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| 1 | Sitagliptin in patients with non-alcoholic steatohepatitis: A randomized, placebo-controlled trial显示文摘AIM To evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of nonalcoholic steatohepatitis(NASH).METHODS Twelve patients with biopsy-proven NASH were randomized to sitagliptin(100 mg daily)(n=6)or placebo(n=6)for 24 wk.The primary outcome was improvement in liver fibrosis after 24 wk.Secondary outcomes included evaluation of changes in NAFLD activity score(NAS),individual components of NAS(hepatocyte ballooning,lobular inflammation,and steatosis),glycemic control and insulin resistance[including measurements of glycated hemoglobin(Hb A1C)and adipocytokines],lipid profile including free fatty acids,adipose distribution measured using magnetic resonance imaging(MRI),and thrombosis markers(platelet aggregation and plasminogen activator inhibitor 1 levels).We also sought to determine the correlation between changes in hepatic fat fraction(%)[as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation(IDEAL)MRI technique]and changes in hepatic steatosis on liver biopsy.RESULTS Sitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy(mean difference between sitagliptin and placebo arms,0.40,P=0.82).There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS.Compared to baseline,those patients who received sitagliptin demonstrated improved Hb A1C(6.7%±0.4%vs 7.9%±1.0%,P=0.02),and trended towards improved adiponectin levels(4.7±3.5μg/m L vs 3.9±2.7μg/m L,P=0.06)and triglyceride levels(1.26±0.43 mmol/L vs 2.80±1.64 mmol/L,P=0.08).However,when compared with placebo,sitagliptin did not cause a statistically significant improvement in Hb A1C(mean difference,-0.7%,P=0.19)nor triglyceride levels(mean difference-1.10mmol/L,P=0.19)but did trend towards improved adiponectin levels only(mean difference,0.60μg/m L,P=0.095).No significant changes in anthropometrics,liver enzymes,other adipocytokines,lipid profile,thrombosis parameters,or adipose distribution were demonstrated.The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment,and the Spearman correlation coefficients ranged from r=0.819(baseline)to r=0.878(post-treatment),P=0.002.CONCLUSION Sitagliptin does not improve fibrosis score or NAS after 24 wk of therapy.The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis. | Tisha R Joy Charles A McKenzie Rommel G Tirona Kelly Summers Shannon Seney Subrata Chakrabarti Neel Malhotra Melanie D Beaton | 2017 | World Journal of Gastroenterology2017，23，1： | 18 |
| 2 | The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. | Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid | 2019 | Genes & Diseases2019，6，3： | 15 |
| 3 | Quantitative analysis of ruminal methanogenic microbial populations in beef cattle divergent in phenotypic residual feed intake(RFI)offered contrasting diets显示文摘Background:Methane(CH_4) emissions in cattle are an undesirable end product of rumen methanogenic fermentative activity as they are associated not only with negative environmental impacts but also with reduced host feed efficiency.The aim of this study was to quantify total and specific rumen microbial methanogenic populations in beef cattle divergently selected for residual feed intake(RFI) while offered(i) a low energy high forage(HF) diet followed by(ii) a high energy low forage(LF) diet.Ruminal fluid was collected from 14 high(H)and 14 low(L) RFI animals across both dietary periods.Quantitative real time PCR(qRT-PCR) analysis was conducted to quantify the abundance of total and specific rumen methanogenic microbes.Spearman correlation analysis was used to investigate the association between the relative abundance of methanogens and animal performance,rumen fermentation variables and diet digestibility.Results:Abundance of methanogens,did not differ between RFI phenotypes.However,relative abundance of total and specific methanogen species was affected(P< 0.05) by diet type,with greater abundance observed while animals were offered the LF compared to the HF diet.Conclusions:These findings suggest that differences in abundance of specific rumen methanogen species may not contribute to variation in CH_4 emissions between efficient and inefficient animals,however dietary manipulation can influence the abundance of total and specific methanogen species. | Ciara A Carberry David A Kenny Alan K Kelly Sinead M Waters | 2014 | Journal of Animal Science and Biotechnology2014，5，4： | 6 |
