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| 1 | High-throughput screening of mouse gene knockouts identifies established and novel skeletal phenotypes显示文摘Screening gene function in vivo is a powerful approach to discover novel drug targets. We present high-throughput screening(HTS) data for 3 762 distinct global gene knockout(KO) mouse lines with viable adult homozygous mice generated using either gene-trap or homologous recombination technologies. Bone mass was determined from DEXA scans of male and female mice at 14 weeks of age and by microCT analyses of bones from male mice at 16 weeks of age. Wild-type(WT) cagemates/littermates were examined for each gene KO. Lethality was observed in an additional 850 KO lines. Since primary HTS are susceptible to false positive findings, additional cohorts of mice from KO lines with intriguing HTS bone data were examined. Aging,ovariectomy, histomorphometry and bone strength studies were performed and possible non-skeletal phenotypes were explored. Together, these screens identified multiple genes affecting bone mass: 23 previously reported genes(Calcr, Cebpb, Crtap, Dcstamp, Dkk1, Duoxa2, Enpp1, Fgf23, Kiss1/Kiss1 r, Kl(Klotho),Lrp5, Mstn, Neo1, Npr2, Ostm1, Postn, Sfrp4, Slc30a5, Slc39a13, Sost, Sumf1, Src, Wnt10b), five novel genes extensively characterized(Cldn18, Fam20 c, Lrrk1, Sgpl1, Wnt16), five novel genes with preliminary characterization(Agpat2, Rassf5, Slc10a7, Slc26a7, Slc30a10) and three novel undisclosed genes coding for potential osteoporosis drug targets. | Robert Brommage Jeff Liu Gwenn M Hansen Laura L Kirkpatrick David G Potter Arthur T Ss Brian Zambrowicz David R Powell Peter Vogel | 2014 | Bone Research2014，2，3： | 7 |
| 2 | Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial显示文摘 | Pierre J Guillou Philip Quirke Helen Thorpe Joanne Walker David G Jayne Adrian MH Smith Richard M Heath Julia M Brown | 2005 | The Lancet . 2005 (9472)2005，，9472： | 6 |
| 3 | 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 |
| 4 | AIDS-associated plasmablastic lymphoma presenting as a poorly differentiated esophageal tumor: A diagnostic dilemma显示文摘Plasmablastic lymphoma (PBL) is a rare form of diffuse large B-cell lymphoma characterized by weak/absent expression of conventional B-cell markers and strong expression of plasma cell markers. It is strongly associated with human immunodeficiency virus (HIV) and Epstein Barr virus infection, and shows an unusual tropism to the oral cavity. Herein we describe a patient with AIDS who presented with weight loss and dysphagia owing to a large gastroesophageal mass. His radiographic and endoscopic findings and long history of cigarette consumption suggested carcinoma. Biopsy demonstrated a poorly differentiated tumor stained negatively to routine lymphoid markers including CD20. However, gene rearrangement studies confirmed a B-cell process and a more detailed immunohistochemical analysis revealed the cells stained positively for CD138 (plasma cell antigen). These findings were diagnostic of PBL. Our report reviews the wide differential diagnosis of PBL and underscores the importance of a broad array of viral and molecular studies needed to establish this diagnosis. | Deepthi Mani Donald G Guinee Jr David M Aboulafia | 2008 | World Journal of Gastroenterology2008，14，27： | 4 |
| 5 | Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial显示文摘 | Pierre J Guillou Philip Quirke Helen Thorpe Joanne Walker David G Jayne Adrian MH Smith Richard M Heath Julia M Brown | 2005 | The Lancet2005，，9472： | 4 |
| 6 | Sentinel-lymph-node resection compared with conventional axillary-lymph-node dissection in clinically node-negative patients with breast cancer: overall survival findings from the NSABP B-32 randomised phase 3 trial显示文摘 | David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Joseph P Costantino Takamaru Ashikaga Donald L Weaver Eleftherios P Mamounas Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Norman Wolmark | 2010 | Lancet Oncology2010，，10： | 3 |
