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| 1 | Nat Genet:单细胞分析解开结直肠癌细胞的神秘面纱显示文摘结合单细胞基因组学和计算机技术,一个研究团队(包括来自杰克逊实验室(JAx)单细胞生物学主任Paul Robson博士在内)鉴定出了11种结直肠癌肿瘤的癌细胞组成及邻近的非癌细胞。这对于更好的肿瘤靶向诊断和治疗很重要。”使用单细胞测序。”JAX科学家、这篇发表在Nature Genetics上的文章共同第一作者Elise Courtois说道。”我们可以根据肿瘤中的细胞组成将结直肠癌进一步分类。因为每种亚型的肿瘤病人生存率存在差别,我们的方法将为肿瘤医生提供更多的关于肿瘤预后和治疗的信息。” | Huipeng Li, Elise T Courtois, Debarka Sengupta, Yuliana Tan Shyam Prabhakar Elise T Courtois, Yuliana Tan Paul Robson Debarka Sengupta Kok Hao Chen, Jolene Jie Lin Goh Paul Jongjoon Choi Say Li Kong, Axel M Hillmer Iain Beehuat Tan Clarinda Chua Iain Beehuat Tan Lim Kiat Hon Wah Siew Tan Mark Wong Lawrence J K Wee Iain Beehuat Tan Paul Robson Paul Robson Paul Robson | 2017 | 现代生物医学进展2017，17，15： | 37 |
| 2 | Association of 25-hydroxy-vitamin D levels with semen and hormonal parameters显示文摘维生素 D 层次包括繁殖混乱被连接了到各种各样的健康结果。这研究的目的是探索在浆液维生素 D 水平(25-hydroxy-vitamin D,或 25OHD ) 和精液和神经质的参数之间的协会。这是包括了从一般人口为精子发生的学习招募的 170 个健康的人的代表性的研究。完成的将军和繁殖健康问询表,和捐赠的血和精液取样的人。主要措施是神经质的(全部、免费的睾丸激素,性荷尔蒙绑定血球素, estradiol ,刺激滤泡的荷尔蒙和 luteinizing 荷尔蒙)并且精液参数,调整( n=147 )好久,身体团索引( BMI ),季节,白酒吸入并且吸烟,在与维生素 D 层次的范畴的关系,决定了 priori 。学习人口的吝啬的年龄是 29.0 ± 8.5 年和吝啬的 BMI 是 24.3 ± 3.2 kg m −2 。吝啬的 25OHD 是 34.1 ± 15.06 ng ml −1 。BMI 与 25OHD 显示出一个否定协会。精子集中,进步活动性,精子形态学,和全部的日益增多地能动的精子数的精子在有 ‘ 的人是更低的; 25OHD ≥ 50 ng ml −1' 什么时候与有 ‘ 的人相比; 20 ng ml −1≤25OHD<50 ng ml −1' 。全部的精子计数和全部的进步能动精子计数在有 ‘ 的人是更低的; 25OHD < 20 ng ml −1' 什么时候与有 ‘ 的人相比; 20 ng ml −1≤25OHD<50 ng ml −1' 。各种各样的神经质的参数的调整工具没在 25OHD 的不同范畴显示出统计差别。在结论,在高度和底层的浆液维生素 D 层次能否定地与精液参数被联系。 | Ahmad O Hammoud A Wayne Meikle C Matthew Peterson Joseph Stanford Mark Gibson Douglas T Carrell | 2012 | Asian Journal of Andrology2012，14，6： | 19 |
| 3 | 超重与男性生殖能力研究进展:睡眠呼吸暂停,一个新领域显示文摘肥胖会对男性生殖产生负面影响,主要是因为肥胖与低睾酮水平和促性腺激素改变有关。男性肥胖已经被发现与男性生育力下降有关,但由于影响的性质和程度不同,肥胖与精子参数相关性的数据存在争议。一些新研究领域的出现,如遗传多态性和睡眠呼吸暂停,将有助于解释研究结果的差异性。已经发现睡眠紊乱与男性睾酮生成的变化和性腺功能低下有关,也可能与勃起功能障碍有关。睡眠紊乱与不育和精子参数的关系还有待研究。忠有性腺功能低下和不育的男性应该进行睡眠呼吸暂停症的筛查。对肥胖和睡眠呼吸暂停的治疗可以改善睾酮水平和勃起功能。 | Ahmad O Hammoud Douglas T Carrell Mark Gibson C Matthew Peterson A Wayne Meikle | 2012 | Asian Journal of Andrology2012，14，1： | 11 |
| 4 | Contractile apparatus dysfunction early in the pathophysiology of diabetic cardiomyopathy显示文摘Diabetes mellitus significantly increases the risk of cardiovascular disease and heart failure in patients.Independent of hypertension and coronary artery disease,diabetes is associated with a specific cardiomyopathy,known as diabetic cardiomyopathy(DCM).Four decades of research in experimental animal models and advances in clinical imaging techniques suggest that DCM is a progressive disease,beginning early after the onset of type 1 and type 2 diabetes,ahead of left ventricular remodeling and overt diastolic dysfunction.Although the molecular pathogenesis of early DCM still remains largely unclear,activation of protein kinase C appears to be central in driving the oxidative stress dependent and independent pathways in the development of contractile