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| 1 | Golgi protein-73:A biomarker for assessing cirrhosis and prognosis of liver disease patients显示文摘BACKGROUND Reliable biomarkers of cirrhosis,hepatocellular carcinoma(HCC),or progression of chronic liver diseases are missing.In this context,Golgi protein-73(GP73)also called Golgi phosphoprotein-2,was originally defined as a resident Golgi type II transmembrane protein expressed in epithelial cells.As a result,GP73 expression was found primarily in biliary epithelial cells,with only slight detection in hepatocytes.However,in patients with acute or chronic liver diseases and especially in HCC,the expression of GP73 is significantly up-regulated in hepatocytes.So far,few studies have assessed GP73 as a diagnostic or prognostic marker of liver fibrosis and disease progression.AIM To assess serum GP73 efficacy as a diagnostic marker of cirrhosis and/or HCC or as predictor of liver disease progression.METHODS GP73 serum levels were retrospectively determined by a novel GP73 ELISA(QUANTA Lite®GP73,Inova Diagnostics,Inc.,Research Use Only)in a large cohort of 632 consecutive patients with chronic viral and non-viral liver diseases collected from two tertiary Academic centers in Larissa,Greece(n=366)and Debrecen,Hungary(n=266).Aspartate aminotransferase(AST)/Platelets(PLT)ratio index(APRI)was also calculated at the relevant time points in all patients.Two hundred and three patients had chronic hepatitis B,183 chronic hepatitis C,198 alcoholic liver disease,28 autoimmune cholestatic liver diseases,15 autoimmune hepatitis,and 5 with other liver-related disorders.The duration of follow-up was 50(57)mo[median(interquartile range)].The development of cirrhosis,liver decompensation and/or HCC during follow-up were assessed according to internationally accepted guidelines.In particular,the surveillance for the development of HCC was performed regularly with ultrasound imaging and alpha-fetoprotein(AFP)determination every 6 mo in cirrhotic and every 12 mo in non-cirrhotic patients.RESULTS Increased serum levels of GP73(>20 units)were detected at initial evaluation in 277 out of 632 patients(43.8%).GP73-seropositivity correlated at baseline with the presence of cirrhosis(96.4%vs 51.5%,P<0.001),decompensation of cirrhosis(60.3%vs 35.5%,P<0.001),presence of HCC(18.4%vs 7.9%,P<0.001)and advanced HCC stage(52.9%vs 14.8%,P=0.002).GP73 had higher diagnostic accuracy for the presence of cirrhosis compared to APRI score[Area under the curve(AUC)(95%CI):0.909(0.885-0.934)vs 0.849(0.813-0.886),P=0.003].Combination of GP73 with APRI improved further the accuracy(AUC:0.925)compared to GP73(AUC:0.909,P=0.005)or APRI alone(AUC:0.849,P<0.001).GP73 levels were significantly higher in HCC patients compared to non-HCC[22.5(29.2)vs 16(20.3)units,P<0.001)and positively associated with BCLC stage[stage 0:13.9(10.8);stage A:17.1(16.8);stage B:19.6(22.3);stage C:32.2(30.8);stage D:45.3(86.6)units,P<0.001]and tumor dimensions[very early:13.9(10.8);intermediate:19.6(18.4);advanced:29.1(33.6)units,P=0.004].However,the discriminative ability for HCC diagnosis was relatively low[AUC(95%CI):0.623(0.570-0.675)].Kaplan-Meier analysis showed that the detection of GP73 in patients with compensated cirrhosis at baseline,was prognostic of higher rates of decompensation(P=0.036),HCC development(P=0.08),and liver-related deaths(P<0.001)during follow-up.CONCLUSION GP73 alone appears efficient for detecting cirrhosis and superior to APRI determination.In combination with APRI,its diagnostic performance can be further improved.Most importantly,the simple GP73 measurement proved promising for predicting a worse outcome of patients with both viral and nonviral chronic liver diseases. | Nikolaos K Gatselis Tamás Tornai Zakera Shums Kalliopi Zachou Asterios Saitis Stella Gabeta Roger Albesa Gary L Norman Mária Papp George N Dalekos | 2020 | World Journal of Gastroenterology2020,26,34: | 21 |
