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| 1 | 植物表型组学:发展、现状与挑战显示文摘随着遥感、机器人技术、计算机视觉和人工智能的发展,植物表型组学研究已经步入了快速成长阶段。本文首先介绍了植物表型组学的发展简史,包括其理论核心、研究方法、在生物研究中的应用以及国际上最新的研究动向。然后,针对各类表型技术载体平台如手持、人载、车载、田间实时监控、大型室内外自动化平台和航空机载等,分析这些技术手段在室内、外植物研究中的应用情况和实际问题。为了对表型研究中产生的巨量图像和传感器数据进行量化分析,把大数据转化为有实际意义的性状信息和生物学知识,本文着重讨论了后期表型数据解析和相应的研发过程。最后,提出表型组学的应用前景与未来展望,以期为中国的表型研究提供指导和建议。 | 周济 Francois Tardieu Tony Pridmore John Doonan Daniel Reynolds Neil Hall Simon Griffiths 程涛 朱艳 王秀娥 姜东 丁艳锋 | 2018 | 南京农业大学学报2018，41，4： | 64 |
| 2 | 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 |
| 3 | The second European evidence-based Consensus on the diagnosis and management of Crohn’s disease: Definitions and diagnosis显示文摘 | Gert Van Assche Axel Dignass Julian Panes Laurent Beaugerie John Karagiannis Mathieu Allez Thomas Ochsenkühn Tim Orchard Gerhard Rogler Edouard Louis Limas Kupcinskas Gerassimos Mantzaris Simon Travis Eduard Stange | 2009 | Journal of Crohn’s and Colitis2009，，1： | 10 |
| 4 | Technical and conceptual considerations forusing animated stimuli in studies of animalbehavior显示文摘Rapid technical advances in the field of computeropened new avenues in animal behavior research.animation (CA) and virtual reality (VR) haveAnimated stimuli are powerful tools as theyoffer standardization, repeatability, and complete control over the stimulus presented, thereby"reducing" and "replacing" the animals used, and "refining" the experimental design in line withthe 3Rs. However, appropriate use of these technologies raises conceptual and technical questions.In this review, we offer guidelines for common technical and conceptual considerations related tothe use of animated stimuli in animal behavior research. Following the steps required to create ananimated stimulus, we discuss (I) the creation, (11) the presentation, and (111) the validation of CAsand VRs. Although our review is geared toward computer-graphically designed stimuli, consider-ations on presentation and validation also apply to video playbacks. CA and VR allow both new be-havioral questions to be addressed and existing questions to be addressed in new ways, thus weexpect a rich future for these methods in both ultimate and proximate studies of animal behavior. | Laura CHOUINARD-THULY Stefanie GIERSZEWSKI Gil G. ROSENTHAL Simon M. READER Guillaume RIEUCAU Kevin L. Woo Robert GERLAI Cynthia TEDORE Spencer J. INGLEY John R. STOWERS Joachim G.FROMMENI Francine L. DOLINS Klaudia WITTE | 2017 | Current Zoology2017，63，1： | 10 |
| 5 | 基于体波有限频层析成像的青藏高原南部和中部下方印度大陆岩石层俯冲和撕裂的三维图像显示文摘使用TIBET-31N无源地震台阵以及以前临时地震台阵记录到的远震体波数据进行了有限频层析成像反演,对青藏高原南部及中部的三维速度结构成像。在喜马拉雅和拉萨地块下方存在向北倾角40°的高速体。我们把这些高速异常区域解释为俯冲的印度大陆岩石层(ICL)。印度大陆岩石层似乎在青藏高原中部比东部向北延伸更多——沿85°E在31°N到达350km深处,而沿91°E则是在30°N到达350km深度。P波和S波低速异常区在当惹雍错裂谷、亚东—谷露裂谷和错那裂谷下方从下地壳延伸至≥180km深度,这表明青藏高原南部的裂谷可能包含了整个岩石层的变形。当惹雍错裂谷下方的异常区向下延伸到约180km,而亚东—谷露裂谷西部和错那裂谷东部的异常延伸到了超过300km的深度。亚东—谷露裂谷西部的低速区上地幔延伸至最北,并且似乎与青藏高原中部下方广阔的上地幔低速区相连。于是,北向俯冲的印度板块沿着南北走向的裂缝撕裂。这些裂缝允许或者导致的软流层上涌同青藏高原北部上地幔相类似。 | Xiaofeng Liang Yun Chen Xiaobo Tian Yongshun John Chen James Ni Andrea Gallegos Simon L.Klemperer Minling Wang Tao Xu Changqing Sun Shaokun Si Haiqiang Lan Jiwen Teng 左思成 | 2016 | 世界地震译丛2016，47，6： | 8 |
| 6 | 20世纪90年代中国国有企业改革对城镇劳动力市场的影响显示文摘本文试图用2000年中国6省13市5300个家庭的入户调查数据来分析和总结上世纪90年代中后期,中国国有企业大幅裁员政策对城镇劳动力市场的影响。在考察未下岗城镇职工、下岗城镇职工和进城农民工等三个群体的工资形成过程之后,我们用Probit模型和半参数模型分别考察了下岗的决定因素以及城镇职工失业持续时间的决定因素。我们发现:城镇劳动力市场对进城农民工的传统歧视和偏见已经大为减少,但是城镇下岗职工却不得不参与日趋激烈的劳动力市场竞争。到数据调查结束时,绝大部分下岗职工依然处于失业状态;少数已经再就业的职工工资也很低,他们的生产特征没有得到相应的回报。至少就短期而言,下岗职工还得受到市场信息不对称和有限就业机会的制约。 | 夏庆杰 宋丽娜 John Knight Simon Appleton | 2009 | 世界经济2009，32，4： | 5 |
