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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 |
| 2 | Relationship between the exocrine and endocrine pancreas after acute pancreatitis显示文摘AIM:To determine the prevalence and time course of pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.METHODS:Relevant literature cited in three major biomedical journal databases(EMBASE,MEDLINE,and Scopus)was reviewed independently by two authors.There were no language constraints but the search was limited to human studies.Studies included were cohort studies of adult patients who were discharged after an attack of acute pancreatitis.Patients were excluded if they were under 18 years of age or had a previous diagnosis of prediabetes or diabetes mellitus,pancreatic exocrine insufficiency,or chronic pancreatitis.The main outcome measure was the prevalence of concomitant pancreatic exocrine insufficiency in patients who were diagnosed with prediabetes and diabetes mellitus after an attack of acute pancreatitis.Subgroup analysis was conducted for patients who were diagnosed with prediabetes only and those who were diagnosed withdiabetes mellitus only.Subgroup analysis looking at the time course of concomitant pancreatic exocrine and endocrine insufficiency was also conducted.Pooled prevalence and corresponding 95%confidence intervals were calculated for all outcome measures and P-values<0.05 were deemed statistically significant.RESULTS:Eight clinical studies comprising of 234patients met all eligibility criteria.The pooled prevalence of newly diagnosed prediabetes or diabetes in individuals after acute pancreatitis was 43%(95%CI:30%-56%).The pooled prevalence of pancreatic exocrine insufficiency in individuals after acute pancreatitis was 29%(95%CI:19%-39%).The prevalence of concomitant pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes was 40%(95%CI:25%-55%).The prevalence of concomitant pancreatic exocrine insufficiency among individuals with prediabetes alone and diabetes mellitus alone was 41%(95%CI:12%-75%)and 39%(95%CI:28%-51%),respectively.Further analysis showed that the prevalence of concomitant pancreatic exocrine insufficiency in individuals with prediabetes or diabetes decreases over time after an attack of acute pancreatitis.CONCLUSION:Pancreatic exocrine insufficiency occurs in 40%of individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis.Further studies are needed to investigate the pathogenesis of diabetes in this setting. | Stephanie L M Das James I C Kennedy Rinki Murphy Anthony R J Phillips John A Windsor Maxim S Petrov | 2014 | World Journal of Gastroenterology2014，20，45： | 9 |
| 3 | Understanding important features of deep learning models for segmentation of high-resolution transmission electron microscopy images显示文摘Cutting edge deep learning techniques allow for image segmentation with great speed and accuracy.However,application to problems in materials science is often difficult since these complex models may have difficultly learning meaningful image features that would enable extension to new datasets.In situ electron microscopy provides a clear platform for utilizing automated image analysis.In this work,we consider the case of studying coarsening dynamics in supported nanoparticles,which is important for understanding,for example,the degradation of industrial catalysts.By systematically studying dataset preparation,neural network architecture,and accuracy evaluation,we describe important considerations in applying deep learning to physical applications,where generalizable and convincing models are required.With a focus on unique challenges that arise in high-resolution images,we propose methods for optimizing performance of image segmentation using convolutional neural networks,critically examining the application of complex deep learning models in favor of motivating intentional process design. | James P.Horwath Dmitri N.Zakharov Rémi Mégret Eric A.Stach | 2020 | npj Computational Materials2020，，1： | 8 |
