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| 1 | Multiplexed activation of endogenous genes by CRISPR-on, an RNA-guided transcriptional activator system显示文摘允许的技术内长的基因的特定的规定为基因功能的学习是珍贵的并且在治疗学有大潜力。我们创造了在 CRISPR 上系统,由核酸酶死者 Cas9 (dCas9 ) 蛋白质组成的二部件的 transcriptional 使活跃之物与互补顺序与 transcriptional 激活域和单个指南 RNA (sgRNAs ) 熔化了到基因倡导者。我们证明在 CRISPR 上能高效地以一种悦耳的方式在人和老鼠房间激活外长的记者基因。另外,我们证明在 vivo 的柔韧的记者基因激活能被把系统部件注入老鼠接合子完成。而且,我们证明在 CRISPR 上能激活内长的 IL1RN, SOX2,和 OCT4 基因。最有效的基因激活被对近似倡导者有约束力的 3-4 sgRNAs 的簇完成,建议他们在基因正式就职的 synergistic 行动。显著地,当指向多重基因的 sgRNAs 同时被介绍进房间时,柔韧的多路的内长的基因激活被完成。染色体宽的表示介绍表明了系统的高特性。 | Albert W Cheng Haoyi Wang Hui Yang Linyu Shi Yarden Katz Thorold W Theunissen Sudharshan Rangarajan Chikdu S Shivalila Daniel B Dadon Rudolf Jaenisch | 2013 | Cell Research2013，23，10： | 65 |
| 2 | Systematic review of colorectal cancer screening guidelines for average-risk adults: Summarizing the current global recommendations显示文摘AIM To summarize and compare worldwide colorectal cancer(CRC) screening recommendations in order to identify similarities and disparities.METHODS A systematic literature search was performed using MEDLINE, EMBASE, Scopus, CENTRAL and ISI Web of knowledge identifying all average-risk CRC screening guideline publications within the last ten years and/or position statements published in the last 2 years. In addition, a hand-search of the webpages of National Gastroenterology Society websites, the National Guideline Clearinghouse, the BMJ Clinical Evidence website,Google and Google Scholar was performed. RESULTS Fifteen guidelines were identified. Six guidelines were published in North America, four in Europe, four in Asia and one from the World Gastroenterology Organization. The majority of guidelines recommend screening average-risk individuals between ages 50 and 75 using colonoscopy(every 10 years), or flexible sigmoidoscopy(FS, every 5 years) or fecal occult blood test(FOBT, mainly the Fecal Immunochemical Test, annually or biennially). Disparities throughout the different guidelines are found relating to the use of colonoscopy, rank order between test, screening intervals and optimal age ranges for screening. CONCLUSION Average risk individuals between 50 and 75 years should undergo CRC screening. Recommendations for optimal surveillance intervals, preferred tests/test cascade as well as the optimal timing when to start and stop screening differ regionally and should be considered for clinical decision making. Furthermore, local resource availability and patient preferences are important to increase CRC screening uptake, as any screening is better than none. | Florence Bénard Alan N Barkun Myriam Martel Daniel von Renteln | 2018 | World Journal of Gastroenterology2018，24，1： | 16 |
| 3 | An integrated approach for increasing breeding efficiency in apple and peach in Europe显示文摘Despite the availability of whole genome sequences of apple and peach,there has been a considerable gap between genomics and breeding.To bridge the gap,the European Union funded the FruitBreedomics project(March 2011 to August 2015)involving 28 research institutes and private companies.Three complementary approaches were pursued:(i)tool and software development,(ii)deciphering genetic control of main horticultural traits taking into account allelic diversity and(iii)developing plant materials,tools and methodologies for breeders.Decisive breakthroughs were made including the making available of ready-to-go DNA diagnostic tests for Marker Assisted Breeding,development of new,dense SNP arrays in apple and peach,new phenotypic methods for some complex traits,software for gene/QTL discovery on breeding germplasm via Pedigree Based Analysis(PBA).This resulted in the discovery of highly predictive molecular markers