France.Participants583 COVID-19 inpatients requiring oxygen and/or ventilatory supportInterventionStandard of care (SoC, control), SoC plus lopinavir/ritonavir (400 mg lopinavir and 100 mg ritonavir every 12h for 14 days), SoC plus lopinavir/ritonavir plus IFN-ß-1a (44 μg of subcutaneous IFN-ß-1a on days 1, 3, and 6), SoC plus hydroxychloroquine (400 mg twice on day 1 then 400 mg once daily for 9 days) or SoC plus remdesivir (200 mg intravenously on day 1 then 100 mg once-daily for hospitalization duration or 10 days).MeasurementsThe primary outcome was the clinical status at day 15, measured by the WHO 7-point ordinal scale. Secondary outcomes included SARS-CoV-2 quantification in respiratory specimens and safety analyses.ResultsAdjusted Odds Ratio (aOR) for the WHO 7-point ordinal scale were not in favor of investigational treatments: lopinavir/ritonavirversuscontrol, aOR 0.83, 95%CI, 0.55 to 1.26, P=0.39; lopinavir/ritonavir-IFN-β-1aversuscontrol, aOR 0.69, 95%CI, 0.45 to 1.04, P=0.08; hydroxychloroquineversuscontrol, aOR 0.93, 95%CI, 0.62 to 1.41, P=0.75. No significant effect on SARS-CoV-2 RNA clearance in respiratory tract was evidenced. Lopinavir/ritonavir-containing treatments were significantly associated with more SAE.LimitationsNot a placebo-controlled, no anti-inflammatory agents tested.ConclusionNo improvement of the clinical status at day 15 nor SARS-CoV-2 RNA clearance in respiratory tract specimens by studied drugs. This comforts the recent Solidarity findings.RegistrationNCT04315948.FundingPHRC 2020, Dim OneHealth, REACTing

Published
2023

29. Major volcanic events from Mohéli, Anjouan and Mayotte Island edification in the Comoros Archipelago at Northern Mozambique Channel inferred by seismic reflection data

Author

Charles Masquelet, Sylvie Leroy, Daniel Sauter, Matthias Delescluse, Nicolas Chamot-Rooke, Isabelle Thinon, Louise Watremez, and Anne Lemoine

Abstract

The timing of volcanic events at the Comoros archipelago (North Mozambique Channel) are currently only known by dating samples from the onshore islands. According to these data, the oldest lavas from the Comoros are 10 Ma and several distinct volcanic periods are inferred (Michon, 2016). However, the onset of the volcanism within the archipelago cannot be constrained by these data. Here we use two different datasets of wide angle, and high resolution multichannel seismic reflexion profiles to provide insights on the birth and early evolution of the volcanism around the islands of Mohéli, Anjouan and Mayotte, in the Comoros basin (SISMAORE cruise, ANR COYOTES project, (Thinon et al., 2022)).The seismic interpretation revealed several distinct volcanic horizons within the sedimentary cover, that could be related to the formation of the Jumelles Ridge, Geyser bank, Mohéli, Anjouan and Mayotte volcanic island. We identify the onset of the main volcanic event that led to the formation of Mayotte island. We show that the corresponding seismic volcanic horizon is located at different depths in the north and the south of Mayotte island. This indicates at least two different major volcanic phases of the Mayotte island edification. Seismic profiles also show the presence of a magmatic feeder complex underneath. Using known regional stratigraphy, we finally propose a chronology of all the volcanic episodes in the regional volcanic context of the construction of the Comoros archipelago.Michon, L., 2016. The Volcanism of the Comoros Archipelago Integrated at a Regional Scale, in: Bachelery, P., Lenat, J.-F., Di Muro, A., Michon, L. (Eds.), Active Volcanoes of the Southwest Indian Ocean, Active Volcanoes of the World. Springer Berlin Heidelberg, Berlin, Heidelberg, pp. 333–344. https://doi.org/10.1007/978-3-642-31395-0_21Thinon, I., Lemoine, A., Leroy, S., Paquet, F., Berthod, C., Zaragosi, S., Famin, V., Feuillet, N., Boymond, P., Masquelet, C., Mercury, N., Rusquet, A., Scalabrin, C., Van der Woerd, J., Bernard, J., Bignon, J., Clouard, V., Doubre, C., Jacques, E., Jorry, S.J., Rolandone, F., Chamot-Rooke, N., Delescluse, M., Franke, D., Watremez, L., Bachèlery, P., Michon, L., Sauter, D., Bujan, S., Canva, A., Dassie, E., Roche, V., Ali, S., Sitti Allaouia, A.H., Deplus, C., Rad, S., Sadeski, L., 2022. Volcanism and tectonics unveiled in the Comoros Archipelago between Africa and Madagascar. Comptes Rendus. Géoscience 354, 1–28. https://doi.org/10.5802/crgeos.159

Published
2023
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30. Halogens dissolved in interstitial water reveal the origin of migrating fluids in sediments of the Alboran Sea (western Mediterranean)

Author

Satoko Owari, Marcelo Ketzer, Nagisa Suzuki, Elia d'Acremont, Sara Lafuerza, Sylvie Leroy, Daniel Praeg, and Alana Oliveira de Sa

Abstract

Fluid migration in sedimentary basins has profound effects on a range of geological processes, including the methane cycle, tectonic and sedimentary geohazards, and microbial communities in the oceans. The Alboran Sea is a tectonically active basin characterized by contourite drifts that host migrating fluids, expressed in places by pockmarks and mud volcanoes, the latter associated with seafloor methane seepage. In this study, we examine the composition and origin of near-seafloor fluids in the Alboran Sea using sediment cores (up to 20 m long) from a pockmark field (site CL06), a nearby background area (site CL04) and a fault zone (site CL55).We use halogens (Cl, Br, and I) dissolved in interstitial water to understand the origin of fluids in the Alboran Sea. Chlorine is considered a conservative ion in interstitial water geochemistry, its concentration changing with pore water salinity. Iodine has a strong biophilic character and is incorporated in organic matter deposited with sediments, which during burial decomposes in response to geothermal heat or microbial activity to produce methane. Iodine and methane concentrations are strongly correlated and highly concentrated compared to seawater, so that iodine has been used as a methane tracer. Bromide also has a weak biophilic character and behaves similarly to iodine.Interstitial water was extracted aboard ship using Rhizon samplers. Chloride concentration was determined by ion chromatography (ICS-1600, DIONEX) at the Tokyo University of Marine Science and Technology; iodine and bromine concentrations were determined by Inductively coupled plasma mass spectrometry (ICP-MS Agilent 7500) at Micro Analysis Laboratory, Tandem accelerator (MALT), University of Tokyo.The results reveal halogen profiles that differ between the pockmark and fault sites, providing evidence of different modes of fluid migration within the contourite drifts of the Alboran Sea:(1)Pockmark and background sites: surprisingly, halogen profiles are similar at these two sites. Cl concentration decreases with depth from 610 to 590 mM over the 15 m length of the cores, a trend indicating fresher water is present in deeper sediments. I and Br concentrations increase with depth (I: 0 to 70 µM, Br: 760 to 820 µM). I and Br are strongly enriched (up to 8% and 60%, respectively) by a deep fluid source, which may relate to high TOC or evaporated seawater in deeper sediment.(2)Fault zone site: in contrast to the other two sites, Cl concentration increases with depth from 600 to 610 mM over the 16 m length of the core 55, a trend indicating saline water is dominant in deeper sediments. I and Br concentrations increase with depth (I: 35 to 70 µM, Br: 800 to 830 µM). I and Br concentrations in near-seafloor sediments are usually less strongly affected by organic decomposition, with concentrations as low as seawater; however, at site 55, I and Br are strongly enriched in near-seafloor sediments. This observation suggests vertical fluid migration is active and reaches the seafloor to maintain high I and Br concentrations.

