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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 lauren. guibaud.paul isen.in. 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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Statin, aspirin and metformin use and risk of hepatocellular carcinoma related outcomes following liver transplantation: A retrospective study

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World Journal of Transplantation 2024年第3期14卷 120-131页

作者： William Chung Kevin Wong Noel Ravindranayagam lauren.Tang Josephine Grace Darren Wong Danny Con Marie Sinclair Avik Majumdar Numan Kutaiba Samuel Hui paul Gow Vijayaragavan Muralidharan Alexander Dobrovic Adam Testro Department of Gastroenterology Austin HealthHeidelberg 3084VictoriaAustralia Victorian Liver Transplant Unit Austin HealthHeidelberg 3084VictoriaAustralia Department of Radiology Austin HealthHeidelberg 3084VictoriaAustralia Department of Gastroenterology Monash HealthClayton 3168VictoriaAustralia Department of Surgery University of MelbourneAustin HealthHeidelberg 3048VictoriaAustralia Department of Surgery Beacon LaboratoryAustin PrecinctThe University of MelbourneAustin HospitalHeidelberg 3048VictoriaAustralia

BACKGROUND Liver transplantation(LT)is a potentially curative therapy for patients with hepatocellular carcinoma(HCC).HCC-recurrence following LT is associated with reduced *** is increasing interest in chemoprophylaxis to improve HCC-related outcomes *** To investigate whether there is any benefit for the use of drugs with proposed chemoprophylactic properties against HCC,and patient outcomes following *** This was a retrospective study of adult patients who received Deceased Donor LT for HCC from 2005-2022,from a single Australian *** use was defined as statin,aspirin or metformin therapy for≥29 days,within 24 months post-LT.A cox proportional-hazards model with time-dependent covariates was used for survival *** measures were the composite-endpoint of HCC-recurrence and all-cause mortality,HCC-recurrence and HCC-related *** analysis was performed to account for immortality time bias and statin *** Three hundred and five patients were included in this study,with 253(82.95%)males with a median age of 58.90 *** of liver disease were 150(49.18%)hepatitis C,73(23.93%)hepatitis B(HBV)and 33(10.82%)non-alcoholic fatty liver disease(NAFLD).56(18.36%)took statins,51(16.72%)aspirin and 50(16.39%)*** a median follow-up time of 59.90 months,34(11.15%)developed HCC-recurrence,48(15.74%)died,17(5.57%)from HCC-related ***,aspirin or metformin use was not associated with statistically significant differences in the composite endpoint of HCC-recurrence or all-cause mortality[hazard ratio(HR):1.16,95%CI:0.58-2.30;HR:1.21,95%CI:0.28-5.27;HR:0.61,95%CI:0.27-1.36],HCC-recurrence(HR:0.52,95%CI:0.20-1.35;HR:0.51,95%CI:0.14-1.93;HR 1.00,95%CI:0.37-2.72),or HCC-related mortality(HR:0.32,95%CI:0.033-3.09;HR:0.71,95%CI:0.14-3.73;HR:1.57,95%CI:0.61-4.04)*** dosing was not associated with statist-ically significant differences in HCC-related ***

关键词： Liver transplantation Hepatocellular carcinoma Transplant oncology Statins HMG-Co-A reductase Aspirin Metformin Mammalian target of rapamycin

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Investigating oil solubilization into nonionic micelles by Raman multivariate curve resolution

Aggregate

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Aggregate 2023年第6期4卷 146-152页

作者： Ciera M.Wentworth Ryan L.Myers paul S.Cremer lauren.D.Zarzar Department of Chemistry The Pennsylvania State UniversityUniversity ParkPennsylvaniaUSA Department of Biochemistry and Molecular Biology The Pennsylvania State UniversityUniversity ParkPennsylvaniaUSA Department of Materials Science and Engineering The Pennsylvania State UniversityUniversity ParkPennsylvaniaUSA Materials Research Institute The Pennsylvania State UniversityUniversity ParkPennsylvaniaUSA