dysfunction.Multiple subcellular alterations to the cardiomyocyte are now being highlighted as critical events in the early changes to the rate of force development,relaxation and stability under pathophysiological stresses.These changes include perturbed calcium handling,suppressed activity of aerobic energy producing enzymes,altered transcriptional and posttranslational modification of membrane and sarcomeric cytoskeletal proteins,reduced actin-myosin cross-bridge cycling and dynamics,and changed myofilament calcium sensitivity.In this review,we will present and discuss novel aspects of the molecular pathogenesis of early DCM,with a special focus on the sarcomeric contractile apparatus. | Mark T Waddingham Amanda J Edgley Hirotsugu Tsuchimochi Darren J Kelly Mikiyasu Shirai James T Pearson | 2015 | World Journal of Diabetes2015，6，7： | 10 |
| 5 | Rectal nitric oxide as biomarker in the treatment of inflammatory bowel disease: Responders versus nonresponders显示文摘瞄准:探索直肠的氮的氧化物(没有) 作为处理的简历标记,在 ulcerative (UC ) 和 Crohn 的反应是疾病(CD ) ,并且检验在之间的关系直肠没有,没有 synthases (NOS ) 的粘膜表示,和支持 inflammatory cytokines。方法:有 UC 的 22 个病人并且 24 在类固醇治疗期间与 CD 被监视。直肠没有层次被测量,临床的活动在天被估计 1, 3, 7 和 28。NOS 和支持 inflammatory cytokines 的粘膜存在被免疫组织化学和 RT-PCR 分析。结果:显著地显示的活跃 UC 和 CD 增加了直肠没有层次(10950 +/- 1280 每十亿分开的 7610 和 5040 +/-(ppb ) ,分别地) 作为与控制相比(154 +/- 71 ppb, P <
0.001 ) 。直肠不在 UC 和 CD 与疾病活动微弱地相关(r = 0.34 为 UC 和 r = 0.48 为 CD, P <
0.01 ) 。在 12 个病人,一堂类固醇倔强的功课导致了结肠切除术。仅仅稍微有的这些病人没增加层次(UC:620 +/- 270 ppb;CD:1260 +/- 550 ppb ) 与那些相比与治疗学的回答(UC:18860 +/- 530 ppb, P <
0.001;CD:10060 +/- 3200 ppb, P <
0.05 ) 。结论:直肠没有水平是在是的 IBD 的治疗反应的一个有用简历标记低没有层次预言差的临床的回答到类固醇治疗。 | Tryggve Ljung Sofie Lundberg Mark Varsanyi Catharina Johansson Peter T Schmidt Max Herulf Jon O Lundberg Per M Hellstr(o|¨)m | 2006 | World Journal of Gastroenterology2006，12，21： | 10 |
| 6 | 普适计算推动数字技术在教育中的应用显示文摘本文介绍了普适计算(Ubiquitous Computing)及其在教育中的定位,同时回顾了普适计算的历史,介绍了普适计算的发展现状,探讨了当前对教育中普适计算的理解及其对教学的影响。本研究阐述了范在学习条件下,教学、学习、学习环境和师生交互发生的变化,也总结了普适计算在教育应用中的一些不足,并展望普适计算教育应用的未来。 | Mark van't Hooft 夏天 | 2007 | 中国电化教育2007，，1： | 7 |
| 7 | INT-767 improves histopathological features in a dietinduced ob/ob mouse model of biopsy-confirmed nonalcoholic steatohepatitis显示文摘AIM To characterize the efficacy of the dual FXR/TGR5 receptor agonist INT-767 upon histological endpoints in a rodent model of diet-induced and biopsy-confirmed non-alcoholic steatohepatitis(NASH).METHODS The effects of INT-767 on histological features of NASH were assessed in two studies using Lep^(ob/ob)(ob/ob) NASH mice fed the AMLN diet(high fat with transfat, cholesterol and fructose). In a proof-of-conceptstudy, Lep^(ob/ob)(ob/ob) NASH mice were first dosed with INT-767(3 or 10 mg/kg for 8 wk). A second ob/ob NASH study compared INT-767(3 and 10 mg/kg) to obeticholic acid(OCA)(10 or 30 mg/kg; 16 wk). Primary histological endpoints included qualitative and quantitative assessments of NASH. Other metabolic and plasma endpoints were also