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| 1 | 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 |
| 2 | Increased hepcidin expression in colorectal carcinogenesis显示文摘AIM:To investigate whether the iron stores regulator hepcidin is implicated in colon cancer-associated anae- mia and whether it might have a role in colorectal car- cinogenesis. METHODS: Mass spectrometry (MALDI-TOF MS and SELDI-TOF MS) was employed to measure hepcidin in urine collected from 56 patients with colorectal cancer. Quantitative Real Time RT-PCR was utilised to determine hepcidin mRNA expression in colorectal cancer tissue. Hepcidin cellular localisation was determined using im- munohistochemistry. RESULTS: We demonstrate that whilst urinary hepcidin expression was not correlated with anaemia it was posi- tively associated with increasing T-stage of colorectal cancer (P < 0.05). Furthermore, we report that hepcidin mRNA is expressed in 34% of colorectal cancer tissue specimens and was correlated with ferroportin repres- sion. This was supported by hepcidin immunoreactivity in colorectal cancer tissue. CONCLUSION: We demonstrate that systemic hepcidin expression is unlikely to be the cause of the systemic anaemia associated with colorectal cancer. However, we demonstrate for the first time that hepcidin is expressed by colorectal cancer tissue and that this may represent a novel oncogenic signalling mechanism. | Douglas G Ward Keith Roberts Matthew J Brookes Howard Joy Ashley Martin Tariq Ismail Robert Spychal Tariq Iqbal Chris Tselepis | 2008 | World Journal of Gastroenterology2008，14，9： | 12 |
| 3 | No difference in mortality among ALPPS,two-staged hepatectomy,and portal vein embolization/ligation:A systematic review by updated traditional and network meta-analyses显示文摘Background:There is an ongoing debate on the feasibility,safety,and oncological efficacy of the associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)technique.The aim of this study was to compare ALPPS,two-staged hepatectomy(TSH),and portal vein embolization(PVE)/ligation(PVL)using updated traditional meta-analysis and network meta-analysis(NMA).Data sources:Electronic databases were used in a systematic literature search.Updated traditional metaanalysis and NMA were performed and compared.Mortality and major morbidity were selected as primary outcomes.Results:Nineteen studies including 1200 patients were selected from the pool of 436 studies.Of these patients,315(31%)and 702(69%)underwent ALPPS and portal vein occlusion(PVO),respectively.Ninetyday mortality based on updated traditional meta-analysis,subgroup analysis of the randomized controlled trials(RCTs),and both Bayesian and frequentist NMA did not demonstrate significant differences between the ALPPS cohort and the PVE,PVL,and TSH cohorts.Moreover,analysis of RCTs did not demonstrate significant differences of major morbidity between the ALPPS and PVO cohorts.The ALPPS cohort demonstrated significantly more favorable outcomes in hypertrophy parameters,time to operation,definitive hepatectomy,and R0 margins rates compared with the PVO cohort.In contrast,1-year disease-free survival was significantly higher in the PVO cohort compared to the ALPPS cohort.Conclusions:This study is the first to use updated traditional meta-analysis and both Bayesian and frequentist NMA and demonstrated no significant differences in 90-day mortality between the ALPPS and other hepatic hypertrophy approaches.Furthermore,two high quality RCTs including 147 patients demonstrated no significant differences in major morbidity between the ALPPS and PVO cohorts. | Paschalis Gavriilidis Robert P Sutcliffe Keith J Roberts Madhava Pai Duncan Spalding Nagy Habib Long R Jiao Mikael H Sodergren | 2020 | Hepatobiliary & Pancreatic Diseases International2020，19，5： | 6 |