| 7 | Impacts of livestock grazing on a savanna grassland in Kenya显示文摘The dynamics of most rangelands in Kenya remain to be poorly understood.This paper provides baseline information on the response of a semiarid rangeland under different livestock grazing regimes on land inhabited by the Massai people in the east side of Amboseli National Park in Kenya.The data were collected from grasslands designated into four types:(1) grassland from previous Massai settlements that had been abandoned for over twenty years;(2) grassland excluded from livestock grazing for eight years;(3) a dry season grazing area;and (4) a continuous grazing area where grazing occurred throughout all seasons.Collected data included grass species composition,grass height,inter-tuft distance,standing grass biomass and soil characteristics.The results indicated that continuous grazing area in semiarid rangelands exhibited loss of vegetation with negative,long-term effects on grass functional qualities and forage production,whereas grassland that used traditional Maasai grazing methods showed efficiency and desirable effects on the rangelands.The results also showed that abandoned homestead sites,though degraded,were important nutrient reservoirs. | John KIOKO John Warui KIRINGE Simon Ole SENO | 2012 | Journal of Arid Land2012，4，1： | 5 |
| 8 | A history of high-power laser research and development in the United Kingdom显示文摘The first demonstration of laser action in ruby was made in 1960 by T.H.Maiman of Hughes Research Laboratories,USA.Many laboratories worldwide began the search for lasers using different materials,operating at different wavelengths.In the UK,academia,industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications.This historical review looks at the contribution the UK has made to the advancement of the technology,the development of systems and components and their exploitation over the last 60 years. | Colin N.Danson Malcolm White John R.M.Barr Thomas Bett Peter Blyth David Bowley Ceri Brenner Robert J.Collins Neal Croxford A.E.Bucker Dangor Laurence Devereux Peter E.Dyer Anthony Dymoke-Bradshaw Christopher B.Edwards Paul Ewart Allister I.Ferguson John M.Girkin Denis R.Hall David C.Hanna Wayne Harris David I.Hillier Christopher J.Hooker Simon M.Hooker Nicholas Hopps Janet Hull David Hunt Dino A.Jaroszynski Mark Kempenaars Helmut Kessler Sir Peter L.Knight Steve Knight Adrian Knowles Ciaran L.S.Lewis Ken S.Lipton Abby Littlechild John Littlechild Peter Maggs Graeme P.A.Malcolm OBE Stuart P.D.Mangles William Martin Paul McKenna Richard O.Moore Clive Morrison Zulfikar Najmudin David Neely Geoff H.C.New Michael J.Norman Ted Paine Anthony W.Parker Rory R.Penman Geoff J.Pert Chris Pietraszewski Andrew Randewich Nadeem H.Rizvi Nigel Seddon MBE Zheng-Ming Sheng David Slater Roland A.Smith Christopher Spindloe Roy Taylor Gary Thomas John W.G.Tisch Justin S.Wark Colin Webb S.Mark Wiggins Dave Willford Trevor Winstone | 2021 | High Power Laser Science and Engineering2021，9，2： | 5 |
