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| 1 | Cirrhotic portal hypertension: From pathophysiology to novel therapeutics显示文摘Portal hypertension and bleeding from gastroesophageal varices is the major cause of morbidity and mortality in patients with cirrhosis. Portal hypertension is initiated by increased intrahepatic vascular resistance and a hyperdynamic circulatory state. The latter is characterized by a high cardiac output, increased total blood volume and splanchnic vasodilatation, resulting in increased mesenteric blood flow. Pharmacological manipulation of cirrhotic portal hypertension targets both the splanchnic and hepatic vascular beds. Drugs such as angiotensin converting enzyme inhibitors and angiotensin Ⅱ type receptor 1 blockers, which target the components of the classical renin angiotensin system(RAS), are expected to reduce intrahepatic vascular tone by reducing extracellular matrix deposition and vasoactivity of contractile cells and thereby improve portal hypertension. However, these drugs have been shown to produce significant offtarget effects such as systemic hypotension and renal failure. Therefore, the current pharmacological mainstay in clinical practice to prevent variceal bleeding and improving patient survival by reducing portal pressure is non-selective-blockers(NSBBs). These NSBBs work by reducing cardiac output and splanchnic vasodilatation but most patients do not achieve an optimal therapeutic response and a significant proportion of patients are unable to tolerate these drugs.Although statins, used alone or in combination with NSBBs, have been shown to improve portal pressure and overall mortality in cirrhotic patients, further randomized clinical trials are warranted involving larger patient populations with clear clinical end points. On the other hand, recent findings from studies that have investigated the potential use of the blockers of the components of the alternate RAS provided compelling evidence that could lead to the development of drugs targeting the splanchnic vascular bed to inhibit splanchnic vasodilatation in portal hypertension. This review outlines the mechanisms related to the pathogenesis of portal hypertension and attempts to provide an update on currently available therapeutic approaches in the management of portal hypertension with special emphasis on how the alternate RAS could be manipulated in our search for development of safe, specific and effective novel therapies to treat portal hypertension in cirrhosis. | Lakmie S Gunarathne Harinda Rajapaksha Nicholas Shackel Peter W Angus Chandana B Herath | 2020 | World Journal of Gastroenterology2020，26，40： | 24 |
| 2 | Software for automated classification of probe-based confocal laser endomicroscopy videos of colorectal polyps显示文摘AIM:To support probe-based confocal laser endomi-croscopy (pCLE) diagnosis by designing software for the automated classification of colonic polyps. METHODS:Intravenous fluorescein pCLE imaging of colorectal lesions was performed on patients under-going screening and surveillance colonoscopies, followed by polypectomies. All resected specimens were reviewed by a reference gastrointestinal pathologist blinded to pCLE information. Histopathology was used as the criterion standard for the differentiation between neoplastic and non-neoplastic lesions. The pCLE video sequences, recorded for each polyp, were analyzed off-line by 2 expert endoscopists who were blinded to the endoscopic characteristics and histopathology. These pCLE videos, along with their histopathology diagnosis, were used to train the automated classification software which is a content-based image retrieval technique followed by k-nearest neighbor classification. The performance of the off-line diagnosis of pCLE videos established by the 2 expert endoscopists was compared with that of automated pCLE software classification. All evaluations were performed using leave-one-patient- out cross-validation to avoid bias. RESULTS:Colorectal lesions (135) were imaged in 71 patients. Based on histopathology, 93 of these 135 lesions were neoplastic and 42 were non-neoplastic. The study found no statistical significance for the difference