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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 | Anticancer immunotherapy by CTLA-4 blockade: obligatory contribution of IL-2 receptors and negative prognostic impact of soluble CD25显示文摘堵住抗体 ipilimumab 的细胞毒素的 T 淋巴细胞 antigen-4 (CTLA-4 ) 在很少的病人导致变形黑瘤的调停免疫者的长期的控制。尽管 ipilimumab 无疑经由 immunostimulation 施加它的治疗学的效果,这样远的临床上有用的、 immunologically 相关的 biomarkers 预言治疗效率是逃犯的。这里,我们显示出 IL-2 的那中立化或堵住 α并且 βIL-2 受体的子单元(CD25 和 CD122,分别地) 否则在现出症状之前的潜的老鼠模型由 CTLA-4 封锁导致了,废除了 antitumor 效果和 intratumoral T 受动器对规章的房间(Tregs ) 的比率的伴随的改进,它是。CTLA-4 封锁导致了在失去了 FoxP3 表示并且在 regressing 肿瘤积累了的 IL-2-producing 受动器房间与伴随物上升表示 Lag3, ICOS, IL-10 和 Egr2 的一个镇压 CD4 + T 房间子集的减小。当 recombinant IL-2 改进了 CTLA-4 封锁的治疗学的功效时,圈套 IL-2 受体 α(IL-2Rα, sCD25 ) 禁止了 CTLA-4 的 anticancer 效果封锁。在收到 ipilimumab 的 262 个变形黑瘤病人, sCD25 的基线浆液集中代表了全面幸存的独立指示物,与预言到治疗的抵抗的高水平。总的来说,这些结果解开为在 CTLA-4 的 anticancer 活动的 IL-2 和 IL-2 受体的一个角色封锁。重要地,我们的学习提供第一 immunologically 相关的 biomarker,也就是提高的浆液 sCD25,那与黑瘤在病人预言抵抗到 CTLA-4 封锁。 | Dalil Hannani Marie Vetizou David Enot Sylvie Rusakiewicz Nathalie Chaput David Klatzmann Melanie Desbois Nicolas Jacquelot Nadege Vimond Salem Chouaib Christine Mateus James P Allison Antoni Ribas Jedd D Wolchok Jianda Yuan Philip Wong Michael Postow Andrzej Mackiewicz Jacek Mackiewicz Dirk Schadendorff Dirk Jaeger Alan J Korman Keith Bahjat Michele Maio Luana Calabro Michele WL Teng Mark J Smyth Alexander Eggennont Caroline Robert Guido Kroemer Laurence Zitvogel | 2015 | Cell Research2015，25，2： | 14 |
| 3 | Elucidation of the ‘Honeycrisp’ pedigree through haplotype analysis with a multi-family integrated SNP linkage map and a large apple (Malus×domestica) pedigree-connected SNP data set显示文摘The apple(Malus×domestica)cultivar Honeycrisp has become important economically and as a breeding parent.An earlier study with SSR markers indicated the original recorded pedigree of‘Honeycrisp’was incorrect and‘Keepsake’was identified as one putative parent,the other being unknown.The objective of this study was to verify‘Keepsake’as a parent and identify and genetically describe the unknown parent and its grandparents.A multi-family based dense and high-quality integrated SNP map was created using the apple 8 K Illumina Infinium SNP array.This map was used alongside a large pedigree-connected data set from the RosBREED project to build extended SNP haplotypes and to identify pedigree relationships.‘Keepsake’was verified as one parent of‘Honeycrisp’and‘Duchess of Oldenburg’and‘Golden Delicious’were identified as grandparents through the unknown parent.Following this finding,siblings of‘Honeycrisp’were identified using the SNP data.Breeding records from several of these siblings suggested that the previously unreported parent is a University of Minnesota selection,MN1627.This selection is no longer available,but now is genetically described through imputed SNP haplotypes.We also present the mosaic grandparental composition of‘Honeycrisp’for each of its 17 chromosome pairs.This new pedigree and genetic information will be useful in future pedigree-based genetic studies to connect‘Honeycrisp’with other cultivars used widely in apple breeding programs.The created SNP linkage map will benefit future research using the data from the Illumina apple 8 and 20 K and Affymetrix 480 K SNP arrays. | Nicholas P Howard Eric van de Weg David S Bedford Cameron P Peace Stijn Vanderzande Matthew D Clark Soon Li Teh Lichun Cai James J Luby | 2017 | Horticulture Research2017，4，1： | 9 |
| 4 | Computed tomography and patient risk:Facts,perceptions and uncertainties显示文摘Since its introduction in the 1970s, computed tomography(CT) has revolutionized diagnostic decision-making. One of the major concerns associated with the widespread use of CT is the associated increased radiation exposure incurred by patients. The link between ionizing radiation and the subsequent development of neoplasia has been largely based on extrapolating data from studies of survivors of the atomic bombs dropped in Japan in 1945 and on assessments of the increased relative risk of neoplasia in those occupationally exposed to radiation within the nuclear industry. However, the association between exposure to