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| 1 | Molecular mechanisms of viral hepatitis induced hepatocellular carcinoma显示文摘Chronic infection with viral hepatitis affects half a billion individuals worldwide and can lead to cirrhosis,cancer,and liver failure.Liver cancer is the third leading cause of cancer-associated mortality,of which hepatocellular carcinoma(HCC)represents 90%of all primary liver cancers.Solid tumors like HCC are complex and have heterogeneous tumor genomic profiles contributing to complexity in diagnosis and management.Chronic infection with hepatitis B virus(HBV),hepatitis delta virus(HDV),and hepatitis C virus(HCV)are the greatest etiological risk factors for HCC.Due to the significant role of chronic viral infection in HCC development,it is important to investigate direct(viral associated)and indirect(immune-associated)mechanisms involved in the pathogenesis of HCC.Common mechanisms used by HBV,HCV,and HDV that drive hepatocarcinogenesis include persistent liver inflammation with an impaired antiviral immune response,immune and viral protein-mediated oxidative stress,and deregulation of cellular signaling pathways by viral proteins.DNA integration to promote genome instability is a feature of HBV infection,and metabolic reprogramming leading to steatosis is driven by HCV infection.The current review aims to provide a brief overview of HBV,HCV and HDV molecular biology,and highlight specific viral-associated oncogenic mechanisms and common molecular pathways deregulated in HCC,and current as well as emerging treatments for HCC. | Simmone D'souza Keith CK Lau Carla S Coffin Trushar R Patel | 2020 | World Journal of Gastroenterology2020，26，38： | 25 |
| 2 | Cancer risk in primary sclerosing cholangitis: Epidemiology,prevention, and surveillance strategies显示文摘Primary sclerosing cholangitis(PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra-and/or extrahepatic biliary ducts. While its features and disease course can be variable,most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly,PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma,hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion. | Brian M Fung Keith D Lindor James H Tabibian | 2019 | World Journal of Gastroenterology2019，25，6： | 15 |
| 3 | 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 |
| 4 | NAFLD fibrosis score:A prognostic predictor for mortality and liver complications among NAFLD patients显示文摘AIM:To study whether the severity of liver fibrosis estimated by the nonalcoholic fatty liver disease(NAFLD) fibrosis score can predict all-cause mortality,cardiac complications,and/or liver complications of patients with NAFLD over long-term follow-up.METHODS:A cohort of well-characterized patients with NAFLD diagnosed during the period of 1980-2000 was identified through the Rochester Epidemiology Project.The NAFLD fibrosis score(NFS) was used to separate NAFLD patients with and without advanced liver fibrosis.We used the NFS score to classify the probability of fibrosis as <-1.5 for low probability,>-1.5 to < 0.67 for intermediate probability,and > 0.67 for high probability.Primary endpoints included allcause death and cardiovascular-and/or liver-related mortality.From the 479 patients with NAFLD assessed,302 patients(63%) greater than 18 years old were included.All patients were followed,and medical charts were reviewed until August 31,2009 or the date when the first primary endpoint occurred.By using a standardized case record form,we recorded a detailed history and physical examination and the use of statins and metformin during the follow-up period.RESULTS:A total of 302/479(63%) NAFLD patients(mean age:47 ± 13 year) were included with a followup period of 12.0 ± 3.9 year.A low probability of advanced fibrosis(NFS <-1.5 