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EGFR Expression Is Unreliable to Decide for Cetuximab Treatment in Patients with Metastatic Colorectal Cancer: Results from “ERBITUX-OUEST”

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Open journal of Internal Medicine 2016年第2期6卷 56-67页

作者： jean-Philippe Metges Erick Gamelin Alain Volant Olivier Capitain jean-François Ramée jean-Luc Raoul jean-Yves Douillard Pierre-Luc Etienne Isabelle Cumin Olivier Dupuis Roger Faroux Marie-Aude Coulon Philippe Deguiral Karine Bideau Nacr Eddine Achour Alain Gourlaouen Corinne Alleaume Annie Wdowik Laurent Miglianico Yann Touchefeu Vincent Klein Alain Penchet Ludovic Rosenfeld Daniel Martin Claire Stampfli jean-jacques Auger Alain Bargain Murielle Broyer-Petit jérome chettrit Louis-Rémi De Ybarlucea Serge Eloit Pierre Marie Girardot Nathalie Heresbach Christian Laboisse Eric Lavoine Gilles Lemasson Claire Magois Sophie Michalak Norbert Padilla joseph Politis Frédéric Staroz Bruno Turlin Arnaud Uguen Viorel Vasiliu Véronique Verriele Fanny Marhuenda Delphine Déniel Lagadec Christian Riché Françoise Grudé Observatoire dédié au Cancer des régions Bretagne et Pays de la Loire France Centre Hospitalier Régional Universitaire (CHRU) Brest France Institut de Cancérologie de l’Ouest (ICO) Paul Papin Angers France Centre Catherine de Sienne Nantes France CRLCC Eugène Marquis Rennes France ICO René Gauducheau Nantes France Centre CARIO-HCPA Plérin France Centre Hospitalier Bretagne Sud (CHBS) Lorient France Clinique Victor Hugo Le Mans France Centre Hospitalier Départemental (CHD) La Roche-sur-Yon France CH Le Mans France Clinique Mutualiste de l’Estuaire Saint-Nazaire France CHIC Quimper France Clinique Pasteur Lanroze Brest France CH MORLAIX France CH Saint-Brieuc France CHBA Vannes France CHP Saint-Grégoire France CHU Nantes France Hopital Privé Océane Vannes France Clinique Saint-Michel et Sainte-Anne Quimper France Pole Santé Sarthe et Loire La Flèche France Polyclinique du Maine Laval France Polyclinique Sud Quimper France CH Laval France Polyclinique Cesson Sévigné France Laboratoire d’anatomie et de cytologie pathologiques Cholet France Cabinet d’anatomie et de cytologie pathologiques Saint-Malo France Laboratoire d’anatomie et de cytologie pathologiques Lorient France Institut d’histopathologie Nantes France Laboratoire de Pathologie Médicale Laval France ARMOR Pathologie Plérin France Laboratoire d’anatomie et de cytologie pathologiques Rennes France Laboratoire d’anatomie et de cytologie pathologiques Angers France Laboratoire Analyses Biologie Glasgow Brest France CHU Angers France Centre d’anatomie et de cytologie pathologiques Le Mans France Cabinet d’anatomie et de cytologie pathologiques Vannes France Laboratoire d’anatomie et de cytologie pathologiques Quimper France CHU Rennes France

Purpose: Although controversial, assessment of epidermal growth factor receptor (EGFR) expression is required for the approved indications of Cetuximab in metastatic colorectal cancer (mCRC). With the objective of improving patient selection, “ERBITUX-OUEST” study aimed at analyzing EGFR status in a large cohort of mCRC patients who received cetuximab without preliminary EGFR screening, and assessing the correlation between EGFR status and response to treatment retrospectively. Patients and methods: 332 patients treated with Irinotecan Cetuximab based regimen after progression on irinotecan or oxaliplatin therapy were included. EGFR status was assessed using three available immunohistochemistry (IHC) tests and in situ hybridization in case of negativity. Clinical outcomes of EGFR-positive and EGFR-non-detected (or considered as negative with at least one test) patients were compared. Results: Of the 332 samples centrally screened, 194 were classified as full-positive (i.e., EGFR-positive for all three tests), 86 as full-negative, and 52 as discordant. One third of the 131 negative samples with FDA approved test should be reclassified as positive with at least one of the two others tests. Regarding results from FDA approved test only, neither objective response rate (ORR), progression-free survival (PFS) nor overall survival (OS) differed significantly between EGFR-negative and EGFR-positive patients (P = 0.788, 0.326 and 0.888, respectively). Similarly, comparison of full-negative to other groups did not show any significant difference in terms of ORR (P = 0.507), PFS (P = 0.222) or OS (P = 0.686). Conclusion: These data strongly argue against mCRC patients selection for Cetuximab treatment based on EGFR expression as measured by currently available IHC technics.