Published
2023
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31. Monogenic early-onset lymphoproliferation and autoimmunity: Natural history of STAT3 gain-of-function syndrome

Author

Jennifer W. Leiding, Tiphanie P. Vogel, Valentine G.J. Santarlas, Rahul Mhaskar, Madison R. Smith, Alexandre Carisey, Alexander Vargas-Hernández, Manuel Silva-Carmona, Maximilian Heeg, Anne Rensing-Ehl, Bénédicte Neven, Jérôme Hadjadj, Sophie Hambleton, Timothy Ronan Leahy, Kornvalee Meesilpavikai, Charlotte Cunningham-Rundles, Cullen M. Dutmer, Svetlana O. Sharapova, Mervi Taskinen, Ignatius Chua, Rosie Hague, Christian Klemann, Larysa Kostyuchenko, Tomohiro Morio, Akaluck Thatayatikom, Ahmet Ozen, Anna Scherbina, Cindy S. Bauer, Sarah E. Flanagan, Eleonora Gambineri, Lisa Giovannini-Chami, Jennifer Heimall, Kathleen E. Sullivan, Eric Allenspach, Neil Romberg, Sean G. Deane, Benjamin T. Prince, Melissa J. Rose, John Bohnsack, Talal Mousallem, Rohith Jesudas, Maria Marluce Dos Santos Vilela, Michael O’Sullivan, Jana Pachlopnik Schmid, Štěpánka Průhová, Adam Klocperk, Matthew Rees, Helen Su, Sami Bahna, Safa Baris, Lisa M. Bartnikas, Amy Chang Berger, Tracy A. Briggs, Shannon Brothers, Vanessa Bundy, Alice Y. Chan, Shanmuganathan Chandrakasan, Mette Christiansen, Theresa Cole, Matthew C. Cook, Mukesh M. Desai, Ute Fischer, David A. Fulcher, Silvanna Gallo, Amelie Gauthier, Andrew R. Gennery, José Gonçalo Marques, Frédéric Gottrand, Bodo Grimbacher, Eyal Grunebaum, Emma Haapaniemi, Sari Hämäläinen, Kaarina Heiskanen, Tarja Heiskanen-Kosma, Hal M. Hoffman, Luis Ignacio Gonzalez-Granado, Anthony L. Guerrerio, Leena Kainulainen, Ashish Kumar, Monica G. Lawrence, Carina Levin, Timi Martelius, Olaf Neth, Peter Olbrich, Alejandro Palma, Niraj C. Patel, Tamara Pozos, Kahn Preece, Saúl Oswaldo Lugo Reyes, Mark A. Russell, Yael Schejter, Christine Seroogy, Jan Sinclair, Effie Skevofilax, Daniel Suan, Daniel Suez, Paul Szabolcs, Helena Velasco, Klaus Warnatz, Kelly Walkovich, Austen Worth, Mikko R.J. Seppänen, Troy R. Torgerson, Georgios Sogkas, Stephan Ehl, Stuart G. Tangye, Megan A. Cooper, Joshua D. Milner, Lisa R. Forbes Satter, Svetlana Aleshkevich, Luis M. Allende, T. Prescott Atkinson, Faranaz Atschekzei, Sezin Aydemir, Utku Aygunes, Vincent Barlogis, Ulrich Baumann, John Belko, Liliana Bezrodnik, Ariane Biebl, Lori Broderick, Nancy J. Bunin, Maria Soledad Caldirola, Martin Castelle, Fatih Celmeli, Louis-Marie Charbonnier, Talal A. Chatila, Deepak Chellapandian, Haluk Cokugras, Niall Conlon, Fionnuala Cox, Etienne Crickx, Buket Dalgic, Virgil ASH Dalm, Silvia Danielian, Nerea Dominguez-Pinilla, Tal Dujovny, Mikael Ebbo, Ahmet Eken, Brittany Esty, Alexandre Fabre, Alain Fischer, Mark Hannibal, Laura Huppert, Marc D. Ikeda, Stephen Jolles, Kent W. Jolly, Neil Jones, Maria Kanariou, Elif Karakoc-Aydiner, Theoni Karamantziani, Charikleia Kelaidi, Mary Keogan, Ayşenur Pac Kisaarslan, Ayca Kiykim, Kosmas Kotsonis, Natalia Kuzmenko, Sylvie Leroy, Dimitra Lianou, Hilary Longhurst, Myriam Ricarda Lorenz, Patrick Maffucci, Ania Manson, Sarah Marchal, Marion Malphettes, Lia Furlaneto Marega, Andrea A. Mauracher, Holly Miller, Joy Mombourquette, Noel G. Morgan, Anna Mukhina, Aladjidi Nathalie, Brigitte Nelken, David Nolan, Anna-Carin Norlin, Matias Oleastro, Alper Ozcan, Marlene Pasquet, José Roberto Pegler, Capucine Picard, Sophia Polychronopoulou, Pierre Quartier, Juan Francisco Quesada, Jan Ramakers, Katrina L. Randall, V. Koneti Rao, Allison Remiker, Geraldine Resin, Peter Richmond, Frederic Rieux-Laucat, Yulia Rodina, Pierre Rohrlich, Johnathan Sachs, Inga Sakovich, Christopher Santarlas, Sinan Sari, Gregory Sawicki, Uwe Schauer, Selma C. Scheffler Mendoza, Oksana Schvetz, Reinhold Ernst Schmidt, Klaus Schwarz, Anna Sediva, Kyle Sinclair, Mary Slatter, John Sleasman, Katerina Stergiou, Narissara Suratannon, Kay Tanita, Grace Thompson, Stephen Travis, Timothy Trojan, Maria Tsinti, Ekrem Unal, Luciano Urdinez, Felisa Vazquez-Gomez, Mariana Villa, Michael Weinrich, Mitchell J. Weiss, Benjamin Wright, Ebru Yilmaz, Radana Zachova, Yu Zhang, Internal Medicine, and Immunology

Subjects
SDG 3 - Good Health and Well-being, Immunology, Immunology and Allergy
Abstract

Background: In 2014, germline signal transducer and activator of transcription (STAT) 3 gain-of-function (GOF) mutations were first described to cause a novel multisystem disease of early-onset lymphoproliferation and autoimmunity. Objective: This pivotal cohort study defines the scope, natural history, treatment, and overall survival of a large global cohort of patients with pathogenic STAT3 GOF variants. Methods: We identified 191 patients from 33 countries with 72 unique mutations. Inclusion criteria included symptoms of immune dysregulation and a biochemically confirmed germline heterozygous GOF variant in STAT3. Results: Overall survival was 88%, median age at onset of symptoms was 2.3 years, and median age at diagnosis was 12 years. Immune dysregulatory features were present in all patients: lymphoproliferation was the most common manifestation (73%); increased frequencies of double-negative (CD4−CD8−) T cells were found in 83% of patients tested. Autoimmune cytopenias were the second most common clinical manifestation (67%), followed by growth delay, enteropathy, skin disease, pulmonary disease, endocrinopathy, arthritis, autoimmune hepatitis, neurologic disease, vasculopathy, renal disease, and malignancy. Infections were reported in 72% of the cohort. A cellular and humoral immunodeficiency was observed in 37% and 51% of patients, respectively. Clinical symptoms dramatically improved in patients treated with JAK inhibitors, while a variety of other immunomodulatory treatment modalities were less efficacious. Thus far, 23 patients have undergone bone marrow transplantation, with a 62% survival rate. Conclusion:: STAT3 GOF patients present with a wide array of immune-mediated disease including lymphoproliferation, autoimmune cytopenias, and multisystem autoimmunity. Patient care tends to be siloed, without a clear treatment strategy. Thus, early identification and prompt treatment implementation are lifesaving for STAT3 GOF syndrome.

Published
2023

33. A Single Dose of BNT162b2 Messenger RNA Vaccine Induces Airway Immunity in Severe Acute Respiratory Syndrome Coronavirus 2 Naive and Recovered Coronavirus Disease 2019 Subjects

Author

Emanuela Martinuzzi, Jonathan Benzaquen, Olivier Guerin, Sylvie Leroy, Thomas Simon, Marius Ilie, Véronique Hofman, Maryline Allegra, Virginie Tanga, Emeline Michel, Jacques Boutros, Charlotte Maniel, Antoine Sicard, Nicolas Glaichenhaus, Cecil Czerkinsky, Philippe Blancou, Paul Hofman, and Charles H Marquette

Subjects
Microbiology (medical), Infectious Diseases
Abstract

Background Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and therefore virus shedding. Parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior mucosal infection compared with injections of a parenteral vaccine in a mucosally naive subject. We investigated whether this was also the case for the BNT162b2 coronavirus disease 2019 (COVID-19) messenger RNA vaccine. Methods Twenty recovered COVID-19 subjects (RCSs) and 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–naive subjects were vaccinated with, respectively, 1 and 2 doses of the BNT162b2 COVID-19 vaccine. Nasal epithelial lining fluid (NELF) and plasma were collected before and after vaccination and assessed for immunoglobulin G (IgG) and IgA antibody levels to Spike and for their ability to neutralize binding of Spike to angiotensin-converting enzyme-2 receptor. Blood was analyzed 1 week after vaccination for the number of Spike-specific antibody-secreting cells (ASCs) with a mucosal tropism. Results All RCSs had both nasal and blood SARS-CoV-2–specific antibodies at least 90 days after initial diagnosis. In RCSs, a single dose of vaccine amplified preexisting Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including Delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2–naive subjects after 2 vaccine doses compared with RCSs after 1 dose. Conclusions Mucosal immune response to the SARS-CoV-2 Spike protein is higher in RCSs after a single vaccine dose compared with SARS-CoV-2–naive subjects after 2 doses.

