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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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REGULARITY FOR A GENERALIZED JEFFREY'S INTEGRAL MODEL FOR VISCOELASTIC FLUIDS

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Acta Mathematica Scientia 2015年第6期35卷 1251-1284页

作者： ivan SOUKUP Department of Numerical Mathematics Faculty of Mathematics and PhysicsCharles University in Prague

We prove a local existence of a strong solution v ：Ω×T→R^3 for a system of nonlinear integrodifferential equations describing motion of an incompressible viscoelastic fluid using standard mathematical tools. The problem is considered in a bounded, smooth domain ΩСR^3 with a Dirichlet boundary condition and a standard initial condition.

关键词： integral model viscoelastic fluid strong solution

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Fulminant Hepatitis Associated with Chronic Consumption of 3,4-Methylenedioxy-Methamphetamine;Case Report

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Open Journal of Gastroenterology 2024年第5期14卷 161-166页

作者： Ulises Solis Gomez Gustavo Adolfo Hernández Valdez Juan Antonio Contreras Escamilla ivan Alejandro Medina Jimenez Jorge Morales Rojas Jocelyn Nataly Quintero Melendez Marco Antonio González Villar Department of Internal Medicine ISSSTE APP General Hospital of Tepic Tepic Nayarit Mexico

The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA), also called ecstasy, is a neurotoxin widely consumed among young people that has increased in recent years because it is a recreational drug, of which immediate effects are known such as a greater sensation of well-being, extroversion, increased sensory perception. However, its long-term effects have been described very little in the medical literature, including damage to the heart, central nervous system, kidney, etc. One of its little-known effects is hepatotoxicity, of which few cases are known associated with fulminant hepatitis, which is a rapidly deteriorating condition that is generally associated with a syndrome of multiple organ dysfunction and death. Therefore, it is very important to know this type of damage in the short and long term. The following case is of a 39-year-old man who came to our service due to jaundice syndrome and the only history of MDMA consumption, who as the days went by met the criteria for fulminant liver failure, with damage to multiple organs (organ dysfunction syndrome).

关键词： Fulminant Hepatitis Acute Liver Failure Methamphetamine Severe Acute Liver Failure in a User of Drugs of Abuse Hepatology

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Topology of Moment-Angle Manifolds Arising from Flag Nestohedra

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Chinese Annals of Mathematics,Series B 2017年第6期38卷 1287-1302页

作者： ivan LIMONCHENKO School of Mathematical Sciences Fudan UniversityShanghai 200433China.

The author constructs a family of manifolds, one for each n ≥ 2, having a nontrivial Massey n-product in their cohomology for any given n. These manifolds turn out to be smooth closed 2-connected manifolds with a compact torus Tm-action called momentangle manifolds ZP, whose orbit spaces are simple n-dimensional polytopes P obtained from an n-cube by a sequence of truncations of faces of codimension 2 only(2-truncated cubes). Moreover, the polytopes P are flag nestohedra but not graph-associahedra. The author also describes the numbers β^(-i,2(i+1))(Q) for an associahedron Q in terms of its graph structure and relates it to the structure of the loop homology(Pontryagin algebra)H_*(?ZQ), and then studies higher Massey products in H*(ZQ) for a graph-associahedron Q.

关键词： Moment-angle manifold Flag nestohedra Stanley-Reisner ring Masseyproducts Graph-associahedron

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From neurogenesis to neuronal regeneration: the amphibian olfactory system as a model to visualize neuronal development in vivo

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Neural Regeneration Research 2015年第6期10卷 872-874页

作者： ivan Manzini Institute of Neurophysiology and Cellular Biophysics University of Gottingen Center for Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB)

How do individual neurons develop and how are they in- tegrated into neuronal circuitry？ To answer this question is essential to understand how the nervous system develops and how it is maintained during the adult life. A neural stem cell must go through several stages of maturation, including proliferation, migration, differentiation, and integration, to become fully embedded to an existing neuronal circuit. The knowledge on this topic so far has come mainly from cell culture studies. Studying the development of individual neurons within intact neuronal networks in vivo is inherently difficult. Most neurons are generated form neural stem cells during embryonic and early postnatal development.

关键词： the amphibian olfactory system as a model to visualize neuronal development in vivo Figure

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Experimental and calculated liquid-liquid interfacial tension in demixing metal alloys

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Rare Metals 2006年第5期25卷 452-456页

作者： Walter Hoyer ivan Kaban Institute of Physics Chemnitz University of Technology D-09107 ChemnitzGermany

Liquid-liquid interracial tension in binary and temary Al-based monotectic systems has been determined experimentally with a tensiometric method in a wide temperature interval. The temperature dependence of the interfacial tension is well described by a power law function of the type σαβ - （1 - T/Tc）δ with the critical exponent δ= 1.3 and a critical temperature Tc. Theoretical models describing the liquid-liquid interface in monotectic alloys and their applicability for calculation of the interfacial tension and its temperature dependence in binary systems are considered.