Hydrophobic hydration,whereby water spontaneously structures around hydrophobic and amphiphilic molecules,plays a key role in the process of surfactant micelle formation and micellar oil *** vibrational Raman multivariate curve resolution spectroscopy,we characterized changes in the hydrophobic hydration occurring within nonionic alkylphenol ethoxylate surfactant Tergitol NP-12 micelles as a function of oil *** report trends in the changes of hydrophobic hydration depending on the chain length of the oil as well as the presence of a halogen atom in the oil chemical *** in hydrophobic hydration directly correlate to changes in the physical properties of the micellar solution,including cloud point and micelle hydrodynamic *** compare hydrophobic hydration of Tergitol NP-12 to nonionic linear alkyl ethoxylate surfactant Makon TD-12 and ionic sodium dodecyl sulfate and observe similar trends;the molecular structure of the oil has the largest impact on the hydrophobic *** believe these studies contribute to a fundamental understanding of the importance of hydrophobic hydration in surfactant and oil aggregates,especially as it relates to micellar oil solubilization,and provide insight into how the molecular solubilizate can impact micellar structure,size,and stability.

关键词： hydrophobic hydration micelle Raman multivariate curve resolution solubilization

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The First-Year Chemistry Laboratory in the United States

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大学化学 2005年第4期20卷 50-62页

作者： lauren.Denofrio paul Kelter Department of Chemistry University of Illinois Urbana-ChampaignUrbana Illinois 61821 USADepartment of ChemistryUniversity of Illinois Urbana-ChampaignUrbana Illinois 61821 USA

本文是张树永教授为《大学化学》杂志向Kelter教授特约的专稿,主要介绍美国大学一年级实行分层次化学教学的一些作法,以及大学一年级化学课程教学体系和实验教学体系、教学内容和教学方法。虽然美国大学化学实验课程的内容不像我国那样... 详细信息

本文是张树永教授为《大学化学》杂志向Kelter教授特约的专稿,主要介绍美国大学一年级实行分层次化学教学的一些作法,以及大学一年级化学课程教学体系和实验教学体系、教学内容和教学方法。虽然美国大学化学实验课程的内容不像我国那样多,但涉及面广,更强调学生的自主学习和自我训练,同时将仪器分析作为实验的必要内容嵌入日常实验当中,使实验内容的综合性、设计性更强,也更贴近日常生活和科学实验。这些作法对我国的大学化学实验教学改革具有借鉴作用。

关键词：美国化学实验室化学教育层次化化学教学教学改革

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位于纳什雕塑中心的安·维罗尼卡·詹森斯展馆美国德州达拉斯市

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世界建筑导报 2022年第1期37卷 58-59页

作者： Yen Ong paul Merrill lauren.Cadieux 无不详纳什雕塑中心

在比利时艺术家安·维罗尼卡·詹森斯的首次美国个人展馆展示中,五人设计工作室与其合作打造了一个独特的特定场地展馆。在过去的三十年里,该艺术家以光线艺术家的身份家喻户晓,她利用科学研究并借助投影、烟雾和其他材料来打造能够提... 详细信息

在比利时艺术家安·维罗尼卡·詹森斯的首次美国个人展馆展示中,五人设计工作室与其合作打造了一个独特的特定场地展馆。在过去的三十年里,该艺术家以光线艺术家的身份家喻户晓,她利用科学研究并借助投影、烟雾和其他材料来打造能够提高观众对自己和周围环境的感知的体验。

关键词：设计工作室周围环境詹森美国德州科学研究展馆比利时

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Scalable and automated CRISPR-based strain engineering using droplet microfluidics

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Microsystems & Nanoengineering 2022年第2期8卷 227-236页

作者： Kosuke Iwai Maren Wehrs Megan Garber Jess Sustarich lauren.Washburn Zachary Costello Peter W.Kim David Ando William R.Gaillard Nathan J.Hillson paul D.Adams Aindrila Mukhopadhyay Hector Garcia Martin Anup K.Singh Technology Division DOE Joint BioEnergy InstituteEmeryvilleCA 94608USA Biotechnology and Bioengineering Department Sandia National LaboratoriesLivermoreCA 94550USA Biofuels and Bioproducts Division DOE Joint BioEnergy InstituteEmeryvilleCA 94608USA Biological Systems and Engineering Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Molecular Biophysics and Integrated Bioimaging Division Lawrence Berkeley National LaboratoryBerkeleyCA 94720USA Department of Bioengineering University of CaliforniaBerkeleyCA 94720USA BCAM Basque Center for Applied MathematicsBilbao 48009Spain