Published
2022
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34. Sustained effectiveness of elexacaftor-tezacaftor-ivacaftor in lung transplant candidates with cystic fibrosis

Author

Clémence, Martin, Martine, Reynaud-Gaubert, Rebecca, Hamidfar, Isabelle, Durieu, Marlène, Murris-Espin, Isabelle, Danner-Boucher, Raphaël, Chiron, Sylvie, Leroy, Benoit, Douvry, Dominique, Grenet, Laurent, Mely, Sophie, Ramel, Sylvie, Montcouquiol, Lydie, Lemonnier, Espérie, Burnet, Jean-Louis, Paillasseur, Jennifer, Da Silva, and Pierre-Régis, Burgel

Subjects
Pulmonary and Respiratory Medicine, Indoles, Pyrrolidines, Cystic Fibrosis, Pyridines, Cystic Fibrosis Transmembrane Conductance Regulator, Quinolones, Aminophenols, Pediatrics, Perinatology and Child Health, Humans, Pyrazoles, Benzodioxoles, Chloride Channel Agonists, Lung Transplantation
Abstract

Elexacaftor-tezacaftor-ivacaftor induces rapid clinical improvement in patients with cystic fibrosis (CF) and advanced pulmonary disease, often leading to suspend the indication for lung transplantation. Yet no long-term data is available in lung transplant candidates.Lung transplant candidates (defined as being waitlisted for lung transplantation or considered for listing within 3 months) who have initiated elexacaftor-tezacaftor-ivacaftor were identified in the French cohort of patients with CF and advanced pulmonary disease. Patients were prospectively followed to evaluate treatment safety and effectiveness from initiation to July 20th, 2021.Among the 331 patients with advanced CF pulmonary disease who initiated elexacaftor-tezacaftor-ivacaftor, 65 were lung transplant candidates (17 listed for transplantation, 48 considered for listing within 3 months). Median [IQR] follow-up time was 363 [329; 377] days. At the end of the follow-up period, two patients were transplanted five and 11 days following treatment initiation, two were listed for transplantation, and 61 no longer met transplantation criteria. Improvement in percent predicted forced expiratory volume in 1 s (ppFEVIn lung transplant candidates eligible for elexacaftor-tezacaftor-ivacaftor, the rapid improvement following initiation of treatment persisted over one year with a reduction in treatment burden and lung transplantation could be safely deferred in most patients.

Published
2022
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35. Rapid Improvement after Starting Elexacaftor–Tezacaftor–Ivacaftor in Patients with Cystic Fibrosis and Advanced Pulmonary Disease

