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| 1 | Intracellular HMGB1 as a novel tumor suppressor of pancreatic cancer显示文摘尽管有最近的进展, oncogenic K 地岬驾驶的胰腺的 ductal 腺癌(PDAC ) 在最致命的人的癌症之中留在现代医学。PDAC 的致病对内在的染色体不稳定性和外来的发炎激活部分可归因。然而,在在胰腺的 tumorigenesis 的这二个事件之间的分子的连接充分还没被建立了。这里,我们证明(HMGB1 ) 细胞内部的高活动性组盒子 1 显著地压制 oncogenic 由禁止染色体的 K-Ras-driven 胰腺的 tumorigenesis 调停不稳定性的支持 inflammatory nucleosome 版本。任何一个单身者的有条件的基因脱离或在胰的 HMGB1 的两等位基因在出生使老鼠变为极其敏感到先锋损害的 oncogenic K-Ras-driven 开始,包括胰腺的 intraepithelial 瘤, intraductal 乳突的 mucinous 瘤,和 mucinous 膀胱的瘤。在胰的 HMGB1 的损失与染色体重新整理和 telomere 畸形描绘的氧化 DNA 损坏和 chromosomal 不稳定性被联系。这些导致煽动性的 nucleosome 版本并且宣传 K-Ras-driven 胰腺的 tumorigenesis。细胞外的 nucleosomes 支持 interleukin 6 (IL-6 ) 由渗入 macrophages/neutrophils 的分泌物并且提高在胰腺的损害表明激活的 oncogenic K 地岬。到 IL-6 或 histone H3 或为先进 glycation 的受体的大美人的抵销的抗体结束产品都限制表明激活的 K 地岬,阻止癌症开发和转移 / 侵略,并且延长在 Pdx1-Cre 的动物幸存; K 地岬 G12D/+;Hmgb1/ 鼠标。由 glycyrrhizin 的 HMGB1 损失的药理学抑制在煽动性的条件下面在老鼠限制 oncogenic K-Ras-driven tumorigenesis。减少在 PDAC 病人的 HMGB1 的原子、全部的细胞的表示与差的全面幸存相关,在 PDAC 与预示、治疗学的关联作为新奇肿瘤 suppressor 支持细胞内部的 HMGB1。 | Rui Kang Yangchun Xie Qiuhong Zhang Wen Hou Qingping Jiang Shan Zhu Jinbao Liu Dexing Zeng Haichao Wang David L Bartlet Timothy R Billiar Herbert J Zeh III Michael T Lotze Daolin Tang | 2017 | Cell Research2017，27，7： | 22 |
| 2 | Autoantibody to MOG suggests two distinct clinical subtypes of NMOSD显示文摘We characterized a unique group of patients with neuromyelitis optica spectrum disorder(NMOSD) who carried autoantibodies of aquaporin-4(AQP4) and myelin-oligodendrocyte glycoprotein(MOG). Among the 125 NMOSD patients, 10(8.0%) were AQP4- and MOG-ab double positive, and 14(11.2%) were MOG-ab single positive. The double-positive patients had a multiphase disease course with a high annual relapse rate(P=0.0431), and severe residual disability(P<0.0001). Of the double-positive patients, 70% had MS-like brain lesions, more severe edematous, multifocal regions on spinal magnetic resonance imaging(MRI), pronounced decreases of retinal nerve fiber layer thickness and atrophy of optic nerves. In contrast, patients with only MOG-ab had a higher ratio of monophasic disease course and mild residual disability. Spinal cord MRI illustrated multifocal cord lesions with mild edema, and brain MRIs showed more lesions around lateral ventricles. NMOSD patients carrying both autoantibodies to AQP4 and MOG existed and exhibited combined features of prototypic NMO and relapsing-remitting form of MS, whereas NMOSD with antibodies to MOG only exhibited an 'intermediate' phenotype between NMOSD and MS. Our study suggests that antibodies against MOG might be pathogenic in NMOSD patients and that determination of anti-MOG antibodies maybe instructive for management of NMOSD patients. | Yaping Yan Yujing Li Ying Fu Li Yang Lei Su Kaibin Shi Minshu Li Qiang Liu Aimee Borazanci Yaou Liu Yong He Jeffrey L Bennett Timothy L Vollmer Fu-Dong Shi | 2016 | Science China(Life Sciences)2016，59，12： | 20 |
| 3 | Direct reprogramming of human fibroblasts into dopaminergic neuron-like cells显示文摘外长的 dopaminergic 神经原(DA 神经原) 的移植是为治疗 Parkinson 的疾病(PD ) 的一条有希望的途径。然而,主要跌倒块是施主 DA 神经原的可靠来源的缺乏。这里,我们证明五 transcriptional 因素 Mash1, Ngn2, Sox2, Nurr1,和 Pitx3 的联合直接并且有效地装改编人成纤维细胞进 DA 像神经原的房间。为为 DA 神经原的各种各样的标记积极的染色的 reprogrammed 房间。他们也显示出典型 DA 举起和生产性质。而且,他们展出了 DA 神经原特定的 electrophysiological 侧面。最后,他们在一个老鼠 PD 模型提供了征兆的地势。因此,我们的直接 reprogrammed DA 像神经原的房间是为 PD 的房间代替治疗的有希望的来源。 | Xinjian Liu Fang Li Elizabeth A Stubblefield Barbara Blanchard Toni L Richards Gaynor A Larson Yujun He Qian Huang Aik-Choon Tan Dabing Zhang Timothy A Benke John R Sladek Nancy R Zahniser Chuan-Yuan Li | 2012 | Cell Research2012，22，2： | 14 |
