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DPhl:A DIA Pan-human Protein Mass Spectrometry library for Robust Biomarker Discovery

Genomics, Proteomics & Bioinformatics 2020年第2期18卷 104-119页

作者： Tiansheng Zhu Yi Zhu Yue Xuan huanhuan Gao Xue Cai Sander R.Piersma Thang V.Pham Tim Schelfhorst Richard R.G.D.haas Irene V.Bijnsdorp Rui Sun liang Yue Guan Ruan Qiushi Zhang Mo hu Yue Zhou Winan j.van houdt Tessa Y.S.le large jacqueline Cloos Anna Wojtuszkiewicz Danijela Koppers-lalic Franziska Bottger Chantal Scheepbouwer Ruud h.Brakenhoff geert j.l.h.van leenders jan N.M.Ijzermans john W.M.Martens Renske D.M.Steenbergen Nicole C.Grieken Sathiyamoorthy Selvarajan Sangeeta Mantoo Sze S.lee Serene j.Y.Yeow Syed M.F.Alkaff Nan Xiang Yaoting Sun Xiao Yi Shaozheng Dai Wei liu Tian lu Zhicheng Wu Xiao liang Man Wang Yingkuan Shao Xi Zheng Kailun Xu Qin Yang Yifan Meng Cong lu jiang Zhu jin'e Zheng Bo Wang Sai lou Yibei Dai Chao Xu Chenhuan Yu huazhong Ying Tony K.lim jianmin Wu Xiaofei Gao Zhongzhi luan Xiaodong Teng Peng Wu Shi'ang huang Zhihua Tao Narayanan G.Iyer Shuigeng Zhou Wenguang Shao henry lam Ding Ma jiafu ji Oi l.Kon Shu Zheng Ruedi Aebersold Connie R.jimenez Tiannan Guo Zhejiang Provincial laboratory of life Sciences and Biomedicine Westlake UniversityHangzhou 310024China Key laboratory of Structural Biology of Zhejiang Province School of Life SciencesWestlake UniversityHangzhou 310024China Institute of Basic Medical Sciences Westlake Institute for Advanced StudyHangzhou 310024China School of Computer Science Shanghai Key Laboratory of Intelligent Information ProcessingFudan UniversityShanghai 200433China Thermo Fisher Scientific(BREMEN)Gmbh Bremen 28195Germany OncoProteomics laboratory Department of Medical OncologyVU University Medical CenterVU UniversityAmsterdam 1011The Netherlands Amsterdam UMC Vrije Universiteit AmsterdamUrologyCancer Center AmsterdamAmsterdam 1011The Netherlands Thermo Fisher Scientific Shanghai 201206China The Netherlands Cancer Institute Surgical OncologyAmsterdam 1011The Netherlands Amsterdam UMC Vrije Universiteit AmsterdamSurgeryCancer Center AmsterdamAmsterdam 1011The Netherlands Amsterdam UMC Vrije Universiteit AmsterdamPediatric Oncology/HematologyCancer Center AmsterdamAmsterdam 1011The Netherlands Amsterdam UMC Vrije Universiteit AmsterdamHematologyCancer Center AmsterdamAmsterdam 1011The Netherlands Amsterdam UMC Vrije Universiteit AmsterdamMedical OncologyCancer Center AmsterdamAmsterdam 1011The Netherlands Amsterdam UMC Vrije Universiteit AmsterdamNeurosurgeryCancer Center AmsterdamAmsterdam 1011The Netherlands Amsterdam UMC Vrije Universiteit AmsterdamPathologyCancer Center AmsterdamAmsterdam 1011The Netherlands Amsterdam UMC Vrije Universiteit AmsterdamOtolaryngology/Head and Neck SurgeryCancer Center AmsterdamAmsterdam 1011The Netherlands Erasmus MC University Medical Center PathologyRotterdam 1016LVThe Netherlands Erasmus MC University Medical Center SurgeryRotterdam 1016LVThe Netherlands Erasmus MC University Medical Center Medical OncologyRotterdam 1016LVThe Netherlands Department of Anatomical Pathology Singapore General HospitalSingapore 169608Singapore Division of Medical Scie