| 4 | Role of endoscopic vacuum therapy in the management of gastrointestinal transmural defects显示文摘A gastrointestinal(GI) transmural defect is defined as total rupture of the GI wall,and these defects can be divided into three categories: perforations,leaks,and fistulas. Surgical management of these defects is usually challenging and may be associated with high morbidity and mortality rates. Recently,several novel endoscopic techniques have been developed,and endoscopy has become a firstline approach for therapy of these conditions. The use of endoscopic vacuum therapy(EVT) is increasing with favorable results. This technique involves endoscopic placement of a sponge connected to a nasogastric tube into the defect cavity or lumen. This promotes healing via five mechanisms,including macrodeformation,microdeformation,changes in perfusion,exudate control,and bacterial clearance,which is similar to the mechanisms in which skin wounds are treated with commonly employed wound vacuums. EVT can be used in the upper GI tract,small bowel,biliopancreatic regions,and lower GI tract,with variable success rates and a satisfactory safety profile. In this article,we review and discuss the mechanism of action,materials,techniques,efficacy,and safety of EVT in the management of patients with GI transmural defects. | Diogo Turiani Hourneaux de Moura Bruna Furia Buzetti Hourneaux de Moura Michael A Manfredi Kelly E Hathorn Ahmad N Bazarbashi Igor Braga Ribeiro Eduardo Guimaraes Hourneaux de Moura Christopher C Thompson | 2019 | World Journal of Gastrointestinal Endoscopy2019，11，5： | 6 |
| 5 | 循证医学在急诊医疗中的局限性显示文摘 | A M Kelly C Horsley 冯丽洁 | 2001 | 中国危重病急救医学2001，13，10： | 6 |
| 6 | Nat Genet:单基因突变导致过敏性皮炎的发生显示文摘最近,研究者们鉴定出了一类导致神经性皮炎发生的关键基因突变:CARDll。来自美国NIH过敏与传染病研究所的研究者们通过对四个没有血缘关系的患病家庭进行分析,发现了这一导致疾病产生的基因、 | Chi A Ma, Yuan Zhang, Michael A Weinreich, Jonathan J Lyons, Celeste G Nelson, Thomas DiMaggio, Kelly D Stone, Joshua D Milner Jeffrey R Stinson, Elisa Ruffo, Batsukh Dorjbal, Swadhinya Arjunaraja, Kelsey Voss, Andrew L Snow Jordan K Abbott, Pia J Hauk, Paul R Reynolds, Erwin W Gelfand Elisa Ruffo Salomé Glauzy, Natsuko Yamakawa, Eric Meffre Jennifer Stoddard, Julie Niemela, Sergio D Rosenzweig Yu Zhang, Helen F Matthews Joshua J McElwee Nina Jones Alejandro Palma, Matías Oleastro, Emma Prieto, Andrea R Bernasconi, Geronimo Dubra, Silvia Danielian, Jonathan Zaiat, Marcelo A Marti Brian Kim Megan A Cooper Neil Romberg | 2017 | 现代生物医学进展2017，17，27： | 3 |
| 7 | Cancer-related inflammation and treatment effectiveness显示文摘 | Connie I Diakos Kellie A Charles Donald C McMillan Stephen J Clarke | 2014 | Lancet Oncology2014，，： | 3 |
| 8 | Testing for HCV Infection: An Update of Guidance for Clinicians and Laboratorians显示文摘 | Getchell Jane P Wroblewski Kelly E DeMaria Alfred Bean Christine L Parker Monica M Pandori Mark Dufour D Robert Busch Michael P Brecher Mark E Meyer William A Pesano Rick L Teo Chong-Gee Beckett Geoffrey A Araujo Aufra C Branson Bernard M D | 2013 | MMWR. Morbidity and Mortality Weekly Report2013，，18： | 3 |
| 9 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 10 | Biliary atresia显示文摘 | Jane L Hartley Mark Davenport Deirdre A Kelly | 2009 | The Lancet . 2009 (9702)2009，，： | 2 |