关键词： Metastatic Colorectal Cancer Cetuximab EGFR Expression

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New 0D/1D Physical Approach for Modelling the Gas Dynamics Behavior Inside the Intake System of an Engine

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journal of Thermal Science 2018年第4期27卷 394-403页

作者： David CHALET Mohamad YASSINE jérome MIGAUD Ecole Centrale de Nantes LHEEA lab. (ECN/CNRS) Nantes France MANN+HUMMEL France Laval France

The competition among carmakers to introduce the most innovative solutions is growing day by day. Since few years, simulation is being used widely in automotive industries. Instead of building costly prototypes and expending fuel for doing tests on a real engine, simulation became a good solution before taking new decisions. Concerning the study of gas dynamics and pressure wave's propagation in the intake system of an internal combustion engine, a precise modelling is needed in order to obtain good results. Unfortunately, the computational time for these simulations is considered as high compared to the real time. The main objective of the new approach presented in this paper, is to reduce simulation time of models in the internal combustion engine simulation code, allowing them to accomplish many engine simulations faster than one-dimensional non-linear approach. A transfer function is defined to link directly the relative pressure and the air mass flow rate. In a second time, the model is included into an internal combustion engine simulation code. The results obtained with this code are compared to experimental ones which are measured on a one-cylinder engine test bench. A good agreement is obtained between the experimental results and the numerical one. The model was improved by adding a transfer function for temperature evolution. The convergence time is then reduced as well as the global simulation time of the model.

关键词： gas dynamics compressible flow transfer function accuracy simulation time engine

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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher j.O’Connell Matthew j.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA james L.Winkle College of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

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Temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries on magnetic resonance imaging

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Neural Regeneration Research 2025年第11期20卷 3144-3150页

作者： Holly Flyger Samantha j.Holdsworth Alistair j.Gunn Laura Bennet Hamid Abbasi Mātai Medical Research Institute Tairāwhiti GisborneNew Zealand Department of Anatomy&Medical Imaging Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand Center for Brain Research The University of AucklandAucklandNew Zealand Auckland Bioengineering Institute The University of AucklandAucklandNew Zealand

Moderate to severe perinatal hypoxic-ischemic encephalopathy occurs in~1 to 3/1000 live births in high-income countries and is associated with a significant risk of death or neurodevelopmental *** assessment is important to help identify highrisk infants,to help families,and to support appropriate interventions.A wide range of monitoring tools is available to assess changes over time,including urine and blood biomarkers,neurological examination,and *** present,magnetic resonance imaging is unique as although it is expensive and not suited to monitoring the early evolution of hypoxic-ischemic encephalopathy by a week of life it can provide direct insight into the anatomical changes in the brain after hypoxic-ischemic encephalopathy and so offers strong prognostic information on the long-term outcome after hypoxic-ischemic *** review investigated the temporal dynamics of neonatal hypoxic-ischemic encephalopathy injuries,with a particular emphasis on exploring the correlation between the prognostic implications of magnetic resonance imaging scans in the first week of life and their relationship to long-term outcome prediction,particularly for infants treated with therapeutic hypothermia.A comprehensive literature search,from 2016 to 2024,identified 20 pertinent *** review highlights that while the optimal timing of magnetic resonance imaging scans is not clear,overall,it suggests that magnetic resonance imaging within the first week of life provides strong prognostic *** challenges limit the timing consistency,particularly the need for intensive care and clinical ***,although most reports examined the prognostic value of scans taken between 4 and 10 days after birth,there is evidence from small numbers of cases that,at times,brain injury may continue to evolve for weeks after *** suggests that in the future it will be important to explore a wider range of times after hypo