low-dose radiation from diagnostic imaging examinations and oncogenesis remains unclear. With improved technology, significant advances have already been achieved with regards to radiation dose reduction. There are several dose optimization strategies available that may be readily employed including omitting unnecessary images at the ends of acquired series, minimizing the number of phases acquired, and the use of automated exposure control as opposed to fixed tube current techniques. In addition, new image reconstruction techniques that reduce radiation dose have been developed in recent years with promising results. These techniques use iterative reconstruction algorithms to attain diagnostic quality images with reduced image noise at lower radiation doses. | Stephen P Power Fiachra Moloney Maria Twomey Karl James Owen J O'Connor Michael M Maher | 2016 | World Journal of Radiology2016，8，12： | 7 |
| 5 | Risk stratification for ST segment elevation myocardial infarction in the era of primary percutaneous coronary intervention显示文摘Acute coronary syndromes presenting with ST elevation are usually treated with emergency reperfusion/revascularisation therapy. In contrast current evidence and national guidelines recommend risk stratification for non ST segment elevation myocardial infarction(NSTEMI) with the decision on revascularisation dependent on perceived clinical risk. Risk stratification for STEMI has no recommendation. Statistical risk scoring techniques in NSTEMI have been demonstrated to improve outcomes however their uptake has been poor perhaps due to questions over their discrimination and concern for application to individuals who may not have been adequately represented in clinical trials. STEMI is perceived to carry sufficient risk to warrant emergency coronary intervention [by primary percutaneous coronary intervention(PPCI)] even if this results in a delay to reperfusion with immediate thrombolysis. Immediate thrombolysis may be as effective in patients presenting early, or at low risk, but physicians are poor at assessing clinical and procedural risks and currently are not required to consider this. Inadequate data on risk stratification in STEMI inhibits the option of immediate fibrinolysis, which may be cost-effective. Currently the mode of reperfusion for STEMI defaults to emergency angiography and percutaneous coronary intervention ignoring alternative strategies. This review article examines the current risk scores and evidence base for risk stratification for STEMI patients. The requirements for an ideal STEMI risk score are discussed. | Richard A Brogan Christopher J Malkin Philip D Batin Alexander D Simms James M McLenachan Christopher P Gale | 2014 | World Journal of Cardiology2014，6，8： | 6 |
| 6 | Role of self-expanding metal stents in the management ofvariceal haemorrhage:Hype or hope?显示文摘Despite the advances of medical,endoscopic and radiological therapy over recent years the mortality rates of acute variceal haemorrhage are still 16%-20% and the medium term outcome has not improved in the last 25 years. Early transjugular intrahepatic portosystemic shunt has proved to be an effective therapy for selected groups of patients with a high risk of re-bleeding and moderate liver disease. However,there is an unmet need for a therapy that can be applied in patients with a high risk of re-bleeding and advanced liver disease either as definitive therapy or as a bridge to permanent therapy. Selfexpanding metal stents can be placed without the need for endoscopic or fluoroscopic control and,once in place,will provide effective haemostasis and allow a route for oral fluids and nutrition. They can remain in place whilst liver function recovers and secondary prophylaxis is initiated. We review the results of 6 case series including a total of 83 patients and the first randomised controlled trial of self-expanding metal stents vs balloon tamponade(BT) in the management of refractory variceal haemorrhage. We report that self-expanding metal stents provide effective haemostasis and perform better than BT in refractory bleeding,where they are associated with fewer complications. Whilst the most effective place for self-expanding metal stents in the management algorithm needs to be determined by further randomised controlled trials,currently they provide an effective alternative to BT in selected patients. | Brian J Hogan James P O’Beirne | 2016 | World Journal of Gastrointestinal Endoscopy2016，8，1： | 5 |