| 9 | Upper esophageal sphincter abnormalities are strongly predictive of treatment response in patients with achalasia显示文摘AIM: To investigate the relationship between upper esophageal sphincter abnormalities achalasia treatment METHODS: We performed a retrospective study of 41 consecutive patients referred for high resolution esophageal manometry with a final manometric diagnosis of achalasia. Patients were sub-divided by presence or absence of Upper esophageal sphincter(UES) abnormality, and clinical and manometric profiles were compared.Correlation between UES abnormality and sub-type(i.e.,hypertensive, hypotensive or impaired relaxation) and a number of variables, including qualitative treatment response, achalasia sub-type, co-morbid medical illness,psychiatric illness, surgical history, dominant presentingsymptom, treatment type, age and gender were also evaluated.RESULTS: Among all 41 patients, 24(58.54%) had a UES abnormality present. There were no significant differences between the groups in terms of age, gender or any other clinical or demographic profiles. Among those with UES abnormalities, the majority were either hypertensive(41.67%) or had impaired relaxation(37.5%) as compared to hypotensive(20.83%), although this did not reach statistical significance(P = 0.42). There was no specific association between treatment response and treatment type received; however, there was a significant association between UES abnormalities and treatment response. In patients with achalasia and concomitant UES abnormalities, 87.5% had poor treatment response, while only 12.5% had favorable response. In contrast, in patients with achalasia and no UES abnormalities, the majority(78.57%) had good treatment response, as compared to 21.43% with poor treatment response(P = 0.0001). After controlling for achalasia sub-type, those with UES abnormality had 26 times greater odds of poor treatment response than those with no UES abnormality(P = 0.009). Similarly, after controlling for treatment type, those with UES abnormality had 13.9 times greater odds of poor treatment response compared to those with no UES abnormality(P = 0.017).CONCLUSION: The presence of UES abnormalities in patients with achalasia significantly predicted poorer treatment response as compared to those with normal UES function. | Simon C Mathews Maria Ciarleglio Yamile Haito Chavez John O Clarke Ellen Stein Bani Chander Roland | 2014 | World Journal of Clinical Cases2014，2，9： | 5 |
| 10 | Utility of tissue microarrays for profiling prognostic biomarkers in clinically localized prostate cancer: the expression of BCL-2, E-cadherin, Ki-67 and p53 as predictors of biochemical failure after radical prostatectomy with nested control for clinical and pathological risk factors显示文摘痊愈不能与经历激进的治疗的临床上局部性的前列腺癌症为所有人被保证。如果他们能改进秘密变形疾病的预言,分子的标记将是无价的。这研究被执行在激进的前列腺切除术标本调查 BCL-2, Ki-67, p53 和 E-cadherin 的表示。我们寻求了估计他们的能力在一个特定的治疗学的背景预言早生物化学的恶化。包括 41 案例对的 82 个病人为病理学的舞台,格利森等级和外科手术前的前列腺特定的抗原(PSA ) 被匹配集中。在每对的一个病人有生物化学的复发(在 2 年外科以内定义为 PSA 0.2 ng mL-1 ) 并且其它没有疾病生物化学地留下了(至少 3 年在外科以后定义同样无法发现的 PSA ) 。Immunohistochemical 分析被执行在四上估计标记表示复制从每个激进的前列腺切除术标本与良性、恶意的织物构造的织物 microarrays。Ki-67, p53 和 BCL-2,然而并非 E-cadherin,显著地在前列腺腺癌的 upregulated 与良性的前列腺织物相比(P < 0.01 ) 。然而,当比较与没有生物化学的复发的病人一起开发了早生物化学的恶化的病人时,在任何标记的表示的重要差别都没被观察。这研究证明 p53, BCL-2 和 Ki-67 的那表情与良性的前列腺织物相比是在临床上局部性的前列腺癌症的 upregulated,没有在 E-cadherin 表示的改变。Biomarker upregulation 没在激进的前列腺切除术以后为生物化学的复发有预示的价值,甚至在考虑病理学的舞台,整个瘤格利森等级和外科手术前的浆液 PSA 水平以后。 | Joseph Nariculam Alex Freeman Simon Bott Phillipa Munson Noriko Cable Nicola Brookman-Amissah Magali Williamson Roger S. Kirby John Masters Mark Feneley | 2009 | Asian Journal of Andrology2009，11，1： | 5 |