for traits of horticultural interest via PBA and via Genome Wide Association Studies(GWAS)on several European genebank collections.FruitBreedomics also developed pre-breeding plant materials in which multiple sources of resistance were pyramided and software that can support breeders in their selection activities.Through FruitBreedomics,significant progresses were made in the field of apple and peach breeding,genetics,genomics and bioinformatics of which advantage will be made by breeders,germplasm curators and scientists.A major part of the data collected during the project has been stored in the FruitBreedomics database and has been made available to the public.This review covers the scientific discoveries made in this major endeavour,and perspective in the apple and peach breeding and genomics in Europe and beyond. | Francois Laurens Maria JoséAranzana Pere Arus Daniele Bassi Marco Bink Joan Bonany Andrea Caprera Luca Corelli-Grappadelli Evelyne Costes Charles-Eric Durel Jehan-Baptiste Mauroux Hélène Muranty Nelson Nazzicari Thierry Pascal Andrea Patocchi Andreas Peil Bénédicte Quilot-Turion Laura Rossini Alessandra Stella Michela Troggio Riccardo Velasco Eric van de Weg | 2018 | Horticulture Research2018，5，1： | 10 |
| 4 | Potential role of metabolomics in diagnosis and surveillance of gastric cancer显示文摘Gastric cancer is one of the deadliest cancers worldwide, and is especially prevalent in Asian countries. With such high morbidity and mortality, early diagnosis is essential to achieving curative intent treatment and long term survival. Metabolomics is a new field of study that analyzes metabolites from biofluids and tissue samples. While metabolomics is still in its infancy, there are numerous potential applications in oncology, specifically early diagnosis. Only a few studies in the literature have examined metabolomics' role in gastric cancer. Various fatty acid, carbohydrate, nucleic acid, and amino acid metabolites have been identified that distinguish gastric cancer from normal tissue and benign gastric disease. However, findings from these few studies are at times conflicting. Most studies demonstrate some relationship of cancer cells to the Warburg Effect, in that glycolysis predominates with conversion of pyruvate to lactate. This is one of the most consistent findings across the literature. There is less consistency in metabolomic signature with respect to nucleic acids, lipids and amino acids. In spite of this, metabolomics holds some promise for cancer surveillance but further studies are necessary to achieve consistency and validation before it can be widely employed as a clinical tool. | Angela W Chan Richdeep S Gill Daniel Schiller Michael B Sawyer | 2014 | World Journal of Gastroenterology2014，20，36： | 9 |
| 5 | Operative complications and economic outcomes of cholecystectomy for acute cholecystitis显示文摘BACKGROUND Recent management of acute cholecystitis favors same admission(SA)or emergent cholecystectomy based on overall shorter hospital stay and therefore cost savings.We adopted the practice of SA cholecystectomy for the treatment of acute cholecystitis at our tertiary care center and wanted to evaluate the economic benefit of this practice.We hypothesized that the existence of complications,particularly among patients with a higher degree of disease severity,during SA cholecystectomy could negate the cost savings.AIM To compare complication rates and hospital costs between SA vs delayed cholecystectomy among patients admitted emergently for acute cholecystitis.METHODS Under an IRB-approved protocol,complications and charges for were obtained for SA,later after conservative management(Delayed),or elective cholecystectomies over an 8.5-year period.Patients were identified using