Author

Pierre-Régis Burgel, Isabelle Durieu, Raphaël Chiron, Sophie Ramel, Isabelle Danner-Boucher, Anne Prevotat, Dominique Grenet, Christophe Marguet, Martine Reynaud-Gaubert, Julie Macey, Laurent Mely, Annlyse Fanton, Sébastien Quetant, Lydie Lemonnier, Jean-Louis Paillasseur, Jennifer Da Silva, Clémence Martin, Claire Andrejak, Arnaud Becourt, Julie Mounard, Claire Poulet, Cinthia Rames, Marie Talleux, Marie-Chantal Chevalier, Estelle Darviot, Marie Jouvenot, Caroline Marien, Audrey Paris, Cécile Pelatan, Christine Person, Pascaline Priou, Françoise Troussier, Thierry Urban, Marie-Laure Dalphin, Jean-Charles Dalphin, Alice Ladaurade, Didier Pernet, Bénédicte Richaud-Thiriez, Pauline Roux-Claude, Nathalia Blanc, Vincent Boisserie-Lacroix, Stephanie Bui, Cyrielle Collet, Stéphane Debelleix, Emmanuel Bergot, Jacques Brouard, Karine Campbell, Muriel Laurans, Virginie Ribault, Corinne Borderon, Marie-Christine Heraud, Guillaume Labbe, Sylvie Montcouquiol, Isabelle Petit, Marc Ruivard, Céline Delestrain, Benoit Douvry, Ralph Epaud, Bernard Maitre, Natascha Remus, Guillaume Beltramo, Anne Houzel, Frédéric Huet, Stéphanie Perez, Amale Boldron-Ghaddar, Manuela Scalbert, Rabah Bouzioukh, Charles Simon, Boubou Camara, Rébecca Hamidfar, Catherine Llerena, Isabelle Pin, Antoine Deschildre, Alice Gicquello, Olivier Le Rouzic, Clara Leroy, Nicolas Paris, Thierry Perez, Caroline Thumerelle, Dominique Turck, Nathalie Wizla, Magali Dupuy-Grasset, Jane Languepin, Alexandra Masson-Rouchaud, Céline Menetrey, Stéphane Durupt, Sophie L’Excellent, Raphaele Nove-Josserand, Camille Ohlmann, Phillipe Reix, Quitterie Reynaud, Marie-Christine Werck-Gallois, Mélissandre Baravalle, Bérangère Coltey, Nadine Desmazes-Dufeu, Jean-Christophe Dubus, Clarisse Gautier, Jean-Baptiste Rey, Nathalie Stremler, Davide Caimmi, Margot Devrait, Johan Moreau, Yves Billon, Aurore Blondé, Anne Guillaumot, Sébastien Kiefer, Laura Peretti, Aurélie Tatopoulos, Angélica Tiotiu, Myriam Benhamida, Tiphaine Bihouee, Emmanuel Eschapasse, Adrien Tissot, Marie Giannantonio, Sylvie Leroy, Carole Piccini-Bailly, Johana Pradelli, Jonathan Messika, Véronique Boussaud, Nicolas Carlier, Isabelle Honoré, Dominique Hubert, Reem Kanaan, Céline Bailly-Botuha, Frédérique Chedevergne, Jacques De Blic, Christophe Delacourt, David Drummond, Brigitte Fauroux, Chantal Karila, Muriel Le Bourgeois, Isabelle Sermet, Bertrand Delaisi, Michèle Gerardin, Veronique Houdouin, Laurence Leclainche, Guillaume Aubertin, Laura Berdah, Annick Clement, Harriet Corvol, Nadia Nathan, Blandine Prevost, Nicolas Richard, Aline Tamalet, Jessica Taytard, Guillaume Thouvenin, Barbara Tourniaire, Michel Abely, Katia Bessaci-Kabouya, Sandra Dury, Bruno Ravoninjatovo, Alain Dabadie, Michel Dagorne, Eric Deneuville, Marie Jamin, Mélanie Ribault, Clémentine Vigier, Chantal Belleguic, Graziella Brinchault, Benoit Desrues, Audrey Barzic, Anne Dirou-Prigent, Jean Le Bihan, Krista Revert, Thomas Ropars, Laure Couderc, Stéphane Dominique, Hélène Morisse-Pradier, Stéphanie Pramil, Luc Thiberville, Nathalie Allou, Laurent Enaud, Elsa Gachelin, Eric Huchot, Annabelle Payet, Caroline Perisson, Saguiraly Piyaraly, Sophie Valois, Audrey Herzog, Romain Kessler, Michele Porzio, Laurence Weiss, Laurence Beaumont, Olivier Brugiere, Sylvie Colin, de Verdiere, Elise Cuquemelle, Sandra De Miranda, Adbdul Monem Hamid, François Parquin, Clément Picard, Antoine Roux, Charlotte Roy, François Bremont, Alain Didier, Marion Dupuis, Guillaume Faviez, Géraldine Labouret, Marie Mittaine, Marlène Murris-Espin, Léa Roditis, Laure Cosson, Patrice Diot, Thomas Flament, Charlotte Giraut, Julie Mankikian, Baptiste Arnouat, Gaétane Mousset, Véronique Storni, Philippe Vigneron, Emmanuelle Coirier-Duet, Asma Gabsi, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Université de Lyon, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fondation ILDYS (ILDYS), Institut du Thorax [Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Hôpital Foch [Suresnes], CHU Rouen, Normandie Université (NU), INSERM-TRANSFERT [Paris] (IT), Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Rouen Normandie (UNIROUEN), Hôpital Nord [CHU - APHM], Aix Marseille Université (AMU), CHU Bordeaux [Bordeaux], Hôpital Renée Sabran [CHU - HCL], CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Universitaire [Grenoble] (CHU), Vaincre la Mucoviscidose, Association de lutte contre la Mucoviscidose, EFFI-STAT, URC/CIC Paris Descartes Necker Cochin, Hôpital Necker, Institut Desbrest de santé publique (IDESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Supported by Vaincre la Mucoviscidose, Fondation Sauver la Vie, Universite Paris Descartes, Filiere Maladies Rares Muco-CFTR, and Legs PascalBonnet., Participating Investigators of the FrenchCystic Fibrosis Reference Network StudyGroup:Claire Andrejak, Arnaud Becourt, JulieMounard, Claire Poulet, Cinthia Rames, MarieTalleux (Amiens), Marie-Chantal Chevalier,Estelle Darviot, Marie Jouvenot, Caroline Marien,Audrey Paris, C ecile Pelatan, Christine Person,Pascaline Priou, Franc ̧oise Troussier, ThierryUrban (Angers-Le Mans), Marie-Laure Dalphin,Jean-Charles Dalphin, Alice Ladaurade, DidierPernet, B en edicte Richaud-Thiriez, PaulineRoux-Claude (Besanc ̧on), Nathalia Blanc,Vincent Boisserie-Lacroix, Stephanie Bui,Cyrielle Collet, St ephane Debelleix, Julie Macey(Bordeaux), Emmanuel Bergot, JacquesBrouard, Karine Campbell, Muriel Laurans,Virginie Ribault (Caen), Corinne Borderon,Marie-Christine Heraud, Guillaume Labbe,SylvieMontcouquiol, Isabelle Petit, Marc Ruivard(Clermont-Ferrand), C eline Delestrain, BenoitDouvry, Ralph Epaud, Bernard Maitre, NataschaRemus (Cr eteil), Guillaume Beltramo, AnnlyseFanton, Anne Houzel, Fr ed eric Huet, St ephaniePerez (Dijon), AmaleBoldron-Ghaddar, ManuelaScalbert (Dunkerque), Rabah Bouzioukh,Laurent Mely, Charles Simon (Giens), BoubouCamara, R ebecca Hamidfar, Catherine Llerena,Isabelle Pin, S ebastien Quetant (Grenoble), Antoine Deschildre, Alice Gicquello, Olivier LeRouzic, Clara Leroy, Nicolas Paris, Thierry Perez,Anne Prevotat, Caroline Thumerelle, DominiqueTurck, Nathalie Wizla (Lille), Magali Dupuy-Grasset, Jane Languepin, Alexandra Masson-Rouchaud, C eline Menetrey (Limoges), IsabelleDurieu, St ephane Durupt, Sophie L’Excellent,Raphaele Nove-Josserand, Camille Ohlmann,Phillipe Reix, Quitterie Reynaud, Marie-ChristineWerck-Gallois (Lyon), M elissandre Baravalle,B erang ere Coltey, Nadine Desmazes-Dufeu,Jean-Christophe Dubus, Clarisse Gautier, Jean-Baptiste Rey, Martine Reynaud-Gaubert,Nathalie Stremler (Marseille), Davide Caimmi,Rapha€el Chiron, Margot Devrait, Johan Moreau(Montpellier), Yves Billon, Aurore Blond e, AnneGuillaumot, S ebastien Kiefer, Laura Peretti,Aur elie Tatopoulos, Ang elica Tiotiu (Nancy), Myriam Benhamida, Tiphaine Bihouee, IsabelleDanner-Boucher, Emmanuel Eschapasse,Adrien Tissot (Nantes), Marie Giannantonio,Sylvie Leroy, Carole Piccini-Bailly, JohanaPradelli (Nice), Jonathan Messika (Paris, Bichat), V eronique Boussaud, Pierre-R egis Burgel,Nicolas Carlier, Isabelle Honor e, DominiqueHubert, Reem Kanaan, Cl emence Martin (Paris,Cochin), C eline Bailly-Botuha, Fr ed eriqueChedevergne, Jacques De Blic, ChristopheDelacourt, David Drummond, Brigitte Fauroux,Chantal Karila, Muriel Le Bourgeois, IsabelleSermet (Paris, Necker), Bertrand Delaisi,Mich ele Gerardin, Veronique Houdouin,Laurence Leclainche (Paris, Robert Debr e), Guillaume Aubertin, Laura Berdah, AnnickClement, Harriet Corvol, Nadia Nathan, BlandinePrevost, Nicolas Richard, Aline Tamalet, JessicaTaytard, Guillaume Thouvenin, BarbaraTourniaire (Paris, Trousseau), Michel Abely,Katia Bessaci-Kabouya, Sandra Dury, BrunoRavoninjatovo (Reims), Alain Dabadie, MichelDagorne, Eric Deneuville, Marie Jamin, M elanieRibault, Cl ementine Vigier (Rennes – SaintBrieuc), Chantal Belleguic, Graziella Brinchault,Benoit Desrues (Rennes), Audrey Barzic, AnneDirou-Prigent, Jean Le Bihan, Sophie Ramel,Krista Revert, Thomas Ropars (Roscoff), LaureCouderc, St ephane Dominique, ChristopheMarguet, H el ene Morisse-Pradier, St ephaniePramil, Luc Thiberville (Rouen), Nathalie Allou,Laurent Enaud, Elsa Gachelin, Eric Huchot,Annabelle Payet, Caroline Perisson, SaguiralyPiyaraly, Sophie Valois (La R eunion), AudreyHerzog, Romain Kessler, Michele Porzio,Laurence Weiss (Strasbourg), LaurenceBeaumont, Olivier Brugiere, Sylvie Colin deVerdiere, Elise Cuquemelle, Sandra De Miranda,Dominique Grenet, Adbdul Monem Hamid,Franc ̧ois Parquin, Cl ementPicard, Antoine Roux,Charlotte Roy (Suresnes), Franc ̧ois Bremont,Alain Didier, Marion Dupuis, Guillaume Faviez,G eraldine Labouret, Marie Mittaine, Marl eneMurris-Espin, L ea Roditis (Toulouse), LaureCosson, Patrice Diot, Thomas Flament, CharlotteGiraut, JulieMankikian(Tours), Baptiste Arnouat,Ga etane Mousset, V eronique Storni, PhilippeVigneron (Vannes-Lorient), and Emmanuelle Coirier-Duet, and Asma Gabsi (Versailles)

Subjects
Lung Diseases, Male, elexacaftor, Indoles, Cystic Fibrosis, Pyridines, medicine.medical_treatment, Regulator, Aminophenols, Critical Care and Intensive Care Medicine, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, Cystic fibrosis, Gastroenterology, Membrane Potentials, Ivacaftor, 0302 clinical medicine, Prospective Studies, 030212 general & internal medicine, Chloride Channel Agonists, Aged, 80 and over, Middle Aged, Transmembrane protein, Drug Combinations, Quinolines, Female, France, medicine.drug, Adult, Pulmonary and Respiratory Medicine, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, cystic fibrosis transmembrane conductance regulator modulators, Adolescent, Pulmonary disease, Young Adult, 03 medical and health sciences, Internal medicine, lung transplantation, medicine, Humans, Lung transplantation, In patient, Aged, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, Editorials, medicine.disease, 030228 respiratory system, Tezacaftor, Pyrazoles, business
Abstract

International audience; Rationale: Elexacaftor-tezacaftor-ivacaftor is a CFTR (cystic fibrosis [CF] transmembrane conductance regulator) modulator combination, developed for patients with CF with at least one Phe508del mutation. Objectives: To evaluate the effects of elexacaftor-tezacaftor- ivacaftor in patients with CF and advanced respiratory disease. Methods: A prospective observational study, including all patients aged ⩾12 years and with a percent-predicted FEV1 (ppFEV1)

Published
2021
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36. Cyclophosphamide added to glucocorticoids in acute exacerbation of idiopathic pulmonary fibrosis (EXAFIP): a randomised, double-blind, placebo-controlled, phase 3 trial