| 4 | Recurrence and survival following microwave, radiofrequency ablation, and hepatic resection of colorectal liver metastases: A systematic review and network meta-analysis显示文摘Background: Gold standard for colorectal liver metastases(CRLM) remains hepatic resection(HR). However, patients with severe comorbidities, unresectable or deep-situated resectable CRLM are candidates for ablation. The aim of the study was to compare recurrence rate and survival benefit of the microwave ablation(MWA), radiofrequency ablation(RFA) and HR by conducting the first network meta-analysis. Data sources: Systematic search of the literature was conducted in the electronic databases. Both updated traditional and network meta-analyses were conducted and the results were compared between them. Results: HR cohort demonstrated significantly less local recurrence rate and better 3-and 5-year diseasefree(DFS) and overall survival(OS) compared to MWA and RFA cohorts. HR cohort included significantly younger patients and with significantly lower preoperative carcinoembryonic antigen(CEA) by 10.28 ng/m L compared to RFA cohort. Subgroup analysis of local recurrence and OS of solitary and ≤3 cm CRLMs did not demonstrate any discrepancies when compared with the whole sample. Conclusions: For resectable CRLM the treatment of choice still remains HR. MWA and RFA can be used as a single or adjunct treatment in patients with unresectable CRLM and/or prohibitive comorbidities. | Paschalis Gavriilidis Keith J Roberts Nicola de’Angelis Luca Aldrighetti Robert P Sutcliffe | 2021 | Hepatobiliary & Pancreatic Diseases International2021，20，4： | 4 |
| 5 | Double-blind randomized sham controlled trial of intraperitoneal bupivacaine during emergency laparoscopic cholecystectomy显示文摘BACKGROUND: Intraperitoneal local anesthesia (IPLA) during elective laparoscopic cholecystectomy (el-LC) decreases post-operative pain. None of the studies have explored the efficacy of IPLA at emergency laparoscopic cholecystectomy (em-LC). A longer operative duration, the greater frequency of washing, and the inflammation associated with cholecystitis or pancreatitis are a few reasons why it cannot be assumed that a benefit in pain scores will be seen in em-LC with IPLA. This study was undertaken to assess the efficacy of IPLA in patients undergoing em-LC. METHODS: Double-blind randomized sham controlled trial was conducted of 41 consecutive subjects undergoing em-LC. IPLA was delivered by a combination of injection to the diaphragmatic and topical wash over the liver and gallbladder with bupivacaine or saline. The primary outcome was visual analogue scale pain scores until discharge. Secondary outcomes included pain scores in theatre recovery and analgesic consumption. RESULTS: One patient had a procedure converted to open and was excluded. There was no significant difference in pain scores in the ward or theatre recovery. Analgesic use, respiratory rate, oxygen saturation, duration to ambulation, eating, satisfaction scores, and time to discharge were comparable between the two groups. CONCLUSIONS: IPLA during em-LC does not influence postoperative pain. Other modalities of analgesia should be explored for decreasing the interval between diagnosis of acute admission and em-LC. | Keith J Roberts Jeff Gilmour Ruplay Pande James Hodson For Tai Lam Saboor Khan | 2013 | Hepatobiliary & Pancreatic Diseases International2013，12，3： | 3 |