the acute care surgery registry and billing database.Data was retrieved via EMR,operative logs,and Revenue Cycle Operations.The severity of acute cholecystitis was graded according to the Tokyo Guidelines.TG18 categorizes acute cholecystitis by Grades 1,2,and 3 representing mild,moderate,and severe,respectively.Comparisons were analyzed withχ2,Fisher’s exact test,ANOVA,ttests,and logistic regression;significance was set at P<0.05.RESULTS Four hundred eighty-six(87.7%)underwent a SA while 68 patients(12.3%)received Delayed cholecystectomy.Complication rates were increased after SA compared to Delayed cholecystectomy(18.5%vs 4.4%,P=0.004).The complication rates of patients undergoing delayed cholecystectomy was similar to the rate for elective cholecystectomy(7.4%,P=0.35).Mortality rates were 0.6%vs 0%for SA vs Delayed.Patients with moderate disease(Tokyo 2)suffered more complications among SA while none who were delayed experienced a complication(16.1%vs 0.0%,P<0.001).Total hospital charges for SA cholecystectomy were increased compared to a Delayed approach($44500±$59000 vs$35300±$16700,P=0.019).The relative risk of developing a complication was 4.2x[95%confidence interval(CI):1.4-12.9]in the SA vs Delayed groups.Among eight patients(95%CI:5.0-12.3)with acute cholecystitis undergoing SA cholecystectomy,one patient will suffer a complication.CONCLUSION Patients with Tokyo Grade 2 acute cholecystitis had more complications and increased hospital charges when undergoing SA cholecystectomy.This data supports a selective approach to SA cholecystectomy for acute cholecystitis. | Christopher P Rice Krishnamurthy B Vaishnavi Celia Chao Daniel Jupiter August B Schaeffer Whitney R Jenson Lance W Griffin William J Mileski | 2019 | World Journal of Gastroenterology2019，25，48： | 8 |
| 6 | 基于随机暴雨移置方法的城市设计暴雨分析显示文摘城市地区暴雨洪灾发生频繁,合理计算设计暴雨是解决城市洪涝的重要前提。采用随机暴雨移置方法(Stochastic Storm Transposition,SST),设定暴雨移置区并提取出暴雨目录,通过区域性概率重采样与暴雨空间变换相结合的方式进行降雨频率分析,估计本地化的极端暴雨频率。以上海地区为例,研究发现暴雨移置区内暴雨分布具有空间异质性,暴雨随机移置概率不均,计算得到的设计暴雨方案包含了降雨时空分布信息,在不同重现期下设计暴雨的时空结构存在变异性,说明传统方法中采用的简化雨型和均一化空间分布假设会增加设计暴雨的不确定性。 | 周正正 刘曙光 Daniel B Wright | 2020 | 水科学进展2020，31，4： | 6 |
| 7 | Maintenance infliximab for Crohn’s disease: the ACCENT I randomised trial显示文摘 | Stephen B Hanauer Brian G Feagan Gary R Lichtenstein Lloyd F Mayer S Schreiber Jean Frederic Colombel Daniel Rachmilewitz Douglas C Wolf Allan Olson Weihang Bao Paul Rutgeerts | 2002 | The Lancet2002，，9317： | 6 |
| 8 | pRB expression in esophageal mucosa of individuals at high risk for squamous cell carcinoma of the esophagus显示文摘AIM: To investigate the pRb expression in a large group of patients with history of chronic exposure to the main risk factors for development of squamous cell carcinoma of the esophagus. METHODS: One hundred and seventy asymptomatic individuals at high risk for esophageal squamous cell carcinoma (consumption of more than 80 g of ethanol and 10 cigarettes/d for at least 10 years) underwent upper gastrointestinal endoscopy with biopsies of the esophageal mucosa. As a control group, specimens of esophageal mucosa obtained from 20 healthy subjects were also studied. Immunohistochemical assessment of the tissues was performed using a monoclonal antibody anti-pRB protein. RESULTS: Absence of the pRB staining, indicating loss of RB function, was observed in 33 (19.4%) of the individuals at risk for esophageal cancer, but in none of the healthy controls (P < 0.02). Loss of pRb expression increased in a stepwise fashion according to the severity of the histological findings (P < 0.005): normal mucosa (11/97 or 11.3%), chronic esophagitis (17/60 or 28.3%), low-grade dysplasia (3/10 or 30%), high-grade dysplasia 1/2 or 50%) and squamous cell carcinoma (1/1 or 100%). CONCLUSION: Our findings suggest that abnormal expression of the pRB protein may be implicated in the process of esophageal carcinogenesis. Additional studies are warranted to define the role of the pRBprotein as a biomarker for development of esophageal squamous cell carcinoma in individuals at high risk for this malignancy. | Simone S Contu Paulo C Contu Daniel C Damin Renato B Fagundes Fabiano Bevilacqua Aline S Rosa Joo C Prolla Luis F Moreira | 2007 | World Journal of Gastroenterology2007，13，11： | 5 |
