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Targeted therapy for capillary-venous malformations

Signal Transduction and Targeted Therapy 2024年第7期9卷 3024-3039页

作者： Lola Zerbib Sophia Ladraa Antoine Fraissenon Charles Bayard Marina Firpion Quitterie Venot Sanela Protic Clément Hoguin Amandine Thomas Sylvie Fraitag Jean-Paul Duong Sophie Kaltenbach Estelle Balducci Coline lefevre Patrick Villarese Vahid Asnafi Christine Broissand Nicolas Goudin Ivan Nemazanyy Gwennhael Autret Bertrand Tavitian Christophe Legendre Nadia Arzouk Veronique Minard-Colin Caroline Chopinet Michael Dussiot Denise MAdams Tristan Mirault Laurent Guibaud Paul Isenring Guillaume Canaud UniversitéParis Cité ParisFrance INSERM U1151 Institut Necker-Enfants MaladesParisFrance Service d’Imagerie Pédiatrique Hôpital Femme-Mère-EnfantHCLBronFrance CREATIS UMR 5220 Villeurbanne 69100France Service de Radiologie Mère-Enfant Hôpital NordSaint EtienneFrance Service d’Anatomie pathologique Hôpital Necker-Enfants MaladesAP-HPParisFrance Laboratoire d’Oncohématologie Hôpital Necker-Enfants MaladesAP-HPParisFrance Pharmacie Hôpital Necker-Enfants MaladesAP-HPParisFrance Necker Bio-Image Analysis INSERM US24/CNRS UMS 3633ParisFrance Platform for Metabolic Analyses Structure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Plateforme Imageries du Vivant Universitéde ParisPARCCINSERMParisFrance Service de Néphrologie Transplantation AdultesHôpital Necker-Enfants MaladesAP-HPParisFrance Service de Transplantation Hôpital La PitiéSalpétrièreAP-HPParisFrance Department of Pediatric and Adolescent Oncology INSERM 1015Gustave RoussyUniversitéParis-SaclayVillejuifFrance Service de Physiologie&Explorations Fonctionnelles Cardiovasculaires CHU de LilleLille 59000France INSERM U1163 Laboratory of Cellular and Molecular Mechanisms of Hematological Disorders and Therapeutic ImplicationsLaboratoire d’Excellence GR-ExParisFrance Division of Oncology Comprehensive Vascular Anomalies ProgramChildren’s Hospital of PhiladelphiaPhiladelphiaPAUSA Service de Médecine Vasculaire hôpital Européen Georges-PompidouParisFrance Nephrology Research Group L’Hôtel-Dieu de Québec Research CenterDepartment of MedicineFaculty of MedicineLaval UniversityQuebecQC G1R2J6Canada Unitéde médecine translationnelle et thérapies ciblées Hôpital Necker-Enfants MaladesAP-HPParisFrance CNRS UMR8253 Institut Necker-Enfants MaladesParisFrance

Sporadic venous malformations are genetic conditions primarily caused by somatic gain-of-function mutation of PIK3CA or TEK,an endothelial transmembrane receptor signaling through *** malformations are associated with pain,bleedings,thrombosis,pulmonary embolism,esthetic deformities and,in severe cases,life-threatening *** authorized medical treatment exists for patients with venous ***,we created a genetic mouse model of PIK3CA-related capillary venous malformations that replicates patient *** showed that these malformations only partially signal through AKT *** compared the efficacy of different drugs,including rapamycin,a mTORC1 inhibitor,miransertib,an AKT inhibitor and alpelisib,a PI3Kαinhibitor at improving the lesions seen in the mouse *** demonstrated the effectiveness of alpelisib in preventing vascular malformations’occurrence,improving the already established ones,and prolonging *** these findings,we were authorized to treat 25 patients with alpelisib,including 7 children displaying PIK3CA(n=16)or TEK(n=9)-related capillary venous malformations resistant to usual therapies including sirolimus,debulking surgical procedures or percutaneous *** assessed the volume of vascular malformations using magnetic resonance imaging(MRI)for each *** demonstrated improvement in all 25 *** malformations previously considered intractable were reduced and clinical symptoms were *** showed a decrease of 33.4%and 27.8%in the median volume of PIK3CA and TEK malformations respectively,over 6 months on *** conclusion,this study supports PI3Kαinhibition as a promising therapeutic strategy in patients with PIK3CA or TEK-related capillary venous malformations.