| 7 | Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial显示文摘 | Kris V Kowdley Eric Lawitz Israel Crespo Tarek Hassanein Mitchell N Davis Michael DeMicco David E Bernstein Nezam Afdhal John M Vierling Stuart C Gordon Jane K Anderson Robert H Hyland Hadas Dvory-Sobol Di An Robert G Hindes Efsevia Albanis William T Symo | 2013 | The Lancet2013，，9883： | 3 |
| 8 | Hepatocellular carcinoma after Iocoregional therapy:Magnetic resonance imaging findings in falsely negative exams显示文摘AIM:To elucidate causes for false negative magnetic resonance imaging(MRI)exams by identifying imaging characteristics that predict viable hepatocellular carcinoma(HCC)in lesions previously treated with locoregional therapy when obvious findings of recurrence are absent.METHODS:This retrospective institutional review board-approved and Health Insurance Portability and Accountability Act-compliant study included patients who underwent liver transplantation at our center between 1/1/2000 and 12/31/2012 after being treated for HCC with locoregional therapy.All selected patients had a contrast-enhanced MRI after locoregional therapy within 90 d of transplant that was prospectively interpreted as without evidence of residual or recurrenttumor.Retrospectively,2 radiologists,blinded to clinica and pathological data,independently reviewed the pre transplant MRIs for 7 imaging features.Liver explan histopathology provided the reference standard,with clinically significant tumor defined as viable tumor≥1.0cm in maximum dimension.Fisher’s exact test was firs performed to identify significant imaging features.RESULTS:Inclusion criteria selected for 42 patients with 65 treated lesions.Fourteen of 42 patients(33%and 16 of 65 treated lesions(25%)had clinically significant viable tumor on explant histology.None o the 7 imaging findings examined could reliably and reproducibly determine which treated lesion had viable tumor when the exam had been prospectively read as without evidence of viable HCC.CONCLUSION:After locoregional therapy some treated lesions that do not demonstrate any MRI evidence o HCC will contain viable tumor.As such even patients with a negative MRI following treatment should receive regular short-term imaging surveillance because some have occult viable tumor.The possibility of occult tumo should be a consideration when contemplating any action which might delay liver transplant. | David Becker-Weidman Jesse M Civan Sandeep P Deshmukh Christopher G Roth Steven K Herrine Laurence Parker Donald G Mitchell | 2016 | World Journal of Hepatology2016，8，16： | 2 |
| 9 | DNA damage induced by chronic inflammation contributes to colon carcinogenesis in mice显示文摘 | Meira Lisiane B Bugni James M Green Stephanie L Lee Chung-Wei Pang Bo Borenshtein Diana Rickman Barry H Rogers Arlin B Moroski-Erkul Catherine A McFaline Jose L Schauer David B Dedon Peter C Fox James G Samson Leona D | 2008 | Journal of Clinical Investigation2008，，7： | 2 |
| 10 | Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial显示文摘 | Pierre J Guillou Philip Quirke Helen Thorpe Joanne Walker David G Jayne Adrian MH Smith Richard M Heath Julia M Brown | 2005 | 2005 (9472)2005，，9472： | 2 |
| 11 | Mechanisms of fibrinolysis resistance and potential targets for thrombolysis in acute ischaemic stroke: lessons from retrieved stroke emboli显示文摘There has been growing interest and insight into the histological composition of retrieved stroke emboli.One of the main focuses of the stroke clot analysis literature has been the implications of clot composition on mechanical thrombectomy procedures.However,the holy grail of clot analysis may not be in the field of clot-device interaction,but rather,in understanding mechanisms of fibrinolysis resistance.The mechanisms underlying the low response to fibrinolytic therapy,even with