关键词： magnetic resonance imaging neonatal hypoxic-ischemic encephalopathy neurodevelopmental outcomes prognostic biomarkers in neuroimaging scan timing therapeutic hypothermia

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Application of None Cement Aluminamagnesia Gunning Mix with Special High Reactive Alumina in Steel Ladles

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China's Refractories 2020年第1期29卷 20-26页

作者： jérome KIENNEMANN Paul SOLER johnson LEE Alteo Gardanne 20062France

During calcining the aluminum hydroxide according to the Bayer process in a rotary kiln,the process of incomplete conversion to alpha alumina by soft calcination leads to a special intermediate alumina product containing microcrystalline of primary crystal alpha alumina particles less than 0.4μm,and other alumina phases with finer microcrystalline of less than 0.2μm *** special alumina powder has similar properties to silica fume or clay,such as high surface area and reactivity,fast wetting,low water demand and high *** can partially or completely replace silica fume and clay in dry gunning *** works towards improving the high temperature resistance of the gunning material matrix as well as the corrosion resistance and service life of the gunning *** application results show that:the ladle cementfree alumina-magnesia dry gunning mix with this special alumina sub-micro powder,compared with traditional dry gunning materials,has lower rebound loss(<10%),better adhesion rate,higher corrosion resistance and peeling resistance;and it can replace the veneering casting repair to achieve the similar performance.A further improvement goal is to replace the initial casting linings,thus this concept will give a new revolution to the monolithic steel ladles.

关键词： none cement gunning mix special reactive alumina monolithic steel ladles

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Gene therapy for spinal muscular atrophy:perspectives on the possibility of optimizing SMN1 delivery to correct all neurological and systemic perturbations

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Neural Regeneration Research 2025年第7期20卷 2011-2012页

作者： Sharon j.Brown Rafael j.Yáñez-Muñoz Heidi R.Fuller School of Pharmacy and Bioengineering Keele UniversityKeeleUK Wolfson Center for Inherited Neuromuscular Disease TORCH BuildingRJAH Orthopaedic HospitalOswestryUK *** Center of Gene and Cell TherapyDepartment of Biological SciencesSchool of Life Sciences and the EnvironmentRoyal Holloway University of LondonEghamUK

Spinal muscular atrophy(SMA)is a genetic condition that results in selective lower motor neuron loss with concomitant muscle weakness and *** genetic cause of SMA was understood in 1995 when loss or impairment of the survival motor neuron 1(SMN1)gene was identified as the main contributing factor(Lefebvre et al.,1995).This,in combination with the discovery that humans have a“back-up”gene,SMN2,which can produce low levels(approximately 10%)of the full-length functional SMN protein,has led to the generation of SMA-specific gene *** was traditionally classified according to age of symptom onset and developmental milestones achieved,with life expectancy and severity varying between ***,SMN2 copy number is used as a proxy for the prediction of disease severity,with higher SMN2 copy number typically being associated with reduced severity of SMA,although this relationship is not absolute:some individuals with low SMN2 copy number have less severe SMA phenotypes and vice ***,the etiology of SMA is further complicated by other factors,such as non-typical nucleotide variants and SMN2-independent modifiers of disease severity.

关键词： atrophy traditionally absolute

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Correction to:On the genetic distinctiveness of tailorbirds(Cisticolidae:Orthotomus)from the South-east Asian mainland with the description of a new subspecies

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Avian Research 2018年第4期9卷 394-395页

作者： jérome Fuchs Dario Zuccon Institut de Systématique EvolutionBiodiversité UMR7205 CNRS MNHN UPMC EPHESorbonne UniversitéMuséum National d’Histoire NaturelleCP 5157 rue Cuvier75231 Paris Cedex 05France

Unfortunately, the original article (Fuchs and Zuccon 2018) contained some errors. The Tables 1, 2 and Additional file 1: Table S2 were displayed incorrectly. The correct tables can be found below.