关键词： PIK3CA malformations venous

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Mountaineering incidents in France: analysis of search and rescue interventions on a 10-year period(from 2008 to 2018)

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Journal of Mountain Science 2021年第2期18卷 446-461页

作者： VANPOULLE Maud lefevre Brice SOULE Bastien Laboratory on Vulnerabilities and Innovation in Sport(L-VIS EA7428)University Claude Bernard Lyon1LyonDoua Campus27/29 Boulevard du 11 Novembre 1918Villeurbanne Cedex 69622France

In Europe and especially in France,there is a growing enthusiasm for outdoor sports and *** the meantime,the risk of both severe and frequent injuries associated with active pursuits is acknowledged,especially in mountainous *** effectiveness of prevention must rely on detailed knowledge of typical circumstances and scenarios but thorough understanding of the mechanisms of accidentality remains limited by the fragmentation of sources and by mostly heterogeneous *** paper aims at giving insights on victims’profiles,season,location,and circumstances of mountaineering accidents in the French Alps,through the study of rescue interventions data from 2008 to *** to the analysis of the exhaustive database of search and rescue interventions from the French mountain national police force,and while questioning its limitations,we strive to answer two questions:what are the characteristics of the hazardous situations leading to a rescue intervention in mountaineering?Among these situations,what are the characteristics that tend to make them more harmful?

关键词： Accident studies Mountaineering Outdoor recreation Mountain rescue Victim profiles Multilevel logistic regression

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Who is at risk in the French mountains? Profiles of the accident victims in outdoor sports and mountain recreation

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Journal of Mountain Science 2017年第8期14卷 1490-1499页

作者： SOULE Bastien REYNIER Véronique lefevre Brice BOUTROY Eric Laboratory of Vulnerabilities & Innovation in Sport University Claude Bernard Lyon 1 Laboratory Sport & Social Environment University Grenoble Alpes

The risk of both severe and frequent injury associated with active pursuits in mountain areas is acknowledged. This phenomenon is all the most relevant to investigate in France that there is a growing enthusiasm for outdoor sports and recreation. This paper focuses on the social-demographic and sporting profiles of accident victims. Our intent is to better understand who is specifically at risk, while practicing mountain recreation, in the French mountains. Such identification doubtlessly constitutes an important asset in order to enhance prevention. Three critical activities are notably tackled, among some others: hiking, a widespread activity that exposes many practitioners to hazardous settings; mountaineering and ski touring, supposedly entailing the most severe *** order to align the information collected, then provide estimations based on the reasoned crossing of these secondary data, we consulted and summarised all the databases that we knew of on the French territory: rescue team intervention reports, aggregated statistics from the sports ministry, sporting federation accident declarations, avalanche experts statistics, mountain guides union accident/incident reports, healthcare facilities admissions, etc. Only the sources consideredto be the most reliable and representative were used, owing to the number of cases processed, the exhaustive nature of data collection, or the level of information detail available. Our method also included consultation of all the parties playing an active role in prevention, training and mountain rescue, thus ensuring a participative, co-constructive approach to the study with the people that have the best knowledge of victim profiles. Around fifty such parties were interviewed on the methods implemented, the benefits and limits of current data, and the main expectations in terms of accidentology progress, thus further enhancing the credibility of the study proposed in this paper. Our results show that the parent populat

关键词： Mountain sports Outdoor recreation Accident victims profile

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Pulsed export of carbon in the north-western Mediterranean Sea