| 11 | Recurrent ectopic pancreatitis of the jejunum and mesentery over a 30-year period显示文摘BACKGROUND:Ectopic pancreas is defined as pancreatic tissue found outside its usual anatomical position,with no ductal or vascular communication with the native pancreas. We describe a case of ectopic pancreas of the small bowel and mesentery causing recurrent episodes of pancreatitis, initially suspected on computed tomography(CT)and magnetic resonance cholangiopancreatography(MRCP),and confirmed on histological review of the resection. METHODS:A 67-year-old woman presented with clinical symptoms and biochemical evidence of pancreatitis.She had similar episodes over the past 30 years with unrevealing investigations,and was concluded to have idiopathic pancreatitis. She underwent CT and MRCP,with findings suggestive of ectopic pancreas,a diagnosis confirmed on histology of the resection. RESULTS:MRCP identified a mass in the proximal small bowel mesentery isointense to the native pancreas,with a small duct draining into a proximal jejunal loop.The resected specimen consisted of normal parenchyma with lobulated acinar tissue with scattered islets of Langerhans,an occasional ductular structure,and admixed areas of adipose tissue.The patient remained asymptomatic with normal biochemistry six months post-operatively. CONCLUSION:In an individual with abdominal pain,elevated serum amylase/lipase,but imaging findings of a normal native pancreas,ectopic pancreatitis should be considered,and can be evaluated by CT and MRCP. | John CT Wong Charlotte Robinson Edward C Jones Alison Harris Charles Zwirewich Robert Wakefield Richard K Simons Eric M Yoshida | 2011 | Hepatobiliary & Pancreatic Diseases International2011，10，2： | 4 |
| 12 | Mesenchymal VEGFA induces aberrant differentiation in heterotopic ossification显示文摘Heterotopic ossification(HO)is a debilitating condition characterized by the pathologic formation of ectopic bone.HO occurs commonly following orthopedic surgeries,burns,and neurologic injuries.While surgical excision may provide palliation,the procedure is often burdened with significant intra-operative blood loss due to a more robust contribution of blood supply to the pathologic bone than to native bone.Based on these clinical observations,we set out to examine the role of vascular signaling in HO.Vascular endothelial growth factor A(VEGFA)has previously been shown to be a crucial pro-angiogenic and pro-osteogenic cue during normal bone development and homeostasis.Our findings,using a validated mouse model of HO,demonstrate that HO lesions are highly vascular,and that VEGFA is critical to ectopic bone formation,despite lacking a contribution of endothelial cells within the developing anlagen. | Charles Hwang Simone Marini Amanda KHuber David MStepien Michael Sorkin Shawn Loder Chase APagani John Li Noelle DVisser Kaetlin Vasquez Mohamed AGarada Shuli Li Jiajia Xu Ching-Yun Hsu Paul BYu Aaron WJames Yuji Mishina Shailesh Agarwal Jun Li Benjamin Levi | 2019 | Bone Research2019，7，4： | 4 |
| 13 | 知证卫生决策工具之一--什么是知证决策显示文摘本文讨论以下3个问题:①什么是证据?②研究证据在知证卫生决策中有何作用?③什么是知证决策?知证卫生决策是一种决策方法,旨在保证基于最佳可及的研究证据做出决策。知证决策的特点是将系统、透明地获取和评价证据的方法引入决策全过程。虽不要求制定政策的整个过程系统和透明,但在制定政策的全过程,采用系统的步骤可以确保合理地查找、评价和使用相关研究。过程透明化旨在确保他人可以检查什么样的研究证据被用于支持决策并评价证据及其意义。知证决策帮助政策制定者了解这些过程。 | Andrew D Oxman John N Lavis Simon Lewin Atle Fretheim 李媛媛 蒋兰慧 王莉 李幼平 | 2010 | 中国循证医学杂志2010，10，3： | 4 |