between the performance of automated pCLE software classification (accuracy 89.6%, sensitivity 92.5%, specificity 83.3%, using leave-one-patient-out cross-validation) and the performance of the off-line diagnosis of pCLE videos established by the 2 expert endoscopists (accuracy 89.6%, sensitivity 91.4%, specificity 85.7%). There was very low power (< 6%) to detect the observed differences. The 95% confidence intervals for equivalence testing were:-0.073 to 0.073 for accuracy, -0.068 to 0.089 for sensitivity and -0.18 to 0.13 for specificity. The classification software proposed in this study is not a 'black box' but an informative tool based on the query by example model that produces, as intermediate results, visually similar annotated videos that are directly interpretable by the endoscopist. CONCLUSION:The proposed software for automated classification of pCLE videos of colonic polyps achieves high performance, comparable to that of off-line diagnosis of pCLE videos established by expert endoscopists. | Barbara André Tom Vercauteren Anna M Buchner Murli Krishna Nicholas Ayache Michael B Wallace | 2012 | World Journal of Gastroenterology2012，18，39： | 5 |
| 3 | Circulating MicroRNA Is a Biomarker of Pediatric Crohn Disease显示文摘 | Adam M Zahm Meena Thayu Nicholas J Hand Amber Horner Mary B Leonard Joshua R Friedman | 2011 | Journal of Pediatric Gastroenterology and Nutrition2011，，1： | 3 |
| 4 | DNA vaccination of infants in the presence of maternal antibody: a measles model in the primate显示文摘 | Mary Premenko-Lanier Paul A Rota Gary Rhodes David Verhoeven Dan H Barouch Nicholas W Lerche Norman L Letvin William J Bellini Michael B McChesney | 2003 | Virology2003，，1： | 2 |
| 5 | Perioperative risk factors associated with delayed graft function following deceased donor kidney transplantation:A retrospective,single center study显示文摘BACKGROUND There is an abundant need to increase the availability of deceased donor kidney transplantation(DDKT)to address the high incidence of kidney failure.Challenges exist in the utilization of higher risk donor organs into what appears to be increasingly complex recipients;thus the identification of modifiable risk factors associated with poor outcomes is paramount.AIM To identify risk factors associated with delayed graft function(DGF).METHODS Consecutive adults undergoing DDKT between January 2016 and July 2017 were identified with a study population of 294 patients.The primary outcome was the occurrence of DGF.RESULTS The incidence of DGF was 27%.Under logistic regression,eight independent risk factors for DGF were identified including recipient body mass index≥30 kg/m^(2),baseline mean arterial pressure<110 mmHg,intraoperative phenylephrine administration,cold storage time≥16 h,donation after cardiac death,donor history of coronary artery disease,donor terminal creatinine≥1.9 mg/dL,and a hypothermic machine perfusion(HMP)pump resistance≥0.23 mmHg/mL/min.CONCLUSION We delineate the association between DGF and recipient characteristics of preinduction mean arterial pressure below 110 mmHg,metabolic syndrome,donorspecific risk factors,HMP pump parameters,and intraoperative use of phenylephrine. | Nicholas V Mendez Yehuda Raveh Joshua J Livingstone Gaetano Ciancio Giselle Guerra George W Burke III Vadim B Shatz Fouad G Souki Linda J Chen Mahmoud Morsi Jose M Figueiro Tony M Ibrahim Werviston L DeFaria Ramona Nicolau-Raducu | 2021 | World Journal of Transplantation2021，11，4： | 2 |
| 6 | Thermal hypersensitivity in a subset of irritable bowel syndrome patients显示文摘AIM:To characterize thermal hypersensitivity in patients with constipation-and diarrhea-predominant irritable bowel syndrome (IBS).METHODS:Thermal pain sensitivity was tested among patients with diarrhea-predominant IBS (D-IBS) and constipation-predominant IBS (C-IBS) compared to healthy subjects.A total of 42 patients (29 female and 13 male;mean age 27.0±6.4 years) with D-IBS;24 patients (16 female and eight male;mean age 32.5±8.8 years) with C-IBS;and 52 control subjects (34 female and 18 male;mean age 27.3±8.0 years) participated in the study.Thermal stimuli were delivered using a Medoc Thermal Sensory Analyzer with a 3 cm × 3 cm surface