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1帕博利珠单抗单用或与放疗联用治疗转移性非小细胞肺癌:两个随机试验的汇总分析显示文摘背景放疗可以提高整个机体对免疫治疗的应答。在Ⅱ期PEMBRO-RT研究和Ⅰ/Ⅱ期MDACC研究中,患有转移性非小细胞肺癌(NSCLC)的患者被随机分配入组,接受免疫治疗(帕博利珠单抗)+放疗联合疗法,或免疫治疗单一疗法。当上述2个研究单独分析时,联合疗法组显示出潜在获益。由于每个研究的样本量较小,缓解率和结局并未显示出统计学意义,然而却有显著的临床获益。因此,本研究进行汇总分析,来判断放疗是否会改善转移性NSCLC患者的免疫治疗应答。方法PEMBRO-RT和MDACC研究纳入标准:患者年龄≥18岁,患有转移性NSCLC,且有≥1处未经放疗照射的病灶,以便进行射野外应答监测。PEMBRO-RT研究纳入曾接受过化疗患者,MDACC研究纳入曾接受过治疗或新诊断患者。2个研究中的患者均未接受过免疫治疗。在PEMBRO-RT研究中患者被等比例随机分配入组,并根据吸烟状态进行分层(分为<10年组和≥10年组)。MDACC研究的患者根据放疗计划可行性被等比例随机分配入2个受试组。由于联合治疗组的干预本质,每个研究中的放疗均不适用盲法。在2个研究中,不论是否进行放疗,均静脉滴入帕博利珠单抗(每3周200 mg)。在PEMBRO-RT研究中,在放疗(24 Gy 3次分割照射)结束后1周给予第1剂帕博利珠单抗。在MDACC研究中,在第1次放疗(50 Gy 4次分割照射或45 Gy 15次分割照射)同时给予帕博利珠单抗。仅检测未经照射病灶的应答。本研究的终点为最佳射野外(远隔)应答率(ARR)、最佳射野外疾病控制率(ACR)、12周时ARR、12周时ACR、无进展生存期(PFS)和总生存期(OS)。2个研究的意向治疗(ITT)人群均纳入分析。PEMBRO-RT研究(NCT02492568)和MDACC研究(NCT02444741)均在ClinicalTrials.gov上注册。发现纳入148例患者,76例接受帕博利珠单抗治疗,72例接受帕博利珠单抗+放疗治疗。所有患者随访时间中位数为33个月[四分位距(IQR):32.4~33.6]。148例患者中124例(84%)组织学特征为非鳞癌,111例(75%)患者曾经接受过化疗。组间没有基线特征差异,包括PD-L1表达状态和转移灶体积。最常见的照射部位为肺转移灶(39%,28/72)、胸腔内淋巴结(21%,15/72)和非原发灶(17%,12/72)。帕博利珠单抗组和联合治疗组的最佳ARR分别为19.7%(15/76)和41.7%(30/72),OR=2.96,95%CI:1.42~6.20,P=0.0039;最佳ACR分别为43.4%(33/76)和65.3%(47/72),OR=2.51,95%CI:1.28~4.91,P=0.0071;PFS中位数分别为4.4(IQR:2.9~5.9)和9.0个月(IQR:6.8~11.2),HR=0.67,95%CI:0.45~0.99,P=0.045;OS中位数分别为8.7(IQR:6.4~11.0)和19.2个月(IQR:14.6~23.8),OR=0.67,95%CI:0.54~0.84,P=0.0004。在汇总分析中没有发现新的安全问题。解读帕博利珠单抗免疫疗法+放疗显著提高转移性NSCLC患者的应答和改善治疗结局。这些结果需要在三期临床试验中进行验证。陈大卫(翻译) 于金明(校对) Willemijn S M E Theelen Vivek Verma Brian P Hobbs Heike M U Peulen Joachim G J V Aerts Idris Bahce Anna Larissa N Niemeijer Joe Y Chang Patricia M de Groot Quynh-Nhu Nguyen Nathan I Comeaux George R Simon Ferdinandos Skoulidis Steven H Lin Kewen He Roshal Patel John Heymach Paul Baas James W Welsh 2021中华肿瘤防治杂志2021,28,24:49
2Evaluation of the updated definition of early allograft dysfunction in donation after brain death and donation after cardiac death liver allografts显示文摘BACKGROUND:An updated definition of early allograft dysfunction(EAD) was recently validated in a multicenter study of 300 deceased donor liver transplant recipients.This analysis did not differentiate between donation after brain death(DBD) and donation after cardiac death(DCD) allograft recipients.METHODS:We reviewed our prospectively entered database for all DBD(n=377) and DCD(n=38) liver transplantations between January 1,2006 and October 30,2011.The incidence of EAD as well as its ability to predict graft failure and survival was compared between DBD and DCD groups.RESULTS:EAD was a valid predictor of both graft and patient survival at six months in DBD allograft recipients,but in DCD allograft recipients there was no significant difference in the rate of graft failure in those with EAD(11.5%) compared with those without EAD(16.7%)(P=0.664) or in the rate of death in recipients with EAD(3.8%) compared with those without EAD(8.3%)(P=0.565).The graft failure rate in the first 6 months in those with international normalized ratio ≥1.6 on day 7 who received a DCD allograft was 37.5% compared with 6.7% for those with international normalized ratio <1.6 on day 7(P=0.022).CONCLUSIONS:The recently validated definition of EAD is a valid predictor of patient and graft survival in recipients of DBD allografts.On initial assessment,it does not appear to be a useful predictor of patient and graft survival in recipients of DCD allografts,however