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Parameter study on numerical simulation of corner separation in LMFA-NACA65 linear compressor cascade

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Chinese journal of Aeronautics 2017年第1期30卷 15-30页

作者： Gao Feng Ma Wei Sun jinjing jérome Boudet Xavier Ottavy Liu Yangwei Lu Lipeng Shao Liang National Key Laboratory of Science and Technology on Aero-Engine Aero-thermodynamics School of Energy and Power Engineering Beihang University Beijing 100191 China Department of Mechanical Engineering Sciences University of Surrey Guildford GU2 7XH UK School of Aeronautics and Astronautics Shanghai Jiao Tong University Shanghai 200240 China Laboratoire de Mecanique des Fluides et d'Acoustique Ecole Centrale de Lyon Ecully 69134 France

Large-eddy simulation（LES） is compared with experiment and Reynolds-averaged Navier-Stokes（RANS）, and LES is shown to be superior to RANS in reproducing corner separation in the LMFA-NACA65 linear compressor cascade, in terms of surface limiting streamlines,blade pressure coefficient, total pressure losses and blade suction side boundary layer profiles. However, LES is too expensive to conduct an influencing parameter study of the corner *** approach, despite over-predicting the corner separation, gives reasonable descriptions of the corner separated flow, and is thus selected to conduct a parametric study in this paper. Two kinds of influencing parameters on corner separation, numerical and physical parameters, are analyzed and discussed： second order spatial scheme is necessary for a RANS simulation; incidence angle and inflow boundary layer thickness are found to show the most significant influences on the corner separation among the parameters studied; unsteady RANS with the imposed inflow unsteadiness（inflow angle varying sinusoidally with fluctuating amplitude of 0.92°） does not show any non-linear effect on the corner separation.

关键词： Corner separation Influencing parameter LES Linear compressor cascade RANS

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Women in visual neural regeneration research

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Neural Regeneration Research 2025年第2期20卷 489-490页

作者： Tonia S.Rex David j.Calkins Vanderbilt Eye Institute Vanderbilt University Medical CenterNashvilleTNUSA

The year 2024 marks the 60^(th)anniversary of Title IX and 25 years since the New York Times revealed bias against female faculty members at the Massachusetts Institute of *** take an opportunity here to examine the state of gender bias in a relatively new yet already prominent field,neural regeneration in the visual system,for which there is a well-defined context useful for this *** National Eye Institute(NEI)provided the first round of research funding for its Audacious Goals Initiative(AGI)on visual neural regeneration in 2013 and the last round in ***,we focus on this *** sources included PubMed,the National Science Foundation(NSF),the NEI,the Blue Ridge Institute for Medical Research and data from the major professional organization for eye and vision research,the Association for Research in Vision and Ophthalmology(ARVO).

关键词： neural visual Times

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Generation of brain vascular heterogeneity:recent advances from the perspective of angiogenesis

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Neural Regeneration Research 2025年第7期20卷 2013-2014页

作者： Nathanael j.Lee Ryota L.Matsuoka Department of Neurosciences Lerner Research InstituteCleveland ClinicClevelandOHUSA Department of Molecular Medicine Cleveland Clinic Lerner College of MedicineCase Western Reserve UniversityClevelandOHUSA

Heterogeneous proper t i es of vascular endothelial cells in the brain:The brain displays large energy dynamics and consumption,and this high level of metabolic demands is fulfilled by a continuous supply of glucose and oxygen through its vascular *** vasculature consists of highly divergent blood vessel branches,giving rise to a dense network of capillaries that supply blood to all cells across the *** elaborated vascular network is thought to develop via angiogenesis,a process in which new blood vessels grow from pre-existing *** capillaries exhibit organotypic features distinct from other tissues and are formed primarily by two major endothelial cell(EC)types:those that form the semi-permeable blood-brain barrier(BBB)and those that develop highly permeable pores known as fenestrae(Matsuoka et al.,2022).The structural and functional differences between BBB and fenestrated vascular ECs represent a fundamental feature of brain vasculature and form the foundation for both brain function and homeostasis.

关键词： angiogenesis homeostasis network

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