| 9 | Multiphase computed tomography radiomics of pancreatic intraductal papillary mucinous neoplasms to predict malignancy显示文摘BACKGROUND Intraductal papillary mucinous neoplasms(IPMNs)are non-invasive pancreatic precursor lesions that can potentially develop into invasive pancreatic ductal adenocarcinoma.Currently,the International Consensus Guidelines(ICG)for IPMNs provides the basis for evaluating suspected IPMNs on computed tomography(CT)imaging.Despite using the ICG,it remains challenging to accurately predict whether IPMNs harbor high grade or invasive disease which would warrant surgical resection.A supplementary quantitative radiological tool,radiomics,may improve diagnostic accuracy of radiological evaluation of IPMNs.We hypothesized that using CT whole lesion radiomics features in conjunction with the ICG could improve the diagnostic accuracy of predicting IPMN histology.AIM To evaluate whole lesion CT radiomic analysis of IPMNs for predicting malignant histology compared to International Consensus Guidelines.METHODS Fifty-one subjects who had pancreatic surgical resection at our institution with histology demonstrating IPMN and available preoperative CT imaging were included in this retrospective cohort.Whole lesion semi-automated segmentation was performed on each preoperative CT using Healthmyne software(Healthmyne,Madison,WI).Thirty-nine relevant radiomic features were extracted from each lesion on each available contrast phase.Univariate analysis of the 39 radiomics features was performed for each contrast phase and values were compared between malignant and benign IPMN groups using logistic regression.Conventional quantitative and qualitative CT measurements were also compared between groups,viaχ2(categorical)and Mann Whitney U(continuous)variables.RESULTS Twenty-nine subjects(15 males,age 71±9 years)with high grade or invasive tumor histology comprised the'malignant'cohort,while 22 subjects(11 males,age 70±7 years)with low grade tumor histology were included in the'benign'cohort.Radiomic analysis showed 18/39 precontrast,19/39 arterial phase,and 21/39 venous phase features differentiated malignant from benign IPMNs(P<0.05).Multivariate analysis including only ICG criteria yielded two significant variables:thickened and enhancing cyst wall and enhancing mural nodule<5 mm with an AUC(95%CI)of 0.817(0.709-0.926).Multivariable post contrast radiomics achieved an AUC(95%CI)of 0.87(0.767-0.974)for a model including arterial phase radiomics features and 0.834(0.716-0.953)for a model including venous phase radiomics features.Combined multivariable model including conventional variables and arterial phase radiomics features achieved an AUC(95%CI)of 0.93(0.85-1.0)with a 5-fold cross validation AUC of 0.90.CONCLUSION Multi-phase CT radiomics evaluation could play a role in improving predictive capability in diagnosing malignancy in IPMNs.Future larger studies may help determine the clinical significance of our findings. | Stuart L Polk Jung W Choi Melissa J McGettigan Trevor Rose Abraham Ahmed Jongphil Kim Kun Jiang Yoganand Balagurunathan Jin Qi Paola T Farah Alisha Rathi Jennifer B Permuth Daniel Jeong | 2020 | World Journal of Gastroenterology2020，26，24： | 5 |