the newer,more powerful agents,remain poorly understood.While factors such as embolus size,location and collateral status influence alteplase delivery and recanalisation rates;compositional analyses focused on histological and ultrastructural characteristics offer unique insights into mechanisms of alteplase resistance.In this review,we strive to provide comprehensive review of current knowledge on clot composition and ultrastructural analyses that help explain resistance to fibrinolysis. | Waleed Brinjikji Oana Madalina Mereuta Daying Dai David F Kallmes Luis Savastano Yang Liu Shahid M Nimjee Raul G Nogueira Mehdi Abbasi Ramanathan Kadirvel | 2021 | Stroke & Vascular Neurology2021，6，4： | 2 |
| 12 | Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial显示文摘 | Brian I Rini Bernard Escudier Piotr Tomczak Andrey Kaprin Cezary Szczylik Thomas E Hutson M Dror Michaelson Vera A Gorbunova Martin E Gore Igor G Rusakov Sylvie Negrier Yen-Chuan Ou Daniel Castellano Ho Yeong Lim Hirotsugu Uemura Jamal Tarazi David Cella | 2011 | The Lancet . 2011 (9807)2011，，9807： | 2 |
| 13 | The impact of ipsilateral testicular atrophy on semen quality and sperm DNA fragmentation response to varicocele repair显示文摘Varicoceles adversely impact semen quality and sperm DNA fragmentation,which typically improve with surgical repair.Some men with varicoceles have ipsilateral testicular atrophy due to damage from the varicocele.This study assessed semen quality and the sperm DNA fragmentation index(DFI)response to varicocele repair in men with ipsilateral testicular atrophy(TA)versus men with no testicular atrophy(NTA).Semen parameter values and DFI in both groups were compared preoperatively and postoperatively.The Mann-Whitney U test and the Wilcoxon signed-rank test were used where appropriate.There were 20 men in the TA group and 121 men in the NTA group with no difference in age,varicocele grade,or preoperative semen parameter values between the two groups.The NTA group had a higher preoperative DFI than the TA group.Both groups showed improvement in semen quality postoperatively,only the TA group showed a significant improvement in DFI,whereas the NTA group showed significant improvements in several parameter values and DFI.The change from preoperative to postoperative parameter values when comparing the two groups revealed a difference in total sperm motile count and DFI,with a larger mean improvement in the NTA group than in the TA group.Both TA and NTA groups showed improved semen quality and DFI after varicocele repair,but the NTA group had more improvement than the TA group.However,only total motile count(TMC)and DFI had a significantly greater mean change in preoperative to postoperative response in the NTA group than in the TA group. | Parviz K Kavoussi Natasha Abdullah Melissa S Gilkey Caitlin Hunn G Luke Machen Shu-Hung Chen Keikhosrow M Kavoussi Amy Esqueda J David Wininger Shahryar K Kavoussi | 2021 | Asian Journal of Andrology2021，23，2： | 2 |
| 14 | Comparative effectiveness of axitinib versus sorafenib in advanced renal cell carcinoma (AXIS): a randomised phase 3 trial显示文摘 | Brian I Rini Bernard Escudier Piotr Tomczak Andrey Kaprin Cezary Szczylik Thomas E Hutson M Dror Michaelson Vera A Gorbunova Martin E Gore Igor G Rusakov Sylvie Negrier Yen-Chuan Ou Daniel Castellano Ho Yeong Lim Hirotsugu Uemura Jamal Tarazi David Cella | 2011 | The Lancet2011，，9807： | 2 |
| 15 | Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials显示文摘 | Naveed Sattar David Preiss Heather M Murray Paul Welsh Brendan M Buckley Anton JM de Craen Sreenivasa Rao Kondapally Seshasai John J McMurray Dilys J Freeman J Wouter Jukema Peter W Macfarlane Chris J Packard David J Stott Rudi G Westendorp James Shepherd | 2010 | The Lancet2010，，9716： | 2 |