| 7 | 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 |
| 8 | Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial显示文摘 | JY Douillard D Cunningham AD Roth M Navarro RD James P Karasek P Jandik T Iveson J Carmichael M Alakl G Gruia L Awad P Rougier | 2000 | The Lancet2000，，9209： | 4 |
| 9 | Meeting report:a hard look at the state of enamel research显示文摘The Encouraging Novel Amelogenesis Models and Ex vivo cell Lines(ENAMEL) Development workshop was held on 23 June 2017 at the Bethesda headquarters of the National Institute of Dental and Craniofacial Research(NIDCR). Discussion topics included model organisms, stem cells/cell lines, and tissues/3 D cell culture/organoids. Scientists from a number of disciplines,representing institutions from across the United States, gathered to discuss advances in our understanding of enamel, as well as future directions for the field. | ophir d klein olivier duverger wendy shaw rodrigo s lacruz derk joester janet moradian-oldak megan k pugach j timothy wright sarah e millar ashok b kulkarni john d bartlett thomas gh diekwisch pamela den besten james p simmer | 2017 | International Journal of Oral Science2017，9，4： | 3 |
| 10 | C-reactive protein and radiographic findings of lower respiratory tract infection in infants显示文摘AIM To evaluate the association between C-reactive protein(CRP) and radiological evidence of lower respiratory tract infection(LRTI) in infants.METHODS All patients aged less than 4 years who presented with suspected lower respiratory tract infection,who received a peri-presentation chest radiograph and CRP blood measurement over an 18-mo period were included in the study.Age,gender,source of referral,CRP,white cell count,neutrophil count along with the patients' symptoms and radiologist's report were recorded.RESULTS Three hundred and eleven patients met the inclusioncriteria.Abnormal chest radiographs were more common in patients with elevated CRP levels(P < 0.01).Radiologic signs of LRTI were identified in 73.7% of chest radiographs when a patient had a CRP level between 50-99 mg/L.CRP levels were a better predictor of positive chest radiograph findings for those aged greater than I year compared to those 1 year or less.CONCLUSION CRP may be used in patients with suspected LRTI diagnosis to select those who are likely to have positive findings on chest radiograph,thus reducing unnecessary chest radiographs. | Maria Twomey Hannah Fleming Fiachra Moloney Kevin P Murphy Lee Crush Siobhan B O’Neill Oisin Flanagan Karl James Conor Bogue Owen J O’Connor Michael M Maher | 2017 | World Journal of Radiology2017，9，4： | 2 |
| 11 | Outcomes after arthroscopic repair of rotator cuff tears in the setting of mild to moderate glenohumeral osteoarthritis显示文摘BACKGROUND Rotator cuff pathology is a very common source of shoulder pain.Similarly,osteoarthritis of the glenohumeral joint can cause shoulder pain and produce similar symptoms.Surgical management can be indicated for both pathologies,however,outcomes data is limited when examining rotator cuff repair(RCR) in the setting of glenohumeral arthritis(GHOA).Thus,this study sought to determine outcomes for patients who undergo RCR in the setting of GHOA.AIM To evaluate if a relationship exists between outcomes of RCR in the setting of GHOA.METHODS This was a retrospective analysis of patients who underwent arthroscopic rotator cuff repair with concurrent glenohumeral osteoarthritis between 2010-2017.Patients were stratified based on rotator cuff tear size and glenohumeral osteoarthritis severity.Cohorts were paired 1:1 with patients without glenohumeral osteoarthritis.Patients included had a minimum two year follow-up.Rate of conversion to total shoulder arthroplasty,complication rates following initial surgery,and patient-reported outcome measures were collected.RESULTS A total of 142 patients were included.The number of patients that required total shoulder arthroplasty within two years after index surgery was low.2/71(2.8%) patients with GHOA,and 1/71(1.4%) without GHOA.Following rotator cuff repair,both groups showed favorable patientreported outcomes.CONCLUSION Patients with glenohumeral osteoarthritis who underwent arthroscopic rotator cuff repair showed comparable outcomes to patients without glenohumeral osteoarthritis. | Ian S Hong Allison J Rao Tyler L CarlLee Joshua D Meade Daniel J Hurwit Gregory Scarola David P Trofa Shadley C Schiffern Nady Hamid Patrick M Connor James E Fleischli Bryan Michael Saltzman | 2022 | World Journal of Orthopedics2022，13，7： | 2 |