We present a droplet-based microfluidic system that enables CRISPR-based gene editing and high-throughput screening on a *** microfluidic device contains a 10x10 element array,and each element contains sets of electrodes for two electric field-actuated operations:electrowetting for merging droplets to mix reagents and electroporation for *** device can perform up to 100 genetic modification reactions in parallel,providing a scalable platform for generating the large number of engineered strains required for the combinatorial optimization of genetic pathways and predictable *** demonstrate the system's capabilities through the CRISPR-based engineering of two test cases:(1)disruption of the function of the enzyme galactokinase(galK)in£coli and(2)targeted engineering of the glutamine synthetase gene(glnA)and the blue-pigment synthetase gene(bpsA)to improve indigoidine production in£coli.

关键词： operations generating fluid

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Identification of habitat controls on northern red-legged frog populations: implications for habitat conservation on an urbanizing landscape in the Pacific Northwest

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Ecological Processes 2017年第1期6卷 463-475页

作者： lauren.A.Grand Marc P.Hayes Kristiina A.Vogt Daniel J.Vogt paul R.Yarnold Klaus O.Richter Christopher D.Anderson Elissa C.Ostergaard Jo O.Wilhelm College of Forestry Oregon State University996 Jefferson StEugeneOR 97402USA. Science Division Habitat ProgramWashington Department of Fish and Wildlife(WDFW)600 Capitol Way NorthOlympiaWA 98501-1091USA. School of Environmental and Forest Sciences(SEFS) University of WashingtonBox 352100SeattleWA 98195-2100USA. Optimal Data Analysis LLC6348 N.Milwaukee Ave.#163ChicagoIL 60646USA. 11040104th Ave NE KirklandWA 98033-4423USA. District 12 King CountyWashington Department of Fish and Wildlife(WDFW)Region 416018 Mill Creek BlvdMill CreekWA 98012USA. King County Department of Natural Resources and Parks(DNRP) Water and Land Resources Division(WLRD)King Street Center201 S Jackson St.Suite 600SeattleWA 98104USA.

Introduction: In the Pacific Northwest of North America, research addressing lentic-breeding amphibian populationvulnerability has emphasized aquatic habitats, frequently neglecting terrestrial habitats. Consequently, wetlandprotection and restoration often fails to preserve or restore adjacent uplands required by lentic-breeding *** to the juxtaposition and connectivity of uplands to wetlands could locally extirpate lentic-breedingamphibians. The objective of this research is to identify the relative importance of juxtaposed terrestrial and aquatichabitats in a lentic-breeding amphibian, the northern red-legged frog (Rana aurora), by evaluating the relationshipbetween its occurrence and abundance with its aquatic and terrestrial habitats. To accomplish this, egg mass countswere used to quantify R. aurora populations in 30 stillwater habitats across an urbanization gradient. Using aGeographic Information System, seven descriptors of aquatic and surrounding terrestrial habitats were measured toevaluate their relationships to R. aurora occurrence and ***: Rana aurora occurrence and breeding abundance both reflect the forested area around wetland breedingsites and forest connectivity to those sites. Rana aurora breeding abundance also strongly reflects the percent offorested perimeter around wetland breeding sites. The forest habitat most important for R. aurora breeding abundanceseems to be > 200 m from the breeding wetlands. The American bullfrog presence and the two aquatic parametersmeasured, wetland area and vegetated area, were unrelated to R. aurora occurrence and breeding ***: Area and connectivity of juxtaposed forested terrestrial habitat may represent a basic control on R. aurorapresence and population size. Urban development policies should consider preservation and restoration of uplandforest habitats beyond current fixed-width buffers and wetland habitat area at landscape scales.

关键词： Northern red-legged frog Amphibian habitat Rana aurora Land use Landscape planning Urban landscapes Amphibian population

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工业4.0实施之路

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新理财（公司理财） 2020年第10期 62-64页

作者： paul Juras lauren.Johnson 不详

工业4.0正在彻底改变企业的经营方式,其速度快于商业史上的任何一次变革。以可保持利润率的成本向要求越来越高的客户提供其想要的商品和服务,变得越来越困难,不是仅仅通过"为客户做得更多"就行得通了。与此同时,数字化转型正成为许多... 详细信息