| 11 | SLC26A4 mutation testing for hearing loss associated with enlargement of the vestibular aqueduct显示文摘Pendred syndrome(PS) is characterized by autosomal recessive inheritance of goiter associated with a defect of iodide organification, hearing loss, enlargement of the vestibular aqueduct(EVA), and mutations of the SLC26A4 gene. However, not all EVA patients have PSor SLC26A4 mutations. Two mutant alleles of SLC26A4 are detected in 1/4 of North American or European EVA populations, one mutant allele is detected in another 1/4 of patient populations, and no mutations are detected in the other 1/2. The presence of two mutant alleles of SLC26A4 is associated with abnormal iodide organification, increased thyroid gland volume, increased severity of hearing loss, and bilateral EVA. The presence of a single mutant allele of SLC26A4 is associated with normal iodide organification, normal thyroid gland volume, less severe hearing loss and either bilateral or unilateral EVA. When other underlying correlations are accounted for, the presence of a cochlear malformation or the size of EVA does not have an effect on hearing thresholds. This is consistent with observations of an Slc26a4 mutant mouse model of EVA in which hearing loss is independent of endolymphatic hydrops or inner ear malformations. Segregation analyses of EVA in families suggest that the patients carrying one mutant allele of SLC26A4 have a second, undetected mutant allele of SLC26A4, and the probability of a sibling having EVA is consistent with its segregation as an autosomal recessive trait. Patients without any mutations are an etiologically heterogeneous group in which siblings have a lower probability of having EVA. SLC26A4 mutation testing can provide prognostic information to guide clinical surveillance and management, as well as the probability of EVA affecting a sibling. | Taku Ito Julie Muskett Parna Chattaraj Byung Yoon Choi Kyu Yup Lee Christopher K Zalewski Kelly A King Xiangming Li Philine Wangemann Thomas Shawker Carmen C Brewer Seth L Alper Andrew J Griffith | 2013 | World Journal of Otorhinolaryngology2013，3，2： | 2 |
| 12 | Biliary atresia显示文摘 | Jane L Hartley Mark Davenport Deirdre A Kelly | 2009 | 2009 (9702)2009，，9702： | 2 |
| 13 | Cost-effectiveness of varicocele surgery in the era ot assisted reproductive technology显示文摘 | Kelly A Chiles Peter N Schlegel | 2016 | Asian Journal of Andrology2016，18，2： | 2 |
| 14 | Nitrogen dynamics following field application of biochar in a temperate North American maize-based production system显示文摘 | David Güere?a Johannes Lehmann Kelly Hanley Akio Enders Charles Hyland Susan Riha | 2013 | Plant and Soil2013，，1： | 2 |
| 15 | Severe Hand, Foot, and Mouth Disease Associated with Coxsackievirus A6 - Alabama, Connecticut, California, and Nevada, November 201 1 - February 2012显示文摘 | McIntyre Mary G Stevens Kelly M Davidson Sherri Pippin Tina Magill Dagny Kulhanjian Julie A Kelly Daniel Greenhow Tara L Salas Maria L Yagi Shigeo Padilla Tasha Berumen Ricardo Glaser Carol Landry Marie Louise Lott Jason Chen Lei Paulson | 2012 | EN2012，，12： | 2 |
| 16 | Human disease modeling with induced pluripotent stem cells显示文摘 | Alan Trounson Kelly A Shepard Natalie D DeWitt | 2012 | Current Opinion in Genetics & Development2012，，5： | 2 |
| 17 | Aggressive surgery for metastatic liver neuroendocrine tumors显示文摘 | Jeffrey A Norton Robert S Warren Mary G Kelly Marlene B Zuraek Robert T Jensen | 2003 | Surgery2003，，： | 2 |
| 18 | Organizational inertia and momentum: A dynamic model of strategic change 显示文摘 | Kelly A Amburgey T L | 1991 | Academy of Management Journal1991，34，3： | 1 |
| 19 | Correlation between bovine milksomatic cell count and polymorphonuclear leukocyte level for samples of bulkmilk and milk from individual cows显示文摘 | Kelly A L Tiernan D O'Sullivan C | 2000 | Journal of Dairy Science2000，83，2： | 1 |
| 20 | Angiotensin type 2 receptor is expressed in the adult rat kidney and promotes cellular proliferation and apoptosis 显示文摘 | Cao Z Kelly D J Cox A | 2000 | Kidney Int2000，58，6： | 1 |
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