| 4 | Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus显示文摘AIM:To assess tumour regression grade(TRG)and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy.METHODS:Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005and 2011 at a single institution were reviewed.Triplet neoadjuvant chemotherapy consisting of platinum,fluoropyrimidine and anthracycline was considered for operable patients(World Health Organization performance status≤2)with clinical stage T2-4 N0-1.Response to neoadjuvant chemotherapy(NAC)was assessed using TRG,as described by Mandard et al.In addition lymph node downstaging was also assessed.Lymph node downstaging was defined by cN1 at diagnosis:assessed radiologically(computed tomography,positron emission tomography,endoscopic ultrasonography),then pathologically recorded as N0 after surgery;ypN0 if NAC given prior to surgery,or pN0if surgery alone.Patients were followed up for 5 years post surgery.Recurrence was defined radiologically,with or without pathological confirmation.An association was examined between t TRG and lymph node downstaging with disease free survival(DFS)and a comprehensive range of clinicopathological characteristics.RESULTS:Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years(median follow up:2.552,95%CI:2.022-3.081).There was a 1.8%(n=4)inpatient mortality rate.One hundred and thirty-six(62.4%)patients received NAC,with 74.3%(n=101)of patients demonstrating some signs of pathological tumour regression(TRG 1-4)and 5.9%(n=8)having a complete pathological response.Forty four point one percent(n=60)had downstaging of their nodal disease(cN1 to ypN0),compared to only 15.9%(n=13)that underwent surgery alone(pre-operatively overstaged:cN1 to pN0),(P<0.0001).Response to NAC was associated with significantly increased DFS(mean DFS;TRG 1-2:5.1years,95%CI:4.6-5.6 vs TRG 3-5:2.8 years,95%CI:2.2-3.3,P<0.0001).Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC(median DFS;TRG 3-5 and nodal down-staging:5.533 years,95%CI:3.558-7.531 vs TRG 3-5 and no nodal down-staging:1.114 years,95%CI:0.961-1.267,P<0.0001).CONCLUSION:Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS. | Fergus Noble Luke Nolan Adrian C Bateman James P Byrne Jamie J Kelly Ian S Bailey Donna M Sharland Charlotte N Rees Timothy J Iveson Tim J Underwood Andrew R Bateman | 2013 | World Journal of Gastroenterology2013，19，48： | 4 |
| 5 | Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer显示文摘 | Douglas K Rex John H Bond Sidney Winawer Theodore R Levin Randall W Burt David A Johnson Lynne M Kirk Scott Litlin David A Lieberman Jerome D Waye James Church John B Marshall Robert H Riddell | 2002 | The American Journal of Gastroenterology2002，，6： | 3 |
| 6 | Perinatal Listeria monocytogenes susceptibility despite preconceptual priming and maintenance of pathogen-specific CD8^+ T cells during pregnancy显示文摘Listeria monocytogenes (Lm ) 为发展中的胎儿在怀孕和疾病的后果期间是有为全身的母亲的感染的唯一的倾向的一个细胞内部的细菌。给与出生前的 Lm 感染联系的高死亡,为在怀孕的极其脆弱的经期期间扩充保护的免疫的策略着急地被需要。此处,保护由在对随后的剧毒的 Lm 出生前的感染的怀孕被评估以前,管理的稀释 Lm 交谈了。因为显著地更多的细菌从母亲的纸巾被恢复,我们证明对在非怀孕的老鼠的第二等的 Lm 感染的保护严厉地在 allogeneic 怀孕期间被节制,尽管有病原体特定的 CD8 + T 房间的数字、功能的保藏。更重要地,因为各在怀孕和天真的怀孕控制以前与稀释 Lm 接种的老鼠在怀孕期间在 Lm 感染以后从单个 concepti 显示出近完全的胎儿的再吞和病原体恢复, preconceptual priming 不在 utero 侵略或胎儿的消耗量免于。显著地,对有在 allogeneic 怀孕的 preconceptual priming 的出生前的 Lm 感染的保护的缺乏在 syngeneic 怀孕期间被恢复。因此,母亲胎儿的抗原不和在出生前的 Lm 感染以后对胎儿的复杂并发症支配 preconceptual 种痘的低效率,尽管有病原体特定的 CD8 + T 房间的数字、功能的保藏。 | Dayna R Clark Vandana Chaturvedi Jeremy M Kinder Tony T Jiang Lijun Xin James M Ertelt Sing Sing Way | 2014 | Cellular & Molecular Immunology2014，11，6： | 3 |
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| 8 | Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study显示文摘 | Olivier Rixe Ronald M Bukowski M Dror Michaelson George Wilding Gary R Hudes Oliver Bolte Robert J Motzer Paul Bycott Katherine F Liau James Freddo Peter C Trask Sinil Kim Brian I Rini | 2007 | Lancet Oncology2007，，： | 2 |