| 6 | Interactive labelling of a multivariate dataset for supervised machine learning using linked visualisations,clustering,and active learning显示文摘Supervised machine learning techniques require labelled multivariate training datasets.Many approaches address the issue of unlabelled datasets by tightly coupling machine learning algorithms with interactive visualisations.Using appropriate techniques,analysts can play an active role in a highly interactive and iterative machine learning process to label the dataset and create meaningful partitions.While this principle has been implemented either for unsupervised,semi-supervised,or supervised machine learning tasks,the combination of all three methodologies remains challenging.In this paper,a visual analytics approach is presented,combining a variety of machine learning capabilities with four linked visualisation views,all integrated within the mVis(multivariate Visualiser)system.The available palette of techniques allows an analyst to perform exploratory data analysis on a multivariate dataset and divide it into meaningful labelled partitions,from which a classifier can be built.In the workflow,the analyst can label interesting patterns or outliers in a semi-supervised process supported by active learning.Once a dataset has been interactively labelled,the analyst can continue the workflow with supervised machine learning to assess to what degree the subsequent classifier has effectively learned the concepts expressed in the labelled training dataset.Using a novel technique called automatic dimension selection,interactions the analyst had with dimensions of the multivariate dataset are used to steer the machine learning algorithms.A real-world football dataset is used to show the utility of mVis for a series of analysis and labelling tasks,from initial labelling through iterations of data exploration,clustering,classification,and active learning to refine the named partitions,to finally producing a high-quality labelled training dataset suitable for training a classifier.The tool empowers the analyst with interactive visualisations including scatterplots,parallel coordinates,similarity maps for records,and a new similarity map for partitions. | Mohammad Chegini Jürgen Bernard Philip Berger Alexei Sourin Keith Andrews Tobias Schreck | 2019 | Visual Informatics2019，3，1： | 3 |
| 7 | Pancreaticopleuralfistula:etiology,treatmentandlong-termfollow-up显示文摘BACKGROUND:Pancreaticopleural fistula(PPF) are uncommon.Complex multidisciplinary treatment is required due to nutritional compromise and sepsis.This is the first description of long-term follow-up of patients with PPF.METHODS:Eleven patients with PPF treated at a specialist unit were identified.Causation,investigation,treatment and outcomes were recorded.RESULTS:Pancreatitis was the etiology of the PPF in 9 patients,and in the remaining 2 the PPF developed following distal pancreatectomy.Cross-sectional imaging demonstrated the site of duct disruption in 10 cases,with endoscopic retrograde cholangiopancreatography identifying the final case.Suppression of pancreatic exocrine secretion and percutaneous drainage formed the mainstay of treatment.Five cases resolved following pancreatic duct stent insertion and three patients required surgical treatment for established empyema.There were no complications.In all cases that resolved there has been no recurrence of PPF over a median follow-up of 50 months(range 15-62).CONCLUSIONS:PPF is an uncommon event complicating pancreatitis or pancreatectomy;pancreatic duct disruption is the common link.A step-up approach consisting of minimally invasive techniques treats the majority with surgery needed for refractory sepsis. | Keith J Roberts Maria Sheridan Gareth Morris-Stiff Andrew M Smith | 2012 | Hepatobiliary & Pancreatic Diseases International2012，11，2： | 2 |
| 8 | Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial显示文摘 | Friedrich W Mohr Marie-Claude Morice A Pieter Kappetein Ted E Feldman Elisabeth St?hle Antonio Colombo Michael J Mack David R Holmes Marie-angèle Morel Nic Van Dyck Vicki M Houle Keith D Dawkins Patrick W Serruys | 2013 | The Lancet . 2013 (9867)2013，，9867： | 2 |