assessed. A comparative assessment of INT-767 and OCA effects on drug distribution and hepatic gene expression was performed in C57 Bl/6 mice on standard chow. C57 Bl/6 mice were orally dosed with INT-767 or OCA(1-30 mg/kg) for 2 wk, and expression levels of candidate genes were assessed by RNA sequencing and tissue drug levels were measured by liquid chromatography tandem-mass spectrometry.RESULTS INT-767 dose-dependently(3 and 10 mg/kg, PO, QD, 8 wk) improved qualitative morphometric scores on steatohepatitis severity, inflammatory infiltrates and fibrosis stage. Quantitative morphometric analyses revealed that INT-767 reduced parenchymal collagen area, collagen fiber density, inflammation(assessed by Galectin-3 immunohistochemistry) and hepatocyte lipid droplet area following INT-767 treatment. In a comparative study(16 wk), the FXR agonists OCA(10 and 30 mg/kg) and INT-767(3 and 10 mg/kg) both improved NASH histopathology, with INT-767 exerting greater therapeutic potency and efficacy than OCA. Mechanistic studies suggest that both drugs accumulate similarly within the liver and ileum, however, the effects of INT-767 may be driven by enhanced hepatic, but not ileal, FXR function. CONCLUSION These findings confirm the potential utility of FXR and dual FXR/TGR5 activation as disease intervention strategies in NASH. | Jonathan D Roth Michael Feigh Sanne S Veidal Louise KD Fensholdt Kristoffer T Rigbolt Henrik H Hansen Li C Chen Mathieu Petitjean Weslyn Friley Niels Vrang Jacob Jelsing Mark Young | 2018 | World Journal of Gastroenterology2018，24，2： | 7 |
| 8 | 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 |
| 9 | Chronic kidney disease after nephrectomy in patients with renal cortical tumours: a retrospective cohort study显示文摘 | William C Huang Andrew S Levey Angel M Serio Mark Snyder Andrew J Vickers Ganesh V Raj Peter T Scardino Paul Russo | 2006 | Lancet Oncology2006，，9： | 4 |
| 10 | Targeting ryanodine receptors for anti-arrhythmic therapy显示文摘Antiarrhythmic 药是压制或阻止反常的心节奏的一组药品,它经常与实质的病态和死亡被联系。典型地指向血浆膜离子隧道的当前的 antiarrhythmic 药限制了临床的成功,在一些,情况被描述了为是支持 arrhythmic。然而,最近的研究建议钙的那个病理学的版本(从经由心脏的 ryanodine 受体(RyR2 ) 的 sarcoplasmic 蜂窝胃的 Ca 2+) 能为 antiarrhythmic 代表一个有希望的目标治疗。心脏舒张的 SR Ca 2+ 版本在两个被连接了到 arrhythmogenesis 继承心律不齐症候群“ catecholaminergic 多态的室的心悸亢进”并且心疾病的获得的形式(例如, atrial 纤维性颤动,心失败) 。药品的几个班被显示了减少反常 RyR2 活动并且可以通过 SR Ca 2+ 漏缝的减小对触发的心律不齐授与保护。在这评论,我们将为稳定 RyR2 评估当前的药理学方法并且基于分子的机制的当前的证据建议处理形式。 | Mark D McCAULEY | 2011 | Acta Pharmacologica Sinica2011，32，6： | 3 |
| 11 | Quantification of ventilation enhancement using the Eye CAN roof support显示文摘Convergence of roof and floor in underground mine openings is a common occurrence. This convergence not only adversely affects the ability of workers, equipment and supplies to travel through the mine, it also reduces the effectiveness of the mine ventilation system, which is essential for the dilution of methane gas and airborne respirable dust. While installing secondary