| 4 | Colorectal cancer and dysplasia in inflammatory bowel disease显示文摘Both ulcerative colitis and Crohn’s disease carry an increased risk of developing colorectal cancer. Established risk factors for cancer among patients with inflammatory bowel disease (IBD) include the younger age at diagnosis, greater extent and duration of disease, increased severity of inflammation, family history of colorectal cancer and coexisting primary sclerosing cholangitis. Recent evidence suggests that current medical therapies and surgical techniques for inflammatory bowel disease may be reducing the incidence of this complication. Nonetheless heightened vigilance and a careful, comprehensive approach to prevent or minimize the complications of invasive cancer are warranted in this unique cohort of patients. Current guidelines for the prevention and early detection of cancer in this high risk population are grounded in the concept of an inflammation-dysplasia- carcinoma sequence. A thorough understanding of the definition and natural history of dysplasia in IBD, as well as the challenges associated with detection and interpretation of dysplasia are fundamental to developing an effective strategy for surveillance and prevention, and understanding the limitations of the current approach to prevention. This article reviews the current consensus guidelines for screening and surveillance of cancer in IBD, as well as presenting the evidence and rationale for chemoprevention of cancer and a discussion of emerging technologies for the detection of dysplasia. | Timothy L Zisman David T Rubin | 2008 | World Journal of Gastroenterology2008，14，17： | 13 |
| 5 | Management of borderline and locally advanced pancreatic cancer:Where do we stand?显示文摘Many patients with pancreas cancer present with locally advanced pancreatic cancer(LAPC).The principle tools used for diagnosis and staging of LAPC include endoscopic ultrasound,axial imaging with computed tomography and magnetic resonance imaging,and diagnostic laparoscopy.The definition of resectability has historically been vague,as there is considerable debate and controversy as to the definition of LAPC.For the patient with LAPC,there is some level of involvement of the surrounding vascular structures,which include the superior mesenteric artery,celiac axis,hepatic artery,superior mesenteric vein,or portal vein.When feasible,most surgeons would recommend possible surgical resection for patients with borderline LAPC,with the goal of an R0 resection.For initially unresectable LAPC,neoadjuvant should be strongly considered.Specifically,these patients should be offered neoadjuvant therapy,and the tumor should be assessed for possible response and eventual resection.The efficacy of neoadjuvant therapy with this approach as a bridge to potential curative resection is broad,ranging from 3%-79%.The different modalities of neoadjuvant therapy include sin-gle or multi-agent chemotherapy combined with radiation,chemotherapy alone,and chemotherapy followed by chemotherapy with radiation.This review focuses on patients with LAPC and addresses recent advances and controversies in the field. | Jin He Andrew J Page Matthew Weiss Christopher L Wolfgang Joseph M Herman Timothy M Pawlik | 2014 | World Journal of Gastroenterology2014，20，9： | 11 |
| 6 | Childhood achalasia: A comprehensive review of disease, diagnosis and therapeutic management显示文摘Achalasia is an esophageal motility disorder character-ized by failure of lower esophageal sphincter(LES) relaxation and is rare in children. The most common symptoms are vomiting, dysphagia, regurgitation, and weight loss. Definitive diagnosis is made with barium swallow study and esophageal manometry. In adults, endoscopic biopsy is recommended to exclude malig-nancy however; it is not as often indicated in children. Medical management often fails resulting in recurrent symptoms and the ultimate definitive treatment is sur-gical. Laparoscopic Heller myotomy with or without an anti-reflux procedure is the treatment of choice and has become standard of care for children with achala-sia. Peroral endoscopic myotomy is a novel therapy uti-lized with increasing frequency for achalasia treatment in adults. More experience is needed to determine the safety, efficacy, and feasibility of peroral endoscopic myotomy in children. | Ashanti L Franklin Mikael Petrosyan Timothy D Kane | 2014 | World Journal of Gastrointestinal Endoscopy2014，6，4： | 9 |