| 14 | Evidence for the involvement of NOD2 in regulating colonic epithelial cell growth and survival显示文摘AIM: To investigate the function of NOD2 in colonic epithelial cells (CEC). METHODS: A combination of in vivo and in vitro analyses of epithelial cell turnover in the presence and absence of a functional NOD2 protein and, in response to enteric Salmonella typhimurium infection, were used. shRNA interference was also used to investigate the consequences of knocking down NOD2 gene expression on the growth and survival of colorectal carcinoma cell lines. RESULTS:In the colonic mucosa the highest levels of NOD2 expression were in proliferating crypt epithelial cells. Muramyl dipeptide (MDP), that is recognized by NOD2, promoted CEC growth in vitro . By contrast,the growth of NOD2-deficient CECs was impaired. In vivo CEC proliferation was also reduced and apoptosis increased in Nod2-/- mice, which were also evident following enteric Salmonella infection. Furthermore, neutralization of NOD2 mRNA expression in human colonic carcinoma cells by shRNA interference resulted in decreased survival due to increased levels of apoptosis. CONCLUSION: These findings are consistent with the involvement of NOD2 protein in promoting CEC growth and survival. Defects in proliferation by CECs in cases of CD may contribute to the underlying pathology of disrupted intestinal homeostasis and excessive inflammation. | Sheena M Cruickshank Louise Wakenshaw John Cardone Peter D Howdle Peter J Murray Simon R Carding | 2008 | World Journal of Gastroenterology2008，14，38： | 3 |
| 15 | Oil-bearing fluid inclusions from the Palaeoproterozoic:A review of biogeochemical results from time-capsules >2.0 Ga old显示文摘The observation of oil inclusions trapped prior to 2.0 Ga in Palaeoproterozoic rocks and the ability to obtain detailed molecular geochemical information from them provide a robust way for understanding the early biogeochemical evolution of the Earth. Oil-bearing fluid inclusions (FI) in ca. 2.45 Ga fluvial metaconglomerate of the Matinenda Formation at Elliot Lake, Canada were trapped in quartz and feldspar during diagenesis and early metamorphism of the host rock, probably before ca. 2.2 Ga. The 2.1 Ga FA Formation sandstone of the Franceville Basin in Gabon that hosts the Oklo natural fission reactors has also been discovered to contain abundant Palaeoproterozoic oil-bearing FIs. This oil occurs within H2O and CO2-dominated inclusions trapped in syntaxial quartz overgrowths and intragranular and transgranular microfractures in detrital quartz, and was most likely trapped 2.1-1.98 Ga. Molecular geochemical analyses of both FI oils reveal a wide range of compounds, including n-alkanes, isoprenoids, monomethylalkanes, aromatic hydrocarbons, and trace amounts of complex multi-ring biomarkers including terpanes, hopanes, methylhopanes, steranes and diasteranes. To ensure a reliable interpretation of oil inclusions, a comprehensive series of outside-rinse blanks and procedural system blanks was analysed by gas chromatography-mass spectrometry; quantitative amounts of the hydrocarbons in these blanks were compared to the FI extracts, so as to provide confidence limits on the experimental integrity of each compound class. Maturity ratios based on reliably detected compound classes show that the FI oils were generated in the oil window, with