at baseline) was found in 181 patients(60%),while an intermediate or high probability of advanced fibrosis(NSF >-1.5) was found in 121 patients(40%).At the end of the follow-up period,55 patients(18%) developed primary endpoints.A total of 39 patients(13%) died during the follow-up.The leading causes of death were non-hepatic malignancy(n = 13/39;33.3%),coronary heart disease(CHD)(n = 8/39;20.5%),and liver-related mortality(n = 5/39;12.8%).Thirty patients had new-onset CHD,whereas 8 of 30 patients(27%) died from CHD-related causes during the follow-up.In a multivariate analysis,a higher NFS at baseline and the presence of new-onset CHD were significantly predictive of death(OR = 2.6 and 9.2,respectively;P < 0.0001).Our study showed a significant,graded relationship between the NFS,as classified into 3 subgroups(low,intermediate and high probability of liver fibrosis),and the occurrence of primary endpoints.The use of metformin or simvastatin for at least 3 mo during the follow-up was associated with fewer deaths in patients with NAFLD(OR = 0.2 and 0.03,respectively;P < 0.05).Additionally,the rate of annual NFS change in patients with an intermediate or high probability of advanced liver fibrosis was significantly lower than those patients with a low probability of advanced liver fibrosis(0.06 vs 0.09,P = 0.004).The annual NFS change in patients who died was significantly higher than those in patients who survived(0.14 vs 0.07,P = 0.03).At the end of the follow-up,we classified the patients into 3 subgroups according to the progression pattern of liver fibrosis by comparing the NFS at baseline to the NFS at the end of the followup period.Most patients were in the stable-fibrosis(60%) and progressive-fibrosis(37%) groups,whereas only 3% were in the regressive fibrosis.CONCLUSION:A higher NAFLD fibrosis score at baseline and a new onset of CHD were significantly predictive of death in patients with NAFLD. | Sombat Treeprasertsuk Einar Bjrnsson Felicity Enders Sompongse Suwanwalaikorn Keith D Lindor | 2013 | World Journal of Gastroenterology2013，19，8： | 13 |
| 5 | Clinical features and management of primary sclerosing cholangitis显示文摘Primary sclerosing cholangitis is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts,resulting in cirrhosis and need for liver transplantation and reduced life expectancy.The majority of cases occur in young and middle-aged men,often in association with inflammatory bowel disease.The etiology of primary sclerosing cholangitis includes immune-mediated components and elements of undefined nature.No effective medical therapy has been identified.The multiple complications of primary sclerosing cholangitis include metabolic bone disease,dominant strictures,bacterial cholangitis,and malignancy,particularly cholangiocarcinoma,which is the most lethal complication of primary sclerosing cholangitis.Liver transplantation is currently the only life-extending therapeutic alternative for patients with end-stage disease,although recurrence in the allografted liver has been described.A PSC-like variant attracting attention is cholangitis marked by raised levels of the immunoglobulin G4 subclass,prominence of plasma cells within the lesions,and steroid responsiveness. | Marina G Silveira Keith D Lindor | 2008 | World Journal of Gastroenterology2008，14，21： | 9 |