a study with a larger sample size of DCD allografts is needed to confirm these findings.The high ALT/AST levels in most recipients of DCD livers as well as the predisposition to biliary complications and early cholestasis make these parameters as poor predictors of graft failure.An alternative definition of EAD that gives greater weight to the INR on day 7 may be more relevant in this population.Kris P Croome William Wall Douglas Quan Sai Vangala Vivian McAlister Paul Marotta Roberto Hernandez-Alejandro 2012Hepatobiliary & Pancreatic Diseases International2012,11,4:15
3MRI-determined fat content of human liver,pancreas and kidney显示文摘AIM:To assess and correlate the lipid content of various organs in obese subjects and in persons with a normal body weight.METHODS:Magnetic resonance spectroscopy and a previously validated gradient echo magnetic resonance imaging method with Dixon's two point technique were used in this study to quantify fat in liver,pancreas as well as kidney.RESULTS:In 36 volunteers with body mass index(BMI) ranging from 20.0 to 42.9 kg/m2,the median fat content of liver,pancreas and kidney was 2.3%(interquartile range:0.2%-7.8%),2.7%(1.0%-6.5%) and 0.7%(0.1%-1.4%),respectively.BMI and subcutaneous fat correlated significantly with liver and pancreas fat content.We show for the first time the significant correlation of liver and pancreas fat content in healthy controls(r = 0.43,P < 0.01).These observations are related to body weight as measured by BMI and the amount of subcutaneous fat.Kidney fat content is very low and correlates with none of the other fat depots.CONCLUSION:Renal lipid accumulation,unlike the coupled accumulations of fat in liver and pancreas,is not observed in obese subjects.Unlike suggestions made in previous studies,renal lipid accumulation appears not to be involved in the pathogenesis of renal disease in humans.Paul E Sijens Mireille A Edens Stephan JL Bakker Ronald P Stolk 2010World Journal of Gastroenterology2010,16,16:14
4海岸湿地在飓风防护中的价值显示文摘海岸湿地可以减少飓风对沿海群落的破坏作用。把1980年以来美国34次主要飓风在其袭击区所造成的单位国民生产总值损失的自然对数值作为因变量,风速和飓风袭击区湿地面积的自然对数值作为自变量,回归模型显示两者之间的差异极显著,说明了其相对损失的差别的60%。在上述模型中,每减少1 hm^2的湿地面积,来自特定风暴造成的风暴损害将平均增加33 000美元的损失(中值5000美元)。利用这个关系,把各年度不同强度飓风发生的概率考虑在内,我们以1km×1km为像素,以州为单元将湿地的年度价值绘制成图,湿地年度价值的变化范围为250~51 000美元/hm^2·a,平均价值为8240美元/hm^2·a(中值3230美元/hm^2·a),这显著高于以前估算的湿地价值。据估算,美国的海岸湿地目前能够提供的保护作用相当于232亿美元/a。在风暴防护中,海岸湿地是一种有价值的、能够自我维持的'水平堤防',并且能够提供垂直堤防所不能提供的许多其他的生态系统功能。对于人类社会来说,对沿海湿地的修复与维护是一种极其划算的战略性投资。Robert Costanza Octavio Pérez-Maqueo M. Luisa Martinez Paul Sutton Sharolyn J. Anderson Kenneth Mulder 唐晓宇(译) 王书磊(校) 张晓琴(校) 2008AMBIO-人类环境杂志2008,37,4:8
5不同激光表面纹理对轴承材料AISI52100摩擦性能的影响显示文摘铬钢因具有高强度和耐磨性而用于轴承。然而,在实际使用中,因滑动摩擦导致的故障而使寿命缩短。为了提高AISI52100铬钢材料的耐久性,本文分析了激光表面纹理(LST)化的效果。利用圆盘摩擦,对不同形状,如椭圆和圆,与未纹理化处理试样的磨损行为进行了对比研究。用于磨损分析的润滑剂是SKFNLGI-3半固体锂基润滑脂。在10、30和50 N的不同载荷下,用750 r/min和1400 r/min 2种滑动速度进行滑动磨损分析。用扫描电子显微镜(SEM)对磨损形貌进行了分析。样品的粗糙度用白光干涉仪测量。与未纹理化处理试样相比,观察到不同形状如圆和椭圆对铬合金摩擦磨损性能的影响。由于磨损碎片和润滑剂被捕获,激光表面纹理显示椭圆的摩擦和磨损与圆形图案相比,明显减少。PAUL JOSHUA S DINESH BABU P 2020Journal of Central South University2020,27,8:6