no evidence of extensive thermal cracking. The presence of biomarkers for cyanobacteria and eukaryotes derived from and trapped in rocks deposited prior to 2.0 Ga is consistent with early evolution of oxygenic photosynthesis and suggests that some aquatic settings had become sufficiently oxygenated for sterol biosynthesis by this time. The extraction of biomarker molecules from Palaeoproterozoic oil-bearing FIs thus establishes a new method, using low detection limits and system blank levels, to trace evolution through Earth's early history that avoids the potential contamination problems affecting shale-hosted hydrocarbons. | Simon C. GEORGE Adriana DUTKIEWICZ Herbert VOLK John RIDLEY David J. MOSSMAN Roger BUICK | 2009 | Science China Earth Sciences2009，52，1： | 3 |
| 16 | Machine learning models compared to existing criteria for noninvasive prediction of endoscopic retrograde cholangiopancreatography-confirmed choledocholithiasis显示文摘Background and aims:Noninvasive predictors of choledocholithiasis have generally exhibited marginal performance characteristics.We aimed to identify noninvasive independent predictors of endoscopic retrograde cholangiopancreatography(ERCP)-confirmed choledocholithiasis and accordingly developed predictive machine learning models(MLMs).Methods:Clinical data of consecutive patients undergoing first-ever ERCP for suspected chol-edocholithiasis from 2015 to 2019 were abstracted from a prospectively-maintained database.Multiple logistic regression was used to identify predictors of ERCP-confirmed choledocholithiasis.MLMs were then trained to predict ERCP-confirmed choledocholithiasis using pre-ERCP ultrasound(US)imaging only as well as using all available noninvasive imaging(US,computed tomography,and/or magnetic reso-nance cholangiopancreatography).The diagnostic performance of American Society for Gastrointestinal Endoscopy(ASGE)“high-likelihood”criteria was compared to MLMs.Results:We identified 270 patients(mean age 46 years,62.2%female,73.7%Hispanic/Latino,59%with noninvasive imaging positive for choledocholithiasis)with native papilla who underwent ERCP for suspected choledocholithiasis,of whom 230(85.2%)were found to have ERCP-confirmed chol-edocholithiasis.Logistic regression identified choledocholithiasis on noninvasive imaging(odds ratio(OR)¼3.045,P¼0.004)and common bile duct(CBD)diameter on noninvasive imaging(OR¼1.157,P¼0.011)as predictors of ERCP-confirmed choledocholithiasis.Among the various MLMs trained,the random forest-based MLM performed best;sensitivity was 61.4%and 77.3%and specificity was 100%and 75.0%,using US-only and using all available imaging,respectively.ASGE high-likelihood criteria demonstrated sensitivity of 90.9%and specificity of 25.0%;using cut-points achieving this specificity,MLMs achieved sensitivity up to 97.7%.Conclusions:MLMs using age,sex,race/ethnicity,presence of diabetes,fever,body mass index(BMI),total bilirubin,maximum CBD diameter,and choledocholithiasis on pre-ERCP noninvasive imaging predict ERCP-confirmed choledocholithiasis with good sensitivity and specificity and outperform the ASGE criteria for patients with suspected choledocholithiasis. | Camellia Dalai John M Azizian Harry Trieu Anand Rajan Formosa C Chen Tien Dong Simon W Beaven James H.Tabibian | 2021 | Liver Research2021，5，4： | 3 |