To address the increasing need for detecting and validating protein biomarkers in clinical specimens,mass spectrometry(MS)-based targeted proteomic techniques,including the selected reaction monitoring(SRM),parallel reaction monitoring(PRM),and massively parallel dataindependent acquisition(DIA),have been *** optimal performance,they require the fragment ion spectra of targeted peptides as prior *** this report,we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue *** build the spectral resource,we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on *** then applied the workflow to generate DPhl,a comprehensive DIA pan-human library,from 1096 data-dependent acquisition(DDA)MS raw files for 16 types of cancer *** extensive spectral resource was then applied to a proteomic study of 17 prostate cancer(PCa)***,PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was *** a second application,the DPhl spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma(DlBCl)patients and 18 healthy control *** expressed proteins between DlBCl patients and healthy control subjects were detected by DIA-MS and confirmed by *** data demonstrate that the DPhl supports DIA and PRM MS pipelines for robust protein biomarker *** is freely accessible at https://***/page/***?id=IPX0001400000.

关键词： Data-independent acquisition Parallel reaction monitoring Spectral library Prostate cancer Diffuse large B cell lymphoma

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Intra-arterial thrombolytics during endovascular thrombectomy for acute ischaemic stroke in the MR ClEAN Registry

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Stroke & Vascular Neurology 2023年第1期8卷 17-25页

作者： Sabine l Collette Reinoud P h Bokkers Aryan Mazuri geert j lycklamaàNijeholt Robert j van Oostenbrugge Natalie E leCouffe Faysal Benali Charles B l M Majoie jan Cees de Groot Gert jan R luijckx Maarten Uyttenboogaart 无 Department of Radiology Medical Imaging CentreUniversity Medical Centre GroningenUniversity of GroningenGroningenthe Netherlands Department of Radiology Haaglanden Medical CentreThe Haguethe Netherlands Department of Neurology Cardiovascular Research Institute Maastricht(CARIM)Maastricht University Medical CentreMaastrichtthe Netherlands Department of Neurology Amsterdam UMCUniversity of AmsterdamAmsterdam NeuroscienceAmsterdamthe Netherlands Department of Radiology Maastricht University Medical CentreMaastrichtthe Netherlands Department of Radiology and Nuclear Medicine Amsterdam UMCUniversity of AmsterdamAmsterdam NeuroscienceAmsterdamthe Netherlands Department of Neurology University Medical Centre GroningenUniversity of GroningenGroningenthe Netherlands On behalf of the MR ClEAN Registry investigators

Introduction The efficacy and safety of local intra-arterial(IA)thrombolytics during endovascular thrombectomy(EVT)for large-vessel occlusions is *** analysed how often IA thrombolytics were administered in the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands(MR ClEAN)Registry,whether it was associated with improved functional outcome and assessed technical and safety outcomes compared with EVT without IA *** In this observational study,we included patients undergoing EVT for an acute ischaemic stroke in the anterior circulation from the MR ClEAN Registry(March 2014-November 2017).The primary endpoint was favourable functional outcome,defined as an modified Rankin Scale score≤2 at 90 *** endpoints were reperfusion status,early neurological recovery and symptomatic intracranial haemorrhage(sICh).Subgroup analyses for IA thrombolytics as primary versus adjuvant revascularisation attempt were *** Of the 2263 included patients,95(4.2%)received IA thrombolytics during *** IA thrombolytics administered were urokinase(median dose,250000 IU(IQR,193750-250000))or alteplase(median dose,20 mg(IQR,12-20)).No association was found between IA thrombolytics and favourable functional outcome(adjusted OR(aOR),1.16;95%CI 0.71 to 1.90).Successful reperfusion was less often observed in those patients treated with IA thrombolytics(aOR,0.57;95%CI 0.36 to 0.90).The odds of sICh(aOR,0.82;95%CI 0.32 to 2.10)and early neurological recovery were comparable between patients treated with and without IA *** primary and adjuvant revascularisation attempts,IA thrombolytics were more often administered for proximal than for distal *** outcomes were comparable for patients receiving IA thrombolytics as a primary versus adjuvant revascularisation *** local IA thrombolytics were rarely used in the MR ClEAN *** the relatively small st