standing supports to control floor and roof convergence, such supports, by nature, partially obstruct a portion of the airway. These added obstructions inhibit the ability of the ventilation system to operate as efficiently as it could by increasing the resistance in and reducing the cross-sectional area of the airway. This study introduces and demonstrates the benefits of The Eye CAN^(TM) standing roof support, which controls floor and roof convergence and is less obstructive to air flow than conventional wooden cribs. Laboratory findings show that the normal resistance of a supported lined airway is reduced by using this new product from Burrell Mining Products, Inc., while providing the same roof support characteristics of an established product—The CANò. Load vs. displacement curves generated from laboratory tests demonstrated that this new product behaves with the same roof support characteristics as others in The CAN product family. Ventilation data gathered from a simulated mine entry was then used for computational fluid dynamics(CFD) modeling.The CFD analysis showed an improvement with The Eye CAN vs. other accepted forms of standing roof support. This proof-of-concept study suggests that, when using this new product made by Burrell Mining Products, Inc., not only will the convergence from the roof and floor be controlled, but airway resistance will also be reduced. | Shook Michael T Sindelar Mark F, Jiang Hua Luo Yi | 2017 | International Journal of Mining Science and Technology2017，27，1： | 3 |
| 12 | Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience显示文摘 | Phil A Hart Mark D Topazian Thomas E Witzig Jonathan E Clain Ferga C Gleeson Robin R Klebig Michael J Levy Randall K Pearson Bret T Petersen Thomas C Smyrk Aravind Sugumar Naoki Takahashi Santhi S Vege Suresh T Chari | 2013 | Gut2013，，11： | 2 |
| 13 | 抑郁症的非药物治疗:系统性综述与证据图显示文摘背景抑郁症非药物治疗的疗效比较目前仍然不清楚。方法我们对一些系统性综述作了概述,回顾了随机对照试验(RCT),比较抑郁症非药物治疗的有效性和认知行为治疗(CBT)。对多个电子数据库在2016年2月之前发表的所有文献进行了检索,不限制语言。成对的评阅人进行资料纳入、数据提炼并评估偏倚的风险。在适用的时候进行了荟萃分析。结果我们收录了367项RCT,纳入了约2000名患者,进行了11种治疗,导出17项独立的头对头比较。通过标准化的量表评估,发现CBT、自然疗法、行为干预与躯体活动干预可以降低抑郁的严重程度。然而,这些非药物干预的相对疗效仍然缺乏。这些干预对临床缓解和复发的效果不清楚。CBT的发生率比抗抑郁药物更低。局限性由于证据缺乏一致性、证据不清或偏倚风险高,导致证据的质量只是低到中等,限制了我们研究结果的可信度。结论抑郁症的非药物治疗能减少抑郁症状,在轻度到重度抑郁症患者中,应当合并抗抑郁药物治疗,一同进行。对于非药物治疗的选择,应当根据患者的价值观、偏好、临床和社会因素来与患者共同作出决定。 | Wigdan H Farah Mouaz Alsawas Maria Mainou Fares Alahdab Magdoleen H Farah Ahmed T Ahmed Essa A Mohamed Jehad Almasri Michael R Gionfriddo Ana Castaneda-Guarderas Khaled Mohammed Zhen Wang Noor Asi Craig N Sawchuk Mark D Williams Larry J Prokop M Hassan Murad Annie LeBlanc | 2017 | 英国医学杂志中文版2017，20，11： | 2 |