Author

Abdellatif Tazi, Aurélie Le Borgne-Krams, Marine Cachanado, Tabassome Simon, Sylvain Marchand-Adam, Morgane Didier, Lidwine Wemeau-Stervinou, Sandrine Hirschi, Frédéric Rivière, Arnaud Bourdin, François Lebargy, Stéphane Dominique, Aude Gibelin, Alexandre Chabrol, Tristan Dégot, Jacques Cadranel, Martine Reynaud-Gaubert, Marie-Pierre Debray, Sylvie Leroy, Frédéric Gagnadoux, Emmanuel Bergot, François-Xavier Blanc, Alexandra Rousseau, Raphael Borie, Pierre Yves Brillet, Guillaume Beltramo, Mallorie Kerjouan, Hilario Nunes, Olivia Freynet, Julie Traclet, Bruno Crestani, Anne-Sophie Gamez, Grégoire Prévot, Jean Pastré, Dominique Israel-Biet, Marie-Christine Dombret, Laurent Plantier, Cécile Chenivesse, Laurence Berard, Ana Nieves, Emmanuel Gomez, Dominique Valeyre, Stéphane Jouneau, Anne Gondouin, Elodie Blanchard, C. Launois, Nathalie Bautin, Jean-Marc Naccache, Vincent Cottin, Antoine Parrot, Philippe Bonniaud, Centre de référence maladies rares des maladies pulmonaires rares de l’adulte (CHU Dijon) (CRMR des maladies pulmonaires rares de l’adulte), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Sorbonne Université (SU), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Foch [Suresnes], CHU Pontchaillou [Rennes], École des Hautes Études en Santé Publique [EHESP] (EHESP), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Avicenne [AP-HP], Laboratoire d'Excellence INFLAMEX [Paris], Université Sorbonne Paris Cité (USPC), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), AP-HP - Hôpital Bichat - Claude Bernard [Paris], CHU Saint-Antoine [AP-HP], Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre régional de pharmacovigilance de Marseille Provence Corse [CHU de Marseille] (CRPV-Marseille), Assistance Publique - Hôpitaux de Marseille (APHM)-CHU Marseille, CHU Dijon, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Les Hôpitaux Universitaires de Strasbourg (HUS), Nouvel Hôpital Civil de Strasbourg, Centre Hospitalier Universitaire de Reims (CHU Reims), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Lille, Hôpital Albert Calmette, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de Référence des Maladies Pulmonaires Rares [Hôpital Louis Pradel - HCL], Hôpital Louis Pradel [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Hospices Civils de Lyon (HCL), Université de Lyon, CIC CHU Lyon (inserm), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Hôpital d'instruction des Armées Percy, Service de Santé des Armées, Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital JeanMinjoz, CHU Bordeaux [Bordeaux], Hôpital Haut-Lévêque [CHU Bordeaux], unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Rouen, Normandie Université (NU), CHU Tenon [AP-HP], Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), CHU Montpellier, Université de Lille, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Roche, Ministere de la Sante et des Solidarites, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Marseille-Assistance Publique-Hôpitaux de Marseille (AP-HM), Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Pulmonary and Respiratory Medicine, medicine.medical_specialty, education.field_of_study, Exacerbation, Cyclophosphamide, business.industry, [SDV]Life Sciences [q-bio], Population, medicine.disease, Placebo, 3. Good health, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, 030228 respiratory system, Methylprednisolone, Internal medicine, Clinical endpoint, Medicine, 030212 general & internal medicine, business, education, Adverse effect, ComputingMilieux_MISCELLANEOUS, medicine.drug
Abstract

Summary Background The use of cyclophosphamide in patients with acute exacerbation of idiopathic pulmonary fibrosis (IPF) is unknown. Our study was designed to evaluate the efficacy and safety of four cyclophosphamide pulses in addition to high-dose methylprednisolone in this population. Methods In this double-blind, placebo-controlled trial done in 35 departments across 31 hospitals in France, adult patients (≥18 years) with acute exacerbation of IPF and those with suspected acute exacerbation of IPF were randomly assigned in a 1:1 ratio using a web-based system to receive either intravenous pulses of cyclophosphamide (600 mg/m2) plus uromitexan as haemorrhagic cystitis prophylaxis (200 mg/m2) at the time of cyclophosphamide administration and then again, 4 h later, or placebo at days 0, 15, 30, and 60. Random assignment was stratified according to the severity of IPF and was block-balanced with variable block sizes of four or six patients. Patients receiving mechanical ventilation, with active infection, with active cancer, or who were registered on the lung transplant waiting list were excluded. All patients received standardised high-dose glucocorticoids. The investigators, patients, and the sponsor were masked to the treatment assignments. The primary endpoint was 3-month all-cause mortality, analysed by a χ2 test adhering to an intention-to-treat principle. The trial is now complete and registered with ClinicalTrials.gov , NCT02460588 . Findings Between Jan 22, 2016, and July 19, 2018, 183 patients were assessed for eligibility, of whom 120 patients were randomly assigned and 119 patients (62 [52%] with severe IPF) received at least one dose of cyclophosphamide (n=60) or placebo (n=59), all of whom were included in the intention-to-treat analysis. The 3-month all-cause mortality was 45% (27/60) in patients given cyclophosphamide compared with 31% (18/59) in the placebo group (difference 14·5% [95% CI −3·1 to 31·6]; p=0·10). Similar results were found after adjustment by IPF severity (odds ratio [OR] 1·89 [95% CI 0·89–4·04]). The risk of death at 3 months, independent of the treatment received, was higher with severe than non-severe IPF (OR 2·62 [1·12–6·12]) and was lower with the use of antifibrotic therapy (OR 0·33 [0·13–0·82]). Adverse events were similar between groups by 6 months (25 [42%] in the cyclophosphamide group vs 30 [51%] in the placebo group) and their proportion, including infections, did not differ. Overall infection was the main adverse event and occurred in 20 (33%) of 60 patients in the cyclophosphamide group versus 21 (36%) of 59 patients in the placebo group. Interpretation In patients with acute exacerbation of IPF, adding intravenous cyclophosphamide pulses to glucocorticoids increased 3-month mortality. These findings provide evidence against the use of intravenous cyclophosphamide in such patients. Funding Programme Hospitalier de Recherche Clinique of the French Ministry of Health (PHRC 2014–502), Roche Pharmaceuticals.

Published
2022
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37. Accurate Detection of SARS-CoV-2 by Next-Generation Sequencing in Low Viral Load Specimens

Author

Marius Ilié, Jonathan Benzaquen, Véronique Hofman, Elodie Long-Mira, Sandra Lassalle, Jacques Boutros, Christophe Bontoux, Virginie Lespinet-Fabre, Olivier Bordone, Virginie Tanga, Maryline Allegra, Myriam Salah, Julien Fayada, Sylvie Leroy, Matteo Vassallo, Irit Touitou, Johan Courjon, Julie Contenti, Michel Carles, Charles-Hugo Marquette, and Paul Hofman

Subjects
Inorganic Chemistry, next generation sequencing, SARS-CoV-2, Organic Chemistry, COVID-19, General Medicine, Physical and Theoretical Chemistry, Genexus, Molecular Biology, low viral load, Spectroscopy, Catalysis, Computer Science Applications
Abstract

As new SARS-CoV-2 variants emerge, there is an urgent need to increase the efficiency and availability of viral genome sequencing, notably to detect the lineage in samples with a low viral load. SARS-CoV-2 genome next-generation sequencing (NGS) was performed retrospectively in a single center on 175 positive samples from individuals. An automated workflow used the Ion AmpliSeq SARS-CoV-2 Insight Research Assay on the Genexus Sequencer. All samples were collected in the metropolitan area of the city of Nice (France) over a period of 32 weeks (from 19 July 2021 to 11 February 2022). In total, 76% of cases were identified with a low viral load (Ct ≥ 32, and ≤200 copies/µL). The NGS analysis was successful in 91% of cases, among which 57% of cases harbored the Delta variant, and 34% the Omicron BA.1.1 variant. Only 9% of cases had unreadable sequences. There was no significant difference in the viral load in patients infected with the Omicron variant compared to the Delta variant (Ct values, p = 0.0507; copy number, p = 0.252). We show that the NGS analysis of the SARS-CoV-2 genome provides reliable detection of the Delta and Omicron SARS-CoV-2 variants in low viral load samples.