关键词： arterial throm acute

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Endovascular treatment in anterior circulation stroke beyond 6.5 hours after onset or time last seen well:results from the MR ClEAN Registry

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Stroke & Vascular Neurology 2021年第4期6卷 572-580,I0037-I0048页

作者： luuk Dekker Esmee Venema F Anne V Pirson Charles B l M Majoie Bart j Emmer Ivo G h jansen Maxim j h l Mulder Robin lemmens Robert-jan B Goldhoorn Marieke j h Wermer jelis Boiten geert j lycklamaàNijeholt Yvo B W E M Roos Adriaan C G M van Es hester F lingsma Diederik W j Dippel Wim h van Zwam Robert j van Oostenbrugge Ido R van den Wijngaard on behalf of the MR ClEAN Registry investigators Neurology Leiden University Medical CentreLeidenThe Netherlands Neurology Erasmus MCRotterdamThe Netherlands Public health Erasmus MCRotterdamThe Netherlands Neurology Maastricht University Medical Centre+MaastrichtThe Netherlands Radiology and Nuclear Medicine Amsterdam University Medical CentreLocation AMCAmsterdamThe Netherlands Neurology University Hospitals LeuvenLeuvenBelgium Neurosciences Experimental Neurology and Leuven Brain InstituteUniversity of LeuvenLeuvenBelgium VIB Center for Brain&Disease ResearchLaboratory of NeurobiologyLeuvenBelgium Neurology Haaglanden Medical CentreDen HaagThe Netherlands Radiology Haaglanden Medical CentreDen HaagThe Netherlands Neurology Amsterdam University Medical CentreLocation AMCAmsterdamThe Netherlands Radiology Leiden University Medical CentreLeidenThe Netherlands Radiology Maastricht University Medical Centre+MaastrichtThe Netherlands

Background Randomised controlled trials with perfusion selection have shown benefit of endovascular treatment(EVT)for ischaemic stroke between 6 and 24 hours after symptom onset or time last seen ***,outcomes after EVT in these late window patients without perfusion imaging are largely *** assessed their characteristics and outcomes in routine clinical *** The Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands Registry,a prospective,multicentre study in the Netherlands,included patients with an anterior circulation occlusion who underwent EVT between 2014 and *** perfusion was no standard imaging *** used adjusted ordinal logistic regression analysis to compare patients treated within versus beyond 6.5 hours after propensity score matching on age,prestroke modified Rankin Scale(mRS),National Institutes of health Stroke Scale,Alberta Stroke Programme Early CT Score(ASPECTS),collateral status,location of occlusion and treatment with intravenous *** included 3-month mRS score,functional independence(defined as mRS 0-2),and *** Of 3264 patients who underwent EVT,106(3.2%)were treated beyond 6.5 hours(median 8.5,IQR 6.9-10.6),of whom 93(87.7%)had unknown time of stroke *** perfusion was not performed in 87/106(80.2%)late window *** window patients were younger(mean 67 vs 70 years,phad slightly lower ASPECTS(median 8 vs 9,pllateral status(collateral score 2-3:68.3%vs 57.7%,p=0.03).No differences were observed in proportions of functional independence(43.3%vs 40.5%,p=0.57)or death(24.0%vs 28.9%,p=0.28).After matching,outcomes remained similar(adjusted common OR for 1 point improvement in mRS 1.04,95%CI 0.56 to 1.93).Conclusions Without the use of CT perfusion selection criteria,EVT in the 6.5-24-hour time window was not associated with poorer outcome in selected patients with favourable clinical and CT/C

