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| 1 | Cardiac rehabilitation and exercise therapy in the elderly: Should we invest in the aged?显示文摘冠的心疾病(CHD ) 是世界范围的死亡的领先的原因并且在病人之中变得逐渐地流行 65 岁以上。老病人在为复杂并发症的更高的风险并且在一个心血管的事件以后加速物理 deconditioning,特别与他们的更年轻的对应物相比。最后几十年是到与 CHD 在病人之中在死亡,锻练能力,心理风险因素,发炎,和肥胖上表明了心脏的康复(CR ) 和锻练治疗的有益的效果的多重研究的厕所。不幸地,这个领域里的可得到的数据的重要部分与更年轻的病人相关。可行解释是更老的病人在为以病人开始并且延长到医生的多重原因的这些节目是非常未被充分代表的。在这篇文章,我们将考察 CR 节目的好处在之中老,以及一些妨碍他们的参予的障碍。 | Arthur R Menezes Carl J Lavie Richard V Milani Ross A Arena Timothy S Church | 2012 | Journal of Geriatric Cardiology2012，9，1： | 25 |
| 2 | 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 |
| 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 | Panitumumab and irinotecan versus irinotecan alone for patients with KRAS wild-type, fluorouracil-resistant advanced colorectal cancer (PICCOLO): a prospectively stratified randomised trial显示文摘 | Matthew T Seymour Sarah R Brown Gary Middleton Timothy Maughan Susan Richman Stephen Gwyther Catherine Lowe Jennifer F Seligmann Jonathan Wadsley Nick Maisey Ian Chau Mark Hill Lesley Dawson Stephen Falk Ann O’Callaghan Kim Benstead Philip Chambers Alfred | 2013 | Lancet Oncology2013，，8： | 6 |
| 5 | Small molecules enable OCT4-mediated direct reprogramming into expandable human neural stem cells显示文摘 | Saiyong Zhu Raiesh Ambasudhan Woong Sun Hyun Jung Kim Maria Talantova Xiaojing Wang Mingliang Zhang Yu Zhang Timothy Laurent James Parker Han-Seop Kim Jeffrey D Zaremba Sofiyan Saleem Sara Sanz-Blasco Eliezer Masliah Scott R McKercher Yee Sook Cho Stuart A Lipton Janghwan Kim Sheng Ding | 2014 | Cell Research2014，24，1： | 6 |
| 6 | Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus显示文摘AIM:To assess tumour regression grade(TRG)and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy.METHODS:Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005and 2011 at a single institution were reviewed.Triplet neoadjuvant chemotherapy consisting of platinum,fluoropyrimidine and anthracycline was considered for operable patients(World Health Organization performance status≤2)with clinical stage T2-4 N0-1.Response to neoadjuvant chemotherapy(NAC)was assessed using TRG,as described by Mandard et al.In addition lymph node downstaging was also assessed.Lymph node downstaging was defined by cN1 at diagnosis:assessed radiologically(computed tomography,positron emission tomography,endoscopic ultrasonography),then pathologically recorded as N0 after surgery;ypN0 if NAC given prior to surgery,or pN0if surgery alone.Patients were followed up for 5 years post surgery.Recurrence was defined radiologically,with or without pathological confirmation.An association was examined between t TRG and lymph node downstaging with disease free survival(DFS)and a comprehensive range of clinicopathological characteristics.RESULTS:Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years(median follow up:2.552,95%CI:2.022-3.081).There was a 1.8%(n=4)inpatient mortality rate.One hundred and thirty-six(62.4%)patients received NAC,with 74.3%(n=101)of patients demonstrating some signs of pathological tumour regression(TRG 1-4)and 5.9%(n=8)having a complete pathological response.Forty four point one percent(n=60)had downstaging of their nodal disease(cN1 to ypN0),compared to only 15.9%(n=13)that underwent surgery alone(pre-operatively overstaged:cN1 to pN0),(P<0.0001).Response to NAC was associated with significantly increased DFS(mean DFS;TRG 1-2:5.1years,95%CI:4.6-5.6 vs TRG 3-5:2.8 years,95%CI:2.2-3.3,P<0.0001).Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC(median DFS;TRG 3-5 and nodal down-staging:5.533 years,95%CI:3.558-7.531 vs TRG 3-5 and no nodal down-staging:1.114 years,95%CI:0.961-1.267,P<0.0001).CONCLUSION:Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS. | Fergus Noble Luke Nolan Adrian C Bateman James P Byrne Jamie J Kelly Ian S Bailey Donna M Sharland Charlotte N Rees Timothy J Iveson Tim J Underwood Andrew R Bateman | 2013 | World Journal of Gastroenterology2013，19，48： | 4 |
