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Adeno-associated virus mediated delivery of Tregitope 167 ameliorates experimental colitis

World Journal of Gastroenterology 2012年第32期18卷 4288-4299页

作者： Sander van der Marel Anna Majowicz Karin Kwikkers Richard van logtenstein Anje A te Velde Anne S De Groot sybren l meijer Sander J van Deventer Harald Petry Daniel W Hommes Valerie Ferreira Department of Research and Development uniQure B.V.1105 BA AmsterdamThe Netherlands Department of Gastroenterology and Hepatology Leiden University Medical Center2333 ZA LeidenThe Netherlands Tytgat Institute for liver and Intestinal Research Academic Medical CenterUniversity of Amsterdam1105 BK AmsterdamThe Netherlands EpiVax Inc. ProvidenceRI 02903United States The Institute for Immunology and Informatics University of Rhode IslandKingstonRI 02881United States Department of Pathology Academic Medical CenterUniversity of Amsterdam1105 AZ AmsterdamThe Netherlands Center for Inflammatory Bowel Diseases UCLA Health SystemLos AngelesCA 90095United States

AIM:To explore the anti-inflammatory potential of adeno-associated virus-mediated delivery of Tregitope 167 in an experimental colitis ***:The trinitrobenzene sulfonate(TNBS) model of induced colitis was used in Balb/c *** after intravenous adeno-associated virusmediated regulatory T-cell epitopes(Tregitope) delivery,acute colitis was initiated by intra-rectal administration of 1.5 mg TNBS in 40% ethanol followed by a second treatment with TNBS(0.75 mg in 20% ethanol) 8 d *** groups included mice not treated with TNBS(healthy control group) and mice treated by TNBS only(diseased group).At the time of sacrifice colon weight,the disease activity index and histology damage score were *** staining of the colonic tissues was performed to asses the cellular infiltrate and the presence of transcription factor forkhead Box-P3(Foxp3).Thymus,mesenteric lymph nodes,liver and spleen tissue were collected and the corresponding lymphocyte populations were further assessed by flow cytometry analysis for the expression of CD4+ T cell and regulatory T cell associated ***:The Tregitope 167 treated mice gained an average of 4% over their initial body weight at the time of *** contrast,the mice treated with TNBS alone(no Tregitope) developed colitis,and lost 4% of their initial body weight at the time of sacrifice(P lower disease activity index and a decreased colon weight as compared to the diseased control group(P ly).Immunohistochemical staining of the colonic tissues for CD4+ showed that inflammatory cell infiltrates were present in TNBS treated mice with or without administration with tregitope 167 and that these cellular infiltrates consisted mainly of CD4+ *** both TNBS treated groups CD4+ T cell infiltrates were observed in the sub-epithelia

关键词： Adeno-associated virus Regulatory T cell epitope Inflammatory bowel diseases Adeno-associated virus

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Supramolecular Polymerization of Hydrogen-Bonded Trimers in Bulk and Aqueous Medium

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CCS Chemistry 2024年第6期6卷 1458-1465页

作者： Freek V.de Graaf Stef A.H.Jansen Sandra M.C.Schoenmakers Bas van Genabeek Marle E.J.Vleugels Bart W.l.van den Bersselaar E.W.meijer Ghislaine Vantomme Institute for Complex Molecular Systems Laboratory of Macromolecular and Organic ChemistryEindhoven University of Technology5600 MBEindhoven School of Chemistry and RNA Institute University of New South WalesSydneyNew South Wales 2052

Synthetic molecules that form functional noncovalent assemblies in water have received much attention for their potential applications as *** this work,we introduce a novel water-compatible monomer based on the phthalhydrazide moiety that assembles into hydrogen-bonded trimeric *** bulk,the material exhibits a cylindrical nanostructure in the liquid-crystalline phase at elevated temperatures,morphologically distinct from the crystalline lamellar *** water,these molecules effectively form cylinders in a one-dimensional fashion,yielding fibrous *** formation of these supramolecular polymers follows a cooperative mechanism,as evidenced by denaturation *** trimerized pattern represents a new category of aqueous su pramolecular polymers with future prospects for functional complex molecular systems.