关键词： treatment beyond Registry

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Reduction of dietary crude protein and feed form:Impact on broiler litter quality,ammonia concentrations,excreta composition,performance,welfare,and meat quality

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Animal Nutrition 2022年第2期9卷 291-303页

作者： Madri Brink geert P.j.janssens Peter Demeyer Ozer Bagci Evelyne Delezie Flanders Research Institute for Agriculture Fisheries and Food(ILVO)Animal Sciences UnitScheldeweg 689090 MelleBelgium Department of Nutrition Genetics and EthologyGhent UniversityHeidestraat 199820 MerelbekeBelgium Flanders Research Institute for Agriculture Fisheries and Food(ILVO)Agricultural Engineering UnitBurg.Van Gansberghelaan 1159820 MerelbekeBelgium Department of Mechanical Engineering Eindhoven University of Technology5600 MB-EindhovenNetherlands.

Nitrogen(N)excreted by poultry is converted to ammonia(Nh3),presenting an environmental risk and a health risk to the farmer and animals.A study was performed to investigate the effect of reduced CP and feed form on broiler performance and welfare,meat and litter quality,N utilization,and Nh3 concentrations at litter level.A total of 2,232 Ross 308 male broilers was divided into 6 treatments and 6 replicates,which was fed diets in both pellet and mash forms with different CP levels of 205.0 g/kg(h,high),187.5 g/kg(M,intermediate)and 175.0 g/kg(l,low)in the grower phase and 195.0 g/kg(h),180.0 g/kg(M)and 165.6 g/kg(l)in the finisher *** amino acids(AA)were supplemented to maintain digestible AA-to-digestible lysine *** dietary CP content to 187.5 g/kg in the grower phase and 180.0 g/kg in the finisher phase reduced Nh3 concentrations at litter level(Pher reduction in dietary CP had no additional *** treatments had better litter qualities and lower incidences of foot and hock lesions than pellet treatments at d 38(Ph reduced CP had lower incidence of foot lesions at d 38(Plers fed pelleted diets had higher ADFI,ADG,and final BW,improved feed conversion ratio(FCR),and heavier carcasses(Phan those fed mash diets over a production period of 39 *** could not be maintained when birds were fed l CP pelleted *** study demonstrated that,with the supplementation of AA to meet requirements,the concentration of dietary CP can be reduced to 187.5 and 180.0 g/kg in the grower and finisher phases respectively,without impairing broiler performance,meat yield and *** diets were favorable when considering the overall litter quality and welfare of the ***,they could not maintain the same broiler performance and slaughter yield as pelleted *** from the present study may assist the poultry sector towards a socially acceptable lowemission

关键词： Broiler Ammonia Crude protein Feed form Performance

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m TOR signaling in liver regeneration: Rapamycin combined with growth factor treatment

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World journal of Transplantation 2013年第3期3卷 36-47页

作者： Suomi MG Fouraschen Petra E de Ruiter jaap Kwekkeboom Ron WF de Bruin geert Kazemier herold j Metselaar hugo W Tilanus luc jW van der laan jeroen de jonge Department of Surgery and laboratory of Experimental Transplantation and Intestinal Surgery Erasmus MC-University Medical Center 3015 CE Rotterdam The Netherlands Department of Gas-troenterology and hepatology Erasmus MC-University Medical Center 3015 CE Rotterdam The Netherlands