| 9 | A comparison of the relative efficiency of ICSI and extended culture with epididymal sperm versus testicular sperm in patients with obstructive azoospermia显示文摘This is a retrospective cohort study comparing blastocyst transfer outcomes following intracytoplasmic sperm injection utilizing epididymal versus testicular sperm for men with obstructive azoospermia.All cases at a single center between 2012 and 2016 were included.Operative approach was selected at the surgeon’s discretion and included microepididymal sperm aspiration or testicular sperm extraction.Blastocyst culture was exclusively utilized prior to transfer.The primary outcome was live birth rate.Secondary outcomes included fertilization rate,blastulation rate,euploidy rate,and implantation rate.A mixed effects model was performed.Seventy-six microepididymal sperm aspiration cases and 93 testicular sperm extraction cases were analyzed.The live birth rate was equivalent(48.6%vs 50.5%,P=0.77).However,on mixed effects model,epididymal sperm resulted in a greater likelihood of fertilization(adjusted OR:1.37,95%CI:1.05–1.81,P=0.02)and produced a higher blastulation rate(adjusted OR:1.41,95%CI:1.1–1.85,P=0.01).As a result,the epididymal sperm group had more supernumerary blastocysts available(4.3 vs 3,P<0.05).The euploidy rate was no different.Pregnancy rates were no different through the first transfer cycle.However,intracytoplasmic sperm injection following microepididymal sperm aspiration resulted in a greater number of usable blastocysts per patient.Thus,the true benefit of epididymal sperm may only be demonstrated via a comparison of cumulative pregnancy rates after multiple transfers from one cohort. | Scott J Morin Brent M Hanson Caroline R Juneau Shelby A Neal Jessica N Landis Richard T Scott Jr James M Hotaling | 2020 | Asian Journal of Andrology2020，22，2： | 2 |
| 10 | Complete genomes of two clinical Staphylococcus aureus strains:evidence for the rapid evolution of virulence and drug resistance显示文摘 | Holden MT Feil EJ Lindsay JA Peacock SJ Day NP Enright MC Foster TJ Moore CE Hurst L Atkin R Barron A Bason N Bentley SD Chillingworth C Chillingworth T Churcher C Clark L Corton C Cronin A Doggett J Dowd L Feltwell T Hance Z Harris B Hauser H Holroyd S Jagels K James KD Lennard N Line A Mayes R Moule S Mungall K Ormond D Quail MA Rabbinowitsch E Rutherford K Sanders M Sharp S Simmonds M Stevens K Whitehead S Barrell BG Spratt BG Parkhill J | 2004 | Proc Natl Acad Sci USA2004，101，26： | 1 |
| 11 | Relationship of superficial scald development and ct-Farnesene oxidation to re- actions of diphenylamine and diphenylamine derivatives in CV, Granny Smith apple peel 显示文摘 | David R R James P M John K F | 2005 | J Agric Food Chem2005，，53： | 1 |
| 12 | Tensile Testing of EP-823 and HT-9 After Irradiation in STIP Ⅱ 显示文摘 | Maloy Stuart A Romero T James M R | 2006 | Journal of Nuclear Materials2006，356，123： | 1 |
| 13 | The mechanical properties of 316L/304L stainless steels, Alloy 718 and Mod 9Cr-lMo after irradiation in a spallation environment显示文摘 | Maloy S A James M R Willcutt G | 2001 | Journal of Nuclear material2001，296，13： | 1 |
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| 15 | Musa genetic diversityrevealed by SRAP and AFLP显示文摘 | Youssef M James A C Rivera M R | 2011 | Molecular Biotechnology2011，47，3： | 1 |
| 16 | Photorefractive volume holographic demodulation of in-fiber Bragg grating sensors 显示文摘 | S W James M L Dockney R P Tatam | 1996 | IEEE Photon Technol Lett1996，8，5： | 1 |
| 17 | Mul- tialternative decision field theory: a dynamic connec- tionist model of decision making显示文摘 | ROBERT M R JEROME R B JAMES T T | 2001 | Psychological Review2001，108，2： | 1 |
| 18 | Influence of pooled colostrum or colostrum replacement on IgG and evaluation of animal plasma in milk replace显示文摘 | Jones C M James R E Quigley J D | 2004 | J Dairy Sci2004，87，18： | 1 |
| 19 | Embrittlement of Irradiated Ferritic/Martensitic Steels in the Absence of Irra diation Hardening 显示文摘 | Maloy Stuart A Romero T James M R | 2008 | Journal of Nuclear Materials2008，377，3： | 1 |
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