| 14 | Widespread use of gastric acid inhibitors in infants:Are they needed? Are they safe?显示文摘Gastroesophageal reflux is a common phenomenon in infants,but the differentiation between gastro-esophageal reflux and gastroesophageal reflux disease can be difficult.Symptoms are non-specific and there is increasing evidence that the majority of symptoms may not be acid-related.Despite this,gastric acid inhibitors such as proton pump inhibitors are widely and increasingly used,often without objective evidence or investigations to guide treatment.Several studies have shown that these medications are ineffective at treating symptoms associated with reflux in the absence of endoscopically proven oesophagitis.With a lack of evidence for efficacy,attention is now being turned to the potential risks of gastric acid suppression.Previously assumed safety of these medications is being challenged with evidence of potential side effects including GI and respiratory infections,bacterial overgrowth,adverse bone health,food allergy and drug interactions. | Mark Safe Wei H Chan Steven T Leach Lee Sutton Kei Lui Usha Krishnan | 2016 | World Journal of Gastrointestinal Pharmacology and Therapeutics2016，7，4： | 2 |
| 15 | Treatment of relapsing autoimmune pancreatitis with immunomodulators and rituximab: the Mayo Clinic experience显示文摘 | Phil A Hart Mark D Topazian Thomas E Witzig Jonathan E Clain Ferga C Gleeson Robin R Klebig Michael J Levy Randall K Pearson Bret T Petersen Thomas C Smyrk Aravind Sugumar Naoki Takahashi Santhi S Vege Suresh T Chari | 2013 | Gut2013，，11： | 2 |
| 16 | Measuring mutual fund performance with characteristic-based benchmarks显示文摘 | Daniel K Mark G Sheridan T | 1997 | Journal of Finance1997，52，： | 2 |
| 17 | Toxicity of Benzotriazole and Benzotriazole Derivatives to Three Aquatic Species显示文摘 | David A Pillard Jeffrey S Cornell Doree L DuFresne Mark T Hernandez | 2000 | Water Research2000，，2： | 2 |
| 18 | Percutaneous transluminal angioplasty balloons for endoscopic ultrasound-guided pancreatic duct interventions显示文摘BACKGROUND Endoscopic ultrasound(EUS)-guided main pancreatic duct(PD)access may be used when conventional endoscopic retrograde cholangiopancreatography(ERCP)techniques fail.The use of a percutaneous transluminal angioplasty balloon(PTAB),originally developed for vascular interventions,can be used to facilitate transmural(e.g.,transgastric)PD access and to dilate high-grade pancreatic strictures.AIM To describe the technique,efficacy,and safety of PTABs for EUS-guided PD interventions.METHODS Patients who underwent EUS with use of a PTAB from March 2011 to August 2021 were retrospectively identified from a tertiary care medical center supply database.PTABs included 3-4 French angioplasty catheters with 3-4 mm balloons designed to use over a 0.018-inch guidewire.The primary outcome was technical success.Secondary outcomes included incidence of adverse events(AEs)and need for early reintervention.RESULTS A total of 23 patients were identified(48%female,mean age 55.8 years).Chronic pancreatitis was the underlying etiology in 13(56.5%)patients,surgically altered anatomy(SAA)with stricture in 7(30.4%),and SAA with post-operative leak in 3(13.0%).Technical success was achieved in 20(87%)cases.Overall AE rate was 26%(n=6).All AEs