AIM: To investigate the effects of mammalian target of rapamycin(mT OR) inhibition on liver regeneration and autophagy in a surgical resection ***: C57Bl/6 mice were subjected to a 70% partial hepatectomy(Ph) and treated intraperitoneally every 24 h with a combination of the m TOR inhibitor rapamycin(2.5 mg/kg per day) and the steroid dexamethasone(2.0 mg/kg per day) in phosphate bufferedsaline(PBS) or with PBS alone as vehicle control. In the immunosuppressant group, part of the group was treated subcutaneously 4 h prior to and 24 h after Ph with a combination of human recombinant interleukin 6(Il-6; 500 μg/kg per day) and hepatocyte growth factor(hGF; 100 μg/kg per day) in PBS. Animals were sacrificed 2, 3 or 5 d after Ph and liver tissue and blood were collected for further analysis. Immunohistochemical staining for 5-Bromo-2'-deoxyuridine(Brd U) was used to quantify hepatocyte proliferation. Western blotting was used to detect hepatic microtubule-associated protein 1 light chain 3(lC3)-Ⅱ protein expression as a marker for autophagy. hepatic gene expression levels of proliferation-, inflammation- and angiogenesisrelated genes were examined by real-time reverse transcription-polymerase chain reaction and serum bilirubin and transaminase levels were analyzed at the clinical chemical core facility of the Erasmus MC-University Medical ***: m TOR inhibition significantly suppressed regeneration, shown by decreased hepatocyte proliferation(2% vs 12% Brd U positive hepatocyte nuclei at day 2, P liver weight reconstitution(63% vs 76% of initial total liver weight at day 3, P = 0.04), and furthermore increased serum transaminase levels(aspartate aminotransferase 641 U/l vs 185 U/l at day 2, P = 0.02). Expression of the autophagy marker lC3-Ⅱ, which was reduced during normal liver regeneration, increased after mT OR inhibition(46% increase at day 2, P = 0.04). hepatic gene expression showed an increased infl

关键词： hepatocyte proliferation Autophagy Microtubule-associated protein 1 light chain 3 Partial hepatectomy Rapamycin

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帕金森病患者的中脑血脑屏障功能异常

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世界核心医学期刊文摘（神经病学分册） 2005年第7期1卷 9-9页

作者： Kortekaas R. leenders K.l. van Oostrom j.C.h. 张殿增 Groningen University hospital Hanzeplein1 9700 RB Groningen Netherlands Dr.

Parkinson’s disease (PD) is associated with a loss of neurons from the midbra in. The cause of PD is unknown, but it is established that certain neurotoxins c an cause similar *** brain is normally protected from these noxious bl ood-borne chemicals by the blood-brain barrier which includes specialized prot eins on the inside of blood vessels in the brain. These act as molecular efflux pumps and P-glycoprotein (P-gp) is an abundant representative. Vulnerability t o PD appears codetermined by the genotype for the P-gp gene. We hypothesized th at PD patients have reduced P-gp function in the blood-brain *** used p ositron emission tomography to measure brain uptake of [11C]-verapamil, which i s normally extruded from the brain by P-gp. here, we show significantly elevate d uptake of [11C]-verapamil (18%) in the midbrain of PD patients relative to c ontrols. This is the first evidence supporting a dysfunctional blood-brain barr ier as a causative mechanism in PD.

关键词：帕金森病血脑屏障维拉帕米神经元缺失基因表型 verapamil 吸收情况神经毒素 specialized representative

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磁共振淋巴系成像检出前列腺癌病人淋巴结转移的成本效益研究

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国际医学放射学杂志 2009年第6期 575-575页

作者： A.M.hvels R.A.M.heesakkers E.M.M.Adang j.O.Barentsz G.j.jager j.l.Severens 王文娟 Department of Radiology Radboud University Nijmegen Medical CentreGeert Grooteplein 216525 EZ Nijmegenthe Netherlands

目的应用决策分析模型研究中度或高度怀疑淋巴结转移的病人行MR淋巴系成像在医疗中是否经济、有效。材料与方法决策分析模型中所用的数据从375例病人的经验性研究中获得。输入决策分析模型的数据来源于几所医院的前瞻性病人数据。该研... 详细信息

目的应用决策分析模型研究中度或高度怀疑淋巴结转移的病人行MR淋巴系成像在医疗中是否经济、有效。材料与方法决策分析模型中所用的数据从375例病人的经验性研究中获得。输入决策分析模型的数据来源于几所医院的前瞻性病人数据。该研究经每

关键词：淋巴系 MR 医疗前列腺癌淋巴结清扫术病人检出

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