| 7 | Interaction of obesity and inflammatory bowel disease显示文摘Inflammatory bowel disease(IBD) is a chronic inflammatory condition of unknown etiology that is thought to result from a combination of genetic, immunologic and environmental factors. The incidence of IBD has been increasing in recent decades, especially in developing and developed nations, and this is hypothesized to be in part related to the change in dietary and lifestyle factors associated with modernization. The prevalence of obesity has risen in parallel with the rise in IBD, suggesting a possible shared environmental link between these two conditions. Studies have shown that obesity impacts disease development and response to therapy in patients with IBD and other autoimmune conditions. The observation that adipose tissue produces pro-inflammatory adipokines provides a potential mechanism for the observed epidemiologic links between obesity and IBD, and this has developed into an active area of investigative inquiry. Additionally, emerging evidence highlights a role for the intestinal microbiota in the development of both obesity and IBD, representing another potential mechanistic connection between the two conditions. In this review we discuss the epidemiology of obesity and IBD, possible pathophysiologic links, and the clinical impact of obesity on IBD disease course and implications for management. | Jason W Harper Timothy L Zisman | 2016 | World Journal of Gastroenterology2016，22，35： | 6 |
| 8 | Femtosecond-laser sharp shaping of millimeter-scale geometries with vertical sidewalls显示文摘As femtosecond(fs)laser machining advances from micro/nanoscale to macroscale,approaches capable of machining macroscale geometries that sustain micro/nanoscale precisions are in great demand.In this research,an fs laser sharp shaping approach was developed to address two key challenges in macroscale machining(i.e.defects on edges and tapered sidewalls).The evolution of edge sharpness(edge transition width)and sidewall tapers were systematically investigated through which the dilemma of simultaneously achieving sharp edges and vertical sidewalls were addressed.Through decreasing the angle of incidence(AOI)from 0◦to−5◦,the edge transition width could be reduced to below 10µm but at the cost of increased sidewall tapers.Furthermore,by analyzing lateral and vertical ablation behaviors,a parameter-compensation strategy was developed by gradually decreasing the scanning diameters along depth and using optimal laser powers to produce non-tapered sidewalls.The fs laser ablation behaviors were precisely controlled and coordinated to optimize the parameter compensations in general manufacturing applications.The AOI control together with the parameter compensation provides a versatile solution to simultaneously achieve vertical sidewalls as well as sharp edges of entrances and exits for geometries of different shapes and dimensions.Both mm-scale diameters and depths were realized with dimensional precisions below 10µm and surface roughness below 1µm.This research establishes a novel strategy to finely control the fs laser machining process,enabling the fs laser applications in macroscale machining with micro/nanoscale precisions. | Qiuchi Zhu Peixun Fan Nan Li Timothy Carlson Bai Cui Jean-François Silvain Jerry L Hudgins Yong Feng Lu | 2021 | International Journal of Extreme Manufacturing2021，3，4： | 6 |