| 17 | Aberrant cholesterol metabolic signaling impairs antitumor immunosurveillance through natural killer T cell dysfunction in obese liver显示文摘Obesity is a major risk factor for cancers including hepatocellular carcinoma(HCC)that develops from a background of non-alcoholic fatty liver disease(NAFLD).Hypercholesterolemia is a common comorbidity of obesity.Although cholesterol biosynthesis mainly occurs in the liver,its role in HCC development of obese people remains obscure.Using high-fat high-carbohydrate diet-associated orthotopic and spontaneous NAFLD-HCC mouse models,we found that hepatic cholesterol accumulation in obesity selectively suppressed natural killer T(NKT)cell-mediated antitumor immunosurveillance.Transcriptome analysis of human liver revealed aberrant cholesterol metabolism and NKT cell dysfunction in NAFLD patients.Notably,cholesterol-lowering rosuvastatin restored NKT expansion and cytotoxicity to prevent obesogenic diet-promoted HCC development.Moreover,suppression of hepatic cholesterol biosynthesis by a mammalian target of rapamycin(mTOR)inhibitor vistusertib preceded tumor regression,which was abolished by NKT inactivation but not CD8^(+)T cell depletion.Mechanistically,sterol regulatory element-binding protein 2(SREBP2)-driven excessive cholesterol production from hepatocytes induced lipid peroxide accumulation and deficient cytotoxicity in NKT cells,which were supported by findings in people with obesity,NAFLD and NAFLD-HCC.This study highlights mTORC1/SREBP2/cholesterol-mediated NKT dysfunction in the tumor-promoting NAFLD liver microenvironment,providing intervention strategies that invigorating NKT cells to control HCC in the obesity epidemic. | Wenshu Tang Jingying Zhou Weiqin Yang Yu Feng Haoran Wu Myth T.S.Mok Lingyun Zhang Zhixian Liang Xiaoyu Liu Zhewen Xiong Xuezhen Zeng Jing Wang Jiahuan Lu Jingqing Li Hanyong Sun Xiaoyu Tian Philip Chun Yeung Yong Hou Heung Man Lee Candice C.H.Lam Howard H.W.Leung Anthony W.H.Chan Ka Fai To John Wong Paul B.S.Lai Kelvin K.C.Ng Simon K.H.Wong Vincent W.S.Wong Alice P.S.Kong Joseph J.Y.Sung Alfred S.L.Cheng | 2022 | Cellular & Molecular Immunology2022，19，7： | 3 |
| 18 | Rates and impact of hepatitis on human immunodeficiency virus infection in a large African cohort显示文摘AIM:To determine the rates and impact of hepatitis B virus(HBV) and hepatitis C virus(HCV) infections on response to long-term highly active antiretroviral therapy(HAART) in a large human immunodeficiency virus(HIV) population in Nigeria.METHODS:HBV and HCV as well as HIV infections are endemic in sub Saharan Africa.This was a retrospective cohort study of 19 408 adults who were recruited between June 2004 and December 2010 in the AIDS Prevention Initiative in Nigeria in Nigeria programme at Jos University Teaching Hospital.Serological assays,including HBV surface antigen(HBsAg) and hepatitis C antibody were used to categorise hepatitis status of the patients.HBsAg was determined using enzyme immunoassay(EIA)(Monolisa HBsAg Ultra3;Bio-Rad).HCV antibody was tested using third generation EIA(DIA.PRO Diagnostic,Bioprobes srl,Milan,Italy).HIV RNA levels were measured using Roche COBAS Amplicor HIV-1 monitor test version 1.5(Roche Diagnostics,GmbH,Mannheim,Germany) with a detection limit of 400 copies/mL.Flow cytometry was used to determine CD4+ cell count(Partec,GmbH Munster,Germany).Comparison of categorical and continuous variables were achieved using Pearson's χ 2 and Kruskal Wallis tests respectively,on