关键词： immiscible systems Al-based alloys interracial tension

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Effects of pre-existing cracks and infillings on strength of natural rocks--Cases of sandstone, argillite and basalt

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Journal of Rock Mechanics and Geotechnical Engineering 2020年第6期12卷 1333-1338页

作者： Chen Cui ivan Gratchev School of Engineering Griffith UniversityGold CoastAustralia

This study aims to examine the influence of pre-existing discontinuities on the strengths of four natural rocks of different origins.A series of unconfined compression tests was performed on specimens of two types of sandstones,argillite and basalt that contain open and filled *** was found that the presence of cracks tends to decrease the overall strength for all studied rocks;however,the magnitude of strength reduction is related to the property of *** larger strength decrease was observed for the relatively harder argillite and basalt,compared to the softer *** was also found that the infill material could increase the strength of rock specimens,while the obtained strength depended on the characteristics of the fill material.

关键词： Pre-existing crack Rock strength Infill material Laboratory test

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Purinergic Modulation of Activity in the Developing Auditory Pathway

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Neuroscience Bulletin 2020年第11期36卷 1285-1298页

作者： Sasa Jovanovic ivan Milenkovic School of Medicine and Health Sciences Carl von Ossietzky University Oldenburg26129 OldenburgGermany

Purinergic P2 receptors,activated by endogenous ATP,are prominently expressed on neuronal and nonneuronal cells during development of the auditory periphery and central auditory *** the mature cochlea,extracellular ATP contributes to ion homeostasis,and has a protective function against noise ***,we focus on the modulation of activity by extracellular ATP during early postnatal development of the lower auditory *** mammals,spontaneous patterned activity is conveyed along afferent auditory pathways before the onset of acoustically evoked signal *** this critical developmental period,inner hair cells fire bursts of action potentials that are believed to provide a developmental code for synaptic maturation and refinement of auditory circuits,thereby establishing a precise tonotopic *** ATP-release triggers such patterned activity by raising the extracellular K+concentration and contributes to firing by increasing the excitability of auditory nerve fibers,spiral ganglion neurons,and specific neuron types within the auditory brainstem,through the activation of diverse P2 *** review recent studies that provide new models on the contribution of purinergic signaling to early development of the afferent auditory ***,we discuss potential future directions of purinergic research in the auditory system.

关键词： Purinergic signaling Auditory system Development Cochlea Spiral ganglion Auditory brainstem

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Dry powder platform for pulmonary drug delivery

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Particuology 2008年第4期6卷 225-238页

作者： Derek ivan Daniher Jesse Zhu Graduate Program in Biomedical Engineering Department of Chemical and Biochemical EngineeringThe University of Western OntarioLondonOntarioCanada

The phenomenon of particle interaction involved in pulmonary drug delivery belongs to a wide variety of disciplines of particle technology, in particular, fluidization. This paper reviews the basic concepts of pulmonary drug delivery with references to fluidization research, in particular, studies on Geldart group C powders. Dry powder inhaler device-formulation combination has been shown to be an effective method for delivering drugs to the lung for treatment of asthma, chronic obstructive pulmonary disease and cystic fibrosis. Even with advanced designs, however, delivery efficiency is still poor mainly due to powder dispersion problems which cause poor lung deposition and high dose variability. Drug particles used in current inhalers must be 1–5 μm in diameter for effective deposition in small-diameter airways and alveoli. These powders are very cohesive, have poor flowability, and are difficult to disperse into aerosol due to cohesion arising from van der Waals attraction. These problems are well known in fluidization research, much of which is highly relevant to pulmonary drug delivery.

关键词： Dry powder inhaler Interparticle forces Aerosol Pulmonary drug delivery Carrier particle Fluidization

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Application of machine learning to the identification of quick and highly sensitive clays from cone penetration tests

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2020年第6期21卷 445-461页

作者： Cristian GODOY ivan DEPINA Vikas THAKUR Department of Civil and Environmental Engineering Norwegian University of Science and TechnologyTrondheim 7031Norway Department of Infrastructure SINTEF CommunityTrondheim 7034Norway Faculty of Civil Engineering Architecture and GeodesyUniversity of SplitSplit 21000Croatia

Geotechnical classification is vital for site characterization and geotechnical *** tests such as the cone penetration test with pore water pressure measurement(CPTu)are widespread because they represent a faster and cheaper alternative for sample recovery and ***,classification schemes based on CPTu measurements are fairly generic because they represent a wide variety of soil conditions and,occasionally,they may fail when used in special soil types like sensitive or quick *** and highly sensitive clay soils in Norway have unique conditions that make them difficult to be identified through general classification ***,new approaches to address this task are *** following study applies machine learning methods such as logistic regression,Naive Bayes,and hidden Markov models to classify quick and highly sensitive clays at two sites in Norway based on normalized CPTu *** showed a considerable increase in the classification accuracy despite limited training sets.

关键词： Machine learning Classification Quick clays Sensitive clays

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