关键词： noncovalent chemistry supramolecular polymers hydrogen bonding cooperativity nanostructure

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Genome-wide Studies Reveal Genetic Risk Factors for Hepatic Fat Content

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Genomics, Proteomics & Bioinformatics 2024年第2期22卷 57-68页

作者： Yanni li Eline H.van den Berg Alexander Kurilshikov Dasha V.Zhernakova Ranko Gacesa Shixian Hu Esteban A.lopera-Maya Alexandra Zhernakova lifelines Cohort Study Vincent E.de meijer Serena Sanna Robin P.F.Dullaart Hans Blokzijl Eleonora A.M.Festen Jingyuan Fu Rinse K.Weersma Department of Gastroenterology and Hepatology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Genetics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Gastroenterology and Hepatology Tianjin Medical University General HospitalTianjin Medical UniversityTianjin 300052China laboratory of Genomic Diversity Center for Computer TechnologiesITMO UniversitySaint Petersburg 199034Russia Institute of Precision Medicine the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510080China Department of Surgery Section of Hepatobiliary Surgery and Liver TransplantationUniversity of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Endocrinology University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands Department of Pediatrics University of GroningenUniversity Medical Center GroningenGroningen 9713 GZThe Netherlands 不详

Genetic susceptibility to metabolic associated fatty liver disease(MAFlD)is complex and poorly *** characterization of the genetic background of hepatic fat content would provide insights into disease etiology and causality of risk *** performed genome-wide association study(GWAS)on two noninvasive definitions of hepatic fat content:magnetic resonance imaging proton density fat fraction(MRI-PDFF)in 16,050 participants and fatty liver index(FlI)in 388,701 participants from the United Kingdom(UK)Biobank(UKBB).Heritability,genetic overlap,and similarity between hepatic fat content phenotypes were analyzed,and replicated in 10,398 participants from the University Medical Center Groningen(UMCG)Genetics lifelines Initiative(UGlI).Meta-analysis of GWASs of MRI-PDFF in UKBB revealed five statistically significant loci,including two novel genomic loci harboring CREB3l1(rs72910057-T,P=5.40E−09)and GCM1(rs1491489378-T,P=3.16E−09),respectively,as well as three previously reported loci:PNPlA3,TM6SF2,and *** of FlI in UKBB identified 196 genome-wide significant loci,of which 49 were replicated in UGlI,with top signals in ZPR1(P=3.35E−13)and FTO(P=2.11E−09).Statistically significant genetic correlation(rg)between MRI-PDFF(UKBB)and FlI(UGlI)GWAS results was found(rg=0.5276,P=1.45E−03).Novel MRI-PDFF genetic signals(CREB3l1 and GCM1)were replicated in the FlI *** identified two novel genes for MRI-PDFF and 49 replicable loci for *** a difference in hepatic fat content assessment between MRI-PDFF and FlI,a substantial similar genetic architecture was *** is identified as an easy and reliable approach to study hepatic fat content at the population level.

关键词： Hepatic fat content MAFlD Genome-wide association study Fatty liver index Magnetic resonance imaging proton density fat fraction

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Phallales (Agaricomycetes, Fungi) from Southern Brazil

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Studies in Fungi 2019年第1期4卷 162-184页

作者： Trierveiler-Pereira l meijer AAR Silveira RMB Programa de Pós-Graduação em Botânica Departamento de BotânicaIBUniversidade Federal do Rio Grande do Sul(UFRGS)Porto Alegre-RSBrazil Rodovia PR-405 km 36GuaraqueçabaParanáBrazil

An illustrated and annotated checklist with key to 24 species of phalloids known to occur in Southern Brazil(States of Paraná,Santa Catarina and Rio Grande do Sul)are *** species belong to the orders Clathraceae,Claustulaceae,lysuraceae,Phallaceae and *** species are also *** floriforme and Staheliomyces cinctus are the first reports from Southern Brazil and laternea pusilla is new to the State of Santa Catarina.