MedCalc for Windows,version 9.5.0.0(MedCalc Software,Mariakerke,Belgium).RESULTS:With an overall hepatitis screening rate of over 90% for each virus;HBV,HCV and HBV/HCV were detected in 3162(17.8%),1983(11.3%) and 453(2.5%) HIV infected adults respectively.The rate of liver disease was low,but highest among HIV monoinfected patients(29,0.11%),followed by HBV coinfected patients(15,0.08%).Patients with HBV coinfection and triple infection had higher log 10 HIV RNA loads(HBV:4.6 copies/mL vs HIV only:4.5 copies/mL,P<0.0001) and more severe immune suppression(HBV:645,55.4%;HBV/HCV:97,56.7%) prior to initiation of HAART compared to HIV mono-infected patients(1852,48.6%)(P<0.0001).Of 3025 patients who were 4.4 years on HAART and whose CD4 cell counts results at baseline and end of follow up were available for analyses,CD4 increase was significantly lower in those with HBV co-infection(HBV:144 cells/mm3 ;HBV/HCV:105 cells/mm3) than in those with HCV co-infection(165 cells/mm3) and HIV mono-infection(150 cells/mm3)(P=0.0008).CONCLUSION:High rates of HBV and HCV infections were found in this HIV cohort.CD4 recovery was significantly diminished in patients with HBV co-infection. | Nimzing Gwamzhi Ladep Patricia Aladi Agaba Oche Agbaji Auwal Muazu Placid Ugoagwu Godwin Imade Graham Cooke Sheena McCormack Simon David Taylor-Robinson John Idoko Phyllis Kanki | 2013 | World Journal of Gastroenterology2013，19，10： | 3 |
| 19 | Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 1 diabetes (BEGIN Basal-Bolus Type 1): a phase 3, randomised, open-label, treat-to-target non-inferiority trial显示文摘 | Simon Heller John Buse Miles Fisher Satish Garg Michel Marre Ludwig Merker Eric Renard David Russell-Jones Areti Philotheou Ann Marie Ocampo Francisco Huiling Pei Bruce Bode | 2012 | The Lancet2012，，9825： | 2 |
| 20 | Effect of 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide concentrations on the mechanical and biological characteristics of cross-linked collagen fibres for tendon repair显示文摘Reconstituted type I collagen fibres have received considerable interest as tendon implant materials due to their chemical and structural similarity to the native tissue.Fibres produced through a semi-continuous extrusion process were cross-linked with different concentrations of the zerolength cross-linker 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide(EDC)in combination with N-hydroxysuccinimide(NHS).Tensile properties of the fibres were considered,along with imaging of both surface structure and fibrillar alignment.Resistance of the fibres to bacterial collagenase was investigated and fibre sections seeded with human tendon cells for biological characterization,including cell adhesion and proliferation.The work clearly demonstrated that whilst the concentration of EDC and NHS had no significant effect on the mechanics,a higher concentration was associated with higher collagenase resistance,but also provided a less attractive surface for cell adhesion and proliferation.A lower cross-linking concentration offered a more biocompatible material without reduction in mechanics and with a potentially more optimal degradability. | Zafar Ahmad Jennifer H.Shepherd David V.Shepherd Siddhartha Ghose Simon J.Kew Ruth E.Cameron Serena M.Best Roger A.Brooks John Wardale Neil Rushton | 2015 | Regenerative Biomaterials2015，2，2： | 2 |
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