6A gene expression estimator of intramuscular fat percentage for use in both cattle and sheep显示文摘Background:The expression of genes encoding proteins involved in triacyglyceride and fatty acid synthesis and storage in cattle muscle are correlated with intramuscular fat(IMF)%.Are the same genes also correlated with IMF%in sheep muscle,and can the same set of genes be used to estimate IMF%in both species?Results:The correlation between gene expression(microarray) and IMF%in the longissimus muscle(LM) of twenty sheep was calculated.An integrated analysis of this dataset with an equivalent cattle correlation dataset and a cattle differential expression dataset was undertaken.A total of 30 genes were identified to be strongly correlated with IMF%in both cattle and sheep.The overlap of genes was highly significant,8 of the 13 genes in the TAG gene set and 8 of the 13 genes in the FA gene set were in the top 100 and 500 genes respertively most correlated with IMF%in sheep,P-value = 0.Of the 30 genes,CIDEA,THRSP,ACSM1,DGAT2 and FABP4 had the highest average rank in both species.Using the data from two small groups of Brahman cattle(control and Hormone growth promotant-treated[known to decrease IMF%in muscle]) and 22 animals in total,the utility of a direct measure and different estimators of IMF%(ultrasound and gene expression) to differentiate between the two groups were examined.Directly measured IMF%and IMF%estimated from ultrasound scanning could not discriminate between the two groups.However,using gene expression to estimate IMF%discriminated between the two groups.Increasing the number of genes used to estimate IMF%from one to five significantly increased the discrimination power;but increasing the number of genes to 15 resulted in little further improvement.Conclusion:We have demonstrated the utility of a comparative approach to identify robust estimators of IMF%in the LM in cattle and sheep.We have also demonstrated a number of approaches(potentially applicable to much smaller groups of animals than conventional methods) to using gene expression to rank animals for IMF%within a single farm/treatment,or to estimate differences in IMF%between two farms/treatments.Bing Guo Kritaya Kongsuwan Paul L Greenwood Guanghong Zhou Wangang Zhang Brian P Dalrymple 2014Journal of Animal Science and Biotechnology2014,5,4:6
7Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732).Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco 2012World Journal of Gastroenterology2012,18,26:6
8High-density SNP-based genetic maps for the parents of an outcrossed and a selfed tetraploid garden rose cross, inferred from admixed progeny using the 68k rose SNP array显示文摘Dense genetic maps create a base for QTL analysis of important traits and future implementation of marker-assisted breeding.In tetraploid rose,the existing linkage maps include<300 markers to cover 28 linkage groups(4 homologous sets of 7 chromosomes).Here we used the 68k WagRhSNP Axiom single-nucleotide polymorphism(SNP)array for rose,in combination with SNP dosage calling at the tetraploid level,to genotype offspring from the garden rose cultivar‘Red New Dawn’.The offspring proved to be not from a single bi-parental cross.In rose breeding,crosses with unintended parents occur regularly.We developed a strategy to separate progeny into putative populations,even while one of the parents was unknown,using principle component analysis on pairwise genetic distances based on sets of selected SNP markers that were homozygous,and therefore uninformative for one parent.One of the inferred populations was consistent with self-fertilization of‘Red New Dawn’.Subsequently,linkage maps were generated for a bi-parental and a self-pollinated population with‘Red New Dawn’as the common maternal parent.The