| 7 | Development of minimally invasive techniques for management of medically-complicated obesity显示文摘The field of bariatric surgery has been rapidly growing and evolving over the past several decades. During the period that obesity has become a worldwide epidemic, new interventions have been developed to combat this complex disorder. The development of new laparoscopic and minimally invasive treatments for medically-complicated obesity has made it essential that gastrointestinal physicians obtain a thorough understanding of past developments and possible future directions in bariatrics. New laparoscopic advancements provide patients and practitioners with a variety of options that have an improved safety profile and better efficacy without open, invasive surgery. The mechanisms of weight loss after bariatric surgery are complex and may in part be related to altered release of regulatory peptide hormones from the gut. Endoscopic techniques designed to mimic the effects of bariatric surgery and endolumenal inter-ventions performed entirely through the gastrointestinal tract offer potential advantages. Several of these new techniques have demonstrated promising, preliminary results. We outline herein historical and current trends in the development of bariatric surgery and its transition to safer and more minimally invasive procedures designed to induce weight loss. | Farzin Rashti Ekta Gupta Suzan Ebrahimi Timothy R Shope Timothy R Koch Christopher J Gostout | 2014 | World Journal of Gastroenterology2014，20，37： | 4 |
| 8 | Venous thromboembolism during active disease and remission in inflammatory bowel disease: a cohort study显示文摘 | Matthew J Grainge Joe West Timothy R Card | 2010 | The Lancet2010，，9715： | 3 |
| 9 | Dysphagia after vertical sleeve gastrectomy: Evaluation of risk factors and assessment of endoscopic intervention显示文摘AIM To evaluate the risks of medical conditions, evaluate gastric sleeve narrowing, and assess hydrostatic balloon dilatation to treat dysphagia after vertical sleeve gastrectomy(VSG).METHODS VSG is being performed more frequently worldwide as a treatment for medically-complicated obesity, and dysphagia is common post-operatively. We hypothesize that post-operative dysphagia is related to underlying medical conditions or narrowing of the gastric sleeve. This is a retrospective, single institution study of consecutive patients who underwent sleeve gastrectomy from 2013 to 2015. Patients with previous bariatric procedures were excluded. Narrowing of a gastric sleeve includes: inability to pass a 9.6 mm gastroscope due to stenosis or sharp angulation or spiral hindering its passage.RESULTS Of 400 consecutive patients, 352 are included; the prevalence of dysphagia is 22.7%; 33 patients(9.3%) have narrowing of the sleeve with 25(7.1%) having sharp angulation or a spiral while 8(2.3%) have a stenosis. All 33 patients underwent balloon dilatation of the gastric sleeve and dysphagia resolved in 13 patients(39%); 10 patients(30%) noted resolution of dysphagia after two additional dilatations. In a multivariate model, medical conditions associated with post-operative dysphagia include diabetes mellitus, symptoms of esophageal reflux, a low whole blood thiamine level, hypothyroidism, use of non-steroidal anti-inflammatory drugs, and use of opioids.CONCLUSION Narrowing of the gastric sleeve and gastric sleeve stenosis are common after VSG. Endoscopic balloon dilatations of the gastric sleeve resolves dysphagia in 69% of patients. | Anand Nath Sayali Yewale Tung Tran John S Brebbia Timothy R Shope Timothy R Koch | 2016 | World Journal of Gastroenterology2016，22，47： | 3 |
| 10 | Organization of future training in bariatric gastroenterology显示文摘A world-wide rise in the prevalence of obesity continues. This rise increases the occurrence of, risks of, and costs of treating obesity-related medical conditions. Diet and activity programs are largely inadequate for the long-term treatment of medically-complicated obesity. Physicians who deliver gastrointestinal care after completing traditional training programs, including gastroenterologists and general surgeons, are not uniformly trained in or familiar with available bariatric care. It is certain that gastrointestinal physicians will incorporate new endoscopic methods into their practice for the treatment of individuals with medically-complicated obesity, although the longterm impact of these endoscopic techniques remains under investigation. It is presently unclear whether gastrointestinal physicians will be able to provide or coordinate important allied services in bariatric surgery, endocrinology, nutrition, psychological evaluation and support, and social work. Obtaining longitudinal results examining the effectiveness of this ad hoc approach will likely be difficult, based on prior experience with other endoscopic measures, such as the adenoma detection rates from screening colonoscopy. As a longterm approach, development of a specific curriculum incorporating one year of subspecialty training in bariatrics to the