area.Heat pain threshold (HPTh) and heat pain tolerance (HPTo) were assessed on the left ventral forearm and left calf using an ascending method of limits.The Functional Bowel Disease Severity Index (FBDSI) was also obtained for all subjects.RESULTS:Controls were less sensitive than C-IBS and D-IBS (both at P < 0.001) with no differences between C-IBS and D-IBS for HPTh and HPTo.Thermal hyperalgesia was present in both groups of IBS patients relative to controls,with IBS patients reporting significantly lower pain threshold and pain tolerance at both test sites.Cluster analysis revealed the presence of subgroups of IBS patients based on thermal hyperalgesia.One cluster (17% of the sample) showed a profile of heat pain sensitivity very similar to that of healthy controls;a second cluster (47% of the sample) showed moderate heat pain sensitivity;and a third cluster (36% of the sample) showed a very high degree of thermal hyperalgesia.CONCLUSION:A subset of IBS patients had thermal hypersensitivity compared to controls,who reported significantly lower HPTh and HPTo.All IBS patients had a higher score on the FBDSI than controls.Interestingly,the subset of IBS patients with high thermal sensitivity (36%) had the highest FBDSI score compared to the other two groups of IBS patients. | QiQi Zhou Roger B Fillingim Joseph L Riley Ⅲ G Nicholas Verne | 2009 | World Journal of Gastroenterology2009，15，26： | 2 |
| 7 | Phase Ⅱ, Randomized, Double - Blind, Placebo - Controlled study of recombinant human intestinal trefoil factor oral spray for prevention of oral mucositis in patients with color- ectal cancer who are receiving fluoroutacil - based chemo- therapy显示文摘 | DOUGLAS E P NICHOLAS P B LILIA I A | 2009 | J Clin Oncol2009，27，： | 1 |
| 8 | Sources of Conflict between Work and Family Roles显示文摘 | GREENHAUS J H NICHOLAS J B | 1985 | Academy of Management Review1985，10，1： | 1 |
| 9 | Density functional study of cluster models of zeolites 1 Structure and acidity of hydroxyl groups in disioxane analogs显示文摘 | STEVE M S NICHOLAS J B | 1993 | J Phys Chem1993，97，38： | 1 |
| 10 | Theoretical study of the methylbenzene side-chain hydrocarbon pool mechanism in methanol to olefin catalysis显示文摘 | Arstad B Nicholas J B Haw J F | 2004 | J Am Chem Soc2004，126，： | 1 |
| 11 | Multichannel Weighted Speech Classification System for Prediction of major depres- sion in adolescents显示文摘 | Kuan E Margaret L Nicholas B | 2013 | IEEE Transactions On Biomedical En- gineering2013，60，2： | 1 |
| 12 | NMR and theoretical study of acid sites formed by adsorption of SO3 onto oxide surfaces显示文摘 | Zhang J Nicholas J B Haw J F | 2000 | Angew Chem2000，112，： | 1 |
| 13 | Distillation with secondary reflux and vaporization: a comparative evaluation 显示文摘 | Mah R S H Nicholas J J Wodnik R B | 1977 | AIChE J1977，23，5： | 1 |
| 14 | Structural and mechanistic investigation of a phosphatemodified HZSM-5 catalyst for methanol conversion显示文摘 | Abubakar S M Marcus D M Lee J C Ehresmann J O Chen C Y Kletnieks P W Guenther D R Hayman M J Pavlova M Nicholas J B Haw J F | | 0，，10： | 1 |
| 15 | Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rats显示文摘 | Tanapat P Nicholas B Hastings NB | 1999 | J Neurosci1999，19，： | 1 |
| 16 | Diagenesis of a tight gas sand reservoir:Upper Cretaceous Mesaverde Group, Poceance Basin,Colorado 显示文摘 | Trevor M Stroker Nicholas B Harris Crawford Elliott | 2013 | Marine and Petroleum Geology2013，40，： | 1 |
| 17 | Serological identification of mycoplasmas by growth and metabolic inhibition tests 显示文摘 | Poveda J B Nicholas R | 1998 | Methods Mol Biol1998，104，： | 1 |
| 18 | Remote instrument diagnosis on the internet显示文摘 | Nicholas H M C Bernard B C David M H | 1998 | IEEE Intelligent System & Their Application1998，13，3： | 1 |
| 19 | SIK2 is a centrosome kinase re- quired for bipolar mitotic spindle formation that provides a po- tential target for therapy in ovarian cancer 显示文摘 | Ashour A Zhen L Nicholas B | 2010 | Cancer Cell2010，18，2： | 1 |
| 20 | Angiotensin I converting enzyme-inhibitory peptides from commercial wet-and dry-milled corn germ显示文摘 | Nicholas Parris Robert A Moreau David B Johnston | | 0，，08： | 1 |
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