| 2 | 针对患者利益的机器学习和人工智能研究:在透明性、可重复性、伦理和有效性等方面的20个关键问题显示文摘机器学习(ML)、人工智能(AI)和其他现代统计方法正为利用先前尚未开发且极速增长的数据资源提供新的机会,以期让患者获益。尽管目前正在进行许多有前景的研究,特别是在图像方面,但就文献整体而言还缺乏透明度、对可重复性清晰的阐述、对潜在伦理问题的探究,以及对有效性的明确验证。这些问题的存在有许多原因,其中最重要的一点(为此我们提供了初步解决方案)就是当前缺乏针对ML和AI的最佳实践指南。我们认为从事研究的跨学科团队和应用ML/AI影响健康的项目,将因解决有关透明度、可重复性、伦理和有效性(TREE)的一系列问题而受益。这里提出的20个关键问题为研究团队提供了一个研究设计、实施和报告框架;帮助编辑和同行评审专家评估文献的贡献;让患者、临床医生和政策制定者评估新发现可能会给患者带来的获益。 | Sebastian Vollmer Bilal A Mateen Gergo Bohner Franz J Kirdly Rayid Ghani Pall Jonsson Sarah Cumbers Adrian Jonas Katherine S L McAllister Puja Myles David Granger Mark Birse Richard Branson Karel G M Moons Gary S Collins John P A Chris Holmes Harry Hemingwayp 李峰(译) 徐磊(校) 赵邑(校) | 2020 | 英国医学杂志中文版2020,23,9: | 5 |
| 3 | Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion显示文摘Ischaemia-reperfusion injury(IRI) is the leading cause of injury seen in the liver following transplantation. IRI also causes injury following liver surgery and haemodynamic shock. The first cells within the liver to be injured by IRI are the liver sinusoidal endothelial cells(LSEC). Recent evidence suggests that LSEC coordinate and regulates the livers response to a variety of injuries. It is becoming increasingly apparent that the cyto-protective cellular process of autophagy is a key regulator of IRI. In particular LSEC autophagy may be an essential gatekeeper to the development of IRI. The recent availability of liver perfusion devices has allowed for the therapeutic targeting of autophagy to reduce IRI. In particular normothermic machine liver perfusion(NMP-L) allow the delivery of pharmacological agents to donor livers whilst maintaining physiological temperature and hepatic flow rates. In this review we summarise the current understanding of endothelial autophagy and how this may be manipulated during NMP-L to reduce liver IRI. | Yuri L Boteon Richard Laing Hynek Mergental Gary M Reynolds Darius F Mirza Simon C Afford Ricky H Bhogal | 2017 | World Journal of Gastroenterology2017,23,48: | 4 |
| 4 | Outcomes of Roux-en-Y gastric bypass and laparoscopic adjustable gastric banding显示文摘AIM:To evaluate weight loss and surgical outcomes of Roux-en-Y gastric bypass(RYGB)and laparoscopic adjustable gastric band(LAGB).METHODS:Data relating to changes in body mass index(BMI)and procedural complications after RYGB(1995-2009;n=609;116M:493F;42.4±0.4 years)or LAGB(2004-2009;n=686;131M:555F;37.2±0.4years)were extracted from prospective databases.RESULTS:Pre-operative BMI was higher in RYGB than LAGB patients(46.8±7.1 kg/m2vs 40.4±4.2 kg/m2,P<001);more patients with BMI<35 kg/m2underwent LAGB than RYGB(17.1%vs 4.1%,P<0.0001).BMI decrease was greater after RYGB.There were direct relationships between weight loss and pre-operative BMI(P<0.001).Although there was no difference in weight loss between genders during the first 3-year post-surgery,male LAGB patients had greater BMI reduction than females(-8.2±4.3 kg/m2vs-3.9±1.9kg/m2,P=0.02).Peri-operative complications occurred more frequently following RYGB than LAGB(8.0%vs0.5%,P<0.001);majority related to wound infection.LAGB had more long-term complications requiring corrective procedures than RYGB(8.9%vs 2.1%,P<0.001).Conversion to RYGB resulted in greater BMI reduction(-9.5±3.8 kg/m2)compared to removal and replacement of the band(-6.0±3.0 kg/m2).Twelve months post-surgery,fasting glucose,total cholesterol and low density lipoprotein levels were significantly lower with the magnitude of reduction greater in RYGB patients.CONCLUSION:RYGB produces substantially greater weight loss than LAGB.Whilst peri-operative complications are greater after RYGB,long-term complication rate is higher following LAGB. | Nam Q Nguyen Philip Game Justin Bessell Tamara L Debreceni Melissa Neo Carly M Burgstad Pennie Taylor Gary A Wittert | 2013 | World Journal of Gastroenterology2013,19,36: | 3 |