| 10 | Rho/Rock signal transduction pathway is required for MSC tenogenic differentiation显示文摘Mesenchymal stem cell(MSC)-based treatments have shown promise for improving tendon healing and repair.MSCs have the potential to differentiate into multiple lineages in response to select chemical and physical stimuli, including into tenocytes. Cell elongation and cytoskeletal tension have been shown to be instrumental to the process of MSC differentiation. Previous studies have shown that inhibition of stress fiber formation leads MSCs to default toward an adipogenic lineage, which suggests that stress fibers are required for MSCs to sense the environmental factors that can induce differentiation into tenocytes. As the Rho/ROCK signal transduction pathway plays a critical role in both stress fiber formation and in cell sensation, we examined whether the activation of this pathway was required when inducing MSC tendon differentiation using rope-like silk scaffolds. To accomplish this, we employed a loss-of-function approach by knocking out ROCK,actin and myosin(two other components of the pathway) using the specific inhibitors Y-27632, Latrunculin A and blebbistatin, respectively. We demonstrated that independently disrupting the cytoskeleton and the Rho/ROCK pathway abolished the expression of tendon differentiation markers and led to a loss of spindle morphology. Together, these studies suggest that the tension that is generated by MSC elongation is essential for MSC teno-differentiation and that the Rho/ROCK pathway is a critical mediator of tendon differentiation on rope-like silk scaffolds. | Edward Maharam Miguel Yaport Nathaniel L Villanueva Takintope Akinyibi Damien Laudier Zhiyong He Daniel J Leong Hui B Sun | 2015 | Bone Research2015，3，3： | 4 |
| 11 | Mechanical circulatory support in cardiogenic shock and post-myocardial infarction mechanical complications显示文摘Despite advanced therapies,the mortality of patients with myocardial infarction(MI)complicated by cardiogenic shock(CS)remains around 50%.Mechanical complications of MI are rare nowadays but associated with high mortality in patients who present with CS.Different treatment strategies and mechanical circulatory support(MCS)devices have been increasingly used to improve the grim prognosis of refractory CS.This article discusses current evidence regarding the use of MCS in MI complicated by CS,ventricular septal rupture,free wall rupture and acute mitral regurgitation.Device selection should be tailored according to the cause and severity of CS.Early MCS initiation and multidisciplinary team cooperation is mandatory for good results.MCS associated bleeding remains a major complication and an obstacle to better outcomes.Ongoing prospective randomized trials will improve current knowledge regarding MCS indications,timing,and patient selection in the coming years. | Daniel Rob Jan Bělohlávek | 2022 | Journal of Geriatric Cardiology2022，19，2： | 3 |
| 12 | EGF promotes mammalian cell growth by suppressing cellular senescence显示文摘 | Peter B Alexander Lifeng Yuan Pengyuan Yang Tao Sun Rui Chen Handan Xiang Jiekai Chen Haoyu Wu Daniel R Radiloff Xiao-Fan Wang | 2015 | Cell Research2015，25，1： | 3 |
| 13 | 光动力疗法治疗非小细胞肺癌显示文摘光动力疗法被越来越多地应用于治疗胸部恶性肿瘤。对于早期非小细胞肺癌(如支气管腔内肺癌)、X线检查阴性或同时性原发癌,光动疗法可作为主要治疗手段进行腔内根治性治疗。作为单一根治疗法,光动力疗法是治疗支气管镜可见≤1 cm且无软骨外浸润的肺部肿瘤的最有效方法。对于晚期非小细胞癌患者,光动力治疗可以作为综合根治疗法的一部分,用于减轻阻塞性支气管内病变,增加可手术性或缩小所需手术范围。本文对现有发表的应用光动力疗法治疗至少10例以上非小细胞肺癌病例的研究文献进行综述,提出了光动力疗法应用的治疗建议并进行了总结。 | Charles B Simone II Joseph S Friedberg Eli Glatstein James P Stevenson Daniel H Sterman Stephen M Hahn Keith A Cengel 袁光金 李金銮 朱宇熹 凌扬 | 2013 | 国际病理科学与临床杂志2013，33，3： | 3 |