present training of gastrointestinal fellows needs to be reconsidered. This approach should be facilitated by gastrointestinal trainees' prior residency training in subspecialties that provide care for individuals with medical complications of obesity, including endocrinology, cardiology, nephrology, and neurology. Such training could incorporate additional rotations with collaborating providers in bariatric surgery, nutrition, and psychiatry. Since such training would be provided in accredited programs, longitudinal studies could be developed to examine the potential impact on accepted measures of care, such as complication rates, outcomes, and costs, in individuals with medically-complicated obesity. | Timothy R Koch Timothy R Shope Christopher J Gostout | 2017 | World Journal of Gastroenterology2017，23，35： | 2 |
| 11 | 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 |
| 12 | Management of the Open Abdomen: From Initial Operation to Definitive Closure显示文摘 | Vargo Daniel Richardson J David Campbell Andre Chang Michael Fabian Timothy Franz Michael Kaplan Mark Moore Frederick Reed R Lawrence Scott Bradford Silverman Ronald | 2009 | The American Surgeon2009，，11： | 2 |
| 13 | Current and future impact of clinical gastrointestinal research on patient care in diabetes mellitus显示文摘The worldwide rise in the prevalence of obesity supports the need for an increased interaction between ongoing clinical research in the allied fields of gastrointestinal medicine/surgery and diabetes mellitus. There have been a number of clinically-relevant advances in diabetes, obesity, and metabolic syndrome emanating from gastroenterological research. Gastric emptying is a significant factor in the development of upper gastrointestinal symptoms. However, it is not the only mechanism whereby such symptoms occur in patients with diabetes. Disorders of intrinsic pacing are involved in the control of stomach motility in patients with gastroparesis; on the other hand, there is limited impact of glycemic control on gastric emptying in patients with established diabetic gastroparesis. Upper gastrointestinal functions related to emptying and satiations are significantly associated with weight gain in obesity. Medications used in the treatment of diabetes or metabolic syndrome, particularly those related to pancreatic hormones and incretins affect upper gastrointestinal tract function and reduce hyperglycemia and facilitate weight loss. The degree of gastric emptying delay is significantly correlated with the weight loss in response to liraglutide, a glucagonlike peptide-1 analog. Network meta-analysis shows that liraglutide is one of the two most efficacious medical treatments of obesity, the other being the combination treatment phentermine-topiramate. Interventional therapies for the joint management of obesity and diabetes mellitus include newer endoscopic procedures, which require long-term follow-up and bariatric surgical procedure for which long-term follow up shows advantages for individuals with diabetes. Newer bariatric procedures are presently undergoing clinical evaluation. On the horizon, combination therapies, in part directed at gastrointestinal functions, appear promising for these indications. Ongoing and future gastroenterological research when translated to care of individuals with diabetes mellitus should provide additional options to improve their clinical outcomes. | Timothy R Koch Timothy R Shope Michael Camilleri | 2018 | World Journal of Diabetes2018，9，11： | 2 |
| 14 | 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 |
| 15 | Arsenic removal from drinking water by flocculation and microfiltration显示文摘 | BINBING H TIMOTHY R JULIO Z | 2002 | Desalination2002，，145： | 1 |
| 16 | 显示文摘 | Timothy A Becker Daryl R Kipke | 2002 | Journal of Biomedical Materials Research2002，61，4： | 1 |
| 17 | Role of metastable phases in the spontaneous precipitation of calcium carbonate显示文摘 | John R Clarkson Timothy J Price Christopher J Adms | 1992 | Chem Soc Faraday Trans1992，88，2： | 1 |
| 18 | Finding drug targets in microbial genomes 显示文摘 | Timothy D R Steven R G Herve T | 2001 | Res Focus2001，6，17： | 1 |
| 19 | Product platform design:method and application 显示文摘 | Timothy W Simpson Jonathan R A Maier Farrokh Mistree | 2001 | Engineering Design2001，13，1： | 1 |
| 20 | Incident vertebral frac- tures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study显示文摘 | Celin R Bianca L Timothy R | 2012 | Arth- ritis Care Res2012，64，： | 1 |
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