Published
2023
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38. Volcanisme et tectonique découverts le long de l’archipel des Comores entre l’Afrique et Madagascar

Author

Isabelle Thinon, Anne Lemoine, Sylvie Leroy, Fabien Paquet, Carole Berthod, Sébastien Zaragosi, Vincent Famin, Nathalie Feuillet, Pierre Boymond, Charles Masquelet, Nicolas Mercury, Anaïs Rusquet, Carla Scalabrin, Jérôme Van der Woerd, Julien Bernard, Julie Bignon, Valérie Clouard, Cécile Doubre, Eric Jacques, Stephan J. Jorry, Frédérique Rolandone, Nicolas Chamot-Rooke, Matthias Delescluse, Dieter Franke, Louise Watremez, Patrick Bachèlery, Laurent Michon, Daniel Sauter, Stéphane Bujan, Albane Canva, Emilie Dassie, Vincent Roche, Said Ali, Abdoul Hamid Sitti Allaouia, Christine Deplus, Setareh Rad, Ludivine Sadeski, Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), 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), Laboratoire Magmas et Volcans (LMV), Institut national des sciences de l'Univers (INSU - CNRS)-Institut de Recherche pour le Développement et la société-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Observatoire de Physique du Globe de Clermont-Ferrand (OPGC), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Environnements et Paléoenvironnements OCéaniques (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Laboratoire GéoSciences Réunion (LGSR), Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris), Institut de Physique du Globe de Paris (IPGP), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS), Institut de Physique du Globe de Paris (IPGP (UMR_7154)), Institut national des sciences de l'Univers (INSU - CNRS)-Université de La Réunion (UR)-Institut de Physique du Globe de Paris (IPG Paris)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Terre Environnement Strasbourg (ITES), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Geo-Ocean (GEO-OCEAN), Université de Bretagne Sud (UBS)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS), Géosciences Marines (GM), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Géosciences Environnement Toulouse (GET), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Institut de physique du globe de Strasbourg (IPGS), Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de géologie de l'ENS (LGENS), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Département des Géosciences - ENS Paris, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Bundesanstalt für Geowissenschaften und Rohstoffe (BGR), Laboratoire d’Océanologie et de Géosciences (LOG) - UMR 8187 (LOG), Institut national des sciences de l'Univers (INSU - CNRS)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Nord]), Ecole et Observatoire des Sciences de la Terre (EOST), Géoazur (GEOAZUR 7329), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Faculté des Sciences et Techniques - Université des Comores, CNDRS, and ANR-19-CE31-0018,COYOTES,COmores & maYotte : vOlcanisme, TEctonique et Sismicité(2019)

Subjects
[SDU.STU.TE]Sciences of the Universe [physics]/Earth Sciences/Tectonics, Comoros Archipelago, Active tectonics, NorthernMozambique Channel, Volcanic province, Northern Mozambique Channel, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Backscatter, Bathymetry, [SDU.STU.VO]Sciences of the Universe [physics]/Earth Sciences/Volcanology, General Earth and Planetary Sciences, Incipient plate boundary, General Environmental Science
Abstract

Geophysical and geological data from the North Mozambique Channel acquired during the 2020–2021 SISMAORE oceanographic cruise reveal a corridor of recent volcanic and tectonic features 200 km wide and 600 km long within and north of Comoros Archipelago. Here we identify and describe two major submarine tectono-volcanic fields: the N’Droundé province oriented N160°E north of Grande-Comore Island, and the Mwezi province oriented N130°E north of Anjouan and Mayotte Islands. The presence of popping basaltic rocks sampled in the Mwezi province suggests post-Pleistocene volcanic activity. The geometry and distribution of recent structures observed on the seafloor are consistent with a current regional dextral transtensional context. Their orientations change progressively from west to east (N160°E, N130°E, EW). The volcanism in the western part appears to be influenced by the pre-existing structural fabric of the Mesozoic crust. The 200 km-wide and 600 km-long tectono-volcanic corridor underlines the incipient Somalia–Lwandle dextral lithospheric plate boundary between the East-African Rift System and Madagascar., Des données géophysiques et géologiques ont été acquises lors de la campagne océanographique SISMAORE (2020–2021). Deux grands champs tectono-volcaniques sous-marins ont été découverts tout le long et principalement au nord de l’archipel des Comores : la province N’Droundé orientée N160°E au nord de Grande-Comore, et la province Mwezi orientée N130°E au nord d’Anjouan-Mayotte où des roches basaltiques de type popping-rocks suggèrent une activité volcanique possiblement actuelle à pléistocène. La géométrie et la distribution des structures récentes sont cohérentes avec un contexte régional actuel transtensif dextre. Leurs orientations évoluent d’Ouest en Est (N160°E, N130°E, EW), suggérant pour la partie occidentale, une mise en place du volcanisme influencée par la structuration crustale préexistante. Le corridor tectono-volcanique de 200 km de large et de 600 km de long dessine une limite de plaque lithosphérique Somalie-Lwandle immature en décrochante dextre entre le système du rift est-africain et Madagascar.

Published
2022
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39. Activation of the P2RX7/IL-18 pathway in immune cells attenuates lung fibrosis

Author

Serena Janho dit Hreich, Thierry Juhel, Sylvie Leroy, Alina Ghinet, Frederic Brau, Véronique Hofman, Paul Hofman, and Valérie Vouret-Craviari

Abstract

Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease associated with progressive and irreversible deterioration of respiratory functions that lacks curative therapies. Despite IPF being associated with a dysregulated immune response, current antifibrotics aim only at limiting fibroproliferation. We show here that theP2RX7/IL-18/IFNGaxis is downregulated in IPF patients and that P2RX7 has immunoregulatory functions. Using our positive modulator of P2RX7, we show that activation of the P2RX7/IL-18 axis in immune cells limits lung fibrosis progression in a mouse model by favoring an anti-fibrotic immune environment, with notably an enhanced IL-18-dependent IFN-γ production by lung T cells leading to a decreased production of IL-17 and TGFβ. Overall, we show the ability of the immune system to limit lung fibrosis progression by targeting the immunomodulator P2RX7. Hence, treatment with a small activator of P2RX7 may represent a promising strategy for patients with lung fibrosis.

Published
2022
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40. Across and along-strike crustal structure variations of the western Afar margin and adjacent plateau: insights from receiver functions analysis

Author

Abdulhakim Ahmed, Cecile Doubre, Sylvie Leroy, Derek Keir, Carolina Pagli, James O.S. Hammond, Atalay Ayele, Maxime Be de Berc, Marc Grunberg, Jerome Vergne, Romain Pestourie, Daniel Mamo, Birhanu Kibret, Nadaya Cubas, Aude Lavayssière, Marianne Janowski, Olivier Lengliné, Alessandro La Rosa, Emma L. Chambers, and Finnigan Illsley-Kemp

Subjects
es, cps, Geology, Earth-Surface Processes
Abstract

We used teleseismic receiver function analysis to image the crustal structure beneath 24 broadband seismic stations densely deployed along two profiles traversing different structural units across the western Afar margin. Our high-resolution receiver function results image pronounced spatial variations in the crustal structure along the profiles and provide improved insights to understand how strain is partitioned in the crust during rifting. Beneath the western plateau next to northern Afar, the crust is likely felsic-to-intermediate in composition (average Vp/Vs 1.74), with a step like thinning of the crust from an average of 38 km beneath the western plateau to an average of 22 km beneath the marginal graben. Consistently thicker crust is observed beneath the southern profile (central Afar), showing four distinct regions of uniform crustal thickness: 1) an average crustal thickness of 42 km beneath the western plateau; 2) 34 km beneath the foothills area; 3) 28 km beneath the marginal graben and the wide extensional basin and 4) 21 km beneath the central rift axis. We use crustal thickness results to estimate a stretching factor β of 2.2 and 2.7 for central Afar and northern Afar respectively. Our estimated values are lower than β > 3.0 predicted from plate reconstructions, and we interpret that the variations are best explained by 2–5 km magmatic addition into the crust. The crustal composition beneath the southern profile is more complex with elevated Vp/Vs ratios ranging between 1.79 and 1.85 beneath the western plateau and marginal graben. This is consistent with a greater mafic component and best explained by crust altered by intrusions due to significant pre and syn-rift magmatic activity. Abnormally high Vp/Vs ratios of more than 1.90 are observed beneath the axial rift zone of central Afar, which most likely suggests the localization of partial melt within the crust.