| 14 | 一种房颤风险评分系统的建立(Framingham心脏研究):基于社区的队列研究显示文摘背景房颤导致了发病率和病死率的显著上升。本研究旨在建立一种预测个体罹患房颤绝对风险的风险评分系统,并提供研究人员评价新危险因素的流程。方法作者评估了Framingham心脏研究中于1968年6月至1987年9月间进行了8044次检测的4764例参与者(55%为女性,年龄45~95岁)。此后,参与者被随访至房颤首发,随访期最长达10年。多变量Coxi回归确认出1(1年内罹患房颤的临床危险因素。次级分析纳入了常规超声心动图检测指标(5152例4参与者,7156次检测)对房颤风险进行再分层评估,并评价超声检测指标能否提高风险预测能力。结果4764例参与者中的457例4(10%)罹患房颤。年龄、性别、体重指数、收缩压、降压治疗、PR间期、有临床意义的心脏杂音及心力衰竭与房颤相关,并被纳入了风险评分模型(除体重指数P=0.08外,其余均为P〈0.05),模型的C统计量为0.78(95%CI0.76~0.80)。10年房颤风险随年龄变化:年龄〈65岁的人群中53例(1%)风险高于15%,而〉65岁的人群中为783例(27%)。为提高预测能力而纳入超声检测指标仅使模型C统计量略微增高,由0.78(95%C10.75~0.80)增至0.79(95%CI0.77~0.82:P=0.005)。超声心动图检测指标并不能改善风险再分层评估(P=0.18)。结论基于社区医疗中易得的临床因素建立的风险评分系统,有助于确认社区个体罹患房颤的风险,评估技术或标志物能否改善风险预测,以及针对高危个体采取预防措施。 | Renate B Schnabel Lisa M Sullivan Daniel Levy Michael J Pencina Joseph M Massaro Ralph B D'Agostino Sr Christopher Newton-Cheh Jennifer F Yamamoto Jared W Magnani Thomas M Tadros William B Kannel Thomas J Wang Patrick T Ellinor Philip A Wolf Ramachanclran S Vasan Emelia J Benjamin 黄刚(译) | 2009 | 世界临床医学2009，，9： | 2 |
| 15 | Takotsubo cardiomyopathy:A comprehensive review显示文摘Takotsubo cardiomyopathy(TCM),also known as stress cardiomyopathy,occurs in the setting of catecholamine surge from an acute stressor.This cardiomyopathy mimics acute myocardial infarction in the absence of coronary disease.The classic feature of TCM is regional wall motion abnormalities with characteristic ballooning of the left ventricle.The etiology of the stressor is often physical or emotional stress,however iatrogenic causes of TCM have been reported in the literature.In our review,we discuss medications,primarily the exogenous administration of catecholamines,and a wide array of procedures with subsequent development of iatrogenic cardiomyopathy.TCM is unique in that it is transient and has favorable outcomes in most individuals.Classically,beta-blockers and ACE-inhibitors have been prescribed in individuals with cardiomyopathy;however,unique to TCM,no specific treatment is required other than temporary supportive measures as this process is transient.Additionally,no improvement in mortality or recurrence have been reported in patients on these drugs.The aim of this review is to elucidate on the iatrogenic causes of TCM,allowing for prompt recognition and management by clinicians. | Walker Barmore Himax Patel Sean Harrell Daniel Garcia Joe B Calkins Jr | 2022 | World Journal of Cardiology2022，14，6： | 2 |
| 16 | Age at Onset Should Be a Major Criterion for Subclassification of Colorectal Cancer显示文摘 | José Perea Daniel Rueda Alicia Canal Yolanda Rodríguez Edurne álvaro Irene Osorio Cristina Alegre Bárbara Rivera Joaquín Martínez Javier Benítez Miguel Urioste | 2014 | The Journal of Molecular Diagnostics2014，，1： | 2 |
| 17 | 站立30s后直立性低血压与老年抑郁之间的纵向关系显示文摘直立性低血压(orthostatic hypotension,OH)与老年抑郁之间存在明确的横向联系。该观察性研究的目的是为了阐明基线症状性OH(symptomatic OH,sOH-30)与抑郁症之问的纵向关系。该样本包含无基线抑郁症的老年人(平均年龄62岁)〉3000名。 | Robert B Daniel C Sean PK Rose AK 刘青 叶鹏 | 2018 | 中华高血压杂志2018，26，5： | 2 |
| 18 | 2009年南极冰穹A的双色天光背景统计和分析显示文摘天光背景是天文台址的一个重要指标。利用2009年位于南极冰穹A的CSTAR望远镜两个波段的观测数据,对南极冰穹A的天光背景进行了统计和分析。结果表明约74%的g波段天光背景的ADU值小于每像素100/s;90.5%的r波段的天光背景的ADU值小于每像素100/s。在不考虑大气消光的情况下,定标后的结果为2009年冰穹A的观测数据中天光背景亮度的中值:g波段为19.9 mag/arcsec2,r波段为20.1 mag/arcsec2。 | 宗伟凯 付建宁 牛家树 Ashley Michael C B 宫雪非 Lawrence J S 刘强 Luong-Van Daniel Pennypacker C R Storey John W V 王灵芝 王力帆 杨惠根 袁祥岩 York Donald G 朱镇熹 | 2014 | 天文研究与技术2014，11，1： | 2 |
| 19 | Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study显示文摘 | Daniel J Drucker John B Buse Kristin Taylor David M Kendall Michael Trautmann Dongliang Zhuang Lisa Porter | 2008 | The Lancet2008，，9645： | 2 |
| 20 | The Information of Historical Cost Earnings Relative to Supplemental Reserve-Based Accounting Data in the Extractive Petroleum Industry显示文摘 | B Michael Doran Daniel W Collins Dan S Dhaliwal | 1988 | The Accounting Review1988，63，3： | 1 |
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