| 9 | 基于一个大型随机试验预测稳定性心绞痛队列患者死亡、心肌梗死和卒中的危险评分显示文摘目的对需要抗心绞痛治疗并且左心室功能代偿症状稳定的心绞痛患者建立预测全因死亡、心肌梗死和导致致残性卒中的复合危险评分。设计大型多中心临床试验数据的多变量Cox回归分析。背景西欧、以色列、加拿大、澳大利亚和新西兰的心脏专科门诊患者。入选者7311例具有全部需要资料的患者被入选。主要结局的测量指标平均随访4.9年时间内所有原因的死亡、心肌梗死或者致残性卒中。结果1063例患者发生任何原因死亡或者持久性心肌梗死或者致残性卒中。这些复合终点的5年危险性在危险性最低的十分位患者为4%,而在危险性最高的十分位患者为35%。危险评分结合16项临床常规变量的降序排序是:年龄、左心室射血分数、吸烟、白细胞计数、糖尿病、随机血糖浓度、肌酐浓度、既往卒中病史、1周至少1次心绞痛发作、冠状动脉造影发现(如果能够获得)、降脂治疗、QT间期、收缩期血压≥150mmHg、抗心绞痛药物数量、陈旧性心肌梗死以及性别。把这个模型分别应用于任何原因所致的死亡、心肌梗死和卒中进行预测评估,所得的结果相似。危险评分似乎不能预测事件性质(39%的死亡、46%心肌梗死以及15%致残性卒中)或者冠状动脉造影或血管重建率(占29%的患者)。结论该危险评分对客观地决定稳定性心绞痛患者进一步治疗措施以减少重要预后事件发生是有帮助的。该危险评分同样可以用于将来的计划性试验。 | Tim C Clayton Stuart J Pocock Jacobus Lubsen Zoltán Vokó Bridget-Anne Kirwan Keith A A Fox Philip A Poole-Wilson | 2006 | 英国医学杂志中文版2006，9，1： | 2 |
| 10 | Transepithelial leak in Barrett's esophagus patients: The role of proton pump inhibitors显示文摘AIM: To determine if the observed paracellular sucrose leak in Barrett's esophagus patients is due to their proton pump inhibitor (PPI) use. METHODS: The in vivo sucrose permeability test was administered to healthy controls, to Barrett's patients and to non-Barrett's patients on continuous PPI therapy. Degree of leak was tested for correlation with presence of Barrett's, use of PPIs, and length of Barrett's segment and duration of PPI use. RESULTS: Barrett's patients manifested a near 3-fold greater, upper gastrointestinal sucrose leak than healthy controls. A decrease of sucrose leak was observed in Barrett's patients who ceased PPI use for 7 d.Although initial introduction of PPI use (in a PPI-na ve population) results in dramatic increase in sucrose leak, long-term, continuous PPI use manifested a slow spontaneous decline in leak. The sucrose leak observed in Barrett's patients showed no correlation to the amount of Barrett's tissue present in the esophagus. CONCLUSION: Although future research is needed to determine the degree of paracellular leak in actual Barrett's mucosa, the relatively high degree of leak observed with in vivo sucrose permeability measurement of Barrett's patients reflects their PPI use and not their Barrett's tissue per se . | Christopher Farrell Melissa Morgan Owen Tully Kevin Wolov Keith Kearney Benjamin Ngo Giancarlo Mercogliano James J Thornton Mary Carmen Valenzano James M Mullin | 2012 | World Journal of Gastroenterology2012，18，22： | 2 |
| 11 | Targeting telomerase for cancer therapeutics显示文摘 | Shay J W Keith W N | 2008 | Br J Cancer2008，98，4： | 1 |
| 12 | Employee performance cues in a hotel service environment: influence on perceived service quality, value, and word-of-mouth intentions显示文摘 | Michael D H Keith C J | 1996 | Journal of Business Research1996，35，6： | 1 |
| 13 | Effects of soil phosphorous availability,temperature and moisture on soil respiration in Eucalyptus pauciflora forest显示文摘 | Keith H Jacobsen L Raison R J | 1997 | Plant and Soil1997，190，1： | 1 |
| 14 | RolEnact:role-basedenactable models of business processes显示文摘 | KEITH T PETER H ROBERT J | 1998 | Information and Soft-ware Technology1998，40，3： | 1 |
| 15 | Cloning of a delta opioid receptor by functional expression显示文摘 | Evans C J Keith D E Morrison H | 1992 | Science1992，258，5090： | 1 |
| 16 | Isotopic composition and environment classification of selected limestone and fossils显示文摘 | Keith M H Weber J H | 1964 | Geochemical Cosmochimica Acta1964，28，： | 1 |
| 17 | Effects of tensile loading on the properties of elastic-wave propagation in a strand显示文摘 | Kwun H Keith A B Hanley J J | 1998 | Journal of the Acoustical Society of A meriea1998，103，6： | 1 |
| 18 | Multiple pulmonary nodules in AIDS:usefulness of CT in distinguishing among potential causes显示文摘 | Keith J Edinburgh MD Robert M | 2000 | Radiology2000，214，2： | 1 |
| 19 | Predicting the ther mal conductivity of multiple carbon fillers in polypropylene- based resins 显示文摘 | Gaxiola D L Keith J M Mo Na | 2011 | J Compos Mater2011，45，12： | 1 |
| 20 | HPLC determi- nation of catechins in tea leaves and tea extracts using relative re- sponse factors显示文摘 | Wang Huafu Provan Gordon J Helliwell Keith | 2003 | Food Chemistry2003，81，11： | 1 |
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