densest map,for the selfed parent,had 1929 SNP markers on 25 linkage groups,covering 1765.5 cM at an average marker distance of 0.9 cM.Synteny with the strawberry(Fragaria vesca)genome was extensive.Rose ICM1 corresponded to F.vesca pseudochromosome 7(Fv7),ICM4 to Fv4,ICM5 to Fv3,ICM6 to Fv2 and ICM7 to Fv5.Rose ICM2 corresponded to parts of F.vesca pseudochromosomes 1 and 6,whereas ICM3 is syntenic to the remainder of Fv6.Mirjana Vukosavljev Paul Arens Roeland E Voorrips Wendy P C van't Westende G D Esselink Peter M Bourke Peter Cox W Eric van de Weg Richard G F Visser Chris Maliepaard Marinus J M Smulders 2016Horticulture Research2016,3,1:6
9Through-needle all-optical ultrasound imaging in vivo: a preclinical swine study显示文摘High-frequency ultrasound imaging can provide exquisite visualizations of tissue to guide minimally invasive procedures.Here,we demonstrate that an all-optical ultrasound transducer,through which light guided by optical fibers is used to generate and receive ultrasound,is suitable for real-time invasive medical imaging in vivo.Broad-bandwidth ultrasound generation was achieved through the photoacoustic excitation of a multiwalled carbon nanotube-polydimethylsiloxane composite coating on the distal end of a 300-μm multi-mode optical fiber by a pulsed laser.The interrogation of a high-finesse Fabry–Pérot cavity on a single-mode optical fiber by a wavelength-tunable continuous-wave laser was applied for ultrasound reception.This transducer was integrated within a custom inner transseptal needle(diameter 1.08 mm;length 78 cm)that included a metallic septum to acoustically isolate the two optical fibers.The use of this needle within the beating heart of a pig provided unprecedented realtime views(50 Hz scan rate)of cardiac tissue(depth:2.5 cm;axial resolution:64μm)and revealed the critical anatomical structures required to safely perform a transseptal crossing:the right and left atrial walls,the right atrial appendage,and the limbus fossae ovalis.This new paradigm will allow ultrasound imaging to be integrated into a broad range of minimally invasive devices in different clinical contexts.Malcolm C Finlay Charles A Mosse Richard J Colchester Sacha Noimark Edward Z Zhang Sebastien Ourselin Paul C Beard Richard J Schilling Ivan P Parkin Ioannis Papakonstantinou Adrien E Desjardins 2017Light(Science & Applications)2017,6,1:6
10Is cardiac resynchronisation therapy feasible, safe and beneficial in the very elderly?显示文摘ObjectiveTo evaluate 心脏的同一时刻治疗(CRT ) 培植是否与经历 CRT 培植的 symptoms.MethodsConsecutive 病人一起在 octogenarians 和协会可行、安全,从二个英国中心被招募。根据年龄组织的病人:<80 &≥80 年。基线人口分布,复杂并发症和结果在 439 个病人的那些 groups.ResultsA 总数之间被比较在这研究, 26%≥ 是谁被包括;80 年。Octogenarians 更经常与心脏的同一时刻治疗使用高压脉冲来消减心脏相比收到了心脏的再同步治疗心律调整器。从心律调整器的升级在两个组是普通的(16%<80 年对 22%≥80 年, P = NS ) 。合作病态在两个组是同样普通的(全面糖尿病:25% , atrial 纤维性颤动:23% ,高血压:45%) 。更耐心的年龄 ≥80 年有重要的长期的肾疾病(CKD,估计的 glomerular 过滤率 <45 mL/min 每 1.73 m 2,44% 对 22% , P <0.01 ) 。全面复杂并发症率(任何东西) 在两个组是类似的(16% 对 17% , P = NS ) 。两个组表明了征兆的利益。一个年死亡率作为与更年轻的队相比是在 octogenarians 更大的几乎四褶层(13.9% 对 3.7% , P <0.01 ).ConclusionsCRT 看起来安全在尽管有广泛的合作病态老、特别地经常严重 CKD。征兆的改进看起来有意义。增加的策略是 CRT 的潜在的候选人的有 CHF 的老病人的适当鉴定被要求。Bartosz Olechowski Rebecca Sands Donah Zachariah Neil P Andrews Richard Balasubramaniam Mark Sopher John Paisey Paul R Kalra 2015Journal of Geriatric Cardiology2015,12,5:5