Published
2022

41. Gondwana break‐up controlled by tectonic inheritance and mantle plume activity: insights from Natal rift development (South Mozambique, Africa)

Author

Vincent Roche, Sylvie Leroy, Sidonie Revillon, François Guillocheau, Gilles Ruffet, William Vétel, 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), Sedisor, Géosciences Rennes (GR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), TotalEnergies, and Total et IFREMER (PAMELA)

Subjects
[SDU.STU.TE]Sciences of the Universe [physics]/Earth Sciences/Tectonics, Geology
Abstract

International audience; The breakup of Eastern Gondwana started during the Early Jurassic with the separation of Antarctica and Madagascar from Africa. While margins architecture has been described along the Western Somalia Basin and the central Mozambique, the spatial extent of rifting further south – i.e. the Natal Valley – remains poorly documented. Seismic reflection profiles interpretation, 40Ar/39Ar ages and isotopic data show the existence of a plume related magma-rich margin – the Natal segment – characterized by a large volume of seaward dipping reflectors inferred to be basalts. In particular, the contrast in lithosphere rheology, probably caused by a Meso-Neoproterozoic belt between the Kaapval and Grunehogna Archean cratons, favored extension and upwelling from a deep mantle thermomechanical anomaly, the so-called Karoo superplume that started at around 180 Ma. Further, the presence of stretched continental crust at around 30°S implies a more southerly position of Antarctica which will need to be considered in future kinematic models.

Published
2022
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42. Structure of a new submarine volcano and magmatic phases to the East of Mayotte, in the Comoros Archipelago, Indian Ocean

Author

Dieter Franke, Charles MASQUELET, Nicolas Chamot-Rooke, and Sylvie LEROY

Abstract

50 km East of Mayotte Island (North Mozambique Channel; Comoros Archipelago), a submarine volcanic edifice formed during the first year of a seismo-volcanic crisis, between May 2018 and May 2019. Thanks to the French ANR Project COYOTES and the SISMAORE oceanographic cruise (2021), a multichannel seismic profile gives the first in-depth image of the new East-Mayotte volcano and its surrounding volcanic area. The seismic interpretation reveals that several distinct magmatic phases affected the area. The new volcano is built on a ~150 m thick sedimentary layer. Beneath this sedimentary layer, we found a major volcanic layer, ~2.5 km thick, which extends ~91 km to the south and ~33 km to the north of the newly formed submarine volcano. This volcanic unit is composed of multiple seismic facies that may indicate distinct successive volcanic phases. We interpret this major volcanic layer as part of the Mayotte volcanic edifice, with the presence of a complex magmatic feeder system underneath. We observe a ~2.2-2.5 km thick sedimentary cover between the main volcanic layer, below the new volcano, and the top of the crust. We tentatively identified the top-Oligocene seismic horizon (~23 Ma) well above the main volcanic layer, and assuming a constant sedimentation rate we estimate the onset of the volcanism at Mayotte Island at 28 Ma.

Published
2022
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43. Volcano-tectonic interactions within two recently discovered submarine volcanic fields: Implication for geodynamics in the Comoros

Author

Pierre Boymond and Sylvie LEROY

Abstract

The birth of a new volcano offshore the eastern coast of Mayotte, one of the oldest volcanic island in the Comoros archipelago rose questions about the origin of the volcanism in this area. The volcano-tectonic context of this region is poorly known mainly because high-resolution marine data was missing. Here we present new marine geophysical data (bathymetry, backscatter and seismic reflexion data) acquired between December 23 2020 and February 11 2021 during the SISMAORE cruise (Thinon et al., 2021) in the framework of the French ANR COYOTES project. The high-resolution multibeam bathymetric and backscatter data reveal the existence of two submarine volcanic provinces we named N’Droundé and Mwezi (Thinon et al., 2022). In these provinces, we identified faults scarps, volcanic structures, lava flows and flat-top sedimentary domes on the seafloor. Those volcanic and tectonic features are very well preserved in the morphology and very reflective in the backscatter attesting that they are recent and probably active. Several seismic reflection profiles crosscut those structures. They reveal that the sedimentary layers are cut by faults and intruded by sills and dykes. We showed that the recent deformations of the seafloor such as flat-topped domes and grabens are promoted by those intrusions. The recent deformation of the sediments accommodating the magmatic intrusions are used as indirect markers to establish a relative chronology of magmatic activity in the two volcanic provinces. We showed that the magmatism is older in the N’Droundé volcanic province, near Grande Comore than in Mwezi’s, North-East of Anjouan. We also showed from the analysis of sills and dykes in the sedimentary cover that the magmatism intruded during two non-concurring episodes.Those volcano-tectonic features align in a mean NW-SE direction and may have likely emplaced in a NE-SW extensional stress field. At a smaller spatial scale, some diking-induced graben form swarms of different directions implying local perturbation of the regional stress field by volcanic intrusions.Overall, those observations are crucial to improve our knowledge of the geodynamics in the area and to constrain boundary conditions for future numerical modeling of deformation at lithospheric scale.

Published
2022
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44. Cuba's northern offshore: a witness to geodynamics evolution of the northern boundary of the Caribbean plate

Author

Alana Oliveira de Sa, Sylvie Leroy, Elia D'Acremont, Sara La Fuerza, and Bernard Mercier de Lepinay

Abstract

The northern boundary of the Caribbean plate is characterized by the oblique collision between the Caribbean (CAR) and North American (NOAM) tectonic plates. The progressive counterclockwise rotation of the two plates accompanying the eastward translation of NOAM vs. CAR is responsible for the increasing obliquity of the collision between these two plates. Consequently, successive southward jumps of major strike-slip faults accommodate the eastward escape of the Caribbean plate and the collisional indentation against the Bahama Banks. During this process, Cuba was progressively welded to the North American Plate. Several strike-slip corridors record this diachronous collision as major left-lateral transfer zones in Cuba: Eastern Yucatan Margin (Upper Cretaceous), Pinar-Varadero (Paleocene), La Trocha (early Eocene), Cauto-Nipe (middle/late Eocene), and Oriente Fault Zone (early Oligocene). The nature and age of the related tectonic events of these tectonic corridors were widely studied onshore. However, offshore northern Cuba remains relatively unknown. We provided a first offshore description of northeastern Cuba based on a multi-channel seismic reflection and swath-bathymetric dataset from the Haiti-SIS cruise. The seismic reflection profiles show that the structural and sedimentary architecture of the insular slope varies significantly from central to eastern Cuba. This lateral variability seems mainly influenced by the proximity with the Bahama Banks, which act as a succession of local indenters. The width of the insular slope varies from 5-10km in central Cuba to more than 50km in width towards the east off the Guacanayabo-Nipe tectonic corridor. In this region, the insular slope shows a thick sedimentary cover suggesting a main subsiding regional block related to the middle/late Eocene onset of the Guacanayabo-Nipe tectonic corridor. Contrasting lateral deformation patterns in this region are probably related to the diachronous strike-slip events related to the activity of the Cauto-Nipe fault. The coexistence of folds, transtensive and transpressive structures affecting the sedimentary infill attests that the local stress regimes of this fault have gradually changed. Our study correlates offshore deformation phases recorded in the offshore northeastern coast of Cuba, with major deformation episodes recorded onshore Cuba from Eocene to present-day. Our tectonostratigraphic evolution of the eastern offshore of Cuba provides new constraints to improve the knowledge of the geodynamics of the northern boundary of the Caribbean plate.