| 6 | Dynamic chromatin states in human ES cells reveal potential regulatory sequences and genes involved in pluripotency显示文摘Pluripotency,一个细胞的能力区分并且产生所有胚胎的系,定义象胚胎的茎(ES ) 那样的哺乳动物的细胞类型的一个小数字细胞。当它通常被保持了时,那 pluripotency 是 transcriptional 的产品激活并且维持关键干细胞基因的表达式的规章的网络,积累的证据在建立并且保卫 ES 房间的 pluripotency 为 epigenetic 进程正在指向一个关键角色,象维持区分的房间类型的身份一样。以便更好在 pluripotency 理解 epigenetic 机制的角色,我们检验了在经历区别进一个 mesendodermal 系的人的 ES 房间(hESCs ) 染色体宽的染色质修正的动力学。我们发现在倡导者的染色质修正在区别期间仍然保持大部分不变,除了在在在 H3K27 的 acetylation 和 methylation 之间的一个动态开关标记在基因表示的激活和 silencing 之间的转变的倡导者的一个小数字,建议在在大多数差别上的房间命运承诺的一个层次表示了基因。我们也在 50 000 潜在的 enhancers 上印射,并且在染色质修正,特别 H3K4me1 和 H3K27ac 观察了大得多的动力学,它与他们的潜在的目标基因的表示相关。这些 enhancers 的进一步的分析揭示了 pluripotency 和可以在 hESCs 授与发展胜任的一个平衡状态的一口染色质签名陈述语气的潜在地关键的 transcriptional 管理者。我们的结果提供在定义 enhancers 和 pluripotency 支持染色质修正的角色的新证据。 | R David Hawkins Gary C Hon Chuhu Yang Jessica E Antosiewicz-Bourget Leonard K Lee Que-Minh Ngo Sarit Klugman Keith A Ching Lee E Edsall Zhen Ye Samantha Kuan Pengzhi Yu Hui Liu Xinmin Zhang Roland D Green Victor V Lobanenkov Ron Stewart James A Thomson Bing Ren | 2011 | Cell Research2011，21，10： | 6 |
| 7 | Impact of a simulation-based induction programme in gastroscopy on trainee outcomes and learning curves显示文摘BACKGROUND Pre-clinical simulation-based training(SBT)in endoscopy has been shown to augment trainee performance in the short-term,but longer-term data are lacking.AIM To assess the impact of a two-day gastroscopy induction course combining theory and SBT(Structured PRogramme of INduction and Training–SPRINT)on trainee outcomes over a 16-mo period.METHODS This prospective case-control study compared outcomes between novice SPRINT attendees and controls matched from a United Kingdom training database.Study outcomes comprised:(1)Unassisted D2 intubation rates;(2)Procedural discomfort scores;(3)Sedation practice;(4)Time to 200 procedures;and(5)Time to certification.RESULTS Total 15 cases and 24 controls were included,with mean procedure counts of 10 and 3(P=0.739)pre-SPRINT.Post-SPRINT,no significant differences between the groups were detected in long-term D2 intubation rates(P=0.332)or discomfort scores(P=0.090).However,the cases had a significantly higher rate of unsedated procedures than controls post-SPRINT(58%vs 44%,P=0.018),which was maintained over the subsequent 200 procedures.Cases tended to perform procedures at a greater frequency than controls in the post-SPRINT period(median:16.2 vs 13.8 per mo,P=0.051),resulting in a significantly greater proportion of cases achieving gastroscopy certification by the end of follow up(75% vs 36%,P=0.017).CONCLUSION In this pilot study,attendees of the SPRINT cohort tended to perform more procedures and achieved gastroscopy certification earlier than controls.These data support the role for wider evaluation of pre-clinical induction involving SBT. | Keith Siau James Hodson Peter Neville Jeff Turner Amanda Beale Susi Green Aravinth Murugananthan Paul Dunckley Neil D Hawkes | 2020 | World Journal of Gastrointestinal Endoscopy2020，12，3： | 2 |
| 8 | Neuromuscular scoliosis and pelvic fixation in 2015: Where do we stand?显示文摘Neuromuscular scoliosis is a challenging problem to treat in a heterogeneous patient population. When thedecision is made for surgery the surgeon must select a technique employed to correct the curve and achieve the goals of surgery, namely a straight spine over a level pelvis. Pre-operatively the surgeon must ask if pelvic fixation is worth the extra complications and infection risk it introduces to an already compromised host. Since the advent of posterior spinal fusion the technology used for instrumentation has changed drastically. However, many of the common problems seen with the unit rod decades ago we are still dealing with today with pedicle screw technology. Screw cut out, pseudoarthrosis, non-union, prominent hardware, wound complications, and infection are all possible complications when extending a spinal fusion construct to the pelvis in a neuromuscular scoliosis patient. Additionally, placing pelvic fixation in a neuromuscular patient results in extra blood loss, greater surgical time, more extensive dissection with creation of a deep dead space, and an incision that extends close to the rectum in patients who are commonly incontinent. Balancing the risk of placing pelvic fixation when the benefit, some may argue, is limited in non-ambulating patients is difficult when the literature is so mottled. Despite frequent advancements in technology issues with neuromuscular scoliosis remain the same and in the next 10 years we must do what we can to make safe neuromuscular spine surgery a reality. | Jason B Anari David A Spiegel Keith D Baldwin | 2015 | World Journal of Orthopedics2015，6，8： | 2 |