关键词： Brazilian mycota fungal taxonomy phalloid fungi Phallomycetidae stinkhorns

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Carotid Intima-media Thickness Measurements： Relations with Atherosclerosis, Risk of Cardiovascular Disease and Application in Randomized Controlled Trials

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Chinese Medical Journal 2016年第2期129卷 215-226页

作者： Michiel l Bots Gregory W Evans Charles H Tegeler Rudy meijer Julius Center for Health Sciences and Primary Care University Medical Center Utrecht Utrecht The Netherlands Department of Biostatistical Sciences and Neurology Wake Forest School of Medicine Winston-Salem NC USA Department of Neuiology Ward A Riley Ultrasound Center Wake Forest School of Medicine Medical Center Boulevard Winston-Salem NC USA

Cardiovascular disease （CVD） is the leading cause of death worldwide and contributes considerably to morbidity The underlying cause is atherosclerosisThe development of new preventive therapies is one of the steps to control the CVD epidemic. It is increasingly demanded that promising therapies be evaluated in trials using cardiovascular （CV） morbidity and mortality （M and M） as a primary outcome.

关键词： Atherosclerosis Cardiovascular Disease Prevention Trials

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FOlFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer

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World Journal of Gastroenterology 2016年第31期22卷 6987-7005页

作者： Chiara Caparello laura l meijer Ingrid Garajova Alfredo Falcone Tessa Y le large Niccola Funel Geert Kazemier Godefridus J Peters Enrico Vasile Elisa Giovannetti University Hospital of Pisa 56124 Pisa Italy Department of Medical Oncology VU University Medical Center 1081 HV Amsterdam The Netherlands Department of Surgery VU University Medical Center 1081 HV Amsterdam The Netherlands Department of Experimental Diagnostic and Speciality Medicine University of Bologna Sant'Orsola-Malpighi Hospital Via Massarenti 9 40138 Bologna Italy Cancer Pharmacology lab AIRC Start-Up Unit University of Pisa 56124 Pisa Italy CNR-Nano Institute of Nanoscience and Nanotechnology University of Pisa 56124 Pisa Italy

Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOlFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOlFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOlFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers.

关键词： FOlFIRINOX Personalized therapy New treatments MicroR NA Pancreatic cancer

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Clinical outcomes of patients with duodenal adenocarcinoma and intestinal-type papilla of Vater adenocarcinoma

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World Journal of Gastrointestinal Oncology 2020年第3期12卷 347-357页

作者： laura l meijer Marin Strijker Jacob K de Bakker Jurgen GJ Toennaer Barbara M Zonderhuis Hans J van der Vliet Hanneke Wilmink Joanne Verheij Freek Daams Olivier R Busch Nicole CT van Grieken Marc G Besselink Geert Kazemier Department of Surgery Cancer Center AmsterdamAmsterdam UMCVU University AmsterdamAmsterdamNoord-Holland 1081HVThe Netherlands Department of Surgery Cancer Center AmsterdamAmsterdam UMCUniversity of AmsterdamAmsterdamNoord-Holland 1105AZThe Netherlands Department of Medical Oncology Cancer Center AmsterdamAmsterdam UMCVU University AmsterdamAmsterdamNoord-Holland 1081HVThe Netherlands Department of Medical Oncology Cancer Center AmsterdamAmsterdam UMCUniversity of Amsterdam AmsterdamNoord-Holland 1105AZThe Netherlands Department of Pathology Cancer Center AmsterdamAmsterdam UMCUniversity of Amsterdam AmsterdamNoord-Holland 1105AZThe Netherlands Department of Pathology Cancer Center AmsterdamAmsterdam UMCVU University Amsterdam Noord-Holland 1081HVThe Netherlands