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Journal of Oceanology and Limnology 2023年第1期41卷 189-202页

作者： Michel DENIS Dominique lefevre Melilotus THYSSEN Ian RJENKINSON Gérald GRÉGORI Aix Marseille Université Universitéde ToulonCNRS/INSUIRDInstitut Méditerranéen d'Océanologie(MIO)Marseille cedex09 13288France Key Laboratory of Marine Ecology and Environmental Sciences Institute of OceanologyChinese Academy of SciencesQingdao 266071China Agency for Consultation and Research in Oceanography Lavergne19320 La Roche CanillacFrance

The short term(hourly scale)variability of heterotrophic prokaryote(HP)vertical distribution and respiratory activity,was investigated in the north-western(NW)Mediterranean *** vertical distribution was determined on board by flow cytometry analysis of seawater samples collected by series of CTD *** counts and viability were determined for all *** respiratory rates were determined later in the laboratory from filtered seawater samples(23 dm^(3))from 300-1150-m *** average cell viability was 94.8%±2.2%(n=240).There was no accumulation of dead cells,due to quick decay of damaged *** the epipelagic layer,three HP groups were distinguished,two(HNA1,HNA2)who se cells exhibited a high nucleic acid content and one(LNA)with low nucleic acid content ***2 was most populated at 50 m but not detected at 90 m and below,presumably aerobic anoxygenic photoheterotrophic bacteria(AAPs).The variability in HP abundance was mainly confined in the upper 80 m.A few secondary peaks of HP abundance were observed(80-150 m)in connection with abundance troughs in the surface *** cells were continuously present in a wide layer around 500 m(mean 191×10^(3)cells/cm^(3)).Below this layer,HP abundance randomly exhibited peaks,coupled to respiratory rate *** HP abundance and variability in the water column was suppressed during a strong wind *** observed sporadic variability was tentatively interpreted through a pulsed carbon-export mechanism induced by the microorganism production of dissolved poly saccharide s,followed by flocculation and rapid *** mechanism would thus contribute to(ⅰ)preventing organic matter accumulation in the epipelagic layer,(ⅱ)seeding the water column with live HP cells,and(ⅲ)supplying the aphotic water column with fre sh and labile organic *** important vertical flux mechanism needs further observations and modelling.

关键词： north-western Mediterranean Sea heterotrophic prokaryote(HP) cell viability cell respiration transparent exopolymeric particle(TEP) aggregation flow cytometry

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Children with abnormal DMSA nuclear scan present a higher risk of recurrent febrile urinary tract infections

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World Journal of Pediatrics 2019年第2期15卷 204-205页

作者： Luke Harper Yan lefevre Xavier Delforge David Bourquard Cyril Ferdynus Department of Pediatric Surgery CHU de La ReunionLa ReunionFrance Department of Pediatric Surgery CHU Pellegrin-EnfantsBordeauxFrance Department of Pediatric Surgery CHU de La ReunionLa ReunionFrance Methodological Support Unit CHU de La ReunionLa ReunionFrance

The ideal management of a child presenting a first episode of febrile urinary tract infection is still under *** the recent guidelines for the diagnosis and management of urinary tract infections (UTI) in children,the American Association of Pediatrics recommend performing a post-UTI sonography,and if there are abnormal findings,a voiding cystourethrogram [1].This change derives from the understanding that we should be avoiding renal damage rather more than diagnosing reflux,since both surgery and antibiotic prophylaxis are progressively being abandoned for most cases of vesicoureteral reflux (VUR) [2,3].The most significant event which will bring a child to active management is recurrence of UTI [4,5].It seems therefore more clinically relevant to differentiate between children who will suffer recurrent episodes of UTI and those who will not,rather than to simply identify which children have *** therefore aimed to evaluate if DMSA nuclear scan could reliably identify which children were at risk of presenting a second febrile UTI.