| 9 | Effects of Ionic Strength, Temperature, and pH on Degradation of Selected Antibiotics显示文摘 | Loftin Keith A Adams Craig D Meyer Michael T Surampalli Rao | 2008 | Journal of Environmental Quality2008，，2： | 2 |
| 10 | Induction of a high incidence of lung tumors in C57BL/6 mice with multiple ethyl carbamate injections显示文摘 | York E Miller Lori D Dwyer-Nield Robert L Keith Mysan Le Wilbur A Franklin Alvin M Malkinson | 2003 | Cancer Letters2003，，2： | 2 |
| 11 | Lymphoepithelial cysts and cystic lymphangiomas: Underrecognized benign cystic lesions of the pancreas显示文摘AIM: To identify their diagnostic and prognostic clinical characteristics in a large series.METHODS: Retrospective review of clinicopathologic and imaging characteristics of patients diagnosed with lymphoepithelial cysts and cystic lymphangiomas of the pancreas at Massachusetts General Hospital.RESULTS: Twelve patients were identified between 1/1/1997 and 8/1/2007. Their median age was 55.5 years(range 19-78 years), and 6 were females. The le-sion was incidentally discovered in half of the patients.Contrast enhanced computed tomography demonstrat-ed that the cysts had thin walls, without calcifications, pancreatic duct dilation or pancreatic parenchyma inva-sion. Endoscopic ultrasound with fine needle aspiration(EUS/FNA) confirmed the diagnosis of a lymphoepithe-lial cyst in 3 patients, one of whom was spared an op-eration and continues to do well after 6 years. Eleven patients had a resection: 3 pancreaticoduodenecto-mies, 7 distal pancreatectomies, and 1 enucleation. The median size of the cysts was 3 cm(range 2-20 cm). At a median follow-up of 57 mo no recurrences or other pancreas-related conditions occurred.CONCLUSION: Lymphoepithelial cysts and cystic lymphangiomas of the pancreas can be diagnosed with a combination of contrast-enhanced computed tomog-raphy scans and EUS/FNA. If the lesion is asymptom-atic, an operation might be avoided. | Ioannis T Konstantinidis Avinash Kambadakone Onofrio A Catalano Dushyant V Sahani Vikram Deshpe David G Forcione Jennifer A Wargo Carlos Fernandez-del Castillo Keith D Lillemoe Andrew L Warshaw Cristina R Ferrone | 2014 | World Journal of Gastrointestinal Surgery2014，6，7： | 2 |
| 12 | Analytical methods for detection of selected estrogenic compounds in aqueous mixtures 显示文摘 | Snyder S A Keith T L Verbrugge D A | 1999 | Environ Sci Technol1999，33，16： | 2 |
| 13 | 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 |
| 14 | 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 |
| 15 | On the role of Mn (IV) vacancies in the photoreductive dissolution of hexagonal birnessite显示文摘 | KIDEOK D K KEITH R GARRISON S | 2009 | Geochimica et Cosmochimica Acta2009，73，： | 1 |
| 16 | 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 |
| 17 | Toxoplasma gondii:a protozoan for the nineties显示文摘 | Keith A Jean D | 1993 | Infect Immun1993，61，4： | 1 |
| 18 | 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 |
| 19 | Managing temperate forests for carbon storage:impacts of logging versus forest protection on carbon stocks显示文摘 | Keith H Lindenmayer D Mackey B | 2014 | Ecosphere2014，5，6： | 1 |
| 20 | Toxoplasma gondii:a protozoan for the nineties显示文摘 | Keith A Jean D | 1993 | Infect Immun1993，61，4： | 1 |
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