工业4.0正在彻底改变企业的经营方式,其速度快于商业史上的任何一次变革。以可保持利润率的成本向要求越来越高的客户提供其想要的商品和服务,变得越来越困难,不是仅仅通过"为客户做得更多"就行得通了。与此同时,数字化转型正成为许多行业未来发展的必然趋势。因此,工业4.0(I4.0)被视为企业应对挑战、利用新兴机遇的关键推动力。

关键词：商业史数字化转型经营方式利润率客户应对挑战推动力行业未来

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A Retrospective Renal Study from a Lupus Vasculitis Clinic

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Open Journal of Nephrology 2015年第3期5卷 75-82页

作者： Gaurav Singh lauren.White Patrick Flynn Sajan Thomas Lakshmanan Jeyaseelan Mani Thenmozhi George John paul Kubler D. Ranganathan Department of Internal Medicine Princess Alexandra Hospital Brisbane Australia Department of Internal Medicine Royal Brisbane and Women’s Hospital Brisbane Australia Department of Nephrology Royal Brisbane and Women’s Hospital Brisbane Australia Department of Biostatistics Christian Medical College Vellore India Department of Rheumatology Royal Brisbane and Women’s Hospital Brisbane Australia

Aim: In July 2009, a combined Renal Rheumatology Lupus Vasculitis (RRLV) clinic, the first of its kind for adult patients in Australia, was started at Royal Brisbane & Women’s Hospital. This is an audit of progression of renal disease to assess if patients attending this clinic had comparable results to published studies of similar cohorts with lupus Nephritis (LN) and vasculitis. Methods: We conducted a retrospective audit of all the patients who attended this clinic from July 2009 to October 2013. There were 33 patients followed up in the vasculitis group and 36 in the LN group. Patients with other connective tissue disorders were excluded from the analysis as the numbers were insignificant. Results: The mean estimated glomerular filtration rate of vasculitis and LN patients improved from 32.06 to 45.82 ml/min/1.73m2 and 62.42 to 65.53 ml/min/1.73m2 respectively. The mean urine protein/creatinine ratio of vasculitis and LN patients improved from 420 to 85 and 406 to 70 respectively. No patients died in either group. One vasculitis and two LN patients required maintenance dialysis. Three LN patients underwent renal transplantation. Conclusion: The results show excellent patient and renal survival and support the concept of a combined renal rheumatology clinic in managing renal disease from systemic connective tissue disorders.

关键词： Vasculitis Lupus Nephritis Survival Estimated Glomerular Filtration Rate Urinary Protein Creatinine Ratio

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Prevalence of Human Immunodeficiency Virus (HIV), Risk Behavior, and Recent Substance Use in a Sample of Urban Drug Users: Findings by Race and Sex

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World Journal of AIDS 2012年第3期2卷 183-193页

作者： Rebecca C. Trenz lauren.R. Pacek Michael Scherer paul T. Harrell Julia Zur William W. Latimer Department of Clinical and Health Psychology College of Public Health and Health Professions University of Florida Gainesville USA Department of Mental Health Bloomberg School of Public Health Johns Hopkins University Baltimore USA Department of Psychology School of Social and Behavioral Sciences Mercy College Dobbs Ferry New York USA

The aim of the current study was to examine the prevalence of HIV, past six-month illicit drug use, and risk behaviors among a population of heavy drug users living in an urban setting. Although many studies investigate substance use, sex-risk behavior, and HIV by race and gender, no studies have examined these variables simultaneously. The current study seeks to fill this gap in the literature by exploring HIV prevalence among a predominantly heterosexual sample of recent substance users by injection drug use (IDU) status, race, and sex. Baseline data from the Baltimore site of the NEURO-HIV epidemiologic study was used in this study. This study examines neuropsychological and social-behavioral risk factors of HIV, hepatitis A, hepatitis B, and hepatitis C among both injection and non-injection drug users. Descriptive statistics and chi-square statistics were used in data analyses. Blood and urine samples were obtained to test for the presence of recent drug use, viral hepatitis, HIV, and other sexually transmitted diseases (STDs). Findings presented here have several important implications for HIV prevention and care among substance users. Intervention programs that incorporate substance use treatment in addition to HIV education, particularly with respect to substance use and sex risk behavior are imperative.

关键词： HIV Prevalence Injection Drug Use Non-Injection Drug Use Sex Risk Behavior

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