| 9 | Radial artery access site complications during cardiac procedures,clinical implications and potential solutions: The role of nitric oxide显示文摘Percutaneous coronary intervention for the treatment of coronary artery disease is most commonly performed in the UK through the radial artery,as this is considered to be safer than the femoral approach.However,despite improvements in technology and techniques,complications can occur.The most common complication,arterial spasm,can cause intense pain and,in some cases,procedural failure.The incidence of spasm is dependent on several variables,including operator experience,artery size,and equipment used.An antispasmolytic cocktail can be applied to reduce spasm,which usually includes an exogenous nitric oxide(NO)donor(glyceryl trinitrate).NO is an endogenous local vasodilator and therefore is a potential target for anti-spasm intervention.However,systemic administration can result in unwanted side-effects,such as hypotension.A method that adopts local delivery of NO might be advantageous.This review article describes the mechanisms involved in radial artery spasm,discusses the advantages and disadvantages of current strategies to reduce spasm,and highlight the potential of NO-loaded nanoporous materials for use in this setting. | Emma M Coghill Timothy Johnson Russell E Morris Ian L Megson Stephen J Leslie | 2020 | World Journal of Cardiology2020，12，1： | 4 |
| 10 | An apple rootstock overexpressing a peach CBF gene alters growth and flowering in the scion but does not impact cold hardiness or dormancy显示文摘The C-repeat binding factor(CBF)transcription factor is involved in responses to low temperature and water deficit in many plant species.Overexpression of CBF genes leads to enhanced freezing tolerance and growth inhibition in many species.The overexpression of a peach CBF(PpCBF1)gene in a transgenic line of own-rooted apple(Malus×domestica)M.26 rootstock(T166)trees was previously reported to have additional effects on the onset of dormancy and time of spring budbreak.In the current study,the commercial apple cultivar‘Royal Gala’(RG)was grafted onto either non-transgenic M.26 rootstocks(RG/M.26)or transgenic M.26(T166)rootstocks(RG/T166)and field grown for 3 years.No PpCBF1 transcript was detected in the phloem or cambium of RG scions grafted on T166 rootstocks indicating that no graft transmission of transgene mRNA had occurred.In contrast to own-rooted T166 trees,no impact of PpCBF1 overexpression in T166 rootstocks was observed on the onset of dormancy,budbreak or non-acclimated leaf-cold hardiness in RG/T166 trees.Growth,however,as measured by stem caliper,current-year shoot extension and overall height,was reduced in RG/T166 trees compared with RG/M.26 trees.Although flowering was evident in both RG/T166 and RG/M.26 trees in the second season,the number of trees in flower,the number of shoots bearing flowers,and the number of flower clusters per shoot was significantly higher in RG/M.26 trees than RG/T166 trees in both the second and third year after planting.Elevated levels of RGL(DELLA)gene expression were observed in RG/T166 trees and T166 trees,which may play a role in the reduced growth observed in these tree types.A model is presented indicating how CBF overexpression in a rootstock might influence juvenility and flower abundance in a grafted scion. | Timothy S Artlip Michael E Wisniewski Rajeev Arora John L Norelli | 2016 | Horticulture Research2016，3，1： | 4 |
| 11 | Comparison of visual acuity outcomes between ranibizumab and bevacizumab treatment in neovascular age-related macular degeneration显示文摘AIM:To compare visual acuity(VA) outcomes between intravitreal injection of bevacizumab and ranibizumab in the treatment of neovascular age-related macular degeneration(AMD).· METHODS:We conducted a consecutive,retrospective case series study in patients with newly diagnosed all type choroidal neovascularization(CNV) secondary to AMD who received an intravitreal injection of bevacizumab(1.25mg) or ranibizumab(0.3mg) at Lions Eye Institute,Western Australia from Mar.2006 to May 2008.All patients received injection at baseline with additional monthly injections given at the discretion of the treating physician.Main outcome measures were changes in VA.