11A comparison of survival and pathologic features of non-alcoholic steatohepatitis and hepatitis C virus patients with hepatocellular carcinoma显示文摘AIM:To compare the clinical outcome and pathologic features of non-alcoholic steatohepatitis(NASH) patients with hepatocellular carcinoma(HCC) and hepatitic C virus(HCV) patients with HCC(another group in which HCC is commonly seen) undergoing liver transplantation.METHODS:Patients transplanted for HCV and NASH at our institution from January 2000 to April 2011 were analyzed.All explanted liver histology and pre-transplant liver biopsies were examined by two specialist liver histopathologists.Patient demographics,disease free survival,explant liver characteristics and HCC features(tumour number,cumulative tumour size,vascular invasion and differentiation) were compared between HCV and NASH liver transplant recipients.RESULTS:A total of 102 patients with NASH and 283 patients with HCV were transplanted.The incidence of HCC in NASH transplant recipients was 16.7%(17/102).The incidence of HCC in HCV transplant recipients was 22.6%(64/283).Patients with NASH-HCC were statistically older than HCV-HCC patients(P < 0.001).A significantly higher proportion of HCV-HCC patients had vascular invasion(23.4% vs 6.4%,P = 0.002) and poorly differentiated HCC(4.7% vs 0%,P < 0.001) compared to the NASH-HCC group.A trend of poorer recurrence free survival at 5 years was seen in HCV-HCC patients compared to NASH-HCC who underwent a Liver transplantation(P = 0.11).CONCLUSION:Patients transplanted for NASH-HCC appear to have less aggressive tumour features compared to those with HCV-HCC,which likely in part accounts for their improved recurrence free survival.Roberto Hernandez-Alejandro Kris P Croome Martin Drage Nathalie Sela Jeremy Parfitt Natasha Chandok Paul Marotta Cheryl Dale William Wall Douglas Quan 2012World Journal of Gastroenterology2012,18,31:5
12Single-atom heterogeneous catalysts based on distinct carbon nitride scaffolds显示文摘Carbon nitrides integrating macroheterocycles offer unique potential as hosts for stabilizing metal atoms due to their rich electronic structure. To date, only graphitic heptazine-based polymers have been studied.Here, we demonstrate that palladium atoms can be effectively isolated on other carbon nitride scaffolds including linear melem oligomers and poly(triazine/heptazine imides). Increased metal uptake was linked to the larger cavity size and the presence of chloride ions in the polyimide structures. Changing the host structure leads to significant variation in the average oxidation state of the metal, which can be tuned by exchange of the ionic species as evidenced by X-ray photoelectron spectroscopy and supported by density functional theory. Evaluation in the semi-hydrogenation of 2-methyl-3-butyn-2-ol reveals an inverse correlation between the activity and the degree of oxidation of palladium, with oligomers exhibiting the highest activity. These findings provide new mechanistic insights into the influence of the carbon nitride structure on metal stabilization.Zupeng Chen Evgeniya Vorobyeva Sharon Mitchell Edvin Fako Núria López Sean M.Collins Rowan K.Leary Paul A.Midgley Roland Hauert Javier Pérez-Ramírez 2018National Science Review2018,5,5:4
13Pathology grading of colon cancer surgical resection and its association with survival: a retrospective observational study显示文摘Nicholas P West Eva JA Morris Olorunda Rotimi Alison Cairns Paul J Finan Philip Quirke 2008Lancet Oncology2008,,9:4
14Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales显示文摘C.P Wilkinson Frederick L Ferris Ronald E Klein Paul P Lee Carl David Agardh Matthew Davis Diana Dills Anselm Kampik R Pararajasegaram Juan T Verdaguer 2003Ophthalmology2003,,9:4
15动态88小时:美国地质调查局国家地震信息中心对2011年3月11日M_W9.0日本地震的响应显示文摘引言 2011年3月11日日本本州岛东海岸附近海域发生的M9.0地震(Tohoku earthquake,以下称“东日本大地震”——译者注)及其引发的海啸造成数以万计的人员死亡,造成的财产损失可能超过1万亿美元,这是有历史记录以来最严重的自然灾害之一。Gavin P Hayes Paul S Earle Harley M Benz David J Wald Richard W Briggs 左玉玲(译) 郑需要(校) 2011国际地震动态2011,,8:4
16Effective expression of small interfering RNA in human cells显示文摘Paul C P Good P D Winer I Engelke D R 0,,:4
17A longitudinal study of SARS-CoV-2-infected patients reveals a high correlation between neutralizing antibodies and COVID-19 severity显示文摘Understanding the immune responses elicited by SARS-CoV-2 infection is critical in terms of protection against reinfection and,thus,for public health policy and vaccine development for COVID-19.In this study,using either live SARS-CoV-2 particles or retroviruses pseudotyped with the SARS-CoV-2 S viral surface protein(Spike),we studied the neutralizing antibody(nAb)response in serum samples from a cohort of 140 SARS-CoV-2 qPCR-confirmed infections,including patients with mild symptoms and also more severe forms,including those that required intensive care.We show that nAb titers correlated strongly with disease severity and with anti-spike IgG levels.Indeed,patients from intensive care units exhibited high nAb titers;conversely,patients with milder disease symptoms had heterogeneous nAb titers,and asymptomatic or exclusive outpatient-care patients had no or low nAbs.We found that nAb activity in SARS-CoV-2-infected patients displayed a relatively rapid decline after recovery compared to individuals infected with other coronaviruses.Moreover,we found an absence of cross-neutralization between endemic coronaviruses and SARS-CoV-2,indicating that previous infection by human coronaviruses may not generate protective nAbs against SARS-CoV-2.Finally,we found that the D614G mutation in the spike protein,which has recently been identified as the current major variant in Europe,does not allow neutralization escape.Altogether,our results contribute to our understanding of the immune correlates of SARS-CoV-2-induced disease,and rapid evaluation of the role of the humoral response in the pathogenesis of SARS-CoV-2 is warranted.Vincent Legros Solène Denolly Manon Vogrig Bertrand Boson Eglantine Siret Josselin Rigaill Sylvie Pillet Florence Grattard Sylvie Gonzalo Paul Verhoeven Omran Allatif Philippe Berthelot Carole Pélissier Guillaume Thiery Elisabeth Botelho-Nevers Guillaume Millet Jérôme Morel Stéphane Paul Thierry Walzer François-Loïc Cosset Thomas Bourlet Bruno Pozzetto 2021Cellular & Molecular Immunology2021,18,2:3
18荧光原位杂交在间期细胞染色体检测中的应用显示文摘荧光原位杂交在间期细胞染色体检测中的应用王明荣王秀琴吴BernardPérisselPaulMalet为探讨间期核荧光原位杂交(FISH)在医学上的应用,我们应用生物素标记的染色体特异探针,对未培养的羊水细胞、外周血细胞、膀胱癌手术标本、膀胱洗液、...王明荣 王秀琴 吴簇 Bernard Périssel Paul Malet 1996中华医学杂志1996,76,6:3
19Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS.Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight 2010Cellular & Molecular Immunology2010,7,3:3
20轮胎工业用更安全的操作油显示文摘在欧洲 ,立法和公众压力正在使欧洲市场上的操作油性质发生变化。这引起欧洲橡胶行业对不使用有潜在致癌危险芳香油的新型轮胎和橡胶配方进行评述。本文对这一状况进行了研究 ,并探讨了美国市场上可能出现的动态 ,介绍了不同产品的需求量以及北美操作油和润滑基油制造不断变化的局面。Paul W H T Juergen E P 吴淑华 2002轮胎工业2002,22,5:3
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