BACKGROUND Duodenal adenocarcinoma(DA)and intestinal-type papilla of Vater adenocarcinoma(it-PVA)are rare malignancies of the gastrointestinal *** therapeutic options are translated nowadays from treatment strategies for patients with colorectal cancer due to histopathological *** To retrospectively investigate the clinical outcome of patients with DA and *** All patients with DA and it-PVA diagnosed between 2000 and 2017 were included at two academic centers in the *** patients with histopathologically-confirmed DA or it-PVA were eligible for *** outcome was compared between DA and it-PVA per disease *** the subgroup of stage IV disease,survival after local treatment of oligometastases was compared with systemic therapy or supportive *** In total,155 patients with DA and it-PVA were *** with it-PVA more often presented with stage I disease,while DA was more often diagnosed at stage IV(Pll patients,79%were treated with curative *** median survival was 39 mo,and no difference in survival was found for patients with DA and it-PVA after stratification for disease ***(23%)of 31 patients with synchronous stage IV disease underwent resection of the primary tumor,combined with local treatment of *** treatment of metastases was associated with an overall survival of 37 mo,compared to 14 and 6 mo for systemic therapy and supportive care,*** Survival of patients with DA and it-PVA is comparable per disease *** results suggest a potential benefit for local treatment strategies in selected patients with oligometastases,although additional prospective studies are needed.

关键词： Duodenal adenocarcinoma Papilla of Vater adenocarcinoma Clinical outcomes local treatment Metastases Survival

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Prevention By Offering Hrhpv Testing On Self-sampled Cervicovaginal Specimens Trial（Prohtect）■C Interim Findings

Prevention By Offering Hrhpv Testing On Self-sampled Cervico...

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24th International Papillomavirus Conference and Clinical Workshop

作者： Murat Gk D.A.M Heideman F.J vanKemenade l Rozendaal Berkhof P.J.F Snijders C.J.l.M meijer Dept of Pathology VU University Medical CenterAmsterdamThe Netherlands Dept of Pathology VU University Medical CenterAmsterdamThe Netherlands Dept of Pathology VU University Medical CenterAmsterdamThe Netherlands Dept of Pathology VU University Medical CenterAmsterdamThe Netherlands Dept.of Clinical Epidemiology and BiostatisticsVUUniversity Medical CenterAmsterdam Dept.of Clinical Epidemiology and Biostatistics VUUniversity Medical CenterAmsterdam Dept of Pathology VU University Medical CenterAmsterdamThe Netherlands Dept of Pathology VU University Medical CenterAmsterdamThe Netherlands

＜正＞Objective Women not attending cervical screening programmes（30% in the Netherlands）are at high risk of cervical *** the PROHTECT trial,we investigate to what extent offering self-sampling of cervico-vaginal specimens for high-risk human papillomavirus（hrHPV）testing would increase participation and therefore the yield of high grade lesions（***2 or worse） within the screening programme.

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与现有的其他重建算法相比，基于深度学习的重建算法可以改善大脑平扫CT影像

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国际医学放射学杂志 2021年第5期 612-613页

作者： l.J.Oostveen F.J.A.meijer F.de lange E.J.Smit S.A.Pegge S.C.A.Steens 余子意

摘要目的在大脑平扫CT(NCCT)中,对比商用的深度学习重建算法(DlR)、混合迭代重建(Hybrid-IR)算法和基于模型的迭代重建(MBIR)算法的影像质量和重建时间。方法

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采用3D影像融合CT全肝容积灌注成像提高肝转移瘤的检出和特征显示

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国际医学放射学杂志 2008年第A6期31卷 527-528页

作者： M.R.meijerink J.H.T.M.van Waesberghe l.van der Weide P.van den Tol S.meijer C.van Kuijk 胡涛 Department of Radiology Vrije Universiteit Medical Center (VUMC) De Boelelaan 1117 1081HV Amsterdam The Netherlands.

评价CT全肝容积灌注技术对肝转移瘤的检出及显示转移瘤特征的可行性。对20例病人进行平扫及静脉注射对比剂后的11次全肝容积螺旋CT扫描。

关键词：灌注 CT 肝转移瘤

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