· RESULTS:There were 371 consecutive patients received injection at least in one eye with at least 6 months of follow up(median of 12.0 months).Bevacizumab treatment prevented 221 out of 278(79.5%) patients from losing <15 letters in VA compared with 79 out of 93(84.9%) of ranibizumab treated patients(P=0.25).While 68(24.5%) of bevacizumab treated patients gained ≥15 letters of VA compared with 24(25.8%) of ranibizumab treated patients(P=0.79).75.3% and 66.2% patients benefited from ranibizumab and bevacizumab respectively with final VA better than 6/60(P=0.10).Multivariate analysis showed that pre-treatment VA was negatively associated with benefit outcome.Assignment of injection was not associated with VA outcome of benefit after adjusting the covariate(P=0.857).CONCLUSION:There are no difference in treatment efficacy in terms of VA between bevacizumab and ranibizumab in routine clinical condition. | Ian J Constable Ian L McAllister Timothy Isaacs | 2011 | International Journal of Ophthalmology(English edition)2011，4，1： | 3 |
| 12 | Image-guided therapies in the treatment of hepatocellular carcinoma: A multidisciplinary perspective显示文摘A multidisciplinary approach to the treatment of patients with unresectable hepatocellular carcinoma(HCC) has led to improvements in screening, detection,and treatments. Interventional techniques includethermal ablation, transarterial chemoembolization, and radioembolization whilst stereotactic body radiation therapy also uses imaging to target the radiation. Both survival rates and cure rates have improved markedly since the introduction of these techniques. This review article describes the image guided techniques used for the treatment of HCC. | Jonathon Willatt Kevin K Hannawa Julie A Ruma Timothy L Frankel Dawn Owen Pranab M Barman | 2015 | World Journal of Hepatology2015，7，2： | 2 |
| 13 | Metastatic recurrence to a solitary lymph node four years after hepatic lobectomy for primary hepatocellular carcinoma显示文摘This report describes a patient that developed recurrent metastatic hepatocellular carcinoma(HCC) to a suprapancreatic lymph node four years after being treated for primary HCC via complete left hepatectomy. Metastatic HCC was proven by pathologic confirmation. The report addresses the role of surgical resection as a treatment modality for recurrent HCC to solitary lymph nodes. The role of biological chemotherapy as adjuvant treatment is also addressed. | Michael L Caparelli Nathan J Roberts Timothy S Braverman Robert M Stevens Edward R Broun Shyam Allamaneni | 2016 | World Journal of Hepatology2016，8，23： | 2 |
| 14 | Drug-Induced Liver Injury Network (DILIN) Prospective Study: Rationale, Design and Conduct显示文摘 | Fontana Robert J Watkins Paul B Bonkovsky Herbert L Chalasani Naga Davern Timothy Serrano Jose Rochon James | 2009 | Drug Safety2009，，1： | 2 |
| 15 | Diet, microbial virulence, and Helicobacter pylori-induced gastric cancer显示文摘 | Timothy L Cover Richard M Peek Jr | 2013 | Gut Microbes2013，，： | 2 |
| 16 | CX3CR1 regulates intestinal macrophage homeostasis, bacterial translocation, and colitogenic Th17 responses in mice显示文摘 | Medina-Contreras Oscar Geem Duke Laur Oskar Williams Ifor R Lira Sergio A Nusrat Asma Parkos Charles A Denning Timothy L | 2011 | Journal of Clinical Investigation2011，，12： | 2 |
| 17 | Sub-Hertz relative frequency stabilization of two-diode laser-pumped Nd: YAG lasers locked to a Fabry-Perot interferometer 显示文摘 | Eric K Gustafson Robert L Byer | 1992 | IEEE Journal of Quantum Electronics1992，28，4： | 1 |
| 18 | Evaluating a Domain-specialist Oriented Knowledge Management System显示文摘 | | 2000 | International Journal of Human-Computer Studies2000，52，6： | 1 |
| 19 | Acute applications of noninvasive positive pressure ventilation显示文摘 | Timothy L Henry K Nicholas S | 2003 | Chest2003，124，： | 1 |
| 20 | Mesenchymalstem cells at the intersection of cell and gene therapy 显示文摘 | Timothy JM Froilan GM Lara L | 2010 | Expert Opin Biol Ther2010，10，： | 1 |
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