| 16 | Age at diagnosis of type 2 diabetes and cardiovascular risk factor profile:A pooled analysis显示文摘BACKGROUND The diagnosis of type 2 diabetes(T2D)in younger adults,an increasingly common public health issue,is associated with a higher risk of cardiovascular complications and mortality,which may be due to a more adverse cardiovascular risk profile in individuals diagnosed at a younger age.AIM To investigate the association between age at diagnosis and the cardiovascular risk profile in adults with T2D.METHODS A pooled dataset was used,comprised of data from five previous studies of adults with T2D,including 1409 participants of whom 196 were diagnosed with T2D under the age of 40 years.Anthropometric and blood biomarker measurements included body weight,body mass index(BMI),waist circumference,body fat percentage,glycaemic control(HbA1c),lipid profile and blood pressure.Univariable and multivariable linear regression models,adjusted for diabetes duration,sex,ethnicity and smoking status,were used to investigate the association between age at diagnosis and each cardiovascular risk factor.RESULTS A higher proportion of participants diagnosed with T2D under the age of 40 were female,current smokers and treated with glucose-lowering medications,compared to participants diagnosed later in life.Participants diagnosed with T2D under the age of 40 also had higher body weight,BMI,waist circumference and body fat percentage,in addition to a more adverse lipid profile,compared to participants diagnosed at an older age.Modelling results showed that each one year reduction in age at diagnosis was significantly associated with 0.67 kg higher body weight[95%confidence interval(CI):0.52-0.82 kg],0.18 kg/m^(2) higher BMI(95%CI:0.10-0.25)and 0.32 cm higher waist circumference(95%CI:0.14-0.49),after adjustment for duration of diabetes and other confounders.Younger age at diagnosis was also significantly associated with higher HbA1c,total cholesterol,low-density lipoprotein cholesterol and triglycerides.CONCLUSION The diagnosis of T2D earlier in life is associated with a worse cardiovascular risk factor profile,compared to those diagnosed later in life. | Mary M Barker Francesco Zaccardi Emer M Brady Gaurav S Gulsin Andrew P Hall Joseph Henson Zin ZinHtike Kamlesh Khunti Gerald P McCann Emma L Redman David R Webb Emma G Wilmot Tom Yates Jian Yeo Melanie J Davies Jack A Sargeant | 2022 | World Journal of Diabetes2022，13，3： | 2 |
| 17 | Increasing diabetes self-management education in community settings显示文摘 | Susan L Norris Phyllis J Nichols Carl J Caspersen Russell E Glasgow Michael M Engelgau Leonard Jack Susan R Snyder Vilma G Carande-Kulis George Isham Sanford Garfield Peter Briss David McCulloch | 2002 | American Journal of Preventive Medicine2002，，4： | 2 |
| 18 | Technical outcomes of sentinel-lymph-node resection and conventional axillary-lymph-node dissection in patients with clinically node-negative breast cancer: results from the NSABP B-32 randomised phase III trial显示文摘 | David N Krag Stewart J Anderson Thomas B Julian Ann M Brown Seth P Harlow Takamaru Ashikaga Donald L Weaver Barbara J Miller Lynne M Jalovec Thomas G Frazier R Dirk Noyes André Robidoux Hugh MC Scarth Denise M Mammolito David R McCready Eleftherios P Mamo | 2007 | Lancet Oncology2007，，10： | 2 |
| 19 | Short-term endpoints of conventional versus laparoscopic-assisted surgery in patients with colorectal cancer (MRC CLASICC trial): multicentre, randomised controlled trial显示文摘 | Pierre J Guillou Philip Quirke Helen Thorpe Joanne Walker David G Jayne Adrian MH Smith Richard M Heath Julia M Brown | 2005 | The Lancet2005，，9472： | 2 |
| 20 | Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials显示文摘 | Naveed Sattar David Preiss Heather M Murray Paul Welsh Brendan M Buckley Anton JM de Craen Sreenivasa Rao Kondapally Seshasai John J McMurray Dilys J Freeman J Wouter Jukema Peter W Macfarlane Chris J Packard David J Stott Rudi G Westendorp James Shepherd | 2010 | The Lancet2010，，9716： | 2 |
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