关键词： Children abnormal DMSA

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Belgium experience in disaster victim identification applied in handling terrorist attack at Brussels Airport 2016

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Forensic Sciences Research 2020年第3期5卷 223-231页

作者： Francois Beauthier Wim Van de Voorde Philippe lefevre Jean-Pol Beauthier Medicolegal and Forensic Anthropology Unit Laboratory of AnatomyBiomechanics and OrganogenesisFaculty of MedicineUniversite libre de BruxellesBruxellesBelgium Forensic Biomedical Sciences Department of Imaging and PathologyUniversity of LeuvenBelgium

The Belgian disaster victim identification(DVI)team is involved in many investigations in our ***,this specialized team of the federal police oversees searching for and investigating criminally buried dead bodies,identification of unknown putrefied corpses,and *** Belgian DVI team also assists with the identification of victims of mass disasters(natural,accidental,and mass murders).In this article,we consider the contributions of different teams(forensic pathology,anthropology,and odontology,federal police,and crime scene investigation)both on the scene of the attack at the Brussels National Airport(Zaventem)and in the laboratory work(autopsies,sample studies).

关键词： Forensic sciences forensic pathology terrorist attack blast injury body fragments identification

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Iron-catalyzed reductive cyclization of nitroarenes: Synthesis of aza-heterocycles and DFT calculations

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Chinese Chemical Letters 2023年第3期34卷 337-341页

作者： Christine Tran Aicha Abdallah Valentin Duchemann Guillaume lefevre Abdallah Hamze CNRS BioCISUniversitéParis-SaclayChatenay-Malabry 92290France Chimie ParisTech CNRSInstitute of Chemistry for Life and Health SciencesPSL UniversityCSB2DParis 75005France

Research into environmentally friendly strategies for hydrogen transfer reduction is increasing, along with the need for more elaborate heterocyclic platforms. Within this context, we develop a new approach for substituted dihydrobenzo[c]carbazoles and indoles. These compounds were synthesized through an iron-catalyzed hydrogen transfer reduction of nitroarenes, followed by intramolecular cyclization. This transformation involves using a Kn?lker-type catalyst, Cs_(2)CO_(3) as the base, and benzyl alcohol as the nonexpensive and low volatile hydrogen donor. We synthesize 30 examples of aza-heterocycles with moderate to excellent yields by applying this strategy. Additionally, DFT calculations demonstrated that the pathway reaction could follow an anionic mechanism.

关键词： Iron Cyclization Nitroarenes Dihydrobenzo[c]carbazoles Indoles

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A Lattice Boltzmann Model to Study Sedimentation Phenomena in Irrigation Canals

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Communications in Computational Physics 2013年第3期13卷 880-899页

作者： Olivier Marcou Bastien Chopard Samira El Yacoubi Boussad Hamroun Laurent lefevre Eduardo Mendes Institut de Modelisation et Analyse en Geo-Environnement et Sante Universite de Perpignan Via DomitiaPerpignanFrance Computer Science Department University of GenevaSwitzerland Laboratoire d’Automatique et de Genie des Procedes Universite Claude BernardLyonFrance Laboratoire de Conception et Integration des Systemes Grenoble INPValenceFrance

Fresh water is one of the most significant resources for human activities and survival,and irrigation is among the most important uses of *** sustainibility and performance of irrigation canals can be greatly affected by sediment transport and *** our previous works,we proposed a Lattice Boltzmann model for simulating a free surface flow in an irrigation canal,as an alternative to more traditional models mainly based on shallow water *** we introduce the sedimentation phenomenon into our model by adding a new algorithm,based on the earlier work by ***,*** and ***[9,11,12,27].Transport,erosion,deposition and toppling of sediments are taken into account and enable the global sedimentation algorithm to simulate different transport modes such as bed load and suspended *** the present work,we study both the behaviour of a sediment deposit located at an underflow submerged gate(depending on the gate opening and the flow discharge)and the influence of the presence of such a deposit on the *** numerical and experimental validations have been *** experiments were realized on the micro-canal of the LCIS laboratory at Valence,*** comparisons between simulations and experiments give good qualitative agreement.