were mild and included 1 pancreatic duct leak,2 cases of post-procedure pancreatitis,and 3 admissions for post-procedural pain.No patients required early re-intervention.CONCLUSION EUS-guided use of PTABs for PD access and/or stricture management is feasible with an acceptable safety profile and can be considered in patients when conventional ERCP cannulation fails. | Jad P AbiMansour Barham K Abu Dayyeh Michael J Levy Andrew C Storm John A Martin Bret T Petersen Ryan J Law Mark D Topazian Vinay Chandrasekhara | 2022 | World Journal of Gastrointestinal Endoscopy2022，14，8： | 2 |
| 19 | End-stage renal disease is associated with increased post endoscopic retrograde cholangiopancreatography adverse events in hospitalized patients显示文摘AIM To determine if end-stage renal disease (ESRD) is a risk factor for post endoscopic retrograde cholangio-pancreatography (ERCP) adverse events (AEs). METHODS We performed a retrospective cohort study using the Nationwide Inpatient Sample (NIS) 2011-2013. We identified adult patients who underwent ERCP using the International Classification of Diseases 9^(th) Revision (ICD-9-CM). Included patients were divided into three groups: ESRD, chronic kidney disease (CKD), and control. The primary outcome was post-ERCP AEs including pancreatitis, bleeding, and perforation determined based on specific ICD-9-CM codes. Secondary outcomes were length of hospital stay, in-hospital mortality, and admission cost. AEs and mortality were compared using multivariate logistic regression analysis.RESULTS There were 492175 discharges that underwent ERCP during the 3 years. The ESRD and CKD groups contained 7347 and 39403 hospitalizations respectively, whereas the control group had 445424 hospitalizations. Post-ERCP pancreatitis (PEP) was significantly higher in the ESRD group (8.3%) compared to the control group (4.6%) with adjusted odd ratio (aOR) = 1.7 (95% CI: 1.4-2.1, ~aP < 0.001). ESRD was associated with significantly higher ERCP-related bleeding (5.1%) compared to the control group 1.5% (aOR = 1.86, 95%CI: 1.4-2.4, ~aP < 0.001). ESRD had increased hospital mortality 7.1% vs 1.15% in the control OR = 6.6 (95%CI: 5.3-8.2, ~aP < 0.001), longer hospital stay with adjusted mean difference (aMD) = 5.9 d (95% CI: 5.0-6.7 d, ~aP < 0.001) and higher hospitalization charges aMD = $+82064 (95%CI: $68221-$95906, ~aP < 0.001). CONCLUSION ESRD is a risk factor for post-ERCP AEs and is associated with higher hospital mortality. Careful selection and close monitoring is warranted to improve outcomes. | Tarek Sawas Fateh Bazerbachi Samir Haffar Won K Cho Michael J Levy John A Martin Bret T Petersen Mark D Topazian Vinay Chandrasekhara Barham K Abu Dayyeh | 2018 | World Journal of Gastroenterology2018，24，41： | 2 |
| 20 | Pollution performance of DC insulators under operating conditions显示文摘 | Changetal T C Steffens H G Marks J | 1981 | IEEE Trans on EI1981，16，3： | 2 |
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