Published
2022
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45. East African Fracture Zones: a long lifespan since the breakup of Gondwana

Author

Vincent Roche, Sylvie Leroy, Jean-Claude Ringenbach, François Sapin, Sidonie Revillon, François Guillocheau, William Vetel, Louise Watremez, 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), TotalEnergies, Sedisor, Géosciences Rennes (GR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Rennes (OSUR), Université de Rennes (UR)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d’Océanologie et de Géosciences (LOG) - UMR 8187 (LOG), Institut national des sciences de l'Univers (INSU - CNRS)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Nord]), and European Geosciences Union

Subjects
[SDU.STU.TE]Sciences of the Universe [physics]/Earth Sciences/Tectonics, [SDU.STU.ST]Sciences of the Universe [physics]/Earth Sciences/Stratigraphy
Abstract

Gondwana splitting started during the Early Jurassic (ca. 180 Ma) with the separation of Antarctica and Madagascar from Africa, followed by the separation of South America and Africa during the Middle Jurassic. Thanks to recent seismic profiles for petroleum exploration, the architecture of rifted margins and the transform faults zones, which developed as a result of the relative motion between tectonic plates have been recently evidenced and studied along the whole eastern and south-eastern Africa (i.e., in the Western Somali Basin, the Mozambique Basin, the Natal Basin, and the Outeniqua Basin). Yet, the structure and overall kinematic evolution of the three major transform faults zones together – i.e., the Agulhas, the Davie, and the Limpopo Fracture Zones – that control the opening of these major oceanic basins remain poorly studied. The interpretation of an extensive regional multichannel seismic dataset coupled with recent studies allows us to propose an accurate regional mapping of the crustal domains and major structural elements along the rifted margins along the whole eastern and south-eastern Africa. We provide new constraints on the structuration and evolution of these three transform systems. Although our findings indicate common features in transform style (e.g., a right-lateral transform system, a wide sheared corridor), the deformation and the thermal regime along these systems appear quite different. In particular, we show that the Davie and Agulhas Fracture Zones recorded spectacular inversions during the transform stage whereas transtensional deformation is observed along the Limpopo Fracture Zone during its activity. This suggests that faults activity controls vertical displacements along transform margins, minimising other processes such as thermal exchanges between the oceanic and continental lithospheres across the transform fault and flexural behaviour of the lithosphere. This different style of deformation may be explained by two main forcing parameters: (i) the magmatic conditions that may modify the rheology of the crust, and (ii) the far-field forces that may induce a rapid change of regional tectonic stress. Further, in the Davie and Agulhas cases, the major transform faults postdate the development of the rift zone-controlling faults. Thus, there are no pre-existing structures that control the initiation of a transform fault zone. Conversely, the Limpopo margin shows an intracontinental transform faulting stage. In both cases, a minimum of several Ma is required to establish a complete kinematic linkage between the two-active spreading centers. During this period, the rifted segments opening possibly triggered rift-parallel mantle flow, which progressively favors the decoupling in-between the continental domain and the future oceanic domain. In the post-drift history, rapid changes of regional tectonic stress are recorded and show that some transform margins are excellent recorders of large plate kinematic changes.

Published
2022
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46. The ALBACORE oceanographic cruise: tectonic and sedimentary processes at distinct temporal and spatial scales in the Alboran Sea

Author

Jaime Frigola, ALAIN RABAUTE, and Sylvie LEROY

Abstract

The Alboran Sea (Western Mediterranean) is a relatively small ocean basin connected with the Atlantic that provides a rich archive of tectonic and sedimentary processes at distinct temporal and spatial scales during the Quaternary. Since the collisional boundary of the Eurasia-Nubia plates crosses the Alboran Sea, this basin is also the locus of active geohazards: the constant seismic activity, concentrated mostly along the Al Idrissi strike-slip fault system and submarine landslides, that can cause tsunami hazards affecting the entire Alboran coasts and damages to submarine cables and infrastructures. Previous understanding of the Alboran Sea has been based on seafloor and subsurface geophysical data of differing resolution and scale, combined with very short sediment coring and IODP and industrial boreholes. In order to obtain new constrains on the geology of the Alboran Sea, the ALBACORE cruise was held in October and November 2021 onboard the R/V Pourquoi Pas? In addition to sites in the northern Alboran Sea targeting contourites, several sites in the southern Alboran Sea were selected as key study areas: the Al-Idrissi active fault zone, the Al-Hoceima shelf, the Xauen/Tofiño and the Francesc Pages banks.The scientific work of the ALBACORE campaign included the acquisition of Calypso cores (up to 28m long), sampling of consolidated strata with Cnexoville, in situ geotechnical measurements (Penfeld) with a seabed cone penetration test device (up to 50m long), heat flow measurements (up to 6m long), swath bathymetric imaging of the seafloor and water column, and sub-bottom profiling. The total length of sediments recovered reached 734m. Results from the ALBACORE cruise address the following scientific objectives:To understand better the causal relationships between the present-day morpho-structural pattern and date Quaternary tectonic pulse and associated sedimentary systems To determine the Late Pleistocene-Holocene stratigraphic pattern and the paleo-oceanographic implications of contourites. To explore the chronological evolution of cold-water coral mounds and their paleoceanographic and palaeoclimatic signature since the Middle Pleistocene. To investigate the causal factors of slope instability processes and evaluate the geological hazard associated with tectonic pulses and fluid seepage. To determine the recent high-resolution sequence stratigraphy of the Al-Hoceima shelf in order to decode the late Pleistocene and Holocene sea-level changes at millennial scale.

Published
2022
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47. An integrated cell atlas of the human lung in health and disease

Author

Malte Luecken, Lisa Sikkema, Daniel Strobl, Luke Zappia, Elo Madissoon, Nikolay Markov, Laure-Emmanuelle Zaragosi, Meshal Ansari, Marie-Jeanne Arguel, Leonie Apperloo, Christophe Becavin, Marijn Berg, Evgeny Chichelnitskiy, Mei-i Chung, Antoine Collin, Aurore Gay, Baharak Hooshiar Kashani, Manu Jain, Theodore Kapellos, Tessa Kole, Christoph Mayr, Michael von Papen, Lance Peter, Ciro Ramírez-Suástegui, Janine Schniering, Chase Taylor, Thomas Walzthoeni, Chuan Xu, Linh Bui, Carlo de Donno, Leander Dony, Minzhe Guo, Austin Gutierrez, Lukas Heumos, Ni Huang, Ignacio Ibarra Del Río, Nathan Jackson, Preetish Kadur Lakshminarasimha Murthy, Mohammad Lotfollahi, Tracy Tabib, Carlos Talavera-Lopez, Kyle Travaglini, Anna Wilbrey-Clark, Kaylee Worlock, Masahiro Yoshida, Tushar Desai, Orit Rozenblatt-Rosen, Christine Falk, Naftali Kaminski, Mark Krasnow, Robert Lafyatis, Marko Nikolic, Joseph Powell, Jay Rajagopal, Max Seibold, Dean Sheppard, Douglas Shepherd, Sarah Teichmann, Alexander Tsankov, Jeffrey Whitsett, Yan Xu, Nicholas Banovich, Pascal Barbry, Thu Duong, Kerstin Meyer, Jonathan Kropski, Dana Pe'er, Herbert Schiller, Purushothama Rao Tata, Joachim Schultze, Maarten van den Berge, Yuexin Chen, James Hagood, Ahmed Hassan, Peter Horvath, Joakim Lundeberg, Sylvie Leroy, Charles Marquette, Gloria Pryhuber, Christos Samakovlis, Xin Sun, Lorraine Ware, Kun Zhang, Alexander Misharin, Martijn Nawijn, and Fabian Theis

Abstract

Organ- and body-scale cell atlases have the potential to transform our understanding of human biology. To capture the variability present in the population, these atlases must include diverse demographics such as age and ethnicity from both healthy and diseased individuals. The growth in both size and number of single-cell datasets, combined with recent advances in computational techniques, for the first time makes it possible to generate such comprehensive large-scale atlases through integration of multiple datasets. Here, we present the integrated Human Lung Cell Atlas (HLCA) combining 46 datasets of the human respiratory system into a single atlas spanning over 2.2 million cells from 444 individuals across health and disease. The HLCA contains a consensus re-annotation of published and newly generated datasets, resolving under- or misannotation of 59% of cells in the original datasets. The HLCA enables recovery of rare cell types, provides consensus marker genes for each cell type, and uncovers gene modules associated with demographic covariates and anatomical location within the respiratory system. To facilitate the use of the HLCA as a reference for single-cell lung research and allow rapid analysis of new data, we provide an interactive web portal to project datasets onto the HLCA. Finally, we demonstrate the value of the HLCA reference for interpreting disease-associated changes. Thus, the HLCA outlines a roadmap for the development and use of organ-scale cell atlases within the Human Cell Atlas.

Published
2022
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49. The Unforeseen Path to the Superior Vena Cava

Author

Charles-Hugo Marquette, Jacques Boutros, Sylvie Leroy, and Jonathan Benzaquen

Subjects
Pulmonary and Respiratory Medicine, Superior Vena Cava Syndrome, medicine.medical_specialty, Lung Neoplasms, Adenocarcinoma of Lung, Pemetrexed, Antibodies, Monoclonal, Humanized, Critical Care and Intensive Care Medicine, Carboplatin, Bronchoscopy, Superior vena cava, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Response Evaluation Criteria in Solid Tumors, Aged, Vascular Fistula, medicine.diagnostic_test, business.industry, Chemoradiotherapy, Path (graph theory), Stents, Bronchial Fistula, Radiology, business
Published
2021
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