| 12 | Abnormal liver chemistries as a predictor of COVID-19 severity and clinical outcomes in hospitalized patients显示文摘BACKGROUND Abnormal liver chemistries are common findings in patients with Coronavirus Disease 2019(COVID-19).However,the association of these abnormalities with the severity of COVID-19 and clinical outcomes is poorly understood AIM We aimed to assess the prevalence of elevated liver chemistries in hospitalized patients with COVID-19 and compare the serum liver chemistries to predict the severity and in-hospital mortality.METHODS This retrospective,observational study included 3380 patients with COVID-19 who were hospitalized in the Johns Hopkins Health System(Baltimore,MD,United States).Demographic data,clinical characteristics,laboratory findings,treatment measures,and outcome data were collected.Cox regression modeling was used to explore variables associated with abnormal liver chemistries on admission with disease severity and prognosis RESULTS A total of 2698(70.4%)had abnormal alanine aminotransferase(ALT)at the time of admission.Other more prevalent abnormal liver chemistries were aspartate aminotransferase(AST)(44.4%),alkaline phosphatase(ALP)(16.1%),and total bilirubin(T-Bil)(5.9%).Factors associated with liver injury were older age,Asian ethnicity,other race,being overweight,and obesity.Higher ALT,AST,T-Bil,and ALP levels were more commonly associated with disease severity.Multivariable adjusted Cox regression analysis revealed that abnormal AST and T-Bil were associated with the highest mortality risk than other liver injury indicators during hospitalization.Abnormal AST,T-Bil,and ALP were associated with a need for vasopressor drugs,whereas higher levels of AST,T-Bil,and a decreased albumin levels were associated with mechanical ventilation CONCLUSION Abnormal liver chemistries are common at the time of hospital admission in COVID-19 patients and can be closely related to the patient’s severity and prognosis.Elevated liver chemistries,specifically ALT,AST,ALP,and T-Bil levels,can be used to stratify risk and predict the need for advanced therapies in these patients. | Arunkumar Krishnan Laura Prichett Xueting Tao Saleh A Alqahtani James P Hamilton Esteban Mezey Alexandra T Strauss Ahyoung Kim James J Potter Po-Hung Chen Tinsay A Woreta | 2022 | World Journal of Gastroenterology2022，28，5： | 2 |
| 13 | The interaction between water movement,sediment dynamics and submersed macrophyte显示文摘 | MADSEN J D CHAMBERS P A JAMES W F | 2001 | Hydrobiologia2001，，444： | 1 |
| 14 | Quantitation of asbestos in synthetic mixtures using instrumental neutron activation analysis 显示文摘 | Pravin P P Richard J J James S W Thomas M S | 1992 | Analytical Chemistry1992，64，3： | 1 |
| 15 | Aluminm alloy 2519 in military vehicles显示文摘 | James J F Lawrence S K Joseph R P | 2002 | Advanced Materials and Processes2002，160，9： | 1 |
| 16 | Aluminum alloy 2519 in military vehicles显示文摘 | James J F Lawrence S K Joseph R P | 2002 | Advanced Materials and Processes2002，160，9： | 1 |
| 17 | Immobilized baker’s yeastreduction of ketones in an ionic liquid, PF6,and watermix显示文摘 | Howarth J James P Dai J F | 2001 | Tetrahedron Letters2001，42，42： | 1 |
| 18 | The Role of Lithosphere Mantle in the Generation of Late Cenozoic Basic Magmas in the Western United States显示文摘 | Fitton J G James D Kempton P D | 1988 | J Petrology1988，，1： | 1 |
| 19 | Diabetes specialist nurses and role evolvement:A survey by diabetes UK and ABCD of specialist diabetes services 2007显示文摘 | James J Winocour P Holt RIG | | 0，，： | 1 |
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