| 5 | Inflammation and Alzheimer’s disease显示文摘 | Haruhiko Akiyama Steven Barger Scott Barnum Bonnie Bradt Joachim Bauer Greg M Cole Neil R Cooper Piet Eikelenboom Mark Emmerling Berndt L Fiebich Caleb E Finch Sally Frautschy W.S.T Griffin Harald Hampel Michael Hull Gary Landreth Lih–Fen Lue Robert Mrak | 2000 | Neurobiology of Aging2000,,3: | 2 |
| 6 | Comprehensive review of autoantibodies in patients with hyper-IgM syndrome显示文摘Hyper-immunoglobulin M syndrome is an X-linked primary immunodeficiency disease caused by mutations in the CD40 ligand gene.The CD40 ligand has been recently highlighted as playing a key role in the pathogenesis of primary biliary cholangitis.In the present study,we assessed an extensive set of serum autoantibodies in a series of well-defined patients with hyper-immunoglobulin M syndrome.Serum,liver-related and liver-not-related autoantibodies IgG,IgM and IgA were tested by ELISA and standard indirect immunofluorescence in HEp-2 cells in 13 Tunisian patients(8 males and 5 females,aged 1–12 years)with hyper-immunoglobulin M syndrome during 1995–2012 and,as controls,21 age-and gender-matched blood donors.The level of IgM antibody against MIT3 was significantly higher in patients than in controls(35.8 vs 10.7,P=0.002).Half of the hyperimmunoglobulin M syndrome patients were found to be anti-MIT3 IgM positive vs none of the controls(Po0.0001).Twenty-three percent of patients were found to be anti-sp100 antibody positive vs only 0.05%of controls.By immunofluorescence,92.3%of patients were MIT3 IgM positive vs none of the controls.In conclusion,the IgM class of anti-MIT3 antibodies was shown to be present by both ELISA and immunofluorescence in most of the patients with hyper-immunoglobulin M syndrome.The presence of the hallmark of primary biliary cholangitis,a disease where the CD40 ligand is a key player,in an immunodeficiency disease caused by mutations in the CD40 ligand gene is very intriguing and opens new scenarios in understanding the immune pathogenesis of primary biliary cholangitis. | Mohamed-Ridha Barbouche Qubo Chen Marco Carbone Imen Ben-Mustapha Zakera Shums Mehdi Trifa Federica Malinverno Francesca Bernuzzi Haiyan Zhang Nourhen Agrebi Gary L Norman Christopher Chang M Eric Gershwin Pietro Invernizzi | 2018 | Cellular & Molecular Immunology2018,15,6: | 2 |
| 7 | Cancer Genome Scanning in Plasma: Detection of Tumor-Associated Copy Number Aberrations, Single-Nucleotide Variants, and Tumoral Heterogeneity by Massively Parallel Sequencing显示文摘 | Chan K C Allen Jiang Peiyong Zheng Yama W L Liao Gary J W Sun Hao Wong John Siu Shing Shun N Chan Wing C Chan Stephen L Chan Anthony T C Lai Paul B S Chiu Rossa W K Lo Y M D | 2013 | Clinical Chemistry2013,,1: | 2 |
| 8 | Depressive symptoms and metabolic control in African 一 Americans with type 2 diabetes 显示文摘 | Gary T L Crum R M Cooper-Patrick L | 2000 | Diabetes Care2000,23,1: | 1 |
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| 17 | Characterization of polyploid wheat genomic diversity using a high-density 90 000 single nucleotide polymorphism array 显示文摘 | Wang SC Debbie W Kerrie F Alexandra A Shiaoman C Bevan EH Marco M Silvio S Sara GM Luigi C Anna MM Alex W Stuart S Gary B Ralf W Joerg P International Wheat Genome Sequencing Consortium Morten L Diane M Rudi A Rudy D Gina BG Abraham K Alina RA Catherine F Jerome S Michele M Curtis P Luo MC Jan DMM Jorge D Martin G Roberto T Cindy L Ivan M Colin C Keith JE Matthew H Eduard A | 2014 | Plant Biotechnol J2014,12,: | 1 |
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