关键词： Lattice Boltzmann method irrigation canals modeling sedimentation

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Integrating flexible electronics for pulsed electric field delivery in a vascularized 3D glioblastoma model

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npj Flexible Electronics 2021年第1期5卷 150-158页

作者： Marie C.lefevre Gerwin Dijk Attila Kaszas Martin Baca David Moreau Rodney P.O’Connor Mines Saint-Etienne Centre CMPDepartment of BioelectronicsGardanneFrance.2Panaxium SASAix-en-ProvenceFrance

Glioblastoma is a highly aggressive brain tumor,very invasive and thus difficult to eradicate with standard oncology *** treatments based on pulsed electric fields have proven to be a successful method to treat cancerous ***,they rely on stiff electrodes,which cause acute and chronic injuries,especially in soft tissues like the *** we demonstrate the feasibility of delivering pulsed electric fields with flexible electronics using an in ovo vascularized tumor *** show with fluorescence widefield and multiphoton microscopy that pulsed electric fields induce vasoconstriction of blood vessels and evoke calcium signals in vascularized glioblastoma spheroids stably expressing a genetically encoded fluorescence *** of the electric field delivery are compared with the measured influence of electric field effects on cell membrane integrity in exposed tumor *** results confirm the feasibility of flexible electronics as a means of delivering intense pulsed electric fields to tumors in an intravital 3D vascularized model of human glioblastoma.

关键词： injuries electronics stiff

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Role of acetic acid on U(Ⅵ) sorption on silica

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Nuclear Science and Techniques 2015年第1期26卷 127-134页

作者：赵羽佳韦悦周 Florence Mercier-Bion Gregory lefevre School of Nuclear Science and Engineering Shanghai Jiao Tong University Institut de Physique Nucleaire d’Orsay CNRS/IN2P3 Universite Paris-Sud 1115 rue Georges Clemenceau Orsay Cedex 91406 France Institut de Recherche de Chimie Paris CNRS-Chimie ParisTech 11 rue Pierre et Marie Curie Paris 75005 France

The influence of acetate on U(Ⅵ) sorption on silica from aqueous solutions was studied at p H 2–7 by complementary experimental methods of macroscopic measurement, spectroscopic investigation and thermodynamic calculation. Sorption percentage of U(Ⅵ) in the absence and in the presence of different acetate concentrations was determined by batch sorption procedures. Attenuated total reflection Fourier transform infra-red spectroscopy(ATR-FTIR) was used to elucidate the mechanisms of uranyl sorption on silica in the presence of acetate, by investigating, in-situ, the changes in the U(Ⅵ) sorption on silica surface in presence of ligand: the absorption bands of carboxylate ν(COO) in the range 1300–1700 cm-1and those around 850–950 cm-1of uranyl species νas(UO2) are followed. The decrease of U(Ⅵ) sorption with increasing acetate concentration was observed. Sorption of U(Ⅵ)-acetate(U-Ac) species on silica surface was demonstrated for the first ***-FTIR investigations clearly evidenced the absorption bands characteristic of sorbed U-Ac complexes both from the acetate and uranyl spectral regions those the wavenumbers correspond to sorbed species. No sequence effect of acetate and uranyl on the sorption on silica in ternary systems U(Ⅵ)-acetate-silica was observed from the sorption data. From the ATR-FTIR investigations, we can induce that the sorption of U-Ac leads to chemical equilibria and makes possible the modeling of sorption isotherms by surface complexation models. The related thermodynamic constants were modeled using CCM surface complexation modeling.

关键词：吸附作用傅里叶变换红外光谱硅胶 VI 醋